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[ { "id": "PMID-10025957__text", "type": "abstract", "text": [ "UCP4, a novel brain-specific mitochondrial protein that reduces membrane potential in mammalian cells. Uncoupling proteins (UCPs) are a family of mitochondrial transporter proteins that have been implicated in thermoregulatory heat production and maintenance of the basal metabolic rate. We have identified and partially characterized a novel member of the human uncoupling protein family, termed uncoupling protein-4 (UCP4). Protein sequence analyses showed that UCP4 is most related to UCP3 and possesses features characteristic of mitochondrial transporter proteins. Unlike other known UCPs, UCP4 transcripts are exclusively expressed in both fetal and adult brain tissues. UCP4 maps to human chromosome 6p11.2-q12. Consistent with its potential role as an uncoupling protein, UCP4 is localized to the mitochondria and its ectopic expression in mammalian cells reduces mitochondrial membrane potential. These findings suggest that UCP4 may be involved in thermoregulatory heat production and metabolism in the brain.\n" ], "offsets": [ [ 0, 1020 ] ] } ]

[ { "id": "PMID-10025957_T1", "type": "Protein", "text": [ "UCP4" ], "offsets": [ [ 0, 4 ] ], "normalized": [] }, { "id": "PMID-10025957_T2", "type": "Tissue", "text": [ "brain" ], "offsets": [ [ 14, 19 ] ], "normalized": [] }, { "id": "PMID-10025957_T3", "type": "CellComponent", "text": [ "mitochondrial" ], "offsets": [ [ 29, 42 ] ], "normalized": [] }, { "id": "PMID-10025957_T4", "type": "Protein", "text": [ "protein" ], "offsets": [ [ 43, 50 ] ], "normalized": [] }, { "id": "PMID-10025957_T5", "type": "Eukaryote", "text": [ "mammalian" ], "offsets": [ [ 86, 95 ] ], "normalized": [] }, { "id": "PMID-10025957_T6", "type": "Cell", "text": [ "cells" ], "offsets": [ [ 96, 101 ] ], "normalized": [] }, { "id": "PMID-10025957_T7", "type": "Protein", "text": [ "Uncoupling proteins" ], "offsets": [ [ 103, 122 ] ], "normalized": [] }, { "id": "PMID-10025957_T8", "type": "Protein", "text": [ "UCPs" ], "offsets": [ [ 124, 128 ] ], "normalized": [] }, { "id": "PMID-10025957_T9", "type": "CellComponent", "text": [ "mitochondrial" ], "offsets": [ [ 146, 159 ] ], "normalized": [] }, { "id": "PMID-10025957_T10", "type": "Protein", "text": [ "transporter proteins" ], "offsets": [ [ 160, 180 ] ], "normalized": [] }, { "id": "PMID-10025957_T13", "type": "Eukaryote", "text": [ "human" ], "offsets": [ [ 357, 362 ] ], "normalized": [] }, { "id": "PMID-10025957_T14", "type": "Protein", "text": [ "uncoupling protein" ], "offsets": [ [ 363, 381 ] ], "normalized": [] }, { "id": "PMID-10025957_T15", "type": "Protein", "text": [ "uncoupling protein-4" ], "offsets": [ [ 397, 417 ] ], "normalized": [] }, { "id": "PMID-10025957_T16", "type": "Protein", "text": [ "UCP4" ], "offsets": [ [ 419, 423 ] ], "normalized": [] }, { "id": "PMID-10025957_T17", "type": "Protein", "text": [ "Protein" ], "offsets": [ [ 426, 433 ] ], "normalized": [] }, { "id": "PMID-10025957_T18", "type": "Protein", "text": [ "UCP4" ], "offsets": [ [ 464, 468 ] ], "normalized": [] }, { "id": "PMID-10025957_T19", "type": "Protein", "text": [ "UCP3" ], "offsets": [ [ 488, 492 ] ], "normalized": [] }, { "id": "PMID-10025957_T20", "type": "CellComponent", "text": [ "mitochondrial" ], "offsets": [ [ 534, 547 ] ], "normalized": [] }, { "id": "PMID-10025957_T21", "type": "Protein", "text": [ "transporter proteins" ], "offsets": [ [ 548, 568 ] ], "normalized": [] }, { "id": "PMID-10025957_T22", "type": "Protein", "text": [ "UCPs" ], "offsets": [ [ 589, 593 ] ], "normalized": [] }, { "id": "PMID-10025957_T23", "type": "Protein", "text": [ "UCP4" ], "offsets": [ [ 595, 599 ] ], "normalized": [] }, { "id": "PMID-10025957_T24", "type": "Transcript", "text": [ "transcripts" ], "offsets": [ [ 600, 611 ] ], "normalized": [] }, { "id": "PMID-10025957_T26", "type": "Tissue", "text": [ "fetal" ], "offsets": [ [ 646, 651 ] ], "normalized": [] }, { "id": "PMID-10025957_T28", "type": "Protein", "text": [ "UCP4" ], "offsets": [ [ 677, 681 ] ], "normalized": [] }, { "id": "PMID-10025957_T29", "type": "Eukaryote", "text": [ "human" ], "offsets": [ [ 690, 695 ] ], "normalized": [] }, { "id": "PMID-10025957_T30", "type": "Chromosome", "text": [ "chromosome" ], "offsets": [ [ 696, 706 ] ], "normalized": [] }, { "id": "PMID-10025957_T31", "type": "Protein", "text": [ "uncoupling protein" ], "offsets": [ [ 760, 778 ] ], "normalized": [] }, { "id": "PMID-10025957_T32", "type": "Protein", "text": [ "UCP4" ], "offsets": [ [ 780, 784 ] ], "normalized": [] }, { "id": "PMID-10025957_T33", "type": "CellComponent", "text": [ "mitochondria" ], "offsets": [ [ 805, 817 ] ], "normalized": [] }, { "id": "PMID-10025957_T35", "type": "Eukaryote", "text": [ "mammalian" ], "offsets": [ [ 848, 857 ] ], "normalized": [] }, { "id": "PMID-10025957_T36", "type": "Cell", "text": [ "cells" ], "offsets": [ [ 858, 863 ] ], "normalized": [] }, { "id": "PMID-10025957_T37", "type": "CellComponent", "text": [ "mitochondrial" ], "offsets": [ [ 872, 885 ] ], "normalized": [] }, { "id": "PMID-10025957_T38", "type": "Protein", "text": [ "UCP4" ], "offsets": [ [ 934, 938 ] ], "normalized": [] }, { "id": "PMID-10025957_T41", "type": "Tissue", "text": [ "brain" ], "offsets": [ [ 1013, 1018 ] ], "normalized": [] }, { "id": "PMID-10025957_T45", "type": "ProteinIdentification", "text": [ "identified" ], "offsets": [ [ 296, 306 ] ], "normalized": [] }, { "id": "PMID-10025957_T27", "type": "Tissue", "text": [ "adult brain tissues" ], "offsets": [ [ 656, 675 ] ], "normalized": [] } ]

[ { "id": "PMID-10025957_E1", "type": "CellularProcess", "trigger": { "text": [ "thermoregulatory heat production" ], "offsets": [ [ 210, 242 ] ] }, "arguments": [] }, { "id": "PMID-10025957_E2", "type": "MetabolicPathway", "trigger": { "text": [ "metabolic" ], "offsets": [ [ 272, 281 ] ] }, "arguments": [] }, { "id": "PMID-10025957_E3", "type": "GeneExpression", "trigger": { "text": [ "expressed" ], "offsets": [ [ 628, 637 ] ] }, "arguments": [ { "role": "hasPatient", "ref_id": "PMID-10025957_T24" } ] }, { "id": "PMID-10025957_E4", "type": "GeneExpression", "trigger": { "text": [ "ectopic expression" ], "offsets": [ [ 826, 844 ] ] }, "arguments": [ { "role": "hasPatient", "ref_id": "PMID-10025957_T32" } ] }, { "id": "PMID-10025957_E5", "type": "CellularProcess", "trigger": { "text": [ "thermoregulatory heat production" ], "offsets": [ [ 958, 990 ] ] }, "arguments": [] }, { "id": "PMID-10025957_E6", "type": "MetabolicPathway", "trigger": { "text": [ "metabolism" ], "offsets": [ [ 995, 1005 ] ] }, "arguments": [] }, { "id": "PMID-10025957_E7", "type": "CellHomeostasis", "trigger": { "text": [ "membrane potential" ], "offsets": [ [ 64, 82 ] ] }, "arguments": [] }, { "id": "PMID-10025957_E8", "type": "Affecting", "trigger": { "text": [ "reduces" ], "offsets": [ [ 56, 63 ] ] }, "arguments": [ { "role": "hasAgent", "ref_id": "PMID-10025957_T4" }, { "role": "hasPatient", "ref_id": "PMID-10025957_E7" } ] }, { "id": "PMID-10025957_E9", "type": "Maintenance", "trigger": { "text": [ "maintenance" ], "offsets": [ [ 247, 258 ] ] }, "arguments": [ { "role": "hasPatient", "ref_id": "PMID-10025957_E2" } ] }, { "id": "PMID-10025957_E10", "type": "CellHomeostasis", "trigger": { "text": [ "membrane potential" ], "offsets": [ [ 886, 904 ] ] }, "arguments": [] }, { "id": "PMID-10025957_E11", "type": "Affecting", "trigger": { "text": [ "reduces" ], "offsets": [ [ 864, 871 ] ] }, "arguments": [ { "role": "hasAgent", "ref_id": "PMID-10025957_E4" }, { "role": "hasPatient", "ref_id": "PMID-10025957_E10" } ] } ]

[]

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[ { "id": "PMID-10025962__text", "type": "abstract", "text": [ "Molecular cloning and characterization of a novel angiopoietin family protein, angiopoietin-3. Using homology-based PCR, we have isolated cDNA encoding a novel member (491 amino acids) of the angiopoietin (Ang) family from human adult heart cDNA and have designated it angiopoietin-3 (Ang3). The NH2-terminal and COOH-terminal portions of Ang-3 contain the characteristic coiled-coil domain and fibrinogen-like domain that are conserved in other known Angs. Ang3 has a highly hydrophobic region at the N-terminus (approximately 21 amino acids) that is typical of a signal sequence for protein secretion. Ang3 mRNA is most abundant in adrenal gland, placenta, thyroid gland, heart and small intestine in human adult tissues. Additionally, Ang3 is a secretory protein, but is not a mitogen in endothelial cells.\n" ], "offsets": [ [ 0, 810 ] ] } ]

[ { "id": "PMID-10025962_T1", "type": "Protein", "text": [ "angiopoietin family protein" ], "offsets": [ [ 50, 77 ] ], "normalized": [] }, { "id": "PMID-10025962_T2", "type": "Protein", "text": [ "angiopoietin-3" ], "offsets": [ [ 79, 93 ] ], "normalized": [] }, { "id": "PMID-10025962_T3", "type": "DNA", "text": [ "cDNA" ], "offsets": [ [ 138, 142 ] ], "normalized": [] }, { "id": "PMID-10025962_T4", "type": "AminoAcid", "text": [ "amino acids" ], "offsets": [ [ 172, 183 ] ], "normalized": [] }, { "id": "PMID-10025962_T5", "type": "Protein", "text": [ "angiopoietin" ], "offsets": [ [ 192, 204 ] ], "normalized": [] }, { "id": "PMID-10025962_T6", "type": "Protein", "text": [ "Ang" ], "offsets": [ [ 206, 209 ] ], "normalized": [] }, { "id": "PMID-10025962_T7", "type": "Eukaryote", "text": [ "human" ], "offsets": [ [ 223, 228 ] ], "normalized": [] }, { "id": "PMID-10025962_T8", "type": "Tissue", "text": [ "heart" ], "offsets": [ [ 235, 240 ] ], "normalized": [] }, { "id": "PMID-10025962_T9", "type": "DNA", "text": [ "cDNA" ], "offsets": [ [ 241, 245 ] ], "normalized": [] }, { "id": "PMID-10025962_T11", "type": "Protein", "text": [ "Ang3" ], "offsets": [ [ 285, 289 ] ], "normalized": [] }, { "id": "PMID-10025962_T12", "type": "Protein", "text": [ "Ang-3" ], "offsets": [ [ 339, 344 ] ], "normalized": [] }, { "id": "PMID-10025962_T13", "type": "ProteinDomain", "text": [ "coiled-coil domain" ], "offsets": [ [ 372, 390 ] ], "normalized": [] }, { "id": "PMID-10025962_T14", "type": "ProteinDomain", "text": [ "fibrinogen-like domain" ], "offsets": [ [ 395, 417 ] ], "normalized": [] }, { "id": "PMID-10025962_T15", "type": "Protein", "text": [ "Angs" ], "offsets": [ [ 452, 456 ] ], "normalized": [] }, { "id": "PMID-10025962_T16", "type": "Protein", "text": [ "Ang3" ], "offsets": [ [ 458, 462 ] ], "normalized": [] }, { "id": "PMID-10025962_T18", "type": "Protein", "text": [ "Ang3" ], "offsets": [ [ 604, 608 ] ], "normalized": [] }, { "id": "PMID-10025962_T19", "type": "MessengerRNA", "text": [ "mRNA" ], "offsets": [ [ 609, 613 ] ], "normalized": [] }, { "id": "PMID-10025962_T20", "type": "Tissue", "text": [ "adrenal gland" ], "offsets": [ [ 634, 647 ] ], "normalized": [] }, { "id": "PMID-10025962_T21", "type": "Tissue", "text": [ "placenta" ], "offsets": [ [ 649, 657 ] ], "normalized": [] }, { "id": "PMID-10025962_T22", "type": "Tissue", "text": [ "thyroid gland" ], "offsets": [ [ 659, 672 ] ], "normalized": [] }, { "id": "PMID-10025962_T23", "type": "Tissue", "text": [ "heart" ], "offsets": [ [ 674, 679 ] ], "normalized": [] }, { "id": "PMID-10025962_T24", "type": "Tissue", "text": [ "small intestine" ], "offsets": [ [ 684, 699 ] ], "normalized": [] }, { "id": "PMID-10025962_T25", "type": "Eukaryote", "text": [ "human" ], "offsets": [ [ 703, 708 ] ], "normalized": [] }, { "id": "PMID-10025962_T26", "type": "Tissue", "text": [ "tissues" ], "offsets": [ [ 715, 722 ] ], "normalized": [] }, { "id": "PMID-10025962_T27", "type": "Protein", "text": [ "Ang3" ], "offsets": [ [ 738, 742 ] ], "normalized": [] }, { "id": "PMID-10025962_T28", "type": "Protein", "text": [ "secretory protein" ], "offsets": [ [ 748, 765 ] ], "normalized": [] }, { "id": "PMID-10025962_T29", "type": "Protein", "text": [ "mitogen" ], "offsets": [ [ 780, 787 ] ], "normalized": [] }, { "id": "PMID-10025962_T30", "type": "Cell", "text": [ "endothelial cells" ], "offsets": [ [ 791, 808 ] ], "normalized": [] }, { "id": "PMID-10025962_T31", "type": "Sequence", "text": [ "signal sequence" ], "offsets": [ [ 565, 580 ] ], "normalized": [] } ]

[ { "id": "PMID-10025962_E1", "type": "ProteinTransport", "trigger": { "text": [ "protein secretion" ], "offsets": [ [ 585, 602 ] ] }, "arguments": [ { "role": "hasAgent", "ref_id": "PMID-10025962_T31" } ] } ]

[]

[ { "id": "PMID-10025962_R1", "type": "encodes", "arg1_id": "PMID-10025962_T3", "arg2_id": "PMID-10025962_T5", "normalized": [] }, { "id": "PMID-10025962_R3", "type": "fromSpecies", "arg1_id": "PMID-10025962_T8", "arg2_id": "PMID-10025962_T7", "normalized": [] }, { "id": "PMID-10025962_R4", "type": "locatedIn", "arg1_id": "PMID-10025962_T9", "arg2_id": "PMID-10025962_T8", "normalized": [] }, { "id": "PMID-10025962_R5", "type": "hasPart", "arg1_id": "PMID-10025962_T12", "arg2_id": "PMID-10025962_T13", "normalized": [] }, { "id": "PMID-10025962_R6", "type": "hasPart", "arg1_id": "PMID-10025962_T12", "arg2_id": "PMID-10025962_T14", "normalized": [] }, { "id": "PMID-10025962_R7", "type": "encodes", "arg1_id": "PMID-10025962_T19", "arg2_id": "PMID-10025962_T18", "normalized": [] }, { "id": "PMID-10025962_R8", "type": "locatedIn", "arg1_id": "PMID-10025962_T19", "arg2_id": "PMID-10025962_T20", "normalized": [] }, { "id": "PMID-10025962_R9", "type": "locatedIn", "arg1_id": "PMID-10025962_T19", "arg2_id": "PMID-10025962_T21", "normalized": [] }, { "id": "PMID-10025962_R10", "type": "locatedIn", "arg1_id": "PMID-10025962_T19", "arg2_id": "PMID-10025962_T22", "normalized": [] }, { "id": "PMID-10025962_R11", "type": "locatedIn", "arg1_id": "PMID-10025962_T19", "arg2_id": "PMID-10025962_T23", "normalized": [] }, { "id": "PMID-10025962_R12", "type": "locatedIn", "arg1_id": "PMID-10025962_T19", "arg2_id": "PMID-10025962_T24", "normalized": [] }, { "id": "PMID-10025962_R13", "type": "locatedIn", "arg1_id": "PMID-10025962_T19", "arg2_id": "PMID-10025962_T26", "normalized": [] }, { "id": "PMID-10025962_R14", "type": "fromSpecies", "arg1_id": "PMID-10025962_T26", "arg2_id": "PMID-10025962_T25", "normalized": [] }, { "id": "PMID-10025962_R15", "type": "locatedIn", "arg1_id": "PMID-10025962_T29", "arg2_id": "PMID-10025962_T30", "normalized": [] } ]

[ { "id": "PMID-10026142__text", "type": "abstract", "text": [ "Purification and identification of a novel subunit of protein serine/threonine phosphatase 4. The catalytic subunit of protein serine/threonine phosphatase 4 (PP4C) has greater than 65% amino acid identity to the catalytic subunit of protein phosphatase 2A (PP2AC). Despite this high homology, PP4 does not appear to associate with known PP2A regulatory subunits. As a first step toward characterization of PP4 holoenzymes and identification of putative PP4 regulatory subunits, PP4 was purified from bovine testis soluble extracts. PP4 existed in two complexes of approximately 270-300 and 400-450 kDa as determined by gel filtration chromatography. The smaller PP4 complex was purified by sequential phenyl-Sepharose, Source 15Q, DEAE2, and Superdex 200 gel filtration chromatographies. The final product contained two major proteins: the PP4 catalytic subunit plus a protein that migrated as a doublet of 120-125 kDa on SDS-polyacrylamide gel electrophoresis. The associated protein, termed PP4R1, and PP4C also bound to microcystin-Sepharose. Mass spectrometry analysis of the purified complex revealed two major peaks, at 35 (PP4C) and 105 kDa (PP4R1). Amino acid sequence information of several peptides derived from the 105 kDa protein was utilized to isolate a human cDNA clone. Analysis of the predicted amino acid sequence revealed 13 nonidentical repeats similar to repeats found in the A subunit of PP2A (PP2AA). The PP4R1 cDNA clone engineered with an N-terminal Myc tag was expressed in COS M6 cells and PP4C co-immunoprecipitated with Myc-tagged PP4R1. These data indicate that one form of PP4 is similar to the core complex of PP2A in that it consists of a catalytic subunit and a \"PP2AA-like\" structural subunit.\n" ], "offsets": [ [ 0, 1730 ] ] } ]

[ { "id": "PMID-10026142_T1", "type": "ProteinSubunit", "text": [ "subunit" ], "offsets": [ [ 43, 50 ] ], "normalized": [] }, { "id": "PMID-10026142_T2", "type": "Enzyme", "text": [ "protein serine/threonine phosphatase 4" ], "offsets": [ [ 54, 92 ] ], "normalized": [] }, { "id": "PMID-10026142_T3", "type": "ProteinSubunit", "text": [ "catalytic subunit" ], "offsets": [ [ 98, 115 ] ], "normalized": [] }, { "id": "PMID-10026142_T4", "type": "Enzyme", "text": [ "protein serine/threonine phosphatase 4" ], "offsets": [ [ 119, 157 ] ], "normalized": [] }, { "id": "PMID-10026142_T5", "type": "ProteinSubunit", "text": [ "PP4C" ], "offsets": [ [ 159, 163 ] ], "normalized": [] }, { "id": "PMID-10026142_T6", "type": "AminoAcid", "text": [ "amino acid" ], "offsets": [ [ 186, 196 ] ], "normalized": [] }, { "id": "PMID-10026142_T7", "type": "ProteinSubunit", "text": [ "catalytic subunit" ], "offsets": [ [ 213, 230 ] ], "normalized": [] }, { "id": "PMID-10026142_T8", "type": "Enzyme", "text": [ "protein phosphatase 2A" ], "offsets": [ [ 234, 256 ] ], "normalized": [] }, { "id": "PMID-10026142_T9", "type": "ProteinSubunit", "text": [ "PP2AC" ], "offsets": [ [ 258, 263 ] ], "normalized": [] }, { "id": "PMID-10026142_T10", "type": "Enzyme", "text": [ "PP4" ], "offsets": [ [ 294, 297 ] ], "normalized": [] }, { "id": "PMID-10026142_T11", "type": "Enzyme", "text": [ "PP2A" ], "offsets": [ [ 338, 342 ] ], "normalized": [] }, { "id": "PMID-10026142_T12", "type": "ProteinSubunit", "text": [ "regulatory subunits" ], "offsets": [ [ 343, 362 ] ], "normalized": [] }, { "id": "PMID-10026142_T13", "type": "Holoenzyme", "text": [ "PP4 holoenzymes" ], "offsets": [ [ 407, 422 ] ], "normalized": [] }, { "id": "PMID-10026142_T14", "type": "Enzyme", "text": [ "putative PP4" ], "offsets": [ [ 445, 457 ] ], "normalized": [] }, { "id": "PMID-10026142_T15", "type": "ProteinSubunit", "text": [ "regulatory subunits" ], "offsets": [ [ 458, 477 ] ], "normalized": [] }, { "id": "PMID-10026142_T16", "type": "Enzyme", "text": [ "PP4" ], "offsets": [ [ 479, 482 ] ], "normalized": [] }, { "id": "PMID-10026142_T17", "type": "Eukaryote", "text": [ "bovine" ], "offsets": [ [ 501, 507 ] ], "normalized": [] }, { "id": "PMID-10026142_T18", "type": "Tissue", "text": [ "testis" ], "offsets": [ [ 508, 514 ] ], "normalized": [] }, { "id": "PMID-10026142_T19", "type": "Enzyme", "text": [ "PP4" ], "offsets": [ [ 533, 536 ] ], "normalized": [] }, { "id": "PMID-10026142_T20", "type": "Enzyme", "text": [ "PP4 complex" ], "offsets": [ [ 663, 674 ] ], "normalized": [] }, { "id": "PMID-10026142_T21", "type": "Protein", "text": [ "proteins" ], "offsets": [ [ 827, 835 ] ], "normalized": [] }, { "id": "PMID-10026142_T22", "type": "Enzyme", "text": [ "PP4" ], "offsets": [ [ 841, 844 ] ], "normalized": [] }, { "id": "PMID-10026142_T23", "type": "ProteinSubunit", "text": [ "catalytic subunit" ], "offsets": [ [ 845, 862 ] ], "normalized": [] }, { "id": "PMID-10026142_T24", "type": "Protein", "text": [ "protein" ], "offsets": [ [ 870, 877 ] ], "normalized": [] }, { "id": "PMID-10026142_T25", "type": "Protein", "text": [ "associated protein" ], "offsets": [ [ 967, 985 ] ], "normalized": [] }, { "id": "PMID-10026142_T26", "type": "ProteinSubunit", "text": [ "PP4R1" ], "offsets": [ [ 994, 999 ] ], "normalized": [] }, { "id": "PMID-10026142_T27", "type": "ProteinSubunit", "text": [ "PP4C" ], "offsets": [ [ 1005, 1009 ] ], "normalized": [] }, { "id": "PMID-10026142_T28", "type": "ProteinComplex", "text": [ "complex" ], "offsets": [ [ 1090, 1097 ] ], "normalized": [] }, { "id": "PMID-10026142_T29", "type": "ProteinSubunit", "text": [ "PP4C" ], "offsets": [ [ 1131, 1135 ] ], "normalized": [] }, { "id": "PMID-10026142_T30", "type": "ProteinSubunit", "text": [ "PP4R1" ], "offsets": [ [ 1150, 1155 ] ], "normalized": [] }, { "id": "PMID-10026142_T31", "type": "AminoAcid", "text": [ "Amino acid" ], "offsets": [ [ 1158, 1168 ] ], "normalized": [] }, { "id": "PMID-10026142_T32", "type": "Peptide", "text": [ "peptides" ], "offsets": [ [ 1201, 1209 ] ], "normalized": [] }, { "id": "PMID-10026142_T33", "type": "Protein", "text": [ "protein" ], "offsets": [ [ 1235, 1242 ] ], "normalized": [] }, { "id": "PMID-10026142_T34", "type": "Eukaryote", "text": [ "human" ], "offsets": [ [ 1269, 1274 ] ], "normalized": [] }, { "id": "PMID-10026142_T35", "type": "DNA", "text": [ "cDNA" ], "offsets": [ [ 1275, 1279 ] ], "normalized": [] }, { "id": "PMID-10026142_T36", "type": "AminoAcid", "text": [ "amino acid" ], "offsets": [ [ 1313, 1323 ] ], "normalized": [] }, { "id": "PMID-10026142_T38", "type": "Protein", "text": [ "PP2A" ], "offsets": [ [ 1411, 1415 ] ], "normalized": [] }, { "id": "PMID-10026142_T39", "type": "ProteinSubunit", "text": [ "PP2AA" ], "offsets": [ [ 1417, 1422 ] ], "normalized": [] }, { "id": "PMID-10026142_T40", "type": "ProteinSubunit", "text": [ "PP4R1" ], "offsets": [ [ 1429, 1434 ] ], "normalized": [] }, { "id": "PMID-10026142_T41", "type": "DNA", "text": [ "cDNA" ], "offsets": [ [ 1435, 1439 ] ], "normalized": [] }, { "id": "PMID-10026142_T44", "type": "Cell", "text": [ "COS M6 cells" ], "offsets": [ [ 1501, 1513 ] ], "normalized": [] }, { "id": "PMID-10026142_T45", "type": "Protein", "text": [ "PP4C" ], "offsets": [ [ 1518, 1522 ] ], "normalized": [] }, { "id": "PMID-10026142_T47", "type": "Protein", "text": [ "PP4R1" ], "offsets": [ [ 1561, 1566 ] ], "normalized": [] }, { "id": "PMID-10026142_T48", "type": "Enzyme", "text": [ "PP4" ], "offsets": [ [ 1605, 1608 ] ], "normalized": [] }, { "id": "PMID-10026142_T49", "type": "ProteinComplex", "text": [ "core complex" ], "offsets": [ [ 1627, 1639 ] ], "normalized": [] }, { "id": "PMID-10026142_T50", "type": "Enzyme", "text": [ "PP2A" ], "offsets": [ [ 1643, 1647 ] ], "normalized": [] }, { "id": "PMID-10026142_T53", "type": "ProteinComplex", "text": [ "complexes" ], "offsets": [ [ 552, 561 ] ], "normalized": [] }, { "id": "PMID-10026142_T37", "type": "ProteinSubunit", "text": [ "A subunit" ], "offsets": [ [ 1398, 1407 ] ], "normalized": [] }, { "id": "PMID-10026142_T42", "type": "BindingAssay", "text": [ "N-terminal Myc tag" ], "offsets": [ [ 1465, 1483 ] ], "normalized": [] }, { "id": "PMID-10026142_T46", "type": "BindingAssay", "text": [ "co-immunoprecipitated" ], "offsets": [ [ 1523, 1544 ] ], "normalized": [] }, { "id": "PMID-10026142_T54", "type": "ProteinSubunit", "text": [ "catalytic subunit" ], "offsets": [ [ 1673, 1690 ] ], "normalized": [] }, { "id": "PMID-10026142_T51", "type": "ProteinSubunit", "text": [ "\"PP2AA-like\" structural subunit" ], "offsets": [ [ 1697, 1728 ] ], "normalized": [] } ]

[ { "id": "PMID-10026142_E1", "type": "GeneExpression", "trigger": { "text": [ "expressed" ], "offsets": [ [ 1488, 1497 ] ] }, "arguments": [ { "role": "hasPatient", "ref_id": "PMID-10026142_T41" } ] } ]

[]

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[ { "id": "PMID-10026181__text", "type": "abstract", "text": [ "Conserved residues of human XPG protein important for nuclease activity and function in nucleotide excision repair. The human XPG endonuclease cuts on the 3' side of a DNA lesion during nucleotide excision repair. Mutations in XPG can lead to the disorders xeroderma pigmentosum (XP) and Cockayne syndrome. XPG shares sequence similarities in two regions with a family of structure-specific nucleases and exonucleases. To begin defining its catalytic mechanism, we changed highly conserved residues and determined the effects on the endonuclease activity of isolated XPG, its function in open complex formation and dual incision reconstituted with purified proteins, and its ability to restore cellular resistance to UV light. The substitution A792V present in two XP complementation group G (XP-G) individuals reduced but did not abolish endonuclease activity, explaining their mild clinical phenotype. Isolated XPG proteins with Asp-77 or Glu-791 substitutions did not cleave DNA. In the reconstituted repair system, alanine substitutions at these positions permitted open complex formation but were inactive for 3' cleavage, whereas D77E and E791D proteins retained considerable activity. The function of each mutant protein in the reconstituted system was mirrored by its ability to restore UV resistance to XP-G cell lines. Hydrodynamic measurements indicated that XPG exists as a monomer in high salt conditions, but immunoprecipitation of intact and truncated XPG proteins showed that XPG polypeptides can interact with each other, suggesting dimerization as an element of XPG function. The mutation results define critical residues in the catalytic center of XPG and strongly suggest that key features of the strand cleavage mechanism and active site structure are shared by members of the nuclease family.\n" ], "offsets": [ [ 0, 1815 ] ] } ]

[ { "id": "PMID-10026181_T1", "type": "Eukaryote", "text": [ "human" ], "offsets": [ [ 22, 27 ] ], "normalized": [] }, { "id": "PMID-10026181_T2", "type": "Enzyme", "text": [ "XPG protein" ], "offsets": [ [ 28, 39 ] ], "normalized": [] }, { "id": "PMID-10026181_T3", "type": "CatalyticActivity", "text": [ "nuclease activity" ], "offsets": [ [ 54, 71 ] ], "normalized": [] }, { "id": "PMID-10026181_T5", "type": "Eukaryote", "text": [ "human" ], "offsets": [ [ 120, 125 ] ], "normalized": [] }, { "id": "PMID-10026181_T6", "type": "Enzyme", "text": [ "XPG endonuclease" ], "offsets": [ [ 126, 142 ] ], "normalized": [] }, { "id": "PMID-10026181_T7", "type": "DNA", "text": [ "DNA" ], "offsets": [ [ 168, 171 ] ], "normalized": [] }, { "id": "PMID-10026181_T10", "type": "Enzyme", "text": [ "XPG" ], "offsets": [ [ 227, 230 ] ], "normalized": [] }, { "id": "PMID-10026181_T13", "type": "Enzyme", "text": [ "XPG" ], "offsets": [ [ 307, 310 ] ], "normalized": [] }, { "id": "PMID-10026181_T14", "type": "Enzyme", "text": [ "nucleases" ], "offsets": [ [ 391, 400 ] ], "normalized": [] }, { "id": "PMID-10026181_T15", "type": "Enzyme", "text": [ "exonucleases" ], "offsets": [ [ 405, 417 ] ], "normalized": [] }, { "id": "PMID-10026181_T16", "type": "CatalyticActivity", "text": [ "endonuclease activity" ], "offsets": [ [ 533, 554 ] ], "normalized": [] }, { "id": "PMID-10026181_T17", "type": "Enzyme", "text": [ "isolated XPG" ], "offsets": [ [ 558, 570 ] ], "normalized": [] }, { "id": "PMID-10026181_T18", "type": "Protein", "text": [ "proteins" ], "offsets": [ [ 657, 665 ] ], "normalized": [] }, { "id": "PMID-10026181_T19", "type": "CatalyticActivity", "text": [ "endonuclease activity" ], "offsets": [ [ 839, 860 ] ], "normalized": [] }, { "id": "PMID-10026181_T20", "type": "Enzyme", "text": [ "Isolated XPG proteins" ], "offsets": [ [ 904, 925 ] ], "normalized": [] }, { "id": "PMID-10026181_T23", "type": "MutantProtein", "text": [ "mutant protein" ], "offsets": [ [ 1213, 1227 ] ], "normalized": [] }, { "id": "PMID-10026181_T24", "type": "Enzyme", "text": [ "XPG" ], "offsets": [ [ 1370, 1373 ] ], "normalized": [] }, { "id": "PMID-10026181_T25", "type": "Enzyme", "text": [ "XPG proteins" ], "offsets": [ [ 1467, 1479 ] ], "normalized": [] }, { "id": "PMID-10026181_T26", "type": "Enzyme", "text": [ "XPG" ], "offsets": [ [ 1492, 1495 ] ], "normalized": [] }, { "id": "PMID-10026181_T27", "type": "Peptide", "text": [ "polypeptides" ], "offsets": [ [ 1496, 1508 ] ], "normalized": [] }, { "id": "PMID-10026181_T29", "type": "Enzyme", "text": [ "XPG" ], "offsets": [ [ 1580, 1583 ] ], "normalized": [] }, { "id": "PMID-10026181_T31", "type": "Enzyme", "text": [ "XPG" ], "offsets": [ [ 1667, 1670 ] ], "normalized": [] }, { "id": "PMID-10026181_T33", "type": "Enzyme", "text": [ "nuclease" ], "offsets": [ [ 1798, 1806 ] ], "normalized": [] }, { "id": "PMID-10026181_T36", "type": "CatalyticActivity", "text": [ "catalytic mechanism" ], "offsets": [ [ 441, 460 ] ], "normalized": [] }, { "id": "PMID-10026181_T39", "type": "Enzyme", "text": [ "XP-G" ], "offsets": [ [ 793, 797 ] ], "normalized": [] }, { "id": "PMID-10026181_T42", "type": "Phenotype", "text": [ "phenotype" ], "offsets": [ [ 893, 902 ] ], "normalized": [] }, { "id": "PMID-10026181_T46", "type": "Cell", "text": [ "XP-G cell lines" ], "offsets": [ [ 1312, 1327 ] ], "normalized": [] }, { "id": "PMID-10026181_T48", "type": "DNA", "text": [ "strand" ], "offsets": [ [ 1717, 1723 ] ], "normalized": [] } ]

[ { "id": "PMID-10026181_E1", "type": "CellularMetabolicProcess", "trigger": { "text": [ "nucleotide excision repair" ], "offsets": [ [ 88, 114 ] ] }, "arguments": [] }, { "id": "PMID-10026181_E2", "type": "CellularMetabolicProcess", "trigger": { "text": [ "nucleotide excision repair" ], "offsets": [ [ 186, 212 ] ] }, "arguments": [] }, { "id": "PMID-10026181_E3", "type": "Mutation", "trigger": { "text": [ "Mutations" ], "offsets": [ [ 214, 223 ] ] }, "arguments": [ { "role": "hasPatient", "ref_id": "PMID-10026181_T10" } ] }, { "id": "PMID-10026181_E5", "type": "Disease", "trigger": { "text": [ "Cockayne syndrome" ], "offsets": [ [ 288, 305 ] ] }, "arguments": [ { "role": "hasAgent", "ref_id": "PMID-10026181_E3" } ] }, { "id": "PMID-10026181_E6", "type": "FormationOfProteinDNAComplex", "trigger": { "text": [ "open complex formation" ], "offsets": [ [ 1070, 1092 ] ] }, "arguments": [] }, { "id": "PMID-10026181_E7", "type": "Cleavage", "trigger": { "text": [ "cleavage" ], "offsets": [ [ 1118, 1126 ] ] }, "arguments": [] }, { "id": "PMID-10026181_E8", "type": "BindingToProtein", "trigger": { "text": [ "interact" ], "offsets": [ [ 1513, 1521 ] ] }, "arguments": [ { "role": "hasPatient", "ref_id": "PMID-10026181_T27" } ] }, { "id": "PMID-10026181_E9", "type": "Mutation", "trigger": { "text": [ "mutation" ], "offsets": [ [ 1598, 1606 ] ] }, "arguments": [ { "role": "hasPatient", "ref_id": "PMID-10026181_T31" } ] }, { "id": "PMID-10026181_E10", "type": "Cleavage", "trigger": { "text": [ "cleavage" ], "offsets": [ [ 1724, 1732 ] ] }, "arguments": [ { "role": "hasPatient", "ref_id": "PMID-10026181_T48" } ] }, { "id": "PMID-10026181_E11", "type": "Cleavage", "trigger": { "text": [ "cuts" ], "offsets": [ [ 143, 147 ] ] }, "arguments": [ { "role": "hasAgent", "ref_id": "PMID-10026181_T6" }, { "role": "hasPatient", "ref_id": "PMID-10026181_T7" } ] }, { "id": "PMID-10026181_E12", "type": "Disease", "trigger": { "text": [ "XP" ], "offsets": [ [ 280, 282 ] ] }, "arguments": [] }, { "id": "PMID-10026181_E13", "type": "ResponseProcess", "trigger": { "text": [ "cellular resistance to UV light" ], "offsets": [ [ 694, 725 ] ] }, "arguments": [] }, { "id": "PMID-10026181_E14", "type": "ActivationOfProcess", "trigger": { "text": [ "restore" ], "offsets": [ [ 686, 693 ] ] }, "arguments": [ { "role": "hasPatient", "ref_id": "PMID-10026181_E13" } ] }, { "id": "PMID-10026181_E15", "type": "Decrease", "trigger": { "text": [ "reduced" ], "offsets": [ [ 811, 818 ] ] }, "arguments": [ { "role": "hasAgent", "ref_id": "PMID-10026181_E16" }, { "role": "hasPatient", "ref_id": "PMID-10026181_T19" } ] }, { "id": "PMID-10026181_E16", "type": "Mutation", "trigger": { "text": [ "substitution A792V" ], "offsets": [ [ 731, 749 ] ] }, "arguments": [ { "role": "hasPatient", "ref_id": "PMID-10026181_T39" } ] }, { "id": "PMID-10026181_E17", "type": "CellularMetabolicProcess", "trigger": { "text": [ "repair system" ], "offsets": [ [ 1004, 1017 ] ] }, "arguments": [] }, { "id": "PMID-10026181_E18", "type": "ActivationOfProcess", "trigger": { "text": [ "restore" ], "offsets": [ [ 1287, 1294 ] ] }, "arguments": [ { "role": "hasPatient", "ref_id": "PMID-10026181_E19" } ] }, { "id": "PMID-10026181_E19", "type": "ResponseProcess", "trigger": { "text": [ "UV resistance" ], "offsets": [ [ 1295, 1308 ] ] }, "arguments": [] }, { "id": "PMID-10026181_E20", "type": "Dimerization", "trigger": { "text": [ "dimerization" ], "offsets": [ [ 1550, 1562 ] ] }, "arguments": [ { "role": "hasPatient", "ref_id": "PMID-10026181_T29" } ] } ]

[]

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[ { "id": "PMID-10026184__text", "type": "abstract", "text": [ "Mapping the functional domains of BRCA1. Interaction of the ring finger domains of BRCA1 and BARD1. Breast cancer 1 (BRCA1) and BRCA1-associated RING domain 1 (BARD1) are multidomain proteins that interact in vivo via their N-terminal RING finger motif regions. To characterize functional aspects of the BRCA1/BARD1 interaction, we have defined the structural domains required for the interaction, as well as their oligomerization state, relative stability, and possible nucleic acid binding activity. We have found that the RING finger motifs do not themselves constitute stable structural domains but are instead part of larger domains comprising residues 1-109 of BRCA1 and residues 26-119 of BARD1. These domains exist as homodimers and preferentially form a stable heterodimer. Shorter BRCA1 RING finger constructs do not interact with BARD1 or with longer BRCA1 constructs, indicating that the heterodimeric and homodimer interactions are mediated by regions outside the canonical RING finger motif. Nucleic acid binding is a generally proposed function of RING finger domains. We show that neither the homodimers nor the heterodimer displays affinity for nucleic acids, indicating that the proposed roles of BRCA1 and BARD1 in DNA repair and/or transcriptional activation must be mediated either by other regions of the proteins or by additional cofactors.\n" ], "offsets": [ [ 0, 1364 ] ] } ]

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[]

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[ { "id": "PMID-10026192__text", "type": "abstract", "text": [ "Characterization of a mutant pancreatic eIF-2alpha kinase, PEK, and co-localization with somatostatin in islet delta cells. Phosphorylation of eukaryotic translation initiation factor-2alpha (eIF-2alpha) is one of the key steps where protein synthesis is regulated in response to changes in environmental conditions. The phosphorylation is carried out in part by three distinct eIF-2alpha kinases including mammalian double-stranded RNA-dependent eIF-2alpha kinase (PKR) and heme-regulated inhibitor kinase (HRI), and yeast GCN2. We report the identification and characterization of a related kinase, PEK, which shares common features with other eIF-2alpha kinases including phosphorylation of eIF-2alpha in vitro. We show that human PEK is regulated by different mechanisms than PKR or HRI. In contrast to PKR or HRI, which are dependent on autophosphorylation for their kinase activity, a point mutation that replaced the conserved Lys-614 with an alanine completely abolished the eIF-2alpha kinase activity, whereas the mutant PEK was still autophosphorylated when expressed in Sf-9 cells. Northern blot analysis indicates that PEK mRNA was predominantly expressed in pancreas, though low expression was also present in several tissues. Consistent with the high levels of mRNA in pancreas, the PEK protein was only detected in human pancreatic islets, and the kinase co-localized with somatostatin, a pancreatic delta cell-specific hormone. Thus PEK is believed to play an important role in regulating protein synthesis in the pancreatic islet, especially in islet delta cells.\n" ], "offsets": [ [ 0, 1581 ] ] } ]

[ { "id": "PMID-10026192_T2", "type": "Tissue", "text": [ "pancreatic" ], "offsets": [ [ 29, 39 ] ], "normalized": [] }, { "id": "PMID-10026192_T3", "type": "Enzyme", "text": [ "eIF-2alpha kinase" ], "offsets": [ [ 40, 57 ] ], "normalized": [] }, { "id": "PMID-10026192_T4", "type": "Enzyme", "text": [ "PEK" ], "offsets": [ [ 59, 62 ] ], "normalized": [] }, { "id": "PMID-10026192_T5", "type": "Protein", "text": [ "somatostatin" ], "offsets": [ [ 89, 101 ] ], "normalized": [] }, { "id": "PMID-10026192_T6", "type": "Cell", "text": [ "islet delta cells" ], "offsets": [ [ 105, 122 ] ], "normalized": [] }, { "id": "PMID-10026192_T8", "type": "Eukaryote", "text": [ "eukaryotic" ], "offsets": [ [ 143, 153 ] ], "normalized": [] }, { "id": "PMID-10026192_T9", "type": "TranslationFactor", "text": [ "translation initiation factor-2alpha" ], "offsets": [ [ 154, 190 ] ], "normalized": [] }, { "id": "PMID-10026192_T10", "type": "TranslationFactor", "text": [ "eIF-2alpha" ], "offsets": [ [ 192, 202 ] ], "normalized": [] }, { "id": "PMID-10026192_T14", "type": "Enzyme", "text": [ "eIF-2alpha kinases" ], "offsets": [ [ 378, 396 ] ], "normalized": [] }, { "id": "PMID-10026192_T15", "type": "Eukaryote", "text": [ "mammalian" ], "offsets": [ [ 407, 416 ] ], "normalized": [] }, { "id": "PMID-10026192_T16", "type": "RNA", "text": [ "double-stranded RNA" ], "offsets": [ [ 417, 436 ] ], "normalized": [] }, { "id": "PMID-10026192_T17", "type": "Enzyme", "text": [ "eIF-2alpha kinase" ], "offsets": [ [ 447, 464 ] ], "normalized": [] }, { "id": "PMID-10026192_T18", "type": "Enzyme", "text": [ "PKR" ], "offsets": [ [ 466, 469 ] ], "normalized": [] }, { "id": "PMID-10026192_T19", "type": "Enzyme", "text": [ "heme-regulated inhibitor kinase" ], "offsets": [ [ 475, 506 ] ], "normalized": [] }, { "id": "PMID-10026192_T20", "type": "Enzyme", "text": [ "HRI" ], "offsets": [ [ 508, 511 ] ], "normalized": [] }, { "id": "PMID-10026192_T21", "type": "Eukaryote", "text": [ "yeast" ], "offsets": [ [ 518, 523 ] ], "normalized": [] }, { "id": "PMID-10026192_T22", "type": "Enzyme", "text": [ "GCN2" ], "offsets": [ [ 524, 528 ] ], "normalized": [] }, { "id": "PMID-10026192_T23", "type": "Enzyme", "text": [ "kinase" ], "offsets": [ [ 593, 599 ] ], "normalized": [] }, { "id": "PMID-10026192_T24", "type": "Enzyme", "text": [ "PEK" ], "offsets": [ [ 601, 604 ] ], "normalized": [] }, { "id": "PMID-10026192_T25", "type": "Enzyme", "text": [ "eIF-2alpha kinases" ], "offsets": [ [ 646, 664 ] ], "normalized": [] }, { "id": "PMID-10026192_T27", "type": "TranslationFactor", "text": [ "eIF-2alpha" ], "offsets": [ [ 694, 704 ] ], "normalized": [] }, { "id": "PMID-10026192_T28", "type": "Eukaryote", "text": [ "human" ], "offsets": [ [ 728, 733 ] ], "normalized": [] }, { "id": "PMID-10026192_T29", "type": "Enzyme", "text": [ "PEK" ], "offsets": [ [ 734, 737 ] ], "normalized": [] }, { "id": "PMID-10026192_T31", "type": "Enzyme", "text": [ "PKR" ], "offsets": [ [ 780, 783 ] ], "normalized": [] }, { "id": "PMID-10026192_T32", "type": "Enzyme", "text": [ "HRI" ], "offsets": [ [ 787, 790 ] ], "normalized": [] }, { "id": "PMID-10026192_T33", "type": "Enzyme", "text": [ "PKR" ], "offsets": [ [ 807, 810 ] ], "normalized": [] }, { "id": "PMID-10026192_T34", "type": "Enzyme", "text": [ "HRI" ], "offsets": [ [ 814, 817 ] ], "normalized": [] }, { "id": "PMID-10026192_T36", "type": "CatalyticActivity", "text": [ "kinase activity" ], "offsets": [ [ 872, 887 ] ], "normalized": [] }, { "id": "PMID-10026192_T39", "type": "TranslationFactor", "text": [ "eIF-2alpha" ], "offsets": [ [ 983, 993 ] ], "normalized": [] }, { "id": "PMID-10026192_T40", "type": "CatalyticActivity", "text": [ "kinase activity" ], "offsets": [ [ 994, 1009 ] ], "normalized": [] }, { "id": "PMID-10026192_T41", "type": "MutantProtein", "text": [ "mutant PEK" ], "offsets": [ [ 1023, 1033 ] ], "normalized": [] }, { "id": "PMID-10026192_T44", "type": "Cell", "text": [ "Sf-9 cells" ], "offsets": [ [ 1081, 1091 ] ], "normalized": [] }, { "id": "PMID-10026192_T45", "type": "Enzyme", "text": [ "PEK" ], "offsets": [ [ 1131, 1134 ] ], "normalized": [] }, { "id": "PMID-10026192_T46", "type": "MessengerRNA", "text": [ "mRNA" ], "offsets": [ [ 1135, 1139 ] ], "normalized": [] }, { "id": "PMID-10026192_T48", "type": "Tissue", "text": [ "pancreas" ], "offsets": [ [ 1171, 1179 ] ], "normalized": [] }, { "id": "PMID-10026192_T50", "type": "Tissue", "text": [ "tissues" ], "offsets": [ [ 1231, 1238 ] ], "normalized": [] }, { "id": "PMID-10026192_T51", "type": "MessengerRNA", "text": [ "mRNA" ], "offsets": [ [ 1275, 1279 ] ], "normalized": [] }, { "id": "PMID-10026192_T52", "type": "Tissue", "text": [ "pancreas" ], "offsets": [ [ 1283, 1291 ] ], "normalized": [] }, { "id": "PMID-10026192_T53", "type": "Enzyme", "text": [ "PEK protein" ], "offsets": [ [ 1297, 1308 ] ], "normalized": [] }, { "id": "PMID-10026192_T54", "type": "Eukaryote", "text": [ "human" ], "offsets": [ [ 1330, 1335 ] ], "normalized": [] }, { "id": "PMID-10026192_T55", "type": "Tissue", "text": [ "pancreatic islets" ], "offsets": [ [ 1336, 1353 ] ], "normalized": [] }, { "id": "PMID-10026192_T56", "type": "Enzyme", "text": [ "kinase" ], "offsets": [ [ 1363, 1369 ] ], "normalized": [] }, { "id": "PMID-10026192_T57", "type": "Peptide", "text": [ "somatostatin" ], "offsets": [ [ 1388, 1400 ] ], "normalized": [] }, { "id": "PMID-10026192_T58", "type": "Tissue", "text": [ "pancreatic" ], "offsets": [ [ 1404, 1414 ] ], "normalized": [] }, { "id": "PMID-10026192_T59", "type": "Cell", "text": [ "delta cell" ], "offsets": [ [ 1415, 1425 ] ], "normalized": [] }, { "id": "PMID-10026192_T60", "type": "Chemical", "text": [ "hormone" ], "offsets": [ [ 1435, 1442 ] ], "normalized": [] }, { "id": "PMID-10026192_T61", "type": "Enzyme", "text": [ "PEK" ], "offsets": [ [ 1449, 1452 ] ], "normalized": [] }, { "id": "PMID-10026192_T64", "type": "Tissue", "text": [ "pancreatic islet" ], "offsets": [ [ 1530, 1546 ] ], "normalized": [] }, { "id": "PMID-10026192_T65", "type": "Cell", "text": [ "islet delta cells" ], "offsets": [ [ 1562, 1579 ] ], "normalized": [] }, { "id": "PMID-10026192_T1", "type": "MutantProtein", "text": [ "mutant" ], "offsets": [ [ 22, 28 ] ], "normalized": [] } ]

[ { "id": "PMID-10026192_E2", "type": "Phosphorylation", "trigger": { "text": [ "Phosphorylation" ], "offsets": [ [ 124, 139 ] ] }, "arguments": [ { "role": "hasPatient", "ref_id": "PMID-10026192_T9" } ] }, { "id": "PMID-10026192_E3", "type": "ProteinBiosynthesis", "trigger": { "text": [ "protein synthesis" ], "offsets": [ [ 234, 251 ] ] }, "arguments": [] }, { "id": "PMID-10026192_E4", "type": "RegulatoryProcess", "trigger": { "text": [ "regulated" ], "offsets": [ [ 255, 264 ] ] }, "arguments": [ { "role": "hasPatient", "ref_id": "PMID-10026192_E3" } ] }, { "id": "PMID-10026192_E5", "type": "Phosphorylation", "trigger": { "text": [ "phosphorylation" ], "offsets": [ [ 321, 336 ] ] }, "arguments": [ { "role": "hasAgent", "ref_id": "PMID-10026192_T14" } ] }, { "id": "PMID-10026192_E6", "type": "Phosphorylation", "trigger": { "text": [ "phosphorylation" ], "offsets": [ [ 675, 690 ] ] }, "arguments": [ { "role": "hasAgent", "ref_id": "PMID-10026192_T24" }, { "role": "hasPatient", "ref_id": "PMID-10026192_T27" } ] }, { "id": "PMID-10026192_E7", "type": "RegulatoryProcess", "trigger": { "text": [ "regulated" ], "offsets": [ [ 741, 750 ] ] }, "arguments": [ { "role": "hasPatient", "ref_id": "PMID-10026192_T29" } ] }, { "id": "PMID-10026192_E8", "type": "Phosphorylation", "trigger": { "text": [ "autophosphorylation" ], "offsets": [ [ 842, 861 ] ] }, "arguments": [ { "role": "hasPatient", "ref_id": "PMID-10026192_T33" } ] }, { "id": "PMID-10026192_E9", "type": "Mutation", "trigger": { "text": [ "point mutation" ], "offsets": [ [ 891, 905 ] ] }, "arguments": [] }, { "id": "PMID-10026192_E10", "type": "NegativeRegulation", "trigger": { "text": [ "abolished" ], "offsets": [ [ 969, 978 ] ] }, "arguments": [ { "role": "hasAgent", "ref_id": "PMID-10026192_E9" }, { "role": "hasPatient", "ref_id": "PMID-10026192_T40" } ] }, { "id": "PMID-10026192_E11", "type": "Phosphorylation", "trigger": { "text": [ "autophosphorylated" ], "offsets": [ [ 1044, 1062 ] ] }, "arguments": [ { "role": "hasPatient", "ref_id": "PMID-10026192_T41" } ] }, { "id": "PMID-10026192_E12", "type": "GeneExpression", "trigger": { "text": [ "expressed" ], "offsets": [ [ 1068, 1077 ] ] }, "arguments": [ { "role": "hasPatient", "ref_id": "PMID-10026192_T41" } ] }, { "id": "PMID-10026192_E13", "type": "TranscriptionOfGene", "trigger": { "text": [ "expressed" ], "offsets": [ [ 1158, 1167 ] ] }, "arguments": [ { "role": "hasPatient", "ref_id": "PMID-10026192_T46" } ] }, { "id": "PMID-10026192_E15", "type": "RegulatoryProcess", "trigger": { "text": [ "regulating" ], "offsets": [ [ 1494, 1504 ] ] }, "arguments": [ { "role": "hasAgent", "ref_id": "PMID-10026192_T61" }, { "role": "hasPatient", "ref_id": "PMID-10026192_E16" } ] }, { "id": "PMID-10026192_E16", "type": "ProteinBiosynthesis", "trigger": { "text": [ "protein synthesis" ], "offsets": [ [ 1505, 1522 ] ] }, "arguments": [] }, { "id": "PMID-10026192_E1", "type": "ResponseProcess", "trigger": { "text": [ "response" ], "offsets": [ [ 268, 276 ] ] }, "arguments": [] }, { "id": "PMID-10026192_E14", "type": "Decrease", "trigger": { "text": [ "low" ], "offsets": [ [ 1188, 1191 ] ] }, "arguments": [ { "role": "hasPatient", "ref_id": "PMID-10026192_E17" } ] }, { "id": "PMID-10026192_E17", "type": "TranscriptionOfGene", "trigger": { "text": [ "expression" ], "offsets": [ [ 1192, 1202 ] ] }, "arguments": [] }, { "id": "PMID-10026192_E18", "type": "Increase", "trigger": { "text": [ "high levels" ], "offsets": [ [ 1260, 1271 ] ] }, "arguments": [ { "role": "hasPatient", "ref_id": "PMID-10026192_T51" } ] }, { "id": "PMID-10026192_E19", "type": "Phosphorylation", "trigger": { "text": [ "autophosphorylation" ], "offsets": [ [ 842, 861 ] ] }, "arguments": [ { "role": "hasPatient", "ref_id": "PMID-10026192_T34" } ] } ]

[]

[ { "id": "PMID-10026192_R1", "type": "locatedIn", "arg1_id": "PMID-10026192_T3", "arg2_id": "PMID-10026192_T2", "normalized": [] }, { "id": "PMID-10026192_R2", "type": "locatedIn", "arg1_id": "PMID-10026192_T3", "arg2_id": "PMID-10026192_T6", "normalized": [] }, { "id": "PMID-10026192_R3", "type": "locatedIn", "arg1_id": "PMID-10026192_T5", "arg2_id": "PMID-10026192_T6", "normalized": [] }, { "id": "PMID-10026192_R4", "type": "fromSpecies", "arg1_id": "PMID-10026192_T9", "arg2_id": "PMID-10026192_T8", "normalized": [] }, { "id": "PMID-10026192_R5", "type": "fromSpecies", "arg1_id": "PMID-10026192_T17", "arg2_id": "PMID-10026192_T15", "normalized": [] }, { "id": "PMID-10026192_R6", "type": "fromSpecies", "arg1_id": "PMID-10026192_T22", "arg2_id": "PMID-10026192_T21", "normalized": [] }, { "id": "PMID-10026192_R7", "type": "fromSpecies", "arg1_id": "PMID-10026192_T29", "arg2_id": "PMID-10026192_T28", "normalized": [] }, { "id": "PMID-10026192_R8", "type": "hasFunction", "arg1_id": "PMID-10026192_T33", "arg2_id": "PMID-10026192_T36", "normalized": [] }, { "id": "PMID-10026192_R9", "type": "hasFunction", "arg1_id": "PMID-10026192_T34", "arg2_id": "PMID-10026192_T36", "normalized": [] }, { "id": "PMID-10026192_R10", "type": "hasFunction", "arg1_id": "PMID-10026192_T39", "arg2_id": "PMID-10026192_T40", "normalized": [] }, { "id": "PMID-10026192_R12", "type": "encodes", "arg1_id": "PMID-10026192_T46", "arg2_id": "PMID-10026192_T45", "normalized": [] }, { "id": "PMID-10026192_R15", "type": "locatedIn", "arg1_id": "PMID-10026192_T51", "arg2_id": "PMID-10026192_T52", "normalized": [] }, { "id": "PMID-10026192_R16", "type": "locatedIn", "arg1_id": "PMID-10026192_T53", "arg2_id": "PMID-10026192_T55", "normalized": [] }, { "id": "PMID-10026192_R17", "type": "fromSpecies", "arg1_id": "PMID-10026192_T55", "arg2_id": "PMID-10026192_T54", "normalized": [] } ]

[ { "id": "PMID-10026197__text", "type": "abstract", "text": [ "Cell adhesion regulates the interaction between the docking protein p130(Cas) and the 14-3-3 proteins. Integrin ligand binding induces a signaling complex formation via the direct association of the docking protein p130(Cas) (Cas) with diverse molecules. We report here that the 14-3-3zeta protein interacts with Cas in the yeast two-hybrid assay. We also found that the two proteins associate in mammalian cells and that this interaction takes place in a phosphoserine-dependent manner, because treatment of Cas with a serine phosphatase greatly reduced its ability to bind 14-3-3zeta. Furthermore, the Cas-14-3-3zeta interaction was found to be regulated by integrin-mediated cell adhesion. Thus, when cells are detached from the extracellular matrix, the binding of Cas to 14-3-3zeta is greatly diminished, whereas replating the cells onto fibronectin rapidly induces the association. Consistent with these results, we found that the subcellular localization of Cas and 14-3-3 is also regulated by integrin ligand binding and that the two proteins display a significant co-localization during cell attachment to the extracellular matrix. In conclusion, our results demonstrate that 14-3-3 proteins participate in integrin-activated signaling pathways through their interaction with Cas, which, in turn, may contribute to important biological responses regulated by cell adhesion to the extracellular matrix.\n" ], "offsets": [ [ 0, 1411 ] ] } ]

[ { "id": "PMID-10026197_T6", "type": "Protein", "text": [ "14-3-3 proteins" ], "offsets": [ [ 86, 101 ] ], "normalized": [] }, { "id": "PMID-10026197_T7", "type": "Protein", "text": [ "Integrin" ], "offsets": [ [ 103, 111 ] ], "normalized": [] }, { "id": "PMID-10026197_T8", "type": "Ligand", "text": [ "ligand" ], "offsets": [ [ 112, 118 ] ], "normalized": [] }, { "id": "PMID-10026197_T14", "type": "Protein", "text": [ "Cas" ], "offsets": [ [ 226, 229 ] ], "normalized": [] }, { "id": "PMID-10026197_T15", "type": "Protein", "text": [ "14-3-3zeta protein" ], "offsets": [ [ 279, 297 ] ], "normalized": [] }, { "id": "PMID-10026197_T17", "type": "Protein", "text": [ "Cas" ], "offsets": [ [ 313, 316 ] ], "normalized": [] }, { "id": "PMID-10026197_T18", "type": "Protein", "text": [ "proteins" ], "offsets": [ [ 375, 383 ] ], "normalized": [] }, { "id": "PMID-10026197_T19", "type": "Eukaryote", "text": [ "mammalian" ], "offsets": [ [ 397, 406 ] ], "normalized": [] }, { "id": "PMID-10026197_T20", "type": "Cell", "text": [ "cells" ], "offsets": [ [ 407, 412 ] ], "normalized": [] }, { "id": "PMID-10026197_T22", "type": "AminoAcid", "text": [ "phosphoserine" ], "offsets": [ [ 456, 469 ] ], "normalized": [] }, { "id": "PMID-10026197_T23", "type": "ExperimentalMethod", "text": [ "treatment" ], "offsets": [ [ 496, 505 ] ], "normalized": [] }, { "id": "PMID-10026197_T24", "type": "Protein", "text": [ "Cas" ], "offsets": [ [ 509, 512 ] ], "normalized": [] }, { "id": "PMID-10026197_T25", "type": "Enzyme", "text": [ "serine phosphatase" ], "offsets": [ [ 520, 538 ] ], "normalized": [] }, { "id": "PMID-10026197_T28", "type": "Protein", "text": [ "14-3-3zeta" ], "offsets": [ [ 575, 585 ] ], "normalized": [] }, { "id": "PMID-10026197_T29", "type": "Protein", "text": [ "Cas-14-3-3zeta" ], "offsets": [ [ 604, 618 ] ], "normalized": [] }, { "id": "PMID-10026197_T32", "type": "Protein", "text": [ "integrin" ], "offsets": [ [ 660, 668 ] ], "normalized": [] }, { "id": "PMID-10026197_T35", "type": "Cell", "text": [ "cells" ], "offsets": [ [ 704, 709 ] ], "normalized": [] }, { "id": "PMID-10026197_T36", "type": "CellComponent", "text": [ "extracellular matrix" ], "offsets": [ [ 732, 752 ] ], "normalized": [] }, { "id": "PMID-10026197_T38", "type": "Protein", "text": [ "Cas" ], "offsets": [ [ 769, 772 ] ], "normalized": [] }, { "id": "PMID-10026197_T39", "type": "Protein", "text": [ "14-3-3zeta" ], "offsets": [ [ 776, 786 ] ], "normalized": [] }, { "id": "PMID-10026197_T43", "type": "Protein", "text": [ "Cas" ], "offsets": [ [ 965, 968 ] ], "normalized": [] }, { "id": "PMID-10026197_T44", "type": "Protein", "text": [ "14-3-3" ], "offsets": [ [ 973, 979 ] ], "normalized": [] }, { "id": "PMID-10026197_T46", "type": "Protein", "text": [ "integrin" ], "offsets": [ [ 1001, 1009 ] ], "normalized": [] }, { "id": "PMID-10026197_T47", "type": "Ligand", "text": [ "ligand" ], "offsets": [ [ 1010, 1016 ] ], "normalized": [] }, { "id": "PMID-10026197_T49", "type": "Protein", "text": [ "proteins" ], "offsets": [ [ 1042, 1050 ] ], "normalized": [] }, { "id": "PMID-10026197_T50", "type": "CellComponent", "text": [ "extracellular matrix" ], "offsets": [ [ 1119, 1139 ] ], "normalized": [] }, { "id": "PMID-10026197_T51", "type": "Protein", "text": [ "14-3-3 proteins" ], "offsets": [ [ 1185, 1200 ] ], "normalized": [] }, { "id": "PMID-10026197_T52", "type": "Protein", "text": [ "integrin" ], "offsets": [ [ 1216, 1224 ] ], "normalized": [] }, { "id": "PMID-10026197_T56", "type": "Protein", "text": [ "Cas" ], "offsets": [ [ 1285, 1288 ] ], "normalized": [] }, { "id": "PMID-10026197_T59", "type": "CellComponent", "text": [ "extracellular matrix" ], "offsets": [ [ 1389, 1409 ] ], "normalized": [] }, { "id": "PMID-10026197_T10", "type": "ProteinComplex", "text": [ "complex formation" ], "offsets": [ [ 147, 164 ] ], "normalized": [] }, { "id": "PMID-10026197_T4", "type": "Protein", "text": [ "docking protein p130(Cas)" ], "offsets": [ [ 52, 77 ] ], "normalized": [] } ]

[ { "id": "PMID-10026197_E1", "type": "CellAdhesion", "trigger": { "text": [ "Cell adhesion" ], "offsets": [ [ 0, 13 ] ] }, "arguments": [] }, { "id": "PMID-10026197_E2", "type": "RegulatoryProcess", "trigger": { "text": [ "regulates" ], "offsets": [ [ 14, 23 ] ] }, "arguments": [ { "role": "hasAgent", "ref_id": "PMID-10026197_E1" }, { "role": "hasPatient", "ref_id": "PMID-10026197_E3" } ] }, { "id": "PMID-10026197_E3", "type": "BindingToProtein", "trigger": { "text": [ "interaction" ], "offsets": [ [ 28, 39 ] ] }, "arguments": [ { "role": "hasPatient", "ref_id": "PMID-10026197_T6" }, { "role": "hasPatient2", "ref_id": "PMID-10026197_T4" } ] }, { "id": "PMID-10026197_E4", "type": "Binding", "trigger": { "text": [ "binding" ], "offsets": [ [ 119, 126 ] ] }, "arguments": [ { "role": "hasPatient", "ref_id": "PMID-10026197_T8" } ] }, { "id": "PMID-10026197_E6", "type": "BindingToProtein", "trigger": { "text": [ "interacts" ], "offsets": [ [ 298, 307 ] ] }, "arguments": [ { "role": "hasPatient", "ref_id": "PMID-10026197_T17" }, { "role": "hasPatient2", "ref_id": "PMID-10026197_T15" } ] }, { "id": "PMID-10026197_E7", "type": "BindingToProtein", "trigger": { "text": [ "interaction" ], "offsets": [ [ 427, 438 ] ] }, "arguments": [] }, { "id": "PMID-10026197_E8", "type": "Decrease", "trigger": { "text": [ "reduced" ], "offsets": [ [ 547, 554 ] ] }, "arguments": [ { "role": "hasAgent", "ref_id": "PMID-10026197_T23" }, { "role": "hasPatient", "ref_id": "PMID-10026197_E9" } ] }, { "id": "PMID-10026197_E9", "type": "BindingToProtein", "trigger": { "text": [ "bind" ], "offsets": [ [ 570, 574 ] ] }, "arguments": [ { "role": "hasPatient", "ref_id": "PMID-10026197_T28" }, { "role": "hasPatient2", "ref_id": "PMID-10026197_T24" } ] }, { "id": "PMID-10026197_E10", "type": "BindingToProtein", "trigger": { "text": [ "interaction" ], "offsets": [ [ 619, 630 ] ] }, "arguments": [ { "role": "hasPatient", "ref_id": "PMID-10026197_T29" } ] }, { "id": "PMID-10026197_E11", "type": "RegulatoryProcess", "trigger": { "text": [ "regulated" ], "offsets": [ [ 647, 656 ] ] }, "arguments": [ { "role": "hasAgent", "ref_id": "PMID-10026197_E13" }, { "role": "hasPatient", "ref_id": "PMID-10026197_E10" } ] }, { "id": "PMID-10026197_E12", "type": "RegulatoryProcess", "trigger": { "text": [ "mediated" ], "offsets": [ [ 669, 677 ] ] }, "arguments": [ { "role": "hasAgent", "ref_id": "PMID-10026197_T32" }, { "role": "hasPatient", "ref_id": "PMID-10026197_E13" } ] }, { "id": "PMID-10026197_E13", "type": "CellAdhesion", "trigger": { "text": [ "cell adhesion" ], "offsets": [ [ 678, 691 ] ] }, "arguments": [] }, { "id": "PMID-10026197_E14", "type": "BindingToProtein", "trigger": { "text": [ "binding" ], "offsets": [ [ 758, 765 ] ] }, "arguments": [ { "role": "hasPatient", "ref_id": "PMID-10026197_T39" }, { "role": "hasPatient2", "ref_id": "PMID-10026197_T38" } ] }, { "id": "PMID-10026197_E15", "type": "NegativeRegulation", "trigger": { "text": [ "diminished" ], "offsets": [ [ 798, 808 ] ] }, "arguments": [ { "role": "hasPatient", "ref_id": "PMID-10026197_E14" } ] }, { "id": "PMID-10026197_E16", "type": "Increase", "trigger": { "text": [ "induces" ], "offsets": [ [ 863, 870 ] ] }, "arguments": [] }, { "id": "PMID-10026197_E17", "type": "Localization", "trigger": { "text": [ "subcellular localization" ], "offsets": [ [ 937, 961 ] ] }, "arguments": [ { "role": "hasPatient", "ref_id": "PMID-10026197_T43" } ] }, { "id": "PMID-10026197_E18", "type": "RegulatoryProcess", "trigger": { "text": [ "regulated" ], "offsets": [ [ 988, 997 ] ] }, "arguments": [ { "role": "hasAgent", "ref_id": "PMID-10026197_E19" }, { "role": "hasPatient", "ref_id": "PMID-10026197_E17" } ] }, { "id": "PMID-10026197_E19", "type": "Binding", "trigger": { "text": [ "binding" ], "offsets": [ [ 1017, 1024 ] ] }, "arguments": [ { "role": "hasPatient", "ref_id": "PMID-10026197_T47" } ] }, { "id": "PMID-10026197_E20", "type": "PositiveRegulation", "trigger": { "text": [ "activated" ], "offsets": [ [ 1225, 1234 ] ] }, "arguments": [ { "role": "hasAgent", "ref_id": "PMID-10026197_T52" }, { "role": "hasPatient", "ref_id": "PMID-10026197_E21" } ] }, { "id": "PMID-10026197_E21", "type": "SignalingPathway", "trigger": { "text": [ "signaling pathways" ], "offsets": [ [ 1235, 1253 ] ] }, "arguments": [] }, { "id": "PMID-10026197_E22", "type": "BindingToProtein", "trigger": { "text": [ "interaction" ], "offsets": [ [ 1268, 1279 ] ] }, "arguments": [ { "role": "hasPatient", "ref_id": "PMID-10026197_T56" }, { "role": "hasPatient2", "ref_id": "PMID-10026197_T51" } ] }, { "id": "PMID-10026197_E23", "type": "RegulatoryProcess", "trigger": { "text": [ "regulated" ], "offsets": [ [ 1355, 1364 ] ] }, "arguments": [ { "role": "hasAgent", "ref_id": "PMID-10026197_E24" } ] }, { "id": "PMID-10026197_E24", "type": "CellAdhesion", "trigger": { "text": [ "cell adhesion" ], "offsets": [ [ 1368, 1381 ] ] }, "arguments": [] }, { "id": "PMID-10026197_E5", "type": "SignalingPathway", "trigger": { "text": [ "signaling" ], "offsets": [ [ 137, 146 ] ] }, "arguments": [ { "role": "hasAgent", "ref_id": "PMID-10026197_E4" } ] }, { "id": "PMID-10026197_E25", "type": "BindingToProtein", "trigger": { "text": [ "direct association" ], "offsets": [ [ 173, 191 ] ] }, "arguments": [ { "role": "hasPatient", "ref_id": "PMID-10026197_T14" } ] }, { "id": "PMID-10026197_E26", "type": "BindingToProtein", "trigger": { "text": [ "associate" ], "offsets": [ [ 384, 393 ] ] }, "arguments": [ { "role": "hasPatient", "ref_id": "PMID-10026197_T18" } ] }, { "id": "PMID-10026197_E27", "type": "Localization", "trigger": { "text": [ "localization" ], "offsets": [ [ 1076, 1088 ] ] }, "arguments": [ { "role": "hasPatient", "ref_id": "PMID-10026197_T49" } ] }, { "id": "PMID-10026197_E28", "type": "CellAdhesion", "trigger": { "text": [ "cell attachment" ], "offsets": [ [ 1096, 1111 ] ] }, "arguments": [] }, { "id": "PMID-10026197_E29", "type": "Localization", "trigger": { "text": [ "subcellular localization" ], "offsets": [ [ 937, 961 ] ] }, "arguments": [ { "role": "hasPatient", "ref_id": "PMID-10026197_T44" } ] }, { "id": "PMID-10026197_E30", "type": "RegulatoryProcess", "trigger": { "text": [ "regulated" ], "offsets": [ [ 988, 997 ] ] }, "arguments": [ { "role": "hasAgent", "ref_id": "PMID-10026197_E19" }, { "role": "hasPatient", "ref_id": "PMID-10026197_E29" } ] } ]

[]

[ { "id": "PMID-10026197_R3", "type": "fromSpecies", "arg1_id": "PMID-10026197_T20", "arg2_id": "PMID-10026197_T19", "normalized": [] } ]

[ { "id": "PMID-10026210__text", "type": "abstract", "text": [ "A novel PDZ domain containing guanine nucleotide exchange factor links heterotrimeric G proteins to Rho. Small GTP-binding proteins of the Rho family play a critical role in signal transduction. However, there is still very limited information on how they are activated by cell surface receptors. Here, we used a consensus sequence for Dbl domains of Rho guanine nucleotide exchange factors (GEFs) to search DNA data bases, and identified a novel human GEF for Rho-related GTPases harboring structural features indicative of its possible regulatory mechanism(s). This protein contained a tandem DH/PH domain closely related to those of Rho-specific GEFs, a PDZ domain, a proline-rich domain, and an area of homology to Lsc, p115-RhoGEF, and a Drosophila RhoGEF that was termed Lsc-homology (LH) domain. This novel molecule, designated PDZ-RhoGEF, activated biological and biochemical pathways specific for Rho, and activation of these pathways required an intact DH and PH domain. However, the PDZ domain was dispensable for these functions, and mutants lacking the LH domain were more active, suggesting a negative regulatory role for the LH domain. A search for additional molecules exhibiting an LH domain revealed a limited homology with the catalytic region of a newly identified GTPase-activating protein for heterotrimeric G proteins, RGS14. This prompted us to investigate whether PDZ-RhoGEF could interact with representative members of each G protein family. We found that PDZ-RhoGEF was able to form, in vivo, stable complexes with two members of the Galpha12 family, Galpha12 and Galpha13, and that this interaction was mediated by the LH domain. Furthermore, we obtained evidence to suggest that PDZ-RhoGEF mediates the activation of Rho by Galpha12 and Galpha13. Together, these findings suggest the existence of a novel mechanism whereby the large family of cell surface receptors that transmit signals through heterotrimeric G proteins activate Rho-dependent pathways: by stimulating the activity of members of the Galpha12 family which, in turn, activate an exchange factor acting on Rho.\n" ], "offsets": [ [ 0, 2106 ] ] } ]

[ { "id": "PMID-10026210_T1", "type": "ProteinDomain", "text": [ "PDZ domain" ], "offsets": [ [ 8, 18 ] ], "normalized": [] }, { "id": "PMID-10026210_T4", "type": "Protein", "text": [ "heterotrimeric G proteins" ], "offsets": [ [ 71, 96 ] ], "normalized": [] }, { "id": "PMID-10026210_T5", "type": "Protein", "text": [ "Rho" ], "offsets": [ [ 100, 103 ] ], "normalized": [] }, { "id": "PMID-10026210_T9", "type": "Protein", "text": [ "Rho" ], "offsets": [ [ 139, 142 ] ], "normalized": [] }, { "id": "PMID-10026210_T12", "type": "CellComponent", "text": [ "cell surface" ], "offsets": [ [ 273, 285 ] ], "normalized": [] }, { "id": "PMID-10026210_T13", "type": "Protein", "text": [ "receptors" ], "offsets": [ [ 286, 295 ] ], "normalized": [] }, { "id": "PMID-10026210_T14", "type": "ProteinDomain", "text": [ "Dbl domains" ], "offsets": [ [ 336, 347 ] ], "normalized": [] }, { "id": "PMID-10026210_T15", "type": "Protein", "text": [ "Rho guanine nucleotide exchange factors" ], "offsets": [ [ 351, 390 ] ], "normalized": [] }, { "id": "PMID-10026210_T16", "type": "Protein", "text": [ "GEFs" ], "offsets": [ [ 392, 396 ] ], "normalized": [] }, { "id": "PMID-10026210_T17", "type": "DNA", "text": [ "DNA" ], "offsets": [ [ 408, 411 ] ], "normalized": [] }, { "id": "PMID-10026210_T18", "type": "Eukaryote", "text": [ "human" ], "offsets": [ [ 447, 452 ] ], "normalized": [] }, { "id": "PMID-10026210_T19", "type": "Protein", "text": [ "GEF" ], "offsets": [ [ 453, 456 ] ], "normalized": [] }, { "id": "PMID-10026210_T20", "type": "Protein", "text": [ "Rho" ], "offsets": [ [ 461, 464 ] ], "normalized": [] }, { "id": "PMID-10026210_T21", "type": "Enzyme", "text": [ "GTPases" ], "offsets": [ [ 473, 480 ] ], "normalized": [] }, { "id": "PMID-10026210_T22", "type": "Protein", "text": [ "protein" ], "offsets": [ [ 568, 575 ] ], "normalized": [] }, { "id": "PMID-10026210_T23", "type": "ProteinDomain", "text": [ "DH/PH domain" ], "offsets": [ [ 595, 607 ] ], "normalized": [] }, { "id": "PMID-10026210_T24", "type": "Protein", "text": [ "Rho" ], "offsets": [ [ 636, 639 ] ], "normalized": [] }, { "id": "PMID-10026210_T25", "type": "Protein", "text": [ "GEFs" ], "offsets": [ [ 649, 653 ] ], "normalized": [] }, { "id": "PMID-10026210_T26", "type": "ProteinDomain", "text": [ "PDZ domain" ], "offsets": [ [ 657, 667 ] ], "normalized": [] }, { "id": "PMID-10026210_T27", "type": "ProteinDomain", "text": [ "proline-rich domain" ], "offsets": [ [ 671, 690 ] ], "normalized": [] }, { "id": "PMID-10026210_T28", "type": "Protein", "text": [ "Lsc" ], "offsets": [ [ 719, 722 ] ], "normalized": [] }, { "id": "PMID-10026210_T29", "type": "Protein", "text": [ "p115-RhoGEF" ], "offsets": [ [ 724, 735 ] ], "normalized": [] }, { "id": "PMID-10026210_T30", "type": "Eukaryote", "text": [ "Drosophila" ], "offsets": [ [ 743, 753 ] ], "normalized": [] }, { "id": "PMID-10026210_T31", "type": "Protein", "text": [ "RhoGEF" ], "offsets": [ [ 754, 760 ] ], "normalized": [] }, { "id": "PMID-10026210_T32", "type": "ProteinDomain", "text": [ "LH" ], "offsets": [ [ 791, 793 ] ], "normalized": [] }, { "id": "PMID-10026210_T33", "type": "Protein", "text": [ "PDZ-RhoGEF" ], "offsets": [ [ 835, 845 ] ], "normalized": [] }, { "id": "PMID-10026210_T35", "type": "Protein", "text": [ "Rho" ], "offsets": [ [ 906, 909 ] ], "normalized": [] }, { "id": "PMID-10026210_T37", "type": "ProteinDomain", "text": [ "DH" ], "offsets": [ [ 963, 965 ] ], "normalized": [] }, { "id": "PMID-10026210_T38", "type": "ProteinDomain", "text": [ "PH domain" ], "offsets": [ [ 970, 979 ] ], "normalized": [] }, { "id": "PMID-10026210_T39", "type": "ProteinDomain", "text": [ "PDZ domain" ], "offsets": [ [ 994, 1004 ] ], "normalized": [] }, { "id": "PMID-10026210_T40", "type": "MutantProtein", "text": [ "mutants" ], "offsets": [ [ 1046, 1053 ] ], "normalized": [] }, { "id": "PMID-10026210_T41", "type": "ProteinDomain", "text": [ "LH domain" ], "offsets": [ [ 1066, 1075 ] ], "normalized": [] }, { "id": "PMID-10026210_T44", "type": "ProteinDomain", "text": [ "LH domain" ], "offsets": [ [ 1140, 1149 ] ], "normalized": [] }, { "id": "PMID-10026210_T45", "type": "ProteinDomain", "text": [ "LH domain" ], "offsets": [ [ 1199, 1208 ] ], "normalized": [] }, { "id": "PMID-10026210_T49", "type": "Protein", "text": [ "heterotrimeric G proteins" ], "offsets": [ [ 1315, 1340 ] ], "normalized": [] }, { "id": "PMID-10026210_T50", "type": "Protein", "text": [ "RGS14" ], "offsets": [ [ 1342, 1347 ] ], "normalized": [] }, { "id": "PMID-10026210_T51", "type": "Protein", "text": [ "PDZ-RhoGEF" ], "offsets": [ [ 1389, 1399 ] ], "normalized": [] }, { "id": "PMID-10026210_T53", "type": "Protein", "text": [ "G protein" ], "offsets": [ [ 1451, 1460 ] ], "normalized": [] }, { "id": "PMID-10026210_T54", "type": "Protein", "text": [ "PDZ-RhoGEF" ], "offsets": [ [ 1483, 1493 ] ], "normalized": [] }, { "id": "PMID-10026210_T55", "type": "Protein", "text": [ "Galpha12" ], "offsets": [ [ 1562, 1570 ] ], "normalized": [] }, { "id": "PMID-10026210_T56", "type": "Protein", "text": [ "Galpha12" ], "offsets": [ [ 1579, 1587 ] ], "normalized": [] }, { "id": "PMID-10026210_T57", "type": "Protein", "text": [ "Galpha13" ], "offsets": [ [ 1592, 1600 ] ], "normalized": [] }, { "id": "PMID-10026210_T60", "type": "ProteinDomain", "text": [ "LH domain" ], "offsets": [ [ 1648, 1657 ] ], "normalized": [] }, { "id": "PMID-10026210_T61", "type": "Protein", "text": [ "PDZ-RhoGEF" ], "offsets": [ [ 1709, 1719 ] ], "normalized": [] }, { "id": "PMID-10026210_T64", "type": "Protein", "text": [ "Rho" ], "offsets": [ [ 1747, 1750 ] ], "normalized": [] }, { "id": "PMID-10026210_T65", "type": "Protein", "text": [ "Galpha12" ], "offsets": [ [ 1754, 1762 ] ], "normalized": [] }, { "id": "PMID-10026210_T66", "type": "Protein", "text": [ "Galpha13" ], "offsets": [ [ 1767, 1775 ] ], "normalized": [] }, { "id": "PMID-10026210_T67", "type": "CellComponent", "text": [ "cell surface" ], "offsets": [ [ 1873, 1885 ] ], "normalized": [] }, { "id": "PMID-10026210_T68", "type": "Protein", "text": [ "receptors" ], "offsets": [ [ 1886, 1895 ] ], "normalized": [] }, { "id": "PMID-10026210_T69", "type": "Protein", "text": [ "heterotrimeric G proteins" ], "offsets": [ [ 1926, 1951 ] ], "normalized": [] }, { "id": "PMID-10026210_T73", "type": "Protein", "text": [ "Galpha12" ], "offsets": [ [ 2031, 2039 ] ], "normalized": [] }, { "id": "PMID-10026210_T76", "type": "Protein", "text": [ "Rho" ], "offsets": [ [ 2101, 2104 ] ], "normalized": [] }, { "id": "PMID-10026210_T2", "type": "Protein", "text": [ "guanine nucleotide exchange factor" ], "offsets": [ [ 30, 64 ] ], "normalized": [] }, { "id": "PMID-10026210_T3", "type": "Protein", "text": [ "Small GTP-binding proteins" ], "offsets": [ [ 105, 131 ] ], "normalized": [] }, { "id": "PMID-10026210_T6", "type": "ProteinDomain", "text": [ "area" ], "offsets": [ [ 699, 703 ] ], "normalized": [] }, { "id": "PMID-10026210_T43", "type": "Protein", "text": [ "GTPase-activating protein" ], "offsets": [ [ 1285, 1310 ] ], "normalized": [] }, { "id": "PMID-10026210_T46", "type": "ProteinComplex", "text": [ "complexes" ], "offsets": [ [ 1528, 1537 ] ], "normalized": [] }, { "id": "PMID-10026210_T71", "type": "Protein", "text": [ "exchange factor" ], "offsets": [ [ 2075, 2090 ] ], "normalized": [] } ]

[ { "id": "PMID-10026210_E2", "type": "SignalingPathway", "trigger": { "text": [ "signal transduction" ], "offsets": [ [ 174, 193 ] ] }, "arguments": [] }, { "id": "PMID-10026210_E3", "type": "PositiveRegulation", "trigger": { "text": [ "activated" ], "offsets": [ [ 260, 269 ] ] }, "arguments": [ { "role": "hasAgent", "ref_id": "PMID-10026210_T13" } ] }, { "id": "PMID-10026210_E4", "type": "PositiveRegulation", "trigger": { "text": [ "activated" ], "offsets": [ [ 847, 856 ] ] }, "arguments": [ { "role": "hasAgent", "ref_id": "PMID-10026210_T33" }, { "role": "hasPatient", "ref_id": "PMID-10026210_E1" } ] }, { "id": "PMID-10026210_E5", "type": "PositiveRegulation", "trigger": { "text": [ "activation" ], "offsets": [ [ 915, 925 ] ] }, "arguments": [ { "role": "hasPatient", "ref_id": "PMID-10026210_E16" } ] }, { "id": "PMID-10026210_E8", "type": "BindingToProtein", "trigger": { "text": [ "interact" ], "offsets": [ [ 1406, 1414 ] ] }, "arguments": [ { "role": "hasPatient", "ref_id": "PMID-10026210_T53" }, { "role": "hasPatient2", "ref_id": "PMID-10026210_T51" } ] }, { "id": "PMID-10026210_E9", "type": "BindingToProtein", "trigger": { "text": [ "interaction" ], "offsets": [ [ 1616, 1627 ] ] }, "arguments": [] }, { "id": "PMID-10026210_E10", "type": "RegulatoryProcess", "trigger": { "text": [ "mediated" ], "offsets": [ [ 1632, 1640 ] ] }, "arguments": [ { "role": "hasAgent", "ref_id": "PMID-10026210_T60" }, { "role": "hasPatient", "ref_id": "PMID-10026210_E9" } ] }, { "id": "PMID-10026210_E11", "type": "RegulatoryProcess", "trigger": { "text": [ "mediates" ], "offsets": [ [ 1720, 1728 ] ] }, "arguments": [ { "role": "hasAgent", "ref_id": "PMID-10026210_T61" }, { "role": "hasPatient", "ref_id": "PMID-10026210_E12" } ] }, { "id": "PMID-10026210_E12", "type": "PositiveRegulation", "trigger": { "text": [ "activation" ], "offsets": [ [ 1733, 1743 ] ] }, "arguments": [ { "role": "hasPatient", "ref_id": "PMID-10026210_T64" }, { "role": "hasAgent", "ref_id": "PMID-10026210_T65" } ] }, { "id": "PMID-10026210_E13", "type": "PositiveRegulation", "trigger": { "text": [ "activate" ], "offsets": [ [ 1952, 1960 ] ] }, "arguments": [ { "role": "hasAgent", "ref_id": "PMID-10026210_T68" }, { "role": "hasPatient", "ref_id": "PMID-10026210_E17" } ] }, { "id": "PMID-10026210_E14", "type": "Increase", "trigger": { "text": [ "stimulating" ], "offsets": [ [ 1988, 1999 ] ] }, "arguments": [ { "role": "hasPatient", "ref_id": "PMID-10026210_T73" } ] }, { "id": "PMID-10026210_E15", "type": "PositiveRegulation", "trigger": { "text": [ "activate" ], "offsets": [ [ 2063, 2071 ] ] }, "arguments": [ { "role": "hasPatient", "ref_id": "PMID-10026210_T71" } ] }, { "id": "PMID-10026210_E1", "type": "Pathway", "trigger": { "text": [ "biological and biochemical pathways" ], "offsets": [ [ 857, 892 ] ] }, "arguments": [ { "role": "hasPatient", "ref_id": "PMID-10026210_T35" } ] }, { "id": "PMID-10026210_E6", "type": "NegativeRegulation", "trigger": { "text": [ "negative regulatory" ], "offsets": [ [ 1107, 1126 ] ] }, "arguments": [ { "role": "hasAgent", "ref_id": "PMID-10026210_T44" } ] }, { "id": "PMID-10026210_E16", "type": "Pathway", "trigger": { "text": [ "pathways" ], "offsets": [ [ 935, 943 ] ] }, "arguments": [] }, { "id": "PMID-10026210_E7", "type": "SignalingPathway", "trigger": { "text": [ "transmit signals" ], "offsets": [ [ 1901, 1917 ] ] }, "arguments": [ { "role": "hasAgent", "ref_id": "PMID-10026210_T69" } ] }, { "id": "PMID-10026210_E17", "type": "SignalingPathway", "trigger": { "text": [ "Rho-dependent pathways" ], "offsets": [ [ 1961, 1983 ] ] }, "arguments": [] }, { "id": "PMID-10026210_E18", "type": "PositiveRegulation", "trigger": { "text": [ "activation" ], "offsets": [ [ 1733, 1743 ] ] }, "arguments": [ { "role": "hasPatient", "ref_id": "PMID-10026210_T64" }, { "role": "hasAgent", "ref_id": "PMID-10026210_T66" } ] }, { "id": "PMID-10026210_E19", "type": "RegulatoryProcess", "trigger": { "text": [ "mediates" ], "offsets": [ [ 1720, 1728 ] ] }, "arguments": [ { "role": "hasAgent", "ref_id": "PMID-10026210_T61" }, { "role": "hasPatient", "ref_id": "PMID-10026210_E18" } ] } ]

[]

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[ { "id": "PMID-10026212__text", "type": "abstract", "text": [ "Human geranylgeranyl diphosphate synthase. cDNA cloning and expression. Geranylgeranyl diphosphate (GGPP) synthase (GGPPSase) catalyzes the synthesis of GGPP, which is an important molecule responsible for the C20-prenylated protein biosynthesis and for the regulation of a nuclear hormone receptor (LXR.RXR). The human GGPPSase cDNA encodes a protein of 300 amino acids which shows 16% sequence identity with the known human farnesyl diphosphate (FPP) synthase (FPPSase). The GGPPSase expressed in Escherichia coli catalyzes the GGPP formation (240 nmol/min/mg) from FPP and isopentenyl diphosphate. The human GGPPSase behaves as an oligomeric molecule with 280 kDa on a gel filtration column and cross-reacts with an antibody directed against bovine brain GGPPSase, which differs immunochemically from bovine brain FPPSase. Northern blot analysis indicates the presence of two forms of the mRNA.\n" ], "offsets": [ [ 0, 898 ] ] } ]

[ { "id": "PMID-10026212_T1", "type": "Eukaryote", "text": [ "Human" ], "offsets": [ [ 0, 5 ] ], "normalized": [] }, { "id": "PMID-10026212_T2", "type": "Enzyme", "text": [ "geranylgeranyl diphosphate synthase" ], "offsets": [ [ 6, 41 ] ], "normalized": [] }, { "id": "PMID-10026212_T3", "type": "DNA", "text": [ "cDNA" ], "offsets": [ [ 43, 47 ] ], "normalized": [] }, { "id": "PMID-10026212_T8", "type": "Enzyme", "text": [ "GGPPSase" ], "offsets": [ [ 116, 124 ] ], "normalized": [] }, { "id": "PMID-10026212_T10", "type": "Chemical", "text": [ "GGPP" ], "offsets": [ [ 153, 157 ] ], "normalized": [] }, { "id": "PMID-10026212_T11", "type": "Protein", "text": [ "C20-prenylated protein" ], "offsets": [ [ 210, 232 ] ], "normalized": [] }, { "id": "PMID-10026212_T14", "type": "CellComponent", "text": [ "nuclear" ], "offsets": [ [ 274, 281 ] ], "normalized": [] }, { "id": "PMID-10026212_T15", "type": "Protein", "text": [ "hormone receptor" ], "offsets": [ [ 282, 298 ] ], "normalized": [] }, { "id": "PMID-10026212_T16", "type": "Eukaryote", "text": [ "human" ], "offsets": [ [ 314, 319 ] ], "normalized": [] }, { "id": "PMID-10026212_T17", "type": "Enzyme", "text": [ "GGPPSase" ], "offsets": [ [ 320, 328 ] ], "normalized": [] }, { "id": "PMID-10026212_T18", "type": "DNA", "text": [ "cDNA" ], "offsets": [ [ 329, 333 ] ], "normalized": [] }, { "id": "PMID-10026212_T19", "type": "Protein", "text": [ "protein" ], "offsets": [ [ 344, 351 ] ], "normalized": [] }, { "id": "PMID-10026212_T20", "type": "AminoAcid", "text": [ "amino acids" ], "offsets": [ [ 359, 370 ] ], "normalized": [] }, { "id": "PMID-10026212_T21", "type": "Eukaryote", "text": [ "human" ], "offsets": [ [ 420, 425 ] ], "normalized": [] }, { "id": "PMID-10026212_T25", "type": "Enzyme", "text": [ "FPPSase" ], "offsets": [ [ 463, 470 ] ], "normalized": [] }, { "id": "PMID-10026212_T26", "type": "Enzyme", "text": [ "GGPPSase" ], "offsets": [ [ 477, 485 ] ], "normalized": [] }, { "id": "PMID-10026212_T28", "type": "Eukaryote", "text": [ "Escherichia coli" ], "offsets": [ [ 499, 515 ] ], "normalized": [] }, { "id": "PMID-10026212_T29", "type": "Chemical", "text": [ "GGPP" ], "offsets": [ [ 530, 534 ] ], "normalized": [] }, { "id": "PMID-10026212_T30", "type": "Chemical", "text": [ "FPP" ], "offsets": [ [ 568, 571 ] ], "normalized": [] }, { "id": "PMID-10026212_T31", "type": "Chemical", "text": [ "isopentenyl diphosphate" ], "offsets": [ [ 576, 599 ] ], "normalized": [] }, { "id": "PMID-10026212_T32", "type": "Eukaryote", "text": [ "human" ], "offsets": [ [ 605, 610 ] ], "normalized": [] }, { "id": "PMID-10026212_T33", "type": "Enzyme", "text": [ "GGPPSase" ], "offsets": [ [ 611, 619 ] ], "normalized": [] }, { "id": "PMID-10026212_T34", "type": "Eukaryote", "text": [ "bovine" ], "offsets": [ [ 745, 751 ] ], "normalized": [] }, { "id": "PMID-10026212_T35", "type": "Tissue", "text": [ "brain" ], "offsets": [ [ 752, 757 ] ], "normalized": [] }, { "id": "PMID-10026212_T36", "type": "Enzyme", "text": [ "GGPPSase" ], "offsets": [ [ 758, 766 ] ], "normalized": [] }, { "id": "PMID-10026212_T37", "type": "Eukaryote", "text": [ "bovine" ], "offsets": [ [ 804, 810 ] ], "normalized": [] }, { "id": "PMID-10026212_T38", "type": "Tissue", "text": [ "brain" ], "offsets": [ [ 811, 816 ] ], "normalized": [] }, { "id": "PMID-10026212_T39", "type": "Enzyme", "text": [ "FPPSase" ], "offsets": [ [ 817, 824 ] ], "normalized": [] }, { "id": "PMID-10026212_T40", "type": "MessengerRNA", "text": [ "mRNA" ], "offsets": [ [ 892, 896 ] ], "normalized": [] }, { "id": "PMID-10026212_T6", "type": "CatalyticActivity", "text": [ "catalyzes" ], "offsets": [ [ 126, 135 ] ], "normalized": [] }, { "id": "PMID-10026212_T23", "type": "CatalyticActivity", "text": [ "catalyzes" ], "offsets": [ [ 516, 525 ] ], "normalized": [] } ]

[ { "id": "PMID-10026212_E1", "type": "GeneExpression", "trigger": { "text": [ "expression" ], "offsets": [ [ 60, 70 ] ] }, "arguments": [ { "role": "hasPatient", "ref_id": "PMID-10026212_T2" } ] }, { "id": "PMID-10026212_E2", "type": "MetabolicPathway", "trigger": { "text": [ "synthesis" ], "offsets": [ [ 140, 149 ] ] }, "arguments": [ { "role": "hasPatient", "ref_id": "PMID-10026212_T10" }, { "role": "hasAgent", "ref_id": "PMID-10026212_T6" } ] }, { "id": "PMID-10026212_E3", "type": "ProteinBiosynthesis", "trigger": { "text": [ "biosynthesis" ], "offsets": [ [ 233, 245 ] ] }, "arguments": [ { "role": "hasPatient", "ref_id": "PMID-10026212_T11" } ] }, { "id": "PMID-10026212_E4", "type": "RegulatoryProcess", "trigger": { "text": [ "regulation" ], "offsets": [ [ 258, 268 ] ] }, "arguments": [ { "role": "hasPatient", "ref_id": "PMID-10026212_T15" } ] }, { "id": "PMID-10026212_E5", "type": "GeneExpression", "trigger": { "text": [ "expressed" ], "offsets": [ [ 486, 495 ] ] }, "arguments": [ { "role": "hasPatient", "ref_id": "PMID-10026212_T26" } ] }, { "id": "PMID-10026212_E6", "type": "MetabolicPathway", "trigger": { "text": [ "formation" ], "offsets": [ [ 535, 544 ] ] }, "arguments": [ { "role": "hasAgent", "ref_id": "PMID-10026212_T23" }, { "role": "hasPatient", "ref_id": "PMID-10026212_T29" } ] }, { "id": "PMID-10026212_E7", "type": "MetabolicPathway", "trigger": { "text": [ "formation" ], "offsets": [ [ 535, 544 ] ] }, "arguments": [ { "role": "hasAgent", "ref_id": "PMID-10026212_T23" }, { "role": "hasPatient", "ref_id": "PMID-10026212_T30" } ] }, { "id": "PMID-10026212_E8", "type": "MetabolicPathway", "trigger": { "text": [ "formation" ], "offsets": [ [ 535, 544 ] ] }, "arguments": [ { "role": "hasAgent", "ref_id": "PMID-10026212_T23" }, { "role": "hasPatient", "ref_id": "PMID-10026212_T31" } ] } ]

[]

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[ { "id": "PMID-10026226__text", "type": "abstract", "text": [ "Skeletal muscle type ryanodine receptor is involved in calcium signaling in human B lymphocytes. The regulation of intracellular free Ca2+ concentration ([Ca2+]i) in B cells remains poorly understood and is presently explained almost solely by inositol 1,4,5-triphosphate (IP3)-mediated Ca2+ release, followed by activation of a store-operated channel mechanism. In fact, there are reports indicating that IP3 production does not always correlate with the magnitude of Ca2+ release. We demonstrate here that human B cells express a ryanodine receptor (RYR) that functions as a Ca2+ release channel during the B cell antigen receptor (BCR)-stimulated Ca2+ signaling process. Immunoblotting studies showed that both human primary CD19(+) B and DAKIKI cells express a 565-kDa immunoreactive protein that is indistinguishable in molecular size and immunoreactivity from the RYR. Selective reverse transcription-polymerase chain reaction, restriction fragment length polymorphism, and sequencing of cloned cDNA indicated that the major isoform of the RYR expressed in primary CD19(+) B and DAKIKI cells is identical to the skeletal muscle type (RYR1). Saturation analysis of [3H]ryanodine binding yielded Bmax = 150 fmol/mg of protein and Kd = 110 nM in DAKIKI cells. In fluo-3-loaded CD19(+) B and DAKIKI cells, 4-chloro-m-cresol, a potent activator of Ca2+ release mediated by the ryanodine-sensitive Ca2+ release channel, induced Ca2+ release in a dose-dependent and ryanodine-sensitive fashion. Furthermore, BCR-mediated Ca2+ release in CD19(+) B cells was significantly altered by 4-chloro-m-cresol and ryanodine. These results indicate that RYR1 functions as a Ca2+ release channel during BCR-stimulated Ca2+ signaling and suggest that complex Ca2+ signals that control the cellular activities of B cells may be generated by cooperation of the IP3 receptor and RYR1.\n" ], "offsets": [ [ 0, 1868 ] ] } ]

[ { "id": "PMID-10026226_T3", "type": "Ion", "text": [ "calcium" ], "offsets": [ [ 55, 62 ] ], "normalized": [] }, { "id": "PMID-10026226_T5", "type": "Eukaryote", "text": [ "human" ], "offsets": [ [ 76, 81 ] ], "normalized": [] }, { "id": "PMID-10026226_T6", "type": "Cell", "text": [ "B lymphocytes" ], "offsets": [ [ 82, 95 ] ], "normalized": [] }, { "id": "PMID-10026226_T8", "type": "Ion", "text": [ "Ca2+" ], "offsets": [ [ 134, 138 ] ], "normalized": [] }, { "id": "PMID-10026226_T9", "type": "Cell", "text": [ "B cells" ], "offsets": [ [ 166, 173 ] ], "normalized": [] }, { "id": "PMID-10026226_T11", "type": "Chemical", "text": [ "IP3" ], "offsets": [ [ 273, 276 ] ], "normalized": [] }, { "id": "PMID-10026226_T13", "type": "Ion", "text": [ "Ca2+" ], "offsets": [ [ 287, 291 ] ], "normalized": [] }, { "id": "PMID-10026226_T17", "type": "Eukaryote", "text": [ "human" ], "offsets": [ [ 508, 513 ] ], "normalized": [] }, { "id": "PMID-10026226_T18", "type": "Cell", "text": [ "B cells" ], "offsets": [ [ 514, 521 ] ], "normalized": [] }, { "id": "PMID-10026226_T21", "type": "Protein", "text": [ "RYR" ], "offsets": [ [ 552, 555 ] ], "normalized": [] }, { "id": "PMID-10026226_T22", "type": "Ion", "text": [ "Ca2+" ], "offsets": [ [ 577, 581 ] ], "normalized": [] }, { "id": "PMID-10026226_T24", "type": "Protein", "text": [ "channel" ], "offsets": [ [ 590, 597 ] ], "normalized": [] }, { "id": "PMID-10026226_T26", "type": "Protein", "text": [ "BCR" ], "offsets": [ [ 634, 637 ] ], "normalized": [] }, { "id": "PMID-10026226_T28", "type": "Ion", "text": [ "Ca2+" ], "offsets": [ [ 650, 654 ] ], "normalized": [] }, { "id": "PMID-10026226_T30", "type": "Eukaryote", "text": [ "human" ], "offsets": [ [ 714, 719 ] ], "normalized": [] }, { "id": "PMID-10026226_T31", "type": "Cell", "text": [ "primary CD19(+) B" ], "offsets": [ [ 720, 737 ] ], "normalized": [] }, { "id": "PMID-10026226_T32", "type": "Cell", "text": [ "DAKIKI cells" ], "offsets": [ [ 742, 754 ] ], "normalized": [] }, { "id": "PMID-10026226_T34", "type": "Protein", "text": [ "protein" ], "offsets": [ [ 788, 795 ] ], "normalized": [] }, { "id": "PMID-10026226_T35", "type": "Protein", "text": [ "RYR" ], "offsets": [ [ 870, 873 ] ], "normalized": [] }, { "id": "PMID-10026226_T36", "type": "Protein", "text": [ "RYR" ], "offsets": [ [ 1046, 1049 ] ], "normalized": [] }, { "id": "PMID-10026226_T38", "type": "Cell", "text": [ "primary CD19(+) B" ], "offsets": [ [ 1063, 1080 ] ], "normalized": [] }, { "id": "PMID-10026226_T39", "type": "Cell", "text": [ "DAKIKI cells" ], "offsets": [ [ 1085, 1097 ] ], "normalized": [] }, { "id": "PMID-10026226_T40", "type": "Tissue", "text": [ "skeletal muscle type" ], "offsets": [ [ 1118, 1138 ] ], "normalized": [] }, { "id": "PMID-10026226_T41", "type": "Protein", "text": [ "RYR1" ], "offsets": [ [ 1140, 1144 ] ], "normalized": [] }, { "id": "PMID-10026226_T42", "type": "Chemical", "text": [ "[3H]ryanodine" ], "offsets": [ [ 1170, 1183 ] ], "normalized": [] }, { "id": "PMID-10026226_T43", "type": "Protein", "text": [ "protein" ], "offsets": [ [ 1222, 1229 ] ], "normalized": [] }, { "id": "PMID-10026226_T44", "type": "Cell", "text": [ "DAKIKI cells" ], "offsets": [ [ 1249, 1261 ] ], "normalized": [] }, { "id": "PMID-10026226_T45", "type": "Cell", "text": [ "CD19(+) B" ], "offsets": [ [ 1280, 1289 ] ], "normalized": [] }, { "id": "PMID-10026226_T46", "type": "Cell", "text": [ "DAKIKI cells" ], "offsets": [ [ 1294, 1306 ] ], "normalized": [] }, { "id": "PMID-10026226_T47", "type": "Chemical", "text": [ "4-chloro-m-cresol" ], "offsets": [ [ 1308, 1325 ] ], "normalized": [] }, { "id": "PMID-10026226_T49", "type": "Ion", "text": [ "Ca2+" ], "offsets": [ [ 1349, 1353 ] ], "normalized": [] }, { "id": "PMID-10026226_T52", "type": "Chemical", "text": [ "ryanodine" ], "offsets": [ [ 1378, 1387 ] ], "normalized": [] }, { "id": "PMID-10026226_T53", "type": "Ion", "text": [ "Ca2+" ], "offsets": [ [ 1398, 1402 ] ], "normalized": [] }, { "id": "PMID-10026226_T55", "type": "Protein", "text": [ "channel" ], "offsets": [ [ 1411, 1418 ] ], "normalized": [] }, { "id": "PMID-10026226_T57", "type": "Ion", "text": [ "Ca2+" ], "offsets": [ [ 1428, 1432 ] ], "normalized": [] }, { "id": "PMID-10026226_T59", "type": "Chemical", "text": [ "ryanodine" ], "offsets": [ [ 1465, 1474 ] ], "normalized": [] }, { "id": "PMID-10026226_T60", "type": "Protein", "text": [ "BCR" ], "offsets": [ [ 1507, 1510 ] ], "normalized": [] }, { "id": "PMID-10026226_T62", "type": "Ion", "text": [ "Ca2+" ], "offsets": [ [ 1520, 1524 ] ], "normalized": [] }, { "id": "PMID-10026226_T64", "type": "Cell", "text": [ "CD19(+) B cells" ], "offsets": [ [ 1536, 1551 ] ], "normalized": [] }, { "id": "PMID-10026226_T66", "type": "Chemical", "text": [ "4-chloro-m-cresol" ], "offsets": [ [ 1581, 1598 ] ], "normalized": [] }, { "id": "PMID-10026226_T67", "type": "Chemical", "text": [ "ryanodine" ], "offsets": [ [ 1603, 1612 ] ], "normalized": [] }, { "id": "PMID-10026226_T68", "type": "Protein", "text": [ "RYR1" ], "offsets": [ [ 1642, 1646 ] ], "normalized": [] }, { "id": "PMID-10026226_T69", "type": "Ion", "text": [ "Ca2+" ], "offsets": [ [ 1662, 1666 ] ], "normalized": [] }, { "id": "PMID-10026226_T71", "type": "Protein", "text": [ "channel" ], "offsets": [ [ 1675, 1682 ] ], "normalized": [] }, { "id": "PMID-10026226_T72", "type": "Protein", "text": [ "BCR" ], "offsets": [ [ 1690, 1693 ] ], "normalized": [] }, { "id": "PMID-10026226_T74", "type": "Ion", "text": [ "Ca2+" ], "offsets": [ [ 1705, 1709 ] ], "normalized": [] }, { "id": "PMID-10026226_T76", "type": "Ion", "text": [ "Ca2+" ], "offsets": [ [ 1745, 1749 ] ], "normalized": [] }, { "id": "PMID-10026226_T78", "type": "Cell", "text": [ "B cells" ], "offsets": [ [ 1798, 1805 ] ], "normalized": [] }, { "id": "PMID-10026226_T80", "type": "Protein", "text": [ "IP3 receptor" ], "offsets": [ [ 1845, 1857 ] ], "normalized": [] }, { "id": "PMID-10026226_T81", "type": "Protein", "text": [ "RYR1" ], "offsets": [ [ 1862, 1866 ] ], "normalized": [] }, { "id": "PMID-10026226_T1", "type": "Protein", "text": [ "Skeletal muscle type ryanodine receptor" ], "offsets": [ [ 0, 39 ] ], "normalized": [] }, { "id": "PMID-10026226_T10", "type": "Chemical", "text": [ "IP3" ], "offsets": [ [ 406, 409 ] ], "normalized": [] }, { "id": "PMID-10026226_T82", "type": "Ion", "text": [ "Ca2+" ], "offsets": [ [ 469, 473 ] ], "normalized": [] } ]

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"GeneExpression", "trigger": { "text": [ "express" ], "offsets": [ [ 522, 529 ] ] }, "arguments": [ { "role": "hasPatient", "ref_id": "PMID-10026226_T21" } ] }, { "id": "PMID-10026226_E7", "type": "Transport", "trigger": { "text": [ "release" ], "offsets": [ [ 582, 589 ] ] }, "arguments": [ { "role": "hasAgent", "ref_id": "PMID-10026226_T24" }, { "role": "hasPatient", "ref_id": "PMID-10026226_T22" } ] }, { "id": "PMID-10026226_E8", "type": "Increase", "trigger": { "text": [ "stimulated" ], "offsets": [ [ 639, 649 ] ] }, "arguments": [ { "role": "hasPatient", "ref_id": "PMID-10026226_E9" }, { "role": "hasAgent", "ref_id": "PMID-10026226_T26" } ] }, { "id": "PMID-10026226_E9", "type": "SignalingPathway", "trigger": { "text": [ "signaling process" ], "offsets": [ [ 655, 672 ] ] }, "arguments": [] }, { "id": "PMID-10026226_E10", "type": "GeneExpression", "trigger": { "text": [ "express" ], "offsets": [ [ 755, 762 ] ] }, "arguments": [ { "role": "hasPatient", "ref_id": "PMID-10026226_T34" } ] }, { "id": "PMID-10026226_E11", "type": "GeneExpression", "trigger": { "text": [ "expressed" ], "offsets": [ [ 1050, 1059 ] ] }, "arguments": [ { "role": "hasPatient", "ref_id": "PMID-10026226_T36" } ] }, { "id": "PMID-10026226_E12", "type": "PositiveRegulation", "trigger": { "text": [ "activator" ], "offsets": [ [ 1336, 1345 ] ] }, "arguments": [ { "role": "hasAgent", "ref_id": "PMID-10026226_T47" }, { "role": "hasPatient", "ref_id": "PMID-10026226_E13" } ] }, { "id": "PMID-10026226_E13", "type": "Transport", "trigger": { "text": [ "release" ], "offsets": [ [ 1354, 1361 ] ] }, "arguments": [ { "role": "hasPatient", "ref_id": "PMID-10026226_T49" } ] }, { "id": "PMID-10026226_E14", "type": "RegulatoryProcess", "trigger": { "text": [ "mediated" ], "offsets": [ [ 1362, 1370 ] ] }, "arguments": [ { "role": "hasAgent", "ref_id": "PMID-10026226_T55" }, { "role": "hasPatient", "ref_id": "PMID-10026226_E13" } ] }, { "id": "PMID-10026226_E15", "type": "Transport", "trigger": { "text": [ "release" ], "offsets": [ [ 1403, 1410 ] ] }, "arguments": [ { "role": "hasAgent", "ref_id": "PMID-10026226_T55" }, { "role": "hasPatient", "ref_id": "PMID-10026226_T53" } ] }, { "id": "PMID-10026226_E16", "type": "PositiveRegulation", "trigger": { "text": [ "induced" ], "offsets": [ [ 1420, 1427 ] ] }, "arguments": [ { "role": "hasPatient", "ref_id": "PMID-10026226_E17" } ] }, { "id": "PMID-10026226_E17", "type": "Transport", "trigger": { "text": [ "release" ], "offsets": [ [ 1433, 1440 ] ] }, "arguments": [ { "role": "hasPatient", "ref_id": "PMID-10026226_T57" } ] }, { "id": "PMID-10026226_E18", "type": "RegulatoryProcess", "trigger": { "text": [ "mediated" ], "offsets": [ [ 1511, 1519 ] ] }, "arguments": [ { "role": "hasAgent", "ref_id": "PMID-10026226_T60" }, { "role": "hasPatient", "ref_id": "PMID-10026226_E19" } ] }, { "id": "PMID-10026226_E19", "type": "Transport", "trigger": { "text": [ "release" ], "offsets": [ [ 1525, 1532 ] ] }, "arguments": [ { "role": "hasPatient", "ref_id": "PMID-10026226_T62" } ] }, { "id": "PMID-10026226_E20", "type": "Affecting", "trigger": { "text": [ "altered" ], "offsets": [ [ 1570, 1577 ] ] }, "arguments": [ { "role": "hasPatient", "ref_id": "PMID-10026226_E19" }, { "role": "hasAgent", "ref_id": "PMID-10026226_T66" } ] }, { "id": "PMID-10026226_E21", "type": "Transport", "trigger": { "text": [ "release" ], "offsets": [ [ 1667, 1674 ] ] }, "arguments": [ { "role": "hasAgent", "ref_id": "PMID-10026226_T71" }, { "role": "hasPatient", "ref_id": "PMID-10026226_T69" } ] }, { "id": "PMID-10026226_E22", "type": "Increase", "trigger": { "text": [ "stimulated" ], "offsets": [ [ 1694, 1704 ] ] }, "arguments": [ { "role": "hasAgent", "ref_id": "PMID-10026226_T72" }, { "role": "hasPatient", "ref_id": "PMID-10026226_E23" } ] }, { "id": "PMID-10026226_E23", "type": "SignalingPathway", "trigger": { "text": [ "signaling" ], "offsets": [ [ 1710, 1719 ] ] }, "arguments": [ { "role": "hasPatient", "ref_id": "PMID-10026226_T74" } ] }, { "id": "PMID-10026226_E24", "type": "RegulatoryProcess", "trigger": { "text": [ "control" ], "offsets": [ [ 1763, 1770 ] ] }, "arguments": [ { "role": "hasAgent", "ref_id": "PMID-10026226_T80" } ] }, { "id": "PMID-10026226_E26", "type": "RegulatoryProcess", "trigger": { "text": [ "regulation" ], "offsets": [ [ 101, 111 ] ] }, "arguments": [] }, { "id": "PMID-10026226_E27", "type": "Transport", "trigger": { "text": [ "release" ], "offsets": [ [ 474, 481 ] ] }, "arguments": [ { "role": "hasPatient", "ref_id": "PMID-10026226_T82" } ] }, { "id": "PMID-10026226_E25", "type": "Affecting", "trigger": { "text": [ "altered" ], "offsets": [ [ 1570, 1577 ] ] }, "arguments": [ { "role": "hasPatient", "ref_id": "PMID-10026226_E19" }, { "role": "hasAgent", "ref_id": "PMID-10026226_T67" } ] }, { "id": "PMID-10026226_E28", "type": "RegulatoryProcess", "trigger": { "text": [ "control" ], "offsets": [ [ 1763, 1770 ] ] }, "arguments": [ { "role": "hasAgent", "ref_id": "PMID-10026226_T81" } ] } ]

[]

[ { "id": "PMID-10026226_R3", "type": "fromSpecies", "arg1_id": "PMID-10026226_T6", "arg2_id": "PMID-10026226_T5", "normalized": [] }, { "id": "PMID-10026226_R6", "type": "fromSpecies", "arg1_id": "PMID-10026226_T18", "arg2_id": "PMID-10026226_T17", "normalized": [] }, { "id": "PMID-10026226_R8", "type": "fromSpecies", "arg1_id": "PMID-10026226_T31", "arg2_id": "PMID-10026226_T30", "normalized": [] }, { "id": "PMID-10026226_R1", "type": "locatedIn", "arg1_id": "PMID-10026226_T8", "arg2_id": "PMID-10026226_T9", "normalized": [] }, { "id": "PMID-10026226_R4", "type": "locatedIn", "arg1_id": "PMID-10026226_T41", "arg2_id": "PMID-10026226_T40", "normalized": [] }, { "id": "PMID-10026226_R13", "type": "locatedIn", "arg1_id": "PMID-10026226_T43", "arg2_id": "PMID-10026226_T44", "normalized": [] } ]

[ { "id": "PMID-10026247__text", "type": "abstract", "text": [ "Zinc-binding site of an S100 protein revealed. Two crystal structures of Ca2+-bound human psoriasin (S100A7) in the Zn2+-loaded and Zn2+-free states. The crystal structure of human psoriasin (S100A7) in the native, calcium-bound form has been determined from two crystal forms of the protein crystallized with and without divalent zinc. The overall structures of the dimeric protein closely resemble the previously determined holmium-substituted structure. The structures also reveal a zinc-binding site of the protein, which is formed by three histidines and an aspartate residue. Together, these residues coordinate the zinc ion in a way similar to the pattern seen in certain metalloproteases and in particular the collagenase family of proteins. Sequence comparison suggests that this zinc site is present in a number of the remaining members of the S100 family. The structure of S100A7 crystallized in the absence of zinc further shows that loss of zinc results in a reorganization of the adjacent empty and distorted EF-hand loop, causing it to resemble a calcium-loaded EF-hand.\n" ], "offsets": [ [ 0, 1086 ] ] } ]

[ { "id": "PMID-10026247_T1", "type": "Ion", "text": [ "Zinc" ], "offsets": [ [ 0, 4 ] ], "normalized": [] }, { "id": "PMID-10026247_T3", "type": "Protein", "text": [ "S100 protein" ], "offsets": [ [ 24, 36 ] ], "normalized": [] }, { "id": "PMID-10026247_T4", "type": "Ion", "text": [ "Ca2+" ], "offsets": [ [ 73, 77 ] ], "normalized": [] }, { "id": "PMID-10026247_T6", "type": "Eukaryote", "text": [ "human" ], "offsets": [ [ 84, 89 ] ], "normalized": [] }, { "id": "PMID-10026247_T7", "type": "Protein", "text": [ "psoriasin" ], "offsets": [ [ 90, 99 ] ], "normalized": [] }, { "id": "PMID-10026247_T8", "type": "Protein", "text": [ "S100A7" ], "offsets": [ [ 101, 107 ] ], "normalized": [] }, { "id": "PMID-10026247_T9", "type": "Ion", "text": [ "Zn2+" ], "offsets": [ [ 116, 120 ] ], "normalized": [] }, { "id": "PMID-10026247_T10", "type": "Ion", "text": [ "Zn2+" ], "offsets": [ [ 132, 136 ] ], "normalized": [] }, { "id": "PMID-10026247_T11", "type": "Eukaryote", "text": [ "human" ], "offsets": [ [ 175, 180 ] ], "normalized": [] }, { "id": "PMID-10026247_T12", "type": "Protein", "text": [ "psoriasin" ], "offsets": [ [ 181, 190 ] ], "normalized": [] }, { "id": "PMID-10026247_T13", "type": "Protein", "text": [ "S100A7" ], "offsets": [ [ 192, 198 ] ], "normalized": [] }, { "id": "PMID-10026247_T14", "type": "Ion", "text": [ "calcium" ], "offsets": [ [ 215, 222 ] ], "normalized": [] }, { "id": "PMID-10026247_T16", "type": "Protein", "text": [ "protein" ], "offsets": [ [ 284, 291 ] ], "normalized": [] }, { "id": "PMID-10026247_T17", "type": "Ion", "text": [ "divalent zinc" ], "offsets": [ [ 322, 335 ] ], "normalized": [] }, { "id": "PMID-10026247_T18", "type": "Protein", "text": [ "dimeric protein" ], "offsets": [ [ 367, 382 ] ], "normalized": [] }, { "id": "PMID-10026247_T19", "type": "Chemical", "text": [ "holmium" ], "offsets": [ [ 426, 433 ] ], "normalized": [] }, { "id": "PMID-10026247_T20", "type": "Ion", "text": [ "zinc" ], "offsets": [ [ 486, 490 ] ], "normalized": [] }, { "id": "PMID-10026247_T22", "type": "BindingSiteOfProtein", "text": [ "site" ], "offsets": [ [ 499, 503 ] ], "normalized": [] }, { "id": "PMID-10026247_T23", "type": "Protein", "text": [ "protein" ], "offsets": [ [ 511, 518 ] ], "normalized": [] }, { "id": "PMID-10026247_T24", "type": "AminoAcid", "text": [ "histidines" ], "offsets": [ [ 545, 555 ] ], "normalized": [] }, { "id": "PMID-10026247_T25", "type": "AminoAcid", "text": [ "aspartate residue" ], "offsets": [ [ 563, 580 ] ], "normalized": [] }, { "id": "PMID-10026247_T26", "type": "Ion", "text": [ "zinc ion" ], "offsets": [ [ 622, 630 ] ], "normalized": [] }, { "id": "PMID-10026247_T27", "type": "Enzyme", "text": [ "metalloproteases" ], "offsets": [ [ 679, 695 ] ], "normalized": [] }, { "id": "PMID-10026247_T28", "type": "Enzyme", "text": [ "collagenase" ], "offsets": [ [ 718, 729 ] ], "normalized": [] }, { "id": "PMID-10026247_T29", "type": "Protein", "text": [ "proteins" ], "offsets": [ [ 740, 748 ] ], "normalized": [] }, { "id": "PMID-10026247_T30", "type": "Ion", "text": [ "zinc" ], "offsets": [ [ 789, 793 ] ], "normalized": [] }, { "id": "PMID-10026247_T31", "type": "Protein", "text": [ "S100" ], "offsets": [ [ 854, 858 ] ], "normalized": [] }, { "id": "PMID-10026247_T32", "type": "Protein", "text": [ "S100A7" ], "offsets": [ [ 884, 890 ] ], "normalized": [] }, { "id": "PMID-10026247_T33", "type": "Ion", "text": [ "zinc" ], "offsets": [ [ 922, 926 ] ], "normalized": [] }, { "id": "PMID-10026247_T34", "type": "Ion", "text": [ "zinc" ], "offsets": [ [ 954, 958 ] ], "normalized": [] }, { "id": "PMID-10026247_T35", "type": "Ion", "text": [ "calcium" ], "offsets": [ [ 1062, 1069 ] ], "normalized": [] }, { "id": "PMID-10026247_T36", "type": "BindingSiteOfProtein", "text": [ "site" ], "offsets": [ [ 13, 17 ] ], "normalized": [] }, { "id": "PMID-10026247_T37", "type": "BindingSiteOfProtein", "text": [ "site" ], "offsets": [ [ 794, 798 ] ], "normalized": [] } ]

[ { "id": "PMID-10026247_E1", "type": "Binding", "trigger": { "text": [ "binding" ], "offsets": [ [ 5, 12 ] ] }, "arguments": [ { "role": "hasPatient", "ref_id": "PMID-10026247_T1" }, { "role": "hasAgent", "ref_id": "PMID-10026247_T36" } ] }, { "id": "PMID-10026247_E2", "type": "Binding", "trigger": { "text": [ "bound" ], "offsets": [ [ 78, 83 ] ] }, "arguments": [ { "role": "hasAgent", "ref_id": "PMID-10026247_T4" }, { "role": "hasPatient", "ref_id": "PMID-10026247_T7" } ] }, { "id": "PMID-10026247_E3", "type": "Binding", "trigger": { "text": [ "bound" ], "offsets": [ [ 223, 228 ] ] }, "arguments": [ { "role": "hasAgent", "ref_id": "PMID-10026247_T14" } ] }, { "id": "PMID-10026247_E4", "type": "Binding", "trigger": { "text": [ "binding" ], "offsets": [ [ 491, 498 ] ] }, "arguments": [ { "role": "hasAgent", "ref_id": "PMID-10026247_T22" }, { "role": "hasPatient", "ref_id": "PMID-10026247_T20" } ] } ]

[]

[ { "id": "PMID-10026247_R1", "type": "fromSpecies", "arg1_id": "PMID-10026247_T7", "arg2_id": "PMID-10026247_T6", "normalized": [] }, { "id": "PMID-10026247_R2", "type": "fromSpecies", "arg1_id": "PMID-10026247_T12", "arg2_id": "PMID-10026247_T11", "normalized": [] }, { "id": "PMID-10026247_R5", "type": "hasPart", "arg1_id": "PMID-10026247_T23", "arg2_id": "PMID-10026247_T22", "normalized": [] }, { "id": "PMID-10026247_R6", "type": "hasPart", "arg1_id": "PMID-10026247_T3", "arg2_id": "PMID-10026247_T36", "normalized": [] }, { "id": "PMID-10026247_R3", "type": "hasPart", "arg1_id": "PMID-10026247_T31", "arg2_id": "PMID-10026247_T37", "normalized": [] } ]

[ { "id": "PMID-10029623__text", "type": "abstract", "text": [ "Formiminotransferase cyclodeaminase is an organ-specific autoantigen recognized by sera of patients with autoimmune hepatitis. Anti-liver cytosol type 1 autoantibodies have been reported in association with anti-liver-kidney microsome type 1 autoantibodies in 30% of patients with autoimmune hepatitis type II. In 10% of cases, anti-liver cytosol type 1 antibodies are the only liver-related circulating autoantibodies. The liver cytosol antigen is a liver-specific 62-kilodalton protein present in the cell as an oligomer of approximately 240 kilodaltons. The aim of this study was to identify the antigen recognized by anti-liver cytosol antibody. To identify the liver cytosol antigen, an anti-liver cytosol type 1-positive serum was used for the screening of a complementary DNA library from HepG2 cells. Double immunodiffusion method was used to show the identity between the cytosolic and the cloned protein. The sequence of two isolated clones showed 85.2% homology with the formiminotransferase cyclodeaminase (FTCD) enzyme from pig liver. Antibodies purified by affinity with the recombinant protein and sera from mice immunized with FTCD recognized a 62-kilodalton human cytosolic protein when tested by immunoblot. The identity of precipitation lines was found between the cytosolic antigen and FTCD. This enzyme is a liver-specific antigen recognized by the sera of patients with autoimmune hepatitis.\n" ], "offsets": [ [ 0, 1414 ] ] } ]

[ { "id": "PMID-10029623_T1", "type": "Enzyme", "text": [ "Formiminotransferase cyclodeaminase" ], "offsets": [ [ 0, 35 ] ], "normalized": [] }, { "id": "PMID-10029623_T2", "type": "Protein", "text": [ "organ-specific autoantigen" ], "offsets": [ [ 42, 68 ] ], "normalized": [] }, { "id": "PMID-10029623_T4", "type": "Protein", "text": [ "anti-liver cytosol type 1 antibodies" ], "offsets": [ [ 328, 364 ] ], "normalized": [] }, { "id": "PMID-10029623_T5", "type": "Tissue", "text": [ "liver" ], "offsets": [ [ 378, 383 ] ], "normalized": [] }, { "id": "PMID-10029623_T6", "type": "Protein", "text": [ "autoantibodies" ], "offsets": [ [ 404, 418 ] ], "normalized": [] }, { "id": "PMID-10029623_T7", "type": "Protein", "text": [ "Anti-liver cytosol type 1 autoantibodies" ], "offsets": [ [ 127, 167 ] ], "normalized": [] }, { "id": "PMID-10029623_T8", "type": "Protein", "text": [ "liver cytosol antigen" ], "offsets": [ [ 424, 445 ] ], "normalized": [] }, { "id": "PMID-10029623_T9", "type": "Protein", "text": [ "anti-liver cytosol antibody" ], "offsets": [ [ 621, 648 ] ], "normalized": [] }, { "id": "PMID-10029623_T10", "type": "Protein", "text": [ "liver cytosol antigen" ], "offsets": [ [ 666, 687 ] ], "normalized": [] }, { "id": "PMID-10029623_T11", "type": "Eukaryote", "text": [ "pig" ], "offsets": [ [ 1037, 1040 ] ], "normalized": [] }, { "id": "PMID-10029623_T12", "type": "Tissue", "text": [ "liver" ], "offsets": [ [ 1041, 1046 ] ], "normalized": [] }, { "id": "PMID-10029623_T13", "type": "Protein", "text": [ "Antibodies" ], "offsets": [ [ 1048, 1058 ] ], "normalized": [] }, { "id": "PMID-10029623_T14", "type": "Enzyme", "text": [ "enzyme" ], "offsets": [ [ 1317, 1323 ] ], "normalized": [] }, { "id": "PMID-10029623_T15", "type": "Protein", "text": [ "liver-specific antigen" ], "offsets": [ [ 1329, 1351 ] ], "normalized": [] }, { "id": "PMID-10029623_T17", "type": "Protein", "text": [ "anti-liver-kidney microsome type 1 autoantibodies" ], "offsets": [ [ 207, 256 ] ], "normalized": [] } ]

[ { "id": "PMID-10029623_E1", "type": "Disease", "trigger": { "text": [ "autoimmune hepatitis" ], "offsets": [ [ 105, 125 ] ] }, "arguments": [] }, { "id": "PMID-10029623_E2", "type": "Disease", "trigger": { "text": [ "autoimmune hepatitis" ], "offsets": [ [ 1392, 1412 ] ] }, "arguments": [] }, { "id": "PMID-10029623_E3", "type": "Disease", "trigger": { "text": [ "autoimmune hepatitis type II" ], "offsets": [ [ 281, 309 ] ] }, "arguments": [] } ]

[]

[ { "id": "PMID-10029623_R1", "type": "locatedIn", "arg1_id": "PMID-10029623_T6", "arg2_id": "PMID-10029623_T5", "normalized": [] }, { "id": "PMID-10029623_R2", "type": "fromSpecies", "arg1_id": "PMID-10029623_T12", "arg2_id": "PMID-10029623_T11", "normalized": [] } ]

[ { "id": "PMID-10030672__text", "type": "abstract", "text": [ "Identification of a human HECT family protein with homology to the Drosophila tumor suppressor gene hyperplastic discs. Use of the differential display technique to isolate progestin-regulated genes in T-47D human breast cancer cells led to identification of a novel gene, EDD. The cDNA sequence contains a 2799 amino acid open reading frame sharing 40% identity with the predicted 2894 amino acid product of the Drosophila melanogaster tumor suppressor gene hyperplastic discs, while the carboxy-terminal 889 amino acids show 96% identity to a rat 100 kDa HECT domain protein. EDD mRNA was progestin-induced in T-47D cells and was highly abundant in testes and expressed at moderately high levels in other tissues, suggesting a broad role for EDD. Anti-EDD antibodies immunoprecipitated an approximately 300 kDa protein from T-47D cell lysates. HECT family proteins function as E3 ubiquitin-protein ligases, targeting specific proteins for ubiquitin-mediated proteolysis. EDD is likely to function as an E3 as in vitro translated protein bound ubiquitin reversibly through a conserved HECT domain cysteine residue. EDD was localized by FISH to chromosome 8q22, a locus disrupted in a variety of cancers. Given the homology between EDD and the hyperplastic discs protein, which is required for control of imaginal disc growth in Drosophila, EDD potentially has a role in regulation of cell proliferation or differentiation.\n" ], "offsets": [ [ 0, 1424 ] ] } ]

[ { "id": "PMID-10030672_T3", "type": "Eukaryote", "text": [ "Drosophila" ], "offsets": [ [ 67, 77 ] ], "normalized": [] }, { "id": "PMID-10030672_T4", "type": "Gene", "text": [ "hyperplastic discs" ], "offsets": [ [ 100, 118 ] ], "normalized": [] }, { "id": "PMID-10030672_T5", "type": "Chemical", "text": [ "progestin" ], "offsets": [ [ 173, 182 ] ], "normalized": [] }, { "id": "PMID-10030672_T7", "type": "Gene", "text": [ "genes" ], "offsets": [ [ 193, 198 ] ], "normalized": [] }, { "id": "PMID-10030672_T8", "type": "Cell", "text": [ "T-47D" ], "offsets": [ [ 202, 207 ] ], "normalized": [] }, { "id": "PMID-10030672_T17", "type": "Eukaryote", "text": [ "Drosophila melanogaster" ], "offsets": [ [ 413, 436 ] ], "normalized": [] }, { "id": "PMID-10030672_T18", "type": "Gene", "text": [ "hyperplastic discs" ], "offsets": [ [ 459, 477 ] ], "normalized": [] }, { "id": "PMID-10030672_T24", "type": "MessengerRNA", "text": [ "EDD mRNA" ], "offsets": [ [ 578, 586 ] ], "normalized": [] }, { "id": "PMID-10030672_T25", "type": "Chemical", "text": [ "progestin" ], "offsets": [ [ 591, 600 ] ], "normalized": [] }, { "id": "PMID-10030672_T27", "type": "Cell", "text": [ "T-47D cells" ], "offsets": [ [ 612, 623 ] ], "normalized": [] }, { "id": "PMID-10030672_T28", "type": "Tissue", "text": [ "testes" ], "offsets": [ [ 651, 657 ] ], "normalized": [] }, { "id": "PMID-10030672_T41", "type": "Protein", "text": [ "ubiquitin" ], "offsets": [ [ 941, 950 ] ], "normalized": [] }, { "id": "PMID-10030672_T49", "type": "Protein", "text": [ "ubiquitin" ], "offsets": [ [ 1045, 1054 ] ], "normalized": [] }, { "id": "PMID-10030672_T50", "type": "ProteinDomain", "text": [ "HECT domain" ], "offsets": [ [ 1086, 1097 ] ], "normalized": [] }, { "id": "PMID-10030672_T51", "type": "AminoAcid", "text": [ "cysteine residue" ], "offsets": [ [ 1098, 1114 ] ], "normalized": [] }, { "id": "PMID-10030672_T52", "type": "Gene", "text": [ "EDD" ], "offsets": [ [ 1116, 1119 ] ], "normalized": [] }, { "id": "PMID-10030672_T59", "type": "Eukaryote", "text": [ "Drosophila" ], "offsets": [ [ 1329, 1339 ] ], "normalized": [] }, { "id": "PMID-10030672_T60", "type": "Gene", "text": [ "EDD" ], "offsets": [ [ 1341, 1344 ] ], "normalized": [] }, { "id": "PMID-10030672_T11", "type": "Eukaryote", "text": [ "human" ], "offsets": [ [ 208, 213 ] ], "normalized": [] }, { "id": "PMID-10030672_T2", "type": "Tissue", "text": [ "imaginal disc" ], "offsets": [ [ 1305, 1318 ] ], "normalized": [] }, { "id": "PMID-10030672_T1", "type": "Protein", "text": [ "HECT family protein" ], "offsets": [ [ 26, 45 ] ], "normalized": [] }, { "id": "PMID-10030672_T12", "type": "Eukaryote", "text": [ "human" ], "offsets": [ [ 20, 25 ] ], "normalized": [] }, { "id": "PMID-10030672_T13", "type": "ProteinIdentification", "text": [ "Identification" ], "offsets": [ [ 0, 14 ] ], "normalized": [] }, { "id": "PMID-10030672_T14", "type": "Gene", "text": [ "tumor suppressor gene" ], "offsets": [ [ 78, 99 ] ], "normalized": [] }, { "id": "PMID-10030672_T15", "type": "Cell", "text": [ "breast cancer cells" ], "offsets": [ [ 214, 233 ] ], "normalized": [] }, { "id": "PMID-10030672_T16", "type": "Gene", "text": [ "EDD" ], "offsets": [ [ 273, 276 ] ], "normalized": [] }, { "id": "PMID-10030672_T19", "type": "Gene", "text": [ "tumor suppressor gene" ], "offsets": [ [ 437, 458 ] ], "normalized": [] }, { "id": "PMID-10030672_T20", "type": "Eukaryote", "text": [ "rat" ], "offsets": [ [ 545, 548 ] ], "normalized": [] }, { "id": "PMID-10030672_T21", "type": "Protein", "text": [ "HECT domain protein" ], "offsets": [ [ 557, 576 ] ], "normalized": [] }, { "id": "PMID-10030672_T22", "type": "Protein", "text": [ "protein" ], "offsets": [ [ 813, 820 ] ], "normalized": [] }, { "id": "PMID-10030672_T23", "type": "Gene", "text": [ "EDD" ], "offsets": [ [ 744, 747 ] ], "normalized": [] }, { "id": "PMID-10030672_T30", "type": "Cell", "text": [ "T-47D cell" ], "offsets": [ [ 826, 836 ] ], "normalized": [] }, { "id": "PMID-10030672_T31", "type": "Protein", "text": [ "HECT family proteins" ], "offsets": [ [ 846, 866 ] ], "normalized": [] }, { "id": "PMID-10030672_T32", "type": "Enzyme", "text": [ "E3 ubiquitin-protein ligases" ], "offsets": [ [ 879, 907 ] ], "normalized": [] }, { "id": "PMID-10030672_T34", "type": "Enzyme", "text": [ "E3" ], "offsets": [ [ 1005, 1007 ] ], "normalized": [] }, { "id": "PMID-10030672_T35", "type": "Protein", "text": [ "EDD" ], "offsets": [ [ 973, 976 ] ], "normalized": [] }, { "id": "PMID-10030672_T36", "type": "Protein", "text": [ "EDD" ], "offsets": [ [ 1232, 1235 ] ], "normalized": [] }, { "id": "PMID-10030672_T37", "type": "Chromosome", "text": [ "chromosome 8q22" ], "offsets": [ [ 1145, 1160 ] ], "normalized": [] }, { "id": "PMID-10030672_T10", "type": "Protein", "text": [ "hyperplastic discs protein" ], "offsets": [ [ 1244, 1270 ] ], "normalized": [] } ]

[ { "id": "PMID-10030672_E1", "type": "RegulatoryProcess", "trigger": { "text": [ "regulated" ], "offsets": [ [ 183, 192 ] ] }, "arguments": [ { "role": "hasAgent", "ref_id": "PMID-10030672_T5" }, { "role": "hasPatient", "ref_id": "PMID-10030672_T7" } ] }, { "id": "PMID-10030672_E2", "type": "Increase", "trigger": { "text": [ "induced" ], "offsets": [ [ 601, 608 ] ] }, "arguments": [ { "role": "hasAgent", "ref_id": "PMID-10030672_T25" }, { "role": "hasPatient", "ref_id": "PMID-10030672_T24" } ] }, { "id": "PMID-10030672_E3", "type": "TranscriptionOfGene", "trigger": { "text": [ "expressed" ], "offsets": [ [ 662, 671 ] ] }, "arguments": [ { "role": "hasPatient", "ref_id": "PMID-10030672_T24" } ] }, { "id": "PMID-10030672_E4", "type": "RegulatoryProcess", "trigger": { "text": [ "mediated" ], "offsets": [ [ 951, 959 ] ] }, "arguments": [ { "role": "hasAgent", "ref_id": "PMID-10030672_T41" }, { "role": "hasPatient", "ref_id": "PMID-10030672_E8" } ] }, { "id": "PMID-10030672_E7", "type": "BindingToProtein", "trigger": { "text": [ "bound" ], "offsets": [ [ 1039, 1044 ] ] }, "arguments": [ { "role": "hasPatient", "ref_id": "PMID-10030672_T49" } ] }, { "id": "PMID-10030672_E9", "type": "Growth", "trigger": { "text": [ "growth" ], "offsets": [ [ 1319, 1325 ] ] }, "arguments": [ { "role": "hasPatient", "ref_id": "PMID-10030672_T2" } ] }, { "id": "PMID-10030672_E6", "type": "RegulatoryProcess", "trigger": { "text": [ "control" ], "offsets": [ [ 1294, 1301 ] ] }, "arguments": [ { "role": "hasPatient", "ref_id": "PMID-10030672_E9" } ] }, { "id": "PMID-10030672_E5", "type": "RegulatoryProcess", "trigger": { "text": [ "regulation" ], "offsets": [ [ 1371, 1381 ] ] }, "arguments": [ { "role": "hasAgent", "ref_id": "PMID-10030672_T60" } ] }, { "id": "PMID-10030672_E8", "type": "ProteinCatabolism", "trigger": { "text": [ "proteolysis" ], "offsets": [ [ 960, 971 ] ] }, "arguments": [] }, { "id": "PMID-10030672_E10", "type": "CellGrowth", "trigger": { "text": [ "cell proliferation" ], "offsets": [ [ 1385, 1403 ] ] }, "arguments": [] }, { "id": "PMID-10030672_E11", "type": "CellDifferentiation", "trigger": { "text": [ "differentiation" ], "offsets": [ [ 1407, 1422 ] ] }, "arguments": [] } ]

[]

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[ { "id": "PMID-10030676__text", "type": "abstract", "text": [ "Isolation and characterization of a human homologue of the latrophilin gene from a region of 1p31.1 implicated in breast cancer. We have identified a region of chromosome 1p31.1 that shows high frequency loss of heterozygosity (LOH) in human breast cancer. This region forms part of a 7 Mb YAC/BAC contig. In order to identify candidate sequences, mutation of which might contribute to the development of disease, we have carried out mapping studies of ESTs localized to 1p31.1. This analysis, coupled with library screening and a modified 5' RACE-PCR strategy, resulted in the identification and characterization of a novel gene (LPHH1) which is located adjacent to the smallest region of overlapping loss (SRO) seen in tumours. The 4209 bp open reading frame of the 7 kb LPHH1 transcript encodes a peptide which shows approximately 65% identity to rat latrophilin, a G-coupled, seven span transmembrane protein, which binds alpha-latrotoxin. In the human sequence, whilst conservation of the transmembrane domain is high, the intra- and extracellular domains show two regions of variable structure, which are presumably generated by alternative splicing. Surprisingly, while expression of the rat gene is tightly restricted to neurological and perhaps some endocrine cells, the human sequence appears to be expressed very widely in all normal tissues tested. Northern and RT-PCR analysis of a panel of tumour cell lines showed that LPHH1 expression was variable, apparently elevated in some lines and absent or markedly reduced in others. Furthermore, characterization of the range of transcripts encoded in a breast tumour cell line, compared to normal breast, suggested that gene product variability was higher in the tumour.\n" ], "offsets": [ [ 0, 1730 ] ] } ]

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[ { "id": "PMID-10030676_E1", "type": "Mutation", "trigger": { "text": [ "mutation" ], "offsets": [ [ 348, 356 ] ] }, "arguments": [] }, { "id": "PMID-10030676_E2", "type": "Disease", "trigger": { "text": [ "disease" ], "offsets": [ [ 405, 412 ] ] }, "arguments": [] }, { "id": "PMID-10030676_E3", "type": "BindingToProtein", "trigger": { "text": [ "binds" ], "offsets": [ [ 920, 925 ] ] }, "arguments": [ { "role": "hasPatient", "ref_id": "PMID-10030676_T21" }, { "role": "hasPatient2", "ref_id": "PMID-10030676_T19" } ] }, { "id": "PMID-10030676_E4", "type": "Splicing", "trigger": { "text": [ "alternative splicing" ], "offsets": [ [ 1135, 1155 ] ] }, "arguments": [] }, { "id": "PMID-10030676_E5", "type": "GeneExpression", "trigger": { "text": [ "expression" ], "offsets": [ [ 1177, 1187 ] ] }, "arguments": [ { "role": "hasPatient", "ref_id": "PMID-10030676_T28" } ] }, { "id": "PMID-10030676_E6", "type": "GeneExpression", "trigger": { "text": [ "expressed" ], "offsets": [ [ 1309, 1318 ] ] }, "arguments": [ { "role": "hasPatient", "ref_id": "PMID-10030676_T32" } ] }, { "id": "PMID-10030676_E7", "type": "GeneExpression", "trigger": { "text": [ "expression" ], "offsets": [ [ 1440, 1450 ] ] }, "arguments": [ { "role": "hasPatient", "ref_id": "PMID-10030676_T36" } ] }, { "id": "PMID-10030676_E8", "type": "Disease", "trigger": { "text": [ "breast cancer" ], "offsets": [ [ 114, 127 ] ] }, "arguments": [] }, { "id": "PMID-10030676_E9", "type": "Disease", "trigger": { "text": [ "breast cancer" ], "offsets": [ [ 242, 255 ] ] }, "arguments": [] }, { "id": "PMID-10030676_E10", "type": "Disease", "trigger": { "text": [ "tumours" ], "offsets": [ [ 721, 728 ] ] }, "arguments": [] }, { "id": "PMID-10030676_E11", "type": "Disease", "trigger": { "text": [ "tumour" ], "offsets": [ [ 1722, 1728 ] ] }, "arguments": [] } ]

[]

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[ { "id": "PMID-10036181__text", "type": "abstract", "text": [ "Discovery of three novel orphan G-protein-coupled receptors. We have discovered three novel human genes, GPR34, GPR44, and GPR45, encoding family A G-protein-coupled receptors (GPCRs). The receptor encoded by GPR34 is most similar to the P2Y receptor subfamily, while the receptor encoded by GPR44 is most similar to chemoattractant receptors. The receptor encoded by GPR45 is the mammalian orthologue of a putative lysophosphatidic acid receptor from Xenopus laevis. Partial sequence of GPR34 was discovered during a search of the GenBank database of expressed sequence tags (ESTs). This sequence information was used both to isolate the full-length translational open reading frame from a human genomic library and to assemble a contig from additional GPR34 EST cDNAs. Northern blot and in situ hybridization analyses revealed GPR34 mRNA transcripts in several human and rat brain regions. Also, we used polymerase chain reaction (PCR) to amplify human genomic DNA using degenerate oligonucleotides designed from sequences encoding transmembrane domains 3 and 7 of opioid and somatostatin receptors. Two PCR products partially encoding novel GPCRs, named GPR44 and GPR45, were discovered and used to isolate the full-length translational open reading frames from a human genomic library. Both GPR44 and GPR45 are expressed in the central nervous system and periphery. For chromosomal localization, fluorescence in situ hybridization analysis was performed to assign GPR34 to chromosomes 4p12 and Xp11. 3, GPR44 to chromosome 11q12-q13.3, and GPR45 to chromosome 2q11. 1-q12.\n" ], "offsets": [ [ 0, 1577 ] ] } ]

[ { "id": "PMID-10036181_T1", "type": "Protein", "text": [ "G-protein-coupled receptors" ], "offsets": [ [ 32, 59 ] ], "normalized": [] }, { "id": "PMID-10036181_T3", "type": "Eukaryote", "text": [ "human" ], "offsets": [ [ 92, 97 ] ], "normalized": [] }, { "id": "PMID-10036181_T4", "type": "Gene", "text": [ "genes" ], "offsets": [ [ 98, 103 ] ], "normalized": [] }, { "id": "PMID-10036181_T5", "type": "Gene", "text": [ "GPR34" ], "offsets": [ [ 105, 110 ] ], "normalized": [] }, { "id": "PMID-10036181_T6", "type": "Gene", "text": [ "GPR44" ], "offsets": [ [ 112, 117 ] ], "normalized": [] }, { "id": "PMID-10036181_T7", "type": "Gene", "text": [ "GPR45" ], "offsets": [ [ 123, 128 ] ], "normalized": [] }, { "id": "PMID-10036181_T9", "type": "Protein", "text": [ "G-protein-coupled receptors" ], "offsets": [ [ 148, 175 ] ], "normalized": [] }, { "id": "PMID-10036181_T10", "type": "Protein", "text": [ "GPCRs" ], "offsets": [ [ 177, 182 ] ], "normalized": [] }, { "id": "PMID-10036181_T11", "type": "Protein", "text": [ "receptor" ], "offsets": [ [ 189, 197 ] ], "normalized": [] }, { "id": "PMID-10036181_T12", "type": "Gene", "text": [ "GPR34" ], "offsets": [ [ 209, 214 ] ], "normalized": [] }, { "id": "PMID-10036181_T13", "type": "Protein", "text": [ "P2Y receptor subfamily" ], "offsets": [ [ 238, 260 ] ], "normalized": [] }, { "id": "PMID-10036181_T14", "type": "Protein", "text": [ "receptor" ], "offsets": [ [ 272, 280 ] ], "normalized": [] }, { "id": "PMID-10036181_T15", "type": "Gene", "text": [ "GPR44" ], "offsets": [ [ 292, 297 ] ], "normalized": [] }, { "id": "PMID-10036181_T16", "type": "Protein", "text": [ "chemoattractant receptors" ], "offsets": [ [ 317, 342 ] ], "normalized": [] }, { "id": "PMID-10036181_T17", "type": "Protein", "text": [ "receptor" ], "offsets": [ [ 348, 356 ] ], "normalized": [] }, { "id": "PMID-10036181_T18", "type": "Gene", "text": [ "GPR45" ], "offsets": [ [ 368, 373 ] ], "normalized": [] }, { "id": "PMID-10036181_T19", "type": "Eukaryote", "text": [ "mammalian" ], "offsets": [ [ 381, 390 ] ], "normalized": [] }, { "id": "PMID-10036181_T20", "type": "Protein", "text": [ "lysophosphatidic acid receptor" ], "offsets": [ [ 416, 446 ] ], "normalized": [] }, { "id": "PMID-10036181_T21", "type": "Eukaryote", "text": [ "Xenopus laevis" ], "offsets": [ [ 452, 466 ] ], "normalized": [] }, { "id": "PMID-10036181_T22", "type": "Gene", "text": [ "GPR34" ], "offsets": [ [ 488, 493 ] ], "normalized": [] }, { "id": "PMID-10036181_T23", "type": "OpenReadingFrame", "text": [ "open reading frame" ], "offsets": [ [ 665, 683 ] ], "normalized": [] }, { "id": "PMID-10036181_T24", "type": "Eukaryote", "text": [ "human" ], "offsets": [ [ 691, 696 ] ], "normalized": [] }, { "id": "PMID-10036181_T25", "type": "Gene", "text": [ "GPR34" ], "offsets": [ [ 754, 759 ] ], "normalized": [] }, { "id": "PMID-10036181_T26", "type": "DNA", "text": [ "cDNAs" ], "offsets": [ [ 764, 769 ] ], "normalized": [] }, { "id": "PMID-10036181_T27", "type": "Gene", "text": [ "GPR34" ], "offsets": [ [ 829, 834 ] ], "normalized": [] }, { "id": "PMID-10036181_T28", "type": "MessengerRNA", "text": [ "mRNA transcripts" ], "offsets": [ [ 835, 851 ] ], "normalized": [] }, { "id": "PMID-10036181_T29", "type": "Eukaryote", "text": [ "human" ], "offsets": [ [ 863, 868 ] ], "normalized": [] }, { "id": "PMID-10036181_T30", "type": "Eukaryote", "text": [ "rat" ], "offsets": [ [ 873, 876 ] ], "normalized": [] }, { "id": "PMID-10036181_T31", "type": "Tissue", "text": [ "brain regions" ], "offsets": [ [ 877, 890 ] ], "normalized": [] }, { "id": "PMID-10036181_T32", "type": "Eukaryote", "text": [ "human" ], "offsets": [ [ 949, 954 ] ], "normalized": [] }, { "id": "PMID-10036181_T33", "type": "DNA", "text": [ "genomic DNA" ], "offsets": [ [ 955, 966 ] ], "normalized": [] }, { "id": "PMID-10036181_T34", "type": "Sequence", "text": [ "sequences" ], "offsets": [ [ 1015, 1024 ] ], "normalized": [] }, { "id": "PMID-10036181_T38", "type": "Protein", "text": [ "GPCRs" ], "offsets": [ [ 1144, 1149 ] ], "normalized": [] }, { "id": "PMID-10036181_T39", "type": "Protein", "text": [ "GPR44" ], "offsets": [ [ 1157, 1162 ] ], "normalized": [] }, { "id": "PMID-10036181_T40", "type": "Protein", "text": [ "GPR45" ], "offsets": [ [ 1167, 1172 ] ], "normalized": [] }, { "id": "PMID-10036181_T41", "type": "OpenReadingFrame", "text": [ "open reading frames" ], "offsets": [ [ 1240, 1259 ] ], "normalized": [] }, { "id": "PMID-10036181_T42", "type": "Eukaryote", "text": [ "human" ], "offsets": [ [ 1267, 1272 ] ], "normalized": [] }, { "id": "PMID-10036181_T43", "type": "Protein", "text": [ "GPR44" ], "offsets": [ [ 1295, 1300 ] ], "normalized": [] }, { "id": "PMID-10036181_T44", "type": "Protein", "text": [ "GPR45" ], "offsets": [ [ 1305, 1310 ] ], "normalized": [] }, { "id": "PMID-10036181_T46", "type": "Chromosome", "text": [ "chromosomal" ], "offsets": [ [ 1374, 1385 ] ], "normalized": [] }, { "id": "PMID-10036181_T48", "type": "Gene", "text": [ "GPR34" ], "offsets": [ [ 1468, 1473 ] ], "normalized": [] }, { "id": "PMID-10036181_T49", "type": "Chromosome", "text": [ "chromosomes" ], "offsets": [ [ 1477, 1488 ] ], "normalized": [] }, { "id": "PMID-10036181_T50", "type": "Gene", "text": [ "GPR44" ], "offsets": [ [ 1507, 1512 ] ], "normalized": [] }, { "id": "PMID-10036181_T51", "type": "Chromosome", "text": [ "chromosome" ], "offsets": [ [ 1516, 1526 ] ], "normalized": [] }, { "id": "PMID-10036181_T52", "type": "Gene", "text": [ "GPR45" ], "offsets": [ [ 1544, 1549 ] ], "normalized": [] }, { "id": "PMID-10036181_T53", "type": "Chromosome", "text": [ "chromosome" ], "offsets": [ [ 1553, 1563 ] ], "normalized": [] }, { "id": "PMID-10036181_T2", "type": "ProteinDomain", "text": [ "transmembrane domains 3 and 7" ], "offsets": [ [ 1034, 1063 ] ], "normalized": [] }, { "id": "PMID-10036181_T8", "type": "Protein", "text": [ "opioid and somatostatin receptors" ], "offsets": [ [ 1067, 1100 ] ], "normalized": [] }, { "id": "PMID-10036181_T35", "type": "Tissue", "text": [ "central nervous system and periphery" ], "offsets": [ [ 1332, 1368 ] ], "normalized": [] }, { "id": "PMID-10036181_T36", "type": "ExperimentalMethod", "text": [ "localization" ], "offsets": [ [ 1386, 1398 ] ], "normalized": [] } ]

[ { "id": "PMID-10036181_E1", "type": "GeneExpression", "trigger": { "text": [ "expressed" ], "offsets": [ [ 1315, 1324 ] ] }, "arguments": [ { "role": "hasPatient", "ref_id": "PMID-10036181_T43" } ] }, { "id": "PMID-10036181_E2", "type": "GeneExpression", "trigger": { "text": [ "expressed" ], "offsets": [ [ 1315, 1324 ] ] }, "arguments": [ { "role": "hasPatient", "ref_id": "PMID-10036181_T44" } ] } ]

[]

[ { "id": "PMID-10036181_R1", "type": "fromSpecies", "arg1_id": "PMID-10036181_T4", "arg2_id": "PMID-10036181_T3", "normalized": [] }, { "id": "PMID-10036181_R2", "type": "encodes", "arg1_id": "PMID-10036181_T5", "arg2_id": "PMID-10036181_T9", "normalized": [] }, { "id": "PMID-10036181_R3", "type": "encodes", "arg1_id": "PMID-10036181_T6", "arg2_id": "PMID-10036181_T9", "normalized": [] }, { "id": "PMID-10036181_R4", "type": "encodes", "arg1_id": "PMID-10036181_T7", "arg2_id": "PMID-10036181_T9", "normalized": [] }, { "id": "PMID-10036181_R5", "type": "encodes", "arg1_id": "PMID-10036181_T12", "arg2_id": "PMID-10036181_T11", "normalized": [] }, { "id": "PMID-10036181_R6", "type": "encodes", "arg1_id": "PMID-10036181_T15", "arg2_id": "PMID-10036181_T14", "normalized": [] }, { "id": "PMID-10036181_R7", "type": "fromSpecies", "arg1_id": "PMID-10036181_T17", "arg2_id": "PMID-10036181_T19", "normalized": [] }, { "id": "PMID-10036181_R8", "type": "encodes", "arg1_id": "PMID-10036181_T18", "arg2_id": "PMID-10036181_T17", "normalized": [] }, { "id": "PMID-10036181_R9", "type": "fromSpecies", "arg1_id": "PMID-10036181_T20", "arg2_id": "PMID-10036181_T21", "normalized": [] }, { "id": "PMID-10036181_R10", "type": "encodes", "arg1_id": "PMID-10036181_T27", "arg2_id": "PMID-10036181_T28", "normalized": [] }, { "id": "PMID-10036181_R11", "type": "locatedIn", "arg1_id": "PMID-10036181_T28", "arg2_id": "PMID-10036181_T31", "normalized": [] }, { "id": "PMID-10036181_R12", "type": "fromSpecies", "arg1_id": "PMID-10036181_T31", "arg2_id": "PMID-10036181_T29", "normalized": [] }, { "id": "PMID-10036181_R13", "type": "fromSpecies", "arg1_id": "PMID-10036181_T31", "arg2_id": "PMID-10036181_T30", "normalized": [] }, { "id": "PMID-10036181_R14", "type": "fromSpecies", "arg1_id": "PMID-10036181_T33", "arg2_id": "PMID-10036181_T32", "normalized": [] }, { "id": "PMID-10036181_R19", "type": "locatedIn", "arg1_id": "PMID-10036181_T48", "arg2_id": "PMID-10036181_T49", "normalized": [] }, { "id": "PMID-10036181_R20", "type": "locatedIn", "arg1_id": "PMID-10036181_T50", "arg2_id": "PMID-10036181_T51", "normalized": [] }, { "id": "PMID-10036181_R21", "type": "locatedIn", "arg1_id": "PMID-10036181_T52", "arg2_id": "PMID-10036181_T53", "normalized": [] }, { "id": "PMID-10036181_R22", "type": "fromSpecies", "arg1_id": "PMID-10036181_T23", "arg2_id": "PMID-10036181_T24", "normalized": [] }, { "id": "PMID-10036181_R15", "type": "encodes", "arg1_id": "PMID-10036181_T34", "arg2_id": "PMID-10036181_T2", "normalized": [] }, { "id": "PMID-10036181_R16", "type": "hasPart", "arg1_id": "PMID-10036181_T8", "arg2_id": "PMID-10036181_T2", "normalized": [] }, { "id": "PMID-10036181_R17", "type": "fromSpecies", "arg1_id": "PMID-10036181_T41", "arg2_id": "PMID-10036181_T42", "normalized": [] } ]

[ { "id": "PMID-10036186__text", "type": "abstract", "text": [ "A gene upregulated in the acoustically damaged chick basilar papilla encodes a novel WD40 repeat protein. The chick WDR1 gene is expressed at higher levels in the chick basilar papilla after acoustic overstimulation. The 3.3-kb WDR1 cDNA encodes a novel 67-kDa protein containing nine WD40 repeats, motifs that mediate protein-protein interactions. The predicted WDR1 protein has high sequence identity to WD40-repeat proteins in budding yeast (Saccharomyces cerevisiae), two slime molds (Dictyostelium discoideum and Physarum polycephalum), and the roundworm (Caenorhabditis elegans). The yeast and P. polycephalum proteins bind actin, suggesting that the novel chick protein may be an actin-binding protein. Sequence database comparisons identified mouse and human cDNAs with high sequence identity to the chick WDR1 cDNA. The mouse Wdr1 and human WDR1 proteins showed 95% sequence identity to each other and 86% identity to the chick WDR1 protein. Northern blot analysis of total RNA from the chick basilar papilla after noise trauma revealed increased levels of a 3.1-kb transcript in the lesioned area. The WDR1 gene was mapped to human chromosome 4, between 22 and 24 cM from the telomere of 4p.\n" ], "offsets": [ [ 0, 1202 ] ] } ]

[ { "id": "PMID-10036186_T3", "type": "Eukaryote", "text": [ "chick" ], "offsets": [ [ 47, 52 ] ], "normalized": [] }, { "id": "PMID-10036186_T4", "type": "Tissue", "text": [ "basilar papilla" ], "offsets": [ [ 53, 68 ] ], "normalized": [] }, { "id": "PMID-10036186_T7", "type": "Eukaryote", "text": [ "chick" ], "offsets": [ [ 110, 115 ] ], "normalized": [] }, { "id": "PMID-10036186_T8", "type": "Gene", "text": [ "WDR1" ], "offsets": [ [ 116, 120 ] ], "normalized": [] }, { "id": "PMID-10036186_T10", "type": "Eukaryote", "text": [ "chick" ], "offsets": [ [ 163, 168 ] ], "normalized": [] }, { "id": "PMID-10036186_T11", "type": "Tissue", "text": [ "basilar papilla" ], "offsets": [ [ 169, 184 ] ], "normalized": [] }, { "id": "PMID-10036186_T33", "type": "Protein", "text": [ "actin" ], "offsets": [ [ 630, 635 ] ], "normalized": [] }, { "id": "PMID-10036186_T36", "type": "Protein", "text": [ "actin" ], "offsets": [ [ 687, 692 ] ], "normalized": [] }, { "id": "PMID-10036186_T42", "type": "Eukaryote", "text": [ "chick" ], "offsets": [ [ 808, 813 ] ], "normalized": [] }, { "id": "PMID-10036186_T44", "type": "Eukaryote", "text": [ "mouse" ], "offsets": [ [ 829, 834 ] ], "normalized": [] }, { "id": "PMID-10036186_T45", "type": "Protein", "text": [ "Wdr1" ], "offsets": [ [ 835, 839 ] ], "normalized": [] }, { "id": "PMID-10036186_T46", "type": "Eukaryote", "text": [ "human" ], "offsets": [ [ 844, 849 ] ], "normalized": [] }, { "id": "PMID-10036186_T48", "type": "Eukaryote", "text": [ "chick" ], "offsets": [ [ 931, 936 ] ], "normalized": [] }, { "id": "PMID-10036186_T51", "type": "Eukaryote", "text": [ "chick" ], "offsets": [ [ 996, 1001 ] ], "normalized": [] }, { "id": "PMID-10036186_T52", "type": "Tissue", "text": [ "basilar papilla" ], "offsets": [ [ 1002, 1017 ] ], "normalized": [] }, { "id": "PMID-10036186_T55", "type": "Eukaryote", "text": [ "human" ], "offsets": [ [ 1136, 1141 ] ], "normalized": [] }, { "id": "PMID-10036186_T56", "type": "Chromosome", "text": [ "chromosome 4" ], "offsets": [ [ 1142, 1154 ] ], "normalized": [] }, { "id": "PMID-10036186_T5", "type": "Protein", "text": [ "WD40 repeat protein" ], "offsets": [ [ 85, 104 ] ], "normalized": [] }, { "id": "PMID-10036186_T6", "type": "Gene", "text": [ "gene" ], "offsets": [ [ 2, 6 ] ], "normalized": [] }, { "id": "PMID-10036186_T12", "type": "DNA", "text": [ "WDR1 cDNA" ], "offsets": [ [ 228, 237 ] ], "normalized": [] }, { "id": "PMID-10036186_T13", "type": "Protein", "text": [ "protein" ], "offsets": [ [ 261, 268 ] ], "normalized": [] }, { "id": "PMID-10036186_T14", "type": "ProteinDomain", "text": [ "WD40 repeats" ], "offsets": [ [ 285, 297 ] ], "normalized": [] }, { "id": "PMID-10036186_T17", "type": "ProteinDomain", "text": [ "motifs" ], "offsets": [ [ 299, 305 ] ], "normalized": [] }, { "id": "PMID-10036186_T18", "type": "Protein", "text": [ "WDR1 protein" ], "offsets": [ [ 363, 375 ] ], "normalized": [] }, { "id": "PMID-10036186_T19", "type": "Protein", "text": [ "WD40-repeat proteins" ], "offsets": [ [ 406, 426 ] ], "normalized": [] }, { "id": "PMID-10036186_T20", "type": "Eukaryote", "text": [ "budding yeast" ], "offsets": [ [ 430, 443 ] ], "normalized": [] }, { "id": "PMID-10036186_T21", "type": "Eukaryote", "text": [ "Saccharomyces cerevisiae" ], "offsets": [ [ 445, 469 ] ], "normalized": [] }, { "id": "PMID-10036186_T22", "type": "Eukaryote", "text": [ "slime molds" ], "offsets": [ [ 476, 487 ] ], "normalized": [] }, { "id": "PMID-10036186_T23", "type": "Eukaryote", "text": [ "Dictyostelium discoideum" ], "offsets": [ [ 489, 513 ] ], "normalized": [] }, { "id": "PMID-10036186_T24", "type": "Eukaryote", "text": [ "Physarum polycephalum" ], "offsets": [ [ 518, 539 ] ], "normalized": [] }, { "id": "PMID-10036186_T25", "type": "Eukaryote", "text": [ "roundworm" ], "offsets": [ [ 550, 559 ] ], "normalized": [] }, { "id": "PMID-10036186_T26", "type": "Eukaryote", "text": [ "Caenorhabditis elegans" ], "offsets": [ [ 561, 583 ] ], "normalized": [] }, { "id": "PMID-10036186_T1", "type": "Eukaryote", "text": [ "yeast" ], "offsets": [ [ 590, 595 ] ], "normalized": [] }, { "id": "PMID-10036186_T27", "type": "Eukaryote", "text": [ "P. polycephalum" ], "offsets": [ [ 600, 615 ] ], "normalized": [] }, { "id": "PMID-10036186_T28", "type": "Protein", "text": [ "proteins" ], "offsets": [ [ 616, 624 ] ], "normalized": [] }, { "id": "PMID-10036186_T29", "type": "Protein", "text": [ "protein" ], "offsets": [ [ 669, 676 ] ], "normalized": [] }, { "id": "PMID-10036186_T30", "type": "Eukaryote", "text": [ "chick" ], "offsets": [ [ 663, 668 ] ], "normalized": [] }, { "id": "PMID-10036186_T31", "type": "DNA", "text": [ "WDR1 cDNA" ], "offsets": [ [ 814, 823 ] ], "normalized": [] }, { "id": "PMID-10036186_T34", "type": "Eukaryote", "text": [ "mouse" ], "offsets": [ [ 751, 756 ] ], "normalized": [] }, { "id": "PMID-10036186_T35", "type": "Eukaryote", "text": [ "human" ], "offsets": [ [ 761, 766 ] ], "normalized": [] }, { "id": "PMID-10036186_T38", "type": "DNA", "text": [ "cDNAs" ], "offsets": [ [ 767, 772 ] ], "normalized": [] }, { "id": "PMID-10036186_T39", "type": "SequenceHomologyAnalysis", "text": [ "Sequence database comparisons" ], "offsets": [ [ 710, 739 ] ], "normalized": [] }, { "id": "PMID-10036186_T40", "type": "Protein", "text": [ "WDR1 proteins" ], "offsets": [ [ 850, 863 ] ], "normalized": [] }, { "id": "PMID-10036186_T41", "type": "Protein", "text": [ "WDR1 protein" ], "offsets": [ [ 937, 949 ] ], "normalized": [] }, { "id": "PMID-10036186_T43", "type": "RNA", "text": [ "RNA" ], "offsets": [ [ 983, 986 ] ], "normalized": [] }, { "id": "PMID-10036186_T49", "type": "Transcript", "text": [ "transcript" ], "offsets": [ [ 1075, 1085 ] ], "normalized": [] }, { "id": "PMID-10036186_T50", "type": "Tissue", "text": [ "lesioned area" ], "offsets": [ [ 1093, 1106 ] ], "normalized": [] }, { "id": "PMID-10036186_T53", "type": "Gene", "text": [ "WDR1 gene" ], "offsets": [ [ 1112, 1121 ] ], "normalized": [] } ]

[ { "id": "PMID-10036186_E1", "type": "PositiveRegulationOfGeneExpression", "trigger": { "text": [ "upregulated" ], "offsets": [ [ 7, 18 ] ] }, "arguments": [ { "role": "hasPatient", "ref_id": "PMID-10036186_T6" } ] }, { "id": "PMID-10036186_E5", "type": "BindingToProtein", "trigger": { "text": [ "bind" ], "offsets": [ [ 625, 629 ] ] }, "arguments": [ { "role": "hasPatient", "ref_id": "PMID-10036186_T33" }, { "role": "hasPatient2", "ref_id": "PMID-10036186_T28" } ] }, { "id": "PMID-10036186_E6", "type": "BindingToProtein", "trigger": { "text": [ "binding" ], "offsets": [ [ 693, 700 ] ] }, "arguments": [ { "role": "hasPatient", "ref_id": "PMID-10036186_T36" }, { "role": "hasPatient2", "ref_id": "PMID-10036186_T29" } ] }, { "id": "PMID-10036186_E2", "type": "PositiveRegulationOfGeneExpression", "trigger": { "text": [ "expressed at higher levels" ], "offsets": [ [ 129, 155 ] ] }, "arguments": [ { "role": "hasPatient", "ref_id": "PMID-10036186_T8" } ] }, { "id": "PMID-10036186_E3", "type": "RegulatoryProcess", "trigger": { "text": [ "mediate" ], "offsets": [ [ 311, 318 ] ] }, "arguments": [ { "role": "hasPatient", "ref_id": "PMID-10036186_E4" }, { "role": "hasAgent", "ref_id": "PMID-10036186_T17" } ] }, { "id": "PMID-10036186_E4", "type": "BindingToProtein", "trigger": { "text": [ "protein-protein interaction" ], "offsets": [ [ 319, 346 ] ] }, "arguments": [] }, { "id": "PMID-10036186_E7", "type": "Increase", "trigger": { "text": [ "increased levels" ], "offsets": [ [ 1046, 1062 ] ] }, "arguments": [ { "role": "hasPatient", "ref_id": "PMID-10036186_T49" } ] } ]

[]

[ { "id": "PMID-10036186_R3", "type": "fromSpecies", "arg1_id": "PMID-10036186_T4", "arg2_id": "PMID-10036186_T3", "normalized": [] }, { "id": "PMID-10036186_R5", "type": "fromSpecies", "arg1_id": "PMID-10036186_T8", "arg2_id": "PMID-10036186_T7", "normalized": [] }, { "id": "PMID-10036186_R7", "type": "fromSpecies", "arg1_id": "PMID-10036186_T11", "arg2_id": "PMID-10036186_T10", "normalized": [] }, { "id": "PMID-10036186_R24", "type": "fromSpecies", "arg1_id": "PMID-10036186_T45", "arg2_id": "PMID-10036186_T44", "normalized": [] }, { "id": "PMID-10036186_R27", "type": "fromSpecies", "arg1_id": "PMID-10036186_T52", "arg2_id": "PMID-10036186_T51", "normalized": [] }, { "id": "PMID-10036186_R28", "type": "fromSpecies", "arg1_id": "PMID-10036186_T56", "arg2_id": "PMID-10036186_T55", "normalized": [] }, { "id": "PMID-10036186_R1", "type": "encodes", "arg1_id": "PMID-10036186_T6", "arg2_id": "PMID-10036186_T5", "normalized": [] }, { "id": "PMID-10036186_R6", "type": "encodes", "arg1_id": "PMID-10036186_T12", "arg2_id": "PMID-10036186_T13", "normalized": [] }, { "id": "PMID-10036186_R8", "type": "hasPart", "arg1_id": "PMID-10036186_T13", "arg2_id": "PMID-10036186_T14", "normalized": [] }, { "id": "PMID-10036186_R9", "type": "fromSpecies", "arg1_id": "PMID-10036186_T19", "arg2_id": "PMID-10036186_T20", "normalized": [] }, { "id": "PMID-10036186_R10", "type": "fromSpecies", "arg1_id": "PMID-10036186_T19", "arg2_id": "PMID-10036186_T22", "normalized": [] }, { "id": "PMID-10036186_R11", "type": "fromSpecies", "arg1_id": "PMID-10036186_T19", "arg2_id": "PMID-10036186_T25", "normalized": [] }, { "id": "PMID-10036186_R12", "type": "fromSpecies", "arg1_id": "PMID-10036186_T28", "arg2_id": "PMID-10036186_T27", "normalized": [] }, { "id": "PMID-10036186_R13", "type": "fromSpecies", "arg1_id": "PMID-10036186_T28", "arg2_id": "PMID-10036186_T1", "normalized": [] }, { "id": "PMID-10036186_R14", "type": "fromSpecies", "arg1_id": "PMID-10036186_T29", "arg2_id": "PMID-10036186_T30", "normalized": [] }, { "id": "PMID-10036186_R15", "type": "fromSpecies", "arg1_id": "PMID-10036186_T31", "arg2_id": "PMID-10036186_T42", "normalized": [] }, { "id": "PMID-10036186_R16", "type": "fromSpecies", "arg1_id": "PMID-10036186_T38", "arg2_id": "PMID-10036186_T34", "normalized": [] }, { "id": "PMID-10036186_R17", "type": "fromSpecies", "arg1_id": "PMID-10036186_T38", "arg2_id": "PMID-10036186_T35", "normalized": [] }, { "id": "PMID-10036186_R18", "type": "fromSpecies", "arg1_id": "PMID-10036186_T40", "arg2_id": "PMID-10036186_T46", "normalized": [] }, { "id": "PMID-10036186_R19", "type": "fromSpecies", "arg1_id": "PMID-10036186_T41", "arg2_id": "PMID-10036186_T48", "normalized": [] }, { "id": "PMID-10036186_R20", "type": "locatedIn", "arg1_id": "PMID-10036186_T49", "arg2_id": "PMID-10036186_T50", "normalized": [] }, { "id": "PMID-10036186_R21", "type": "locatedIn", "arg1_id": "PMID-10036186_T53", "arg2_id": "PMID-10036186_T56", "normalized": [] } ]

[ { "id": "PMID-10036192__text", "type": "abstract", "text": [ "DCAMKL1, a brain-specific transmembrane protein on 13q12.3 that is similar to doublecortin (DCX). Mutations in the human doublecortin (DCX), a brain-specific putative signaling protein, cause X-linked lissencephaly and subcortical band heterotopia. A predicted 740-amino-acid protein from human brain has two distinct regions, an N-terminal 345-amino-acid region 78% similar to the DCX protein and a C-terminal 427-amino-acid region that contains two transmembrane domains and is 98% homologous to a rat Ca2+/calmodulin-dependent protein kinase. We have designated this protein DCAMKL1. It maps to chromosome 13q12.3-q13, within a 540-kb YAC clone containing markers D13S805 and D13S1164. Northern analysis detected three major transcript isoforms of the DCAMKL1 gene expressed differentially and predominantly in human fetal and adult brain and during mouse embryogenesis (11-17 dpc). These results and its homology with the DCX and Ca2+/calmodulin dependent kinase proteins suggest a likely role for DCAMKL1 transmembrane protein in developing and adult brain, possibly in a pathway of cortical development.\n" ], "offsets": [ [ 0, 1110 ] ] } ]

[ { "id": "PMID-10036192_T1", "type": "Protein", "text": [ "DCAMKL1" ], "offsets": [ [ 0, 7 ] ], "normalized": [] }, { "id": "PMID-10036192_T2", "type": "Tissue", "text": [ "brain" ], "offsets": [ [ 11, 16 ] ], "normalized": [] }, { "id": "PMID-10036192_T3", "type": "Protein", "text": [ "transmembrane protein" ], "offsets": [ [ 26, 47 ] ], "normalized": [] }, { "id": "PMID-10036192_T4", "type": "Protein", "text": [ "doublecortin" ], "offsets": [ [ 78, 90 ] ], "normalized": [] }, { "id": "PMID-10036192_T5", "type": "Protein", "text": [ "DCX" ], "offsets": [ [ 92, 95 ] ], "normalized": [] }, { "id": "PMID-10036192_T7", "type": "Eukaryote", "text": [ "human" ], "offsets": [ [ 115, 120 ] ], "normalized": [] }, { "id": "PMID-10036192_T8", "type": "Protein", "text": [ "doublecortin" ], "offsets": [ [ 121, 133 ] ], "normalized": [] }, { "id": "PMID-10036192_T9", "type": "Protein", "text": [ "DCX" ], "offsets": [ [ 135, 138 ] ], "normalized": [] }, { "id": "PMID-10036192_T10", "type": "Tissue", "text": [ "brain" ], "offsets": [ [ 143, 148 ] ], "normalized": [] }, { "id": "PMID-10036192_T11", "type": "Protein", "text": [ "signaling protein" ], "offsets": [ [ 167, 184 ] ], "normalized": [] }, { "id": "PMID-10036192_T14", "type": "AminoAcid", "text": [ "amino-acid" ], "offsets": [ [ 265, 275 ] ], "normalized": [] }, { "id": "PMID-10036192_T15", "type": "Protein", "text": [ "protein" ], "offsets": [ [ 276, 283 ] ], "normalized": [] }, { "id": "PMID-10036192_T16", "type": "Eukaryote", "text": [ "human" ], "offsets": [ [ 289, 294 ] ], "normalized": [] }, { "id": "PMID-10036192_T17", "type": "Tissue", "text": [ "brain" ], "offsets": [ [ 295, 300 ] ], "normalized": [] }, { "id": "PMID-10036192_T18", "type": "AminoAcid", "text": [ "amino-acid" ], "offsets": [ [ 345, 355 ] ], "normalized": [] }, { "id": "PMID-10036192_T19", "type": "Protein", "text": [ "DCX protein" ], "offsets": [ [ 382, 393 ] ], "normalized": [] }, { "id": "PMID-10036192_T20", "type": "AminoAcid", "text": [ "amino-acid" ], "offsets": [ [ 415, 425 ] ], "normalized": [] }, { "id": "PMID-10036192_T21", "type": "ProteinDomain", "text": [ "transmembrane domains" ], "offsets": [ [ 451, 472 ] ], "normalized": [] }, { "id": "PMID-10036192_T22", "type": "Eukaryote", "text": [ "rat" ], "offsets": [ [ 500, 503 ] ], "normalized": [] }, { "id": "PMID-10036192_T25", "type": "Protein", "text": [ "protein" ], "offsets": [ [ 570, 577 ] ], "normalized": [] }, { "id": "PMID-10036192_T26", "type": "Protein", "text": [ "DCAMKL1" ], "offsets": [ [ 578, 585 ] ], "normalized": [] }, { "id": "PMID-10036192_T27", "type": "Chromosome", "text": [ "chromosome" ], "offsets": [ [ 598, 608 ] ], "normalized": [] }, { "id": "PMID-10036192_T28", "type": "Transcript", "text": [ "transcript" ], "offsets": [ [ 728, 738 ] ], "normalized": [] }, { "id": "PMID-10036192_T29", "type": "Gene", "text": [ "DCAMKL1 gene" ], "offsets": [ [ 755, 767 ] ], "normalized": [] }, { "id": "PMID-10036192_T31", "type": "Eukaryote", "text": [ "human" ], "offsets": [ [ 814, 819 ] ], "normalized": [] }, { "id": "PMID-10036192_T32", "type": "Tissue", "text": [ "fetal" ], "offsets": [ [ 820, 825 ] ], "normalized": [] }, { "id": "PMID-10036192_T33", "type": "Tissue", "text": [ "adult brain" ], "offsets": [ [ 830, 841 ] ], "normalized": [] }, { "id": "PMID-10036192_T34", "type": "Eukaryote", "text": [ "mouse" ], "offsets": [ [ 853, 858 ] ], "normalized": [] }, { "id": "PMID-10036192_T36", "type": "Protein", "text": [ "DCX" ], "offsets": [ [ 926, 929 ] ], "normalized": [] }, { "id": "PMID-10036192_T39", "type": "Protein", "text": [ "DCAMKL1" ], "offsets": [ [ 1002, 1009 ] ], "normalized": [] }, { "id": "PMID-10036192_T40", "type": "Protein", "text": [ "transmembrane protein" ], "offsets": [ [ 1010, 1031 ] ], "normalized": [] }, { "id": "PMID-10036192_T41", "type": "Tissue", "text": [ "adult brain" ], "offsets": [ [ 1050, 1061 ] ], "normalized": [] }, { "id": "PMID-10036192_T23", "type": "Enzyme", "text": [ "Ca2+/calmodulin-dependent protein kinase" ], "offsets": [ [ 504, 544 ] ], "normalized": [] }, { "id": "PMID-10036192_T24", "type": "Protein", "text": [ "Ca2+/calmodulin dependent kinase proteins" ], "offsets": [ [ 934, 975 ] ], "normalized": [] } ]

[ { "id": "PMID-10036192_E1", "type": "Mutation", "trigger": { "text": [ "Mutations" ], "offsets": [ [ 98, 107 ] ] }, "arguments": [ { "role": "hasPatient", "ref_id": "PMID-10036192_T8" } ] }, { "id": "PMID-10036192_E2", "type": "Disease", "trigger": { "text": [ "X-linked lissencephaly" ], "offsets": [ [ 192, 214 ] ] }, "arguments": [] }, { "id": "PMID-10036192_E3", "type": "Disease", "trigger": { "text": [ "subcortical band heterotopia" ], "offsets": [ [ 219, 247 ] ] }, "arguments": [] }, { "id": "PMID-10036192_E4", "type": "GeneExpression", "trigger": { "text": [ "expressed" ], "offsets": [ [ 768, 777 ] ] }, "arguments": [ { "role": "hasPatient", "ref_id": "PMID-10036192_T29" } ] }, { "id": "PMID-10036192_E5", "type": "DevelopmentalProcess", "trigger": { "text": [ "embryogenesis" ], "offsets": [ [ 859, 872 ] ] }, "arguments": [] }, { "id": "PMID-10036192_E6", "type": "DevelopmentalProcess", "trigger": { "text": [ "cortical development" ], "offsets": [ [ 1088, 1108 ] ] }, "arguments": [] } ]

[]

[ { "id": "PMID-10036192_R3", "type": "fromSpecies", "arg1_id": "PMID-10036192_T8", "arg2_id": "PMID-10036192_T7", "normalized": [] }, { "id": "PMID-10036192_R4", "type": "locatedIn", "arg1_id": "PMID-10036192_T15", "arg2_id": "PMID-10036192_T17", "normalized": [] }, { "id": "PMID-10036192_R5", "type": "hasPart", "arg1_id": "PMID-10036192_T15", "arg2_id": "PMID-10036192_T18", "normalized": [] }, { "id": "PMID-10036192_R6", "type": "hasPart", "arg1_id": "PMID-10036192_T15", "arg2_id": "PMID-10036192_T20", "normalized": [] }, { "id": "PMID-10036192_R8", "type": "fromSpecies", "arg1_id": "PMID-10036192_T17", "arg2_id": "PMID-10036192_T16", "normalized": [] }, { "id": "PMID-10036192_R9", "type": "hasPart", "arg1_id": "PMID-10036192_T20", "arg2_id": "PMID-10036192_T21", "normalized": [] }, { "id": "PMID-10036192_R11", "type": "encodes", "arg1_id": "PMID-10036192_T29", "arg2_id": "PMID-10036192_T28", "normalized": [] }, { "id": "PMID-10036192_R14", "type": "fromSpecies", "arg1_id": "PMID-10036192_T32", "arg2_id": "PMID-10036192_T31", "normalized": [] }, { "id": "PMID-10036192_R15", "type": "fromSpecies", "arg1_id": "PMID-10036192_T33", "arg2_id": "PMID-10036192_T31", "normalized": [] }, { "id": "PMID-10036192_R17", "type": "locatedIn", "arg1_id": "PMID-10036192_T39", "arg2_id": "PMID-10036192_T41", "normalized": [] }, { "id": "PMID-10036192_R18", "type": "locatedIn", "arg1_id": "PMID-10036192_T3", "arg2_id": "PMID-10036192_T2", "normalized": [] }, { "id": "PMID-10036192_R1", "type": "locatedIn", "arg1_id": "PMID-10036192_T11", "arg2_id": "PMID-10036192_T10", "normalized": [] }, { "id": "PMID-10036192_R2", "type": "fromSpecies", "arg1_id": "PMID-10036192_T23", "arg2_id": "PMID-10036192_T22", "normalized": [] } ]

[ { "id": "PMID-10036195__text", "type": "abstract", "text": [ "The human POP2 gene: identification, sequencing, and mapping to the critical region of the 5q- syndrome.\n" ], "offsets": [ [ 0, 105 ] ] } ]

[ { "id": "PMID-10036195_T1", "type": "Eukaryote", "text": [ "human" ], "offsets": [ [ 4, 9 ] ], "normalized": [] }, { "id": "PMID-10036195_T2", "type": "Gene", "text": [ "POP2 gene" ], "offsets": [ [ 10, 19 ] ], "normalized": [] } ]

[ { "id": "PMID-10036195_E1", "type": "Disease", "trigger": { "text": [ "5q- syndrome" ], "offsets": [ [ 91, 103 ] ] }, "arguments": [] } ]

[]

[]

[ { "id": "PMID-10036235__text", "type": "abstract", "text": [ "ARF6 requirement for Rac ruffling suggests a role for membrane trafficking in cortical actin rearrangements. The ARF6 GTPase regulates a novel endosomal-plasma membrane recycling pathway and influences cortical actin remodeling. Here we examined the relationship between ARF6 and Rac1, a Rho family GTPase, implicated in cortical actin rearrangements. Endogenous Rac1 colocalized with ARF6 at the plasma membrane and on the ARF6 recycling endosome in untransfected HeLa and primary human fibroblast cells. In transfected HeLa cells Rac1 and ARF6 also colocalized. Cells expressing wild-type ARF6 or Rac1 formed actin-containing surface protrusions and membrane ruffles, respectively, upon treatment with the G protein activator aluminum fluoride. Aluminum fluoride-treatment of cells transfected with equivalent amounts of plasmid resulted in enhanced membrane ruffling, with protrusions appearing as Rac expression was lowered. Co-expression of the dominant negative, GTP binding-defective ARF6 T27N mutant inhibited the aluminum fluoride-induced ruffling observed in cells expressing Rac1, and the constitutive ruffling observed in cells expressing the activated Rac1 Q61L mutant. In contrast, co-expression of the GTP-binding-defective, T17N mutant of either Rac1 or Cdc42 with ARF6 did not inhibit the aluminum fluoride-induced surface protrusions, nor did inactivation of Rho with C3-transferase. These observations suggest that ARF6, a non-Rho family GTPase, can, by itself, alter cortical actin and can influence the ability of Rac1 to form lamellipodia, in part, by regulating its trafficking to the plasma membrane.\n" ], "offsets": [ [ 0, 1625 ] ] } ]

[ { "id": "PMID-10036235_T1", "type": "Enzyme", "text": [ "ARF6" ], "offsets": [ [ 0, 4 ] ], "normalized": [] }, { "id": "PMID-10036235_T3", "type": "CellComponent", "text": [ "membrane" ], "offsets": [ [ 54, 62 ] ], "normalized": [] }, { "id": "PMID-10036235_T5", "type": "Protein", "text": [ "cortical actin" ], "offsets": [ [ 78, 92 ] ], "normalized": [] }, { "id": "PMID-10036235_T7", "type": "Enzyme", "text": [ "ARF6 GTPase" ], "offsets": [ [ 113, 124 ] ], "normalized": [] }, { "id": "PMID-10036235_T9", "type": "CellComponent", "text": [ "endosomal-plasma membrane" ], "offsets": [ [ 143, 168 ] ], "normalized": [] }, { "id": "PMID-10036235_T10", "type": "Protein", "text": [ "cortical actin" ], "offsets": [ [ 202, 216 ] ], "normalized": [] }, { "id": "PMID-10036235_T12", "type": "Enzyme", "text": [ "ARF6" ], "offsets": [ [ 271, 275 ] ], "normalized": [] }, { "id": "PMID-10036235_T13", "type": "Enzyme", "text": [ "Rac1" ], "offsets": [ [ 280, 284 ] ], "normalized": [] }, { "id": "PMID-10036235_T14", "type": "Enzyme", "text": [ "GTPase" ], "offsets": [ [ 299, 305 ] ], "normalized": [] }, { "id": "PMID-10036235_T15", "type": "Protein", "text": [ "cortical actin" ], "offsets": [ [ 321, 335 ] ], "normalized": [] }, { "id": "PMID-10036235_T17", "type": "Enzyme", "text": [ "Rac1" ], "offsets": [ [ 363, 367 ] ], "normalized": [] }, { "id": "PMID-10036235_T18", "type": "Enzyme", "text": [ "ARF6" ], "offsets": [ [ 385, 389 ] ], "normalized": [] }, { "id": "PMID-10036235_T19", "type": "CellComponent", "text": [ "plasma membrane" ], "offsets": [ [ 397, 412 ] ], "normalized": [] }, { "id": "PMID-10036235_T20", "type": "Enzyme", "text": [ "ARF6" ], "offsets": [ [ 424, 428 ] ], "normalized": [] }, { "id": "PMID-10036235_T21", "type": "Cell", "text": [ "HeLa" ], "offsets": [ [ 465, 469 ] ], "normalized": [] }, { "id": "PMID-10036235_T22", "type": "Eukaryote", "text": [ "human" ], "offsets": [ [ 482, 487 ] ], "normalized": [] }, { "id": "PMID-10036235_T23", "type": "Cell", "text": [ "fibroblast cells" ], "offsets": [ [ 488, 504 ] ], "normalized": [] }, { "id": "PMID-10036235_T24", "type": "Cell", "text": [ "HeLa cells" ], "offsets": [ [ 521, 531 ] ], "normalized": [] }, { "id": "PMID-10036235_T25", "type": "Enzyme", "text": [ "Rac1" ], "offsets": [ [ 532, 536 ] ], "normalized": [] }, { "id": "PMID-10036235_T26", "type": "Enzyme", "text": [ "ARF6" ], "offsets": [ [ 541, 545 ] ], "normalized": [] }, { "id": "PMID-10036235_T27", "type": "Cell", "text": [ "Cells" ], "offsets": [ [ 564, 569 ] ], "normalized": [] }, { "id": "PMID-10036235_T29", "type": "Enzyme", "text": [ "ARF6" ], "offsets": [ [ 591, 595 ] ], "normalized": [] }, { "id": "PMID-10036235_T30", "type": "Enzyme", "text": [ "Rac1" ], "offsets": [ [ 599, 603 ] ], "normalized": [] }, { "id": "PMID-10036235_T32", "type": "Protein", "text": [ "G protein" ], "offsets": [ [ 708, 717 ] ], "normalized": [] }, { "id": "PMID-10036235_T34", "type": "InorganicChemical", "text": [ "aluminum fluoride" ], "offsets": [ [ 728, 745 ] ], "normalized": [] }, { "id": "PMID-10036235_T35", "type": "InorganicChemical", "text": [ "Aluminum fluoride" ], "offsets": [ [ 747, 764 ] ], "normalized": [] }, { "id": "PMID-10036235_T36", "type": "Cell", "text": [ "cells" ], "offsets": [ [ 778, 783 ] ], "normalized": [] }, { "id": "PMID-10036235_T38", "type": "Enzyme", "text": [ "Rac" ], "offsets": [ [ 901, 904 ] ], "normalized": [] }, { "id": "PMID-10036235_T44", "type": "InorganicChemical", "text": [ "aluminum fluoride" ], "offsets": [ [ 1022, 1039 ] ], "normalized": [] }, { "id": "PMID-10036235_T47", "type": "Cell", "text": [ "cells" ], "offsets": [ [ 1069, 1074 ] ], "normalized": [] }, { "id": "PMID-10036235_T49", "type": "Enzyme", "text": [ "Rac1" ], "offsets": [ [ 1086, 1090 ] ], "normalized": [] }, { "id": "PMID-10036235_T51", "type": "Cell", "text": [ "cells" ], "offsets": [ [ 1134, 1139 ] ], "normalized": [] }, { "id": "PMID-10036235_T58", "type": "Enzyme", "text": [ "Rac1" ], "offsets": [ [ 1262, 1266 ] ], "normalized": [] }, { "id": "PMID-10036235_T59", "type": "Enzyme", "text": [ "ARF6" ], "offsets": [ [ 1281, 1285 ] ], "normalized": [] }, { "id": "PMID-10036235_T61", "type": "InorganicChemical", "text": [ "aluminum fluoride" ], "offsets": [ [ 1306, 1323 ] ], "normalized": [] }, { "id": "PMID-10036235_T62", "type": "Enzyme", "text": [ "C3-transferase" ], "offsets": [ [ 1386, 1400 ] ], "normalized": [] }, { "id": "PMID-10036235_T63", "type": "Enzyme", "text": [ "ARF6" ], "offsets": [ [ 1434, 1438 ] ], "normalized": [] }, { "id": "PMID-10036235_T64", "type": "Enzyme", "text": [ "GTPase" ], "offsets": [ [ 1457, 1463 ] ], "normalized": [] }, { "id": "PMID-10036235_T65", "type": "Protein", "text": [ "cortical actin" ], "offsets": [ [ 1487, 1501 ] ], "normalized": [] }, { "id": "PMID-10036235_T66", "type": "Enzyme", "text": [ "Rac1" ], "offsets": [ [ 1535, 1539 ] ], "normalized": [] }, { "id": "PMID-10036235_T67", "type": "CellComponent", "text": [ "lamellipodia" ], "offsets": [ [ 1548, 1560 ] ], "normalized": [] }, { "id": "PMID-10036235_T70", "type": "CellComponent", "text": [ "plasma membrane" ], "offsets": [ [ 1608, 1623 ] ], "normalized": [] }, { "id": "PMID-10036235_T72", "type": "CellComponent", "text": [ "endosome" ], "offsets": [ [ 439, 447 ] ], "normalized": [] }, { "id": "PMID-10036235_T73", "type": "CellComponent", "text": [ "membrane ruffles" ], "offsets": [ [ 652, 668 ] ], "normalized": [] }, { "id": "PMID-10036235_T31", "type": "CellComponent", "text": [ "actin-containing surface protrusions" ], "offsets": [ [ 611, 647 ] ], "normalized": [] }, { "id": "PMID-10036235_T41", "type": "MutantProtein", "text": [ "GTP binding-defective ARF6 T27N mutant" ], "offsets": [ [ 969, 1007 ] ], "normalized": [] }, { "id": "PMID-10036235_T42", "type": "MutantProtein", "text": [ "Rac1 Q61L mutant" ], "offsets": [ [ 1165, 1181 ] ], "normalized": [] }, { "id": "PMID-10036235_T54", "type": "Enzyme", "text": [ "Cdc42" ], "offsets": [ [ 1270, 1275 ] ], "normalized": [] }, { "id": "PMID-10036235_T56", "type": "MutantProtein", "text": [ "GTP-binding-defective, T17N mutant" ], "offsets": [ [ 1217, 1251 ] ], "normalized": [] }, { "id": "PMID-10036235_T57", "type": "CellComponent", "text": [ "surface protrusions" ], "offsets": [ [ 1332, 1351 ] ], "normalized": [] }, { "id": "PMID-10036235_T78", "type": "Enzyme", "text": [ "Rho" ], "offsets": [ [ 1377, 1380 ] ], "normalized": [] } ]

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"id": "PMID-10036235_E6", "type": "CellularComponentOrganizationAndBiogenesis", "trigger": { "text": [ "rearrangements" ], "offsets": [ [ 336, 350 ] ] }, "arguments": [ { "role": "hasPatient", "ref_id": "PMID-10036235_T15" } ] }, { "id": "PMID-10036235_E7", "type": "GeneExpression", "trigger": { "text": [ "expressing" ], "offsets": [ [ 570, 580 ] ] }, "arguments": [ { "role": "hasAgent", "ref_id": "PMID-10036235_T27" }, { "role": "hasPatient", "ref_id": "PMID-10036235_T29" } ] }, { "id": "PMID-10036235_E8", "type": "PositiveRegulation", "trigger": { "text": [ "activator" ], "offsets": [ [ 718, 727 ] ] }, "arguments": [ { "role": "hasPatient", "ref_id": "PMID-10036235_T32" }, { "role": "hasAgent", "ref_id": "PMID-10036235_T34" } ] }, { "id": "PMID-10036235_E9", "type": "CellularComponentOrganizationAndBiogenesis", "trigger": { "text": [ "membrane ruffling" ], "offsets": [ [ 852, 869 ] ] }, "arguments": [] }, { "id": "PMID-10036235_E10", "type": "GeneExpression", "trigger": { "text": [ "expression" ], "offsets": [ [ 905, 915 ] ] }, "arguments": [ { "role": "hasPatient", "ref_id": "PMID-10036235_T38" } ] }, { "id": "PMID-10036235_E11", "type": "GeneExpression", "trigger": { "text": [ "Co-expression" ], "offsets": [ [ 929, 942 ] ] }, "arguments": [ { "role": "hasPatient", "ref_id": "PMID-10036235_T41" } ] }, { "id": "PMID-10036235_E13", "type": "NegativeRegulation", "trigger": { "text": [ "inhibited" ], "offsets": [ [ 1008, 1017 ] ] }, "arguments": [ { "role": "hasAgent", "ref_id": "PMID-10036235_E11" }, { "role": "hasPatient", "ref_id": "PMID-10036235_E17" } ] }, { "id": "PMID-10036235_E14", "type": "PositiveRegulation", "trigger": { "text": [ "induced" ], "offsets": [ [ 1040, 1047 ] ] }, "arguments": [ { "role": "hasPatient", "ref_id": "PMID-10036235_E15" }, { "role": "hasAgent", "ref_id": "PMID-10036235_T44" } ] }, { "id": "PMID-10036235_E15", "type": "CellularComponentOrganizationAndBiogenesis", "trigger": { "text": [ "ruffling" ], "offsets": [ [ 1048, 1056 ] ] }, "arguments": [] }, { "id": "PMID-10036235_E16", "type": "GeneExpression", "trigger": { "text": [ "expressing" ], "offsets": [ [ 1075, 1085 ] ] }, "arguments": [ { "role": "hasAgent", "ref_id": "PMID-10036235_T47" }, { "role": "hasPatient", "ref_id": "PMID-10036235_T49" } ] }, { "id": "PMID-10036235_E17", "type": "CellularComponentOrganizationAndBiogenesis", "trigger": { "text": [ "constitutive ruffling" ], "offsets": [ [ 1100, 1121 ] ] }, "arguments": [] }, { "id": "PMID-10036235_E18", "type": "GeneExpression", "trigger": { "text": [ "expressing" ], "offsets": [ [ 1140, 1150 ] ] }, "arguments": [ { "role": "hasAgent", "ref_id": "PMID-10036235_T51" }, { "role": "hasPatient", "ref_id": "PMID-10036235_T42" } ] }, { "id": "PMID-10036235_E19", "type": "PositiveRegulation", "trigger": { "text": [ "activated" ], "offsets": [ [ 1155, 1164 ] ] }, "arguments": [ { "role": "hasPatient", "ref_id": "PMID-10036235_T42" } ] }, { "id": "PMID-10036235_E20", "type": "GeneExpression", "trigger": { "text": [ "co-expression" ], "offsets": [ [ 1196, 1209 ] ] }, "arguments": [ { "role": "hasPatient", "ref_id": "PMID-10036235_T56" } ] }, { "id": "PMID-10036235_E22", "type": "NegativeRegulation", "trigger": { "text": [ "inhibit" ], "offsets": [ [ 1294, 1301 ] ] }, "arguments": [] }, { "id": "PMID-10036235_E23", "type": "RegulatoryProcess", "trigger": { "text": [ "regulating" ], "offsets": [ [ 1574, 1584 ] ] }, "arguments": [ { "role": "hasPatient", "ref_id": "PMID-10036235_E24" } ] }, { "id": "PMID-10036235_E24", "type": "Transport", "trigger": { "text": [ "trafficking" ], "offsets": [ [ 1589, 1600 ] ] }, "arguments": [] }, { "id": "PMID-10036235_E25", "type": "Pathway", "trigger": { "text": [ "recycling pathway" ], "offsets": [ [ 169, 186 ] ] }, "arguments": [] }, { "id": "PMID-10036235_E26", "type": "Increase", "trigger": { "text": [ "enhanced" ], "offsets": [ [ 843, 851 ] ] }, "arguments": [ { "role": "hasPatient", "ref_id": "PMID-10036235_E9" } ] }, { "id": "PMID-10036235_E27", "type": "Decrease", "trigger": { "text": [ "lowered" ], "offsets": [ [ 920, 927 ] ] }, "arguments": [ { "role": "hasPatient", "ref_id": "PMID-10036235_E10" } ] }, { "id": "PMID-10036235_E12", "type": "Increase", "trigger": { "text": [ "induced" ], "offsets": [ [ 1324, 1331 ] ] }, "arguments": [ { "role": "hasAgent", "ref_id": "PMID-10036235_T61" }, { "role": "hasPatient", "ref_id": "PMID-10036235_T57" } ] }, { "id": "PMID-10036235_E21", "type": "NegativeRegulation", "trigger": { "text": [ "inactivation" ], "offsets": [ [ 1361, 1373 ] ] }, "arguments": [ { "role": "hasPatient", "ref_id": "PMID-10036235_T78" }, { "role": "hasAgent", "ref_id": "PMID-10036235_T62" } ] }, { "id": "PMID-10036235_E28", "type": "GeneExpression", "trigger": { "text": [ "expressing" ], "offsets": [ [ 570, 580 ] ] }, "arguments": [ { "role": "hasAgent", "ref_id": "PMID-10036235_T27" }, { "role": "hasPatient", "ref_id": "PMID-10036235_T30" } ] }, { "id": "PMID-10036235_E29", "type": "NegativeRegulation", "trigger": { "text": [ "inhibited" ], "offsets": [ [ 1008, 1017 ] ] }, "arguments": [ { "role": "hasAgent", "ref_id": "PMID-10036235_E11" }, { "role": "hasPatient", "ref_id": "PMID-10036235_E15" } ] } ]

[]

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[ { "id": "PMID-10037602__text", "type": "abstract", "text": [ "Function of WW domains as phosphoserine- or phosphothreonine-binding modules. Protein-interacting modules help determine the specificity of signal transduction events, and protein phosphorylation can modulate the assembly of such modules into specific signaling complexes. Although phosphotyrosine-binding modules have been well-characterized, phosphoserine- or phosphothreonine-binding modules have not been described. WW domains are small protein modules found in various proteins that participate in cell signaling or regulation. WW domains of the essential mitotic prolyl isomerase Pin1 and the ubiquitin ligase Nedd4 bound to phosphoproteins, including physiological substrates of enzymes, in a phosphorylation-dependent manner. The Pin1 WW domain functioned as a phosphoserine- or phosphothreonine-binding module, with properties similar to those of SRC homology 2 domains. Phosphoserine- or phosphothreonine-binding activity was required for Pin1 to interact with its substrates in vitro and to perform its essential function in vivo.\n" ], "offsets": [ [ 0, 1042 ] ] } ]

[ { "id": "PMID-10037602_T1", "type": "ProteinDomain", "text": [ "WW domains" ], "offsets": [ [ 12, 22 ] ], "normalized": [] }, { "id": "PMID-10037602_T2", "type": "AminoAcid", "text": [ "phosphoserine" ], "offsets": [ [ 26, 39 ] ], "normalized": [] }, { "id": "PMID-10037602_T3", "type": "AminoAcid", "text": [ "phosphothreonine" ], "offsets": [ [ 44, 60 ] ], "normalized": [] }, { "id": "PMID-10037602_T7", "type": "Protein", "text": [ "protein" ], "offsets": [ [ 172, 179 ] ], "normalized": [] }, { "id": "PMID-10037602_T9", "type": "AminoAcid", "text": [ "phosphotyrosine" ], "offsets": [ [ 282, 297 ] ], "normalized": [] }, { "id": "PMID-10037602_T11", "type": "AminoAcid", "text": [ "phosphoserine" ], "offsets": [ [ 344, 357 ] ], "normalized": [] }, { "id": "PMID-10037602_T12", "type": "AminoAcid", "text": [ "phosphothreonine" ], "offsets": [ [ 362, 378 ] ], "normalized": [] }, { "id": "PMID-10037602_T14", "type": "ProteinDomain", "text": [ "WW domains" ], "offsets": [ [ 420, 430 ] ], "normalized": [] }, { "id": "PMID-10037602_T15", "type": "Protein", "text": [ "protein" ], "offsets": [ [ 441, 448 ] ], "normalized": [] }, { "id": "PMID-10037602_T16", "type": "Protein", "text": [ "proteins" ], "offsets": [ [ 474, 482 ] ], "normalized": [] }, { "id": "PMID-10037602_T17", "type": "Cell", "text": [ "cell" ], "offsets": [ [ 503, 507 ] ], "normalized": [] }, { "id": "PMID-10037602_T20", "type": "ProteinDomain", "text": [ "WW domains" ], "offsets": [ [ 533, 543 ] ], "normalized": [] }, { "id": "PMID-10037602_T21", "type": "Enzyme", "text": [ "mitotic prolyl isomerase" ], "offsets": [ [ 561, 585 ] ], "normalized": [] }, { "id": "PMID-10037602_T22", "type": "Enzyme", "text": [ "Pin1" ], "offsets": [ [ 586, 590 ] ], "normalized": [] }, { "id": "PMID-10037602_T25", "type": "Enzyme", "text": [ "Nedd4" ], "offsets": [ [ 616, 621 ] ], "normalized": [] }, { "id": "PMID-10037602_T27", "type": "AminoAcid", "text": [ "phosphoproteins" ], "offsets": [ [ 631, 646 ] ], "normalized": [] }, { "id": "PMID-10037602_T28", "type": "Enzyme", "text": [ "enzymes" ], "offsets": [ [ 686, 693 ] ], "normalized": [] }, { "id": "PMID-10037602_T30", "type": "Enzyme", "text": [ "Pin1" ], "offsets": [ [ 738, 742 ] ], "normalized": [] }, { "id": "PMID-10037602_T31", "type": "ProteinDomain", "text": [ "WW domain" ], "offsets": [ [ 743, 752 ] ], "normalized": [] }, { "id": "PMID-10037602_T32", "type": "AminoAcid", "text": [ "phosphoserine" ], "offsets": [ [ 769, 782 ] ], "normalized": [] }, { "id": "PMID-10037602_T33", "type": "AminoAcid", "text": [ "phosphothreonine" ], "offsets": [ [ 787, 803 ] ], "normalized": [] }, { "id": "PMID-10037602_T35", "type": "ProteinDomain", "text": [ "SRC homology 2 domains" ], "offsets": [ [ 856, 878 ] ], "normalized": [] }, { "id": "PMID-10037602_T36", "type": "AminoAcid", "text": [ "Phosphoserine" ], "offsets": [ [ 880, 893 ] ], "normalized": [] }, { "id": "PMID-10037602_T37", "type": "AminoAcid", "text": [ "phosphothreonine" ], "offsets": [ [ 898, 914 ] ], "normalized": [] }, { "id": "PMID-10037602_T39", "type": "Enzyme", "text": [ "Pin1" ], "offsets": [ [ 949, 953 ] ], "normalized": [] }, { "id": "PMID-10037602_T8", "type": "ProteinComplex", "text": [ "complexes" ], "offsets": [ [ 262, 271 ] ], "normalized": [] }, { "id": "PMID-10037602_T23", "type": "Enzyme", "text": [ "ubiquitin ligase" ], "offsets": [ [ 599, 615 ] ], "normalized": [] }, { "id": "PMID-10037602_T24", "type": "Substrate", "text": [ "substrates" ], "offsets": [ [ 672, 682 ] ], "normalized": [] }, { "id": "PMID-10037602_T42", "type": "Substrate", "text": [ "substrates" ], "offsets": [ [ 975, 985 ] ], "normalized": [] } ]

[ { "id": "PMID-10037602_E1", "type": "Binding", "trigger": { "text": [ "binding" ], "offsets": [ [ 61, 68 ] ] }, "arguments": [ { "role": "hasPatient", "ref_id": "PMID-10037602_T2" } ] }, { "id": "PMID-10037602_E3", "type": "Binding", "trigger": { "text": [ "binding" ], "offsets": [ [ 298, 305 ] ] }, "arguments": [ { "role": "hasPatient", "ref_id": "PMID-10037602_T9" } ] }, { "id": "PMID-10037602_E4", "type": "Binding", "trigger": { "text": [ "binding" ], "offsets": [ [ 379, 386 ] ] }, "arguments": [ { "role": "hasPatient", "ref_id": "PMID-10037602_T11" } ] }, { "id": "PMID-10037602_E5", "type": "SignalingPathway", "trigger": { "text": [ "signaling" ], "offsets": [ [ 508, 517 ] ] }, "arguments": [] }, { "id": "PMID-10037602_E6", "type": "RegulatoryProcess", "trigger": { "text": [ "regulation" ], "offsets": [ [ 521, 531 ] ] }, "arguments": [] }, { "id": "PMID-10037602_E7", "type": "Binding", "trigger": { "text": [ "bound" ], "offsets": [ [ 622, 627 ] ] }, "arguments": [ { "role": "hasPatient", "ref_id": "PMID-10037602_T27" } ] }, { "id": "PMID-10037602_E8", "type": "Phosphorylation", "trigger": { "text": [ "phosphorylation" ], "offsets": [ [ 700, 715 ] ] }, "arguments": [] }, { "id": "PMID-10037602_E9", "type": "Binding", "trigger": { "text": [ "binding" ], "offsets": [ [ 804, 811 ] ] }, "arguments": [ { "role": "hasPatient", "ref_id": "PMID-10037602_T32" } ] }, { "id": "PMID-10037602_E10", "type": "Binding", "trigger": { "text": [ "binding" ], "offsets": [ [ 915, 922 ] ] }, "arguments": [ { "role": "hasPatient", "ref_id": "PMID-10037602_T36" } ] }, { "id": "PMID-10037602_E11", "type": "Binding", "trigger": { "text": [ "interact" ], "offsets": [ [ 957, 965 ] ] }, "arguments": [ { "role": "hasPatient", "ref_id": "PMID-10037602_T42" } ] }, { "id": "PMID-10037602_E12", "type": "SignalingPathway", "trigger": { "text": [ "signal transduction" ], "offsets": [ [ 140, 159 ] ] }, "arguments": [] }, { "id": "PMID-10037602_E2", "type": "BindingToProtein", "trigger": { "text": [ "Protein-interacting" ], "offsets": [ [ 78, 97 ] ] }, "arguments": [] }, { "id": "PMID-10037602_E13", "type": "Phosphorylation", "trigger": { "text": [ "phosphorylation" ], "offsets": [ [ 180, 195 ] ] }, "arguments": [ { "role": "hasPatient", "ref_id": "PMID-10037602_T7" } ] }, { "id": "PMID-10037602_E14", "type": "Binding", "trigger": { "text": [ "binding" ], "offsets": [ [ 379, 386 ] ] }, "arguments": [ { "role": "hasPatient", "ref_id": "PMID-10037602_T12" } ] }, { "id": "PMID-10037602_E15", "type": "Binding", "trigger": { "text": [ "binding" ], "offsets": [ [ 915, 922 ] ] }, "arguments": [ { "role": "hasPatient", "ref_id": "PMID-10037602_T37" } ] }, { "id": "PMID-10037602_E16", "type": "Binding", "trigger": { "text": [ "interact" ], "offsets": [ [ 957, 965 ] ] }, "arguments": [ { "role": "hasPatient", "ref_id": "PMID-10037602_T39" } ] }, { "id": "PMID-10037602_E17", "type": "Binding", "trigger": { "text": [ "binding" ], "offsets": [ [ 804, 811 ] ] }, "arguments": [ { "role": "hasPatient", "ref_id": "PMID-10037602_T33" } ] }, { "id": "PMID-10037602_E18", "type": "Binding", "trigger": { "text": [ "binding" ], "offsets": [ [ 61, 68 ] ] }, "arguments": [ { "role": "hasPatient", "ref_id": "PMID-10037602_T3" } ] }, { "id": "PMID-10037602_E19", "type": "Binding", "trigger": { "text": [ "bound" ], "offsets": [ [ 622, 627 ] ] }, "arguments": [ { "role": "hasPatient", "ref_id": "PMID-10037602_T20" } ] } ]

[]

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[ { "id": "PMID-10037736__text", "type": "abstract", "text": [ "Molecular cloning and functional characterization of a new Cap'n' collar family transcription factor Nrf3. The NF-E2-binding sites or Maf recognition elements (MARE) are essential cis-acting elements in the regulatory regions of erythroid-specific genes recognized by the erythroid transcription factor NF-E2, composed of p45 and MafK. Recently, two p45-related factors Nrf1 and Nrf2 were isolated, and they are now collectively grouped as the Cap'n' collar (CNC) family. CNC factors bind to MARE through heterodimer formation with small Maf proteins. We report here the identification and characterization of a novel CNC factor, Nrf3, encoding a predicted 73-kDa protein with a basic region-leucine zipper domain highly homologous to those of other CNC proteins. In vitro and in vivo analyses showed that Nrf3 can heterodimerize with MafK and that this complex binds to the MARE in the chicken beta-globin enhancer and can activate transcription. Nrf3 mRNA is highly expressed in human placenta and B cell and monocyte lineage. Chromosomal localization of human Nrf3 is 7p14-15, which lies near the hoxA gene locus. As the genetic loci of p45, nrf1, and nrf2 have been mapped close to those of hoxC, hoxB, and hoxD, respectively, the present study strongly argues for the idea that a single ancestral gene for the CNC family members may have been localized near the ancestral Hox cluster and have diverged to give rise to four closely related CNC factors through chromosome duplication.\n" ], "offsets": [ [ 0, 1488 ] ] } ]

[ { "id": "PMID-10037736_T1", "type": "TranscriptionFactor", "text": [ "transcription factor" ], "offsets": [ [ 80, 100 ] ], "normalized": [] }, { "id": "PMID-10037736_T2", "type": "TranscriptionFactor", "text": [ "Nrf3" ], "offsets": [ [ 101, 105 ] ], "normalized": [] }, { "id": "PMID-10037736_T5", "type": "TranscriptionFactorBindingSiteOfDNA", "text": [ "Maf recognition elements" ], "offsets": [ [ 134, 158 ] ], "normalized": [] }, { "id": "PMID-10037736_T6", "type": "TranscriptionFactorBindingSiteOfDNA", "text": [ "MARE" ], "offsets": [ [ 160, 164 ] ], "normalized": [] }, { "id": "PMID-10037736_T7", "type": "Cell", "text": [ "erythroid" ], "offsets": [ [ 229, 238 ] ], "normalized": [] }, { "id": "PMID-10037736_T8", "type": "Gene", "text": [ "genes" ], "offsets": [ [ 248, 253 ] ], "normalized": [] }, { "id": "PMID-10037736_T9", "type": "Cell", "text": [ "erythroid" ], "offsets": [ [ 272, 281 ] ], "normalized": [] }, { "id": "PMID-10037736_T10", "type": "TranscriptionFactor", "text": [ "transcription factor" ], "offsets": [ [ 282, 302 ] ], "normalized": [] }, { "id": "PMID-10037736_T11", "type": "TranscriptionFactor", "text": [ "NF-E2" ], "offsets": [ [ 303, 308 ] ], "normalized": [] }, { "id": "PMID-10037736_T12", "type": "ProteinSubunit", "text": [ "p45" ], "offsets": [ [ 322, 325 ] ], "normalized": [] }, { "id": "PMID-10037736_T13", "type": "ProteinSubunit", "text": [ "MafK" ], "offsets": [ [ 330, 334 ] ], "normalized": [] }, { "id": "PMID-10037736_T14", "type": "ProteinSubunit", "text": [ "p45" ], "offsets": [ [ 350, 353 ] ], "normalized": [] }, { "id": "PMID-10037736_T15", "type": "TranscriptionFactor", "text": [ "factors" ], "offsets": [ [ 362, 369 ] ], "normalized": [] }, { "id": "PMID-10037736_T16", "type": "TranscriptionFactor", "text": [ "Nrf1" ], "offsets": [ [ 370, 374 ] ], "normalized": [] }, { "id": "PMID-10037736_T17", "type": "TranscriptionFactor", "text": [ "Nrf2" ], "offsets": [ [ 379, 383 ] ], "normalized": [] }, { "id": "PMID-10037736_T18", "type": "TranscriptionFactor", "text": [ "CNC factors" ], "offsets": [ [ 472, 483 ] ], "normalized": [] }, { "id": "PMID-10037736_T20", "type": "TranscriptionFactorBindingSiteOfDNA", "text": [ "MARE" ], "offsets": [ [ 492, 496 ] ], "normalized": [] }, { "id": "PMID-10037736_T22", "type": "Protein", "text": [ "Maf proteins" ], "offsets": [ [ 538, 550 ] ], "normalized": [] }, { "id": "PMID-10037736_T23", "type": "TranscriptionFactor", "text": [ "CNC factor" ], "offsets": [ [ 618, 628 ] ], "normalized": [] }, { "id": "PMID-10037736_T24", "type": "Gene", "text": [ "Nrf3" ], "offsets": [ [ 630, 634 ] ], "normalized": [] }, { "id": "PMID-10037736_T25", "type": "Protein", "text": [ "protein" ], "offsets": [ [ 664, 671 ] ], "normalized": [] }, { "id": "PMID-10037736_T26", "type": "bZIP", "text": [ "leucine zipper domain" ], "offsets": [ [ 692, 713 ] ], "normalized": [] }, { "id": "PMID-10037736_T27", "type": "TranscriptionFactor", "text": [ "CNC proteins" ], "offsets": [ [ 750, 762 ] ], "normalized": [] }, { "id": "PMID-10037736_T28", "type": "TranscriptionFactor", "text": [ "Nrf3" ], "offsets": [ [ 806, 810 ] ], "normalized": [] }, { "id": "PMID-10037736_T30", "type": "ProteinSubunit", "text": [ "MafK" ], "offsets": [ [ 835, 839 ] ], "normalized": [] }, { "id": "PMID-10037736_T31", "type": "TranscriptionFactorComplex", "text": [ "complex" ], "offsets": [ [ 854, 861 ] ], "normalized": [] }, { "id": "PMID-10037736_T33", "type": "TranscriptionFactorBindingSiteOfDNA", "text": [ "MARE" ], "offsets": [ [ 875, 879 ] ], "normalized": [] }, { "id": "PMID-10037736_T34", "type": "Eukaryote", "text": [ "chicken" ], "offsets": [ [ 887, 894 ] ], "normalized": [] }, { "id": "PMID-10037736_T35", "type": "Gene", "text": [ "beta-globin" ], "offsets": [ [ 895, 906 ] ], "normalized": [] }, { "id": "PMID-10037736_T36", "type": "Enhancer", "text": [ "enhancer" ], "offsets": [ [ 907, 915 ] ], "normalized": [] }, { "id": "PMID-10037736_T39", "type": "TranscriptionFactor", "text": [ "Nrf3" ], "offsets": [ [ 948, 952 ] ], "normalized": [] }, { "id": "PMID-10037736_T40", "type": "MessengerRNA", "text": [ "mRNA" ], "offsets": [ [ 953, 957 ] ], "normalized": [] }, { "id": "PMID-10037736_T42", "type": "Eukaryote", "text": [ "human" ], "offsets": [ [ 981, 986 ] ], "normalized": [] }, { "id": "PMID-10037736_T43", "type": "Cell", "text": [ "placenta" ], "offsets": [ [ 987, 995 ] ], "normalized": [] }, { "id": "PMID-10037736_T44", "type": "Cell", "text": [ "B cell" ], "offsets": [ [ 1000, 1006 ] ], "normalized": [] }, { "id": "PMID-10037736_T45", "type": "Cell", "text": [ "monocyte lineage" ], "offsets": [ [ 1011, 1027 ] ], "normalized": [] }, { "id": "PMID-10037736_T46", "type": "Chromosome", "text": [ "Chromosomal" ], "offsets": [ [ 1029, 1040 ] ], "normalized": [] }, { "id": "PMID-10037736_T48", "type": "Eukaryote", "text": [ "human" ], "offsets": [ [ 1057, 1062 ] ], "normalized": [] }, { "id": "PMID-10037736_T49", "type": "TranscriptionFactor", "text": [ "Nrf3" ], "offsets": [ [ 1063, 1067 ] ], "normalized": [] }, { "id": "PMID-10037736_T50", "type": "HomeoboxTF", "text": [ "hoxA gene" ], "offsets": [ [ 1100, 1109 ] ], "normalized": [] }, { "id": "PMID-10037736_T51", "type": "HomeoboxTF", "text": [ "hoxC" ], "offsets": [ [ 1195, 1199 ] ], "normalized": [] }, { "id": "PMID-10037736_T52", "type": "HomeoboxTF", "text": [ "hoxB" ], "offsets": [ [ 1201, 1205 ] ], "normalized": [] }, { "id": "PMID-10037736_T53", "type": "HomeoboxTF", "text": [ "hoxD" ], "offsets": [ [ 1211, 1215 ] ], "normalized": [] }, { "id": "PMID-10037736_T54", "type": "Gene", "text": [ "gene" ], "offsets": [ [ 1302, 1306 ] ], "normalized": [] }, { "id": "PMID-10037736_T55", "type": "HomeoboxTF", "text": [ "Hox cluster" ], "offsets": [ [ 1377, 1388 ] ], "normalized": [] }, { "id": "PMID-10037736_T56", "type": "TranscriptionFactor", "text": [ "CNC factors" ], "offsets": [ [ 1444, 1455 ] ], "normalized": [] }, { "id": "PMID-10037736_T57", "type": "Chromosome", "text": [ "chromosome" ], "offsets": [ [ 1464, 1474 ] ], "normalized": [] }, { "id": "PMID-10037736_T3", "type": "TranscriptionFactorBindingSiteOfDNA", "text": [ "NF-E2-binding sites" ], "offsets": [ [ 111, 130 ] ], "normalized": [] }, { "id": "PMID-10037736_T4", "type": "RegulatoryDNARegion", "text": [ "regulatory regions" ], "offsets": [ [ 207, 225 ] ], "normalized": [] }, { "id": "PMID-10037736_T59", "type": "TranscriptionFactorBindingSiteOfDNA", "text": [ "cis-acting elements" ], "offsets": [ [ 180, 199 ] ], "normalized": [] }, { "id": "PMID-10037736_T60", "type": "BasicDomain", "text": [ "basic region" ], "offsets": [ [ 679, 691 ] ], "normalized": [] }, { "id": "PMID-10037736_T47", "type": "Chromosome", "text": [ "7p14-15" ], "offsets": [ [ 1071, 1078 ] ], "normalized": [] }, { "id": "PMID-10037736_T61", "type": "Locus", "text": [ "locus" ], "offsets": [ [ 1110, 1115 ] ], "normalized": [] }, { "id": "PMID-10037736_T62", "type": "ProteinSubunit", "text": [ "p45" ], "offsets": [ [ 1140, 1143 ] ], "normalized": [] }, { "id": "PMID-10037736_T63", "type": "TranscriptionFactor", "text": [ "nrf1" ], "offsets": [ [ 1145, 1149 ] ], "normalized": [] }, { "id": "PMID-10037736_T64", "type": "TranscriptionFactor", "text": [ "nrf2" ], "offsets": [ [ 1155, 1159 ] ], "normalized": [] } ]

[ { "id": "PMID-10037736_E1", "type": "BindingOfTranscriptionFactorToDNA", "trigger": { "text": [ "bind" ], "offsets": [ [ 484, 488 ] ] }, "arguments": [ { "role": "hasAgent", "ref_id": "PMID-10037736_T18" }, { "role": "hasPatient", "ref_id": "PMID-10037736_T20" } ] }, { "id": "PMID-10037736_E2", "type": "Heterodimerization", "trigger": { "text": [ "heterodimer formation" ], "offsets": [ [ 505, 526 ] ] }, "arguments": [ { "role": "hasPatient", "ref_id": "PMID-10037736_T22" } ] }, { "id": "PMID-10037736_E3", "type": "Heterodimerization", "trigger": { "text": [ "heterodimerize" ], "offsets": [ [ 815, 829 ] ] }, "arguments": [ { "role": "hasPatient", "ref_id": "PMID-10037736_T30" } ] }, { "id": "PMID-10037736_E4", "type": "BindingOfTranscriptionFactorToDNA", "trigger": { "text": [ "binds" ], "offsets": [ [ 862, 867 ] ] }, "arguments": [ { "role": "hasAgent", "ref_id": "PMID-10037736_T31" }, { "role": "hasPatient", "ref_id": "PMID-10037736_T33" } ] }, { "id": "PMID-10037736_E5", "type": "PositiveRegulationOfTranscription", "trigger": { "text": [ "activate" ], "offsets": [ [ 924, 932 ] ] }, "arguments": [ { "role": "hasAgent", "ref_id": "PMID-10037736_T31" }, { "role": "hasPatient", "ref_id": "PMID-10037736_E6" } ] }, { "id": "PMID-10037736_E6", "type": "Transcription", "trigger": { "text": [ "transcription" ], "offsets": [ [ 933, 946 ] ] }, "arguments": [] }, { "id": "PMID-10037736_E7", "type": "PositiveRegulationOfTranscriptionOfGene", "trigger": { "text": [ "expressed" ], "offsets": [ [ 968, 977 ] ] }, "arguments": [ { "role": "hasPatient", "ref_id": "PMID-10037736_T40" } ] }, { "id": "PMID-10037736_E9", "type": "Mutation", "trigger": { "text": [ "duplication" ], "offsets": [ [ 1475, 1486 ] ] }, "arguments": [ { "role": "hasPatient", "ref_id": "PMID-10037736_T57" } ] }, { "id": "PMID-10037736_E8", "type": "Heterodimerization", "trigger": { "text": [ "heterodimerize" ], "offsets": [ [ 815, 829 ] ] }, "arguments": [ { "role": "hasPatient", "ref_id": "PMID-10037736_T28" } ] } ]

[]

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[ { "id": "PMID-10037746__text", "type": "abstract", "text": [ "Molecular characterization of a third member of the guanylyl cyclase-activating protein subfamily. The mammalian retina contains at least two guanylyl cyclases (GC1 and GC2) and two guanylyl cyclase-activating proteins (GCAP1 and GCAP2). Here we present evidence of the presence of a new photoreceptor-specific GCAP, termed GCAP3, which is closely related to GCAP1. The sequence similarity of GCAP3 with GCAP1 and GCAP2 is 57 and 49%, respectively. Recombinant GCAP3 and GCAP2 stimulate GC1 and GC2 in low [Ca2+]free and inhibit GCs when [Ca2+]free is elevated, unlike GCAP1, which only stimulates GC1. GCAP3 is encoded by a distinct gene present in other mammalian species but could not be detected by genomic Southern blotting in rodents, amphibians, and lower vertebrates. The intron/exon arrangement of the GCAP3 gene is identical to that of the other GCAP genes. While the GCAP1 and GCAP2 genes are arranged in a tail-to-tail array on chromosome 6p in human, the GCAP3 gene is located on 3q13.1, suggesting an ancestral gene duplication/translocation event. The identification of multiple Ca2+-binding proteins that interact with GC is suggestive of complex regulatory mechanisms for photoreceptor GC.\n" ], "offsets": [ [ 0, 1207 ] ] } ]

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"Protein", "text": [ "GCAP" ], "offsets": [ [ 311, 315 ] ], "normalized": [] }, { "id": "PMID-10037746_T16", "type": "Protein", "text": [ "GCAP3" ], "offsets": [ [ 324, 329 ] ], "normalized": [] }, { "id": "PMID-10037746_T17", "type": "Protein", "text": [ "GCAP1" ], "offsets": [ [ 359, 364 ] ], "normalized": [] }, { "id": "PMID-10037746_T18", "type": "Protein", "text": [ "GCAP3" ], "offsets": [ [ 393, 398 ] ], "normalized": [] }, { "id": "PMID-10037746_T19", "type": "Protein", "text": [ "GCAP1" ], "offsets": [ [ 404, 409 ] ], "normalized": [] }, { "id": "PMID-10037746_T20", "type": "Protein", "text": [ "GCAP2" ], "offsets": [ [ 414, 419 ] ], "normalized": [] }, { "id": "PMID-10037746_T21", "type": "Protein", "text": [ "GCAP3" ], "offsets": [ [ 461, 466 ] ], "normalized": [] }, { "id": "PMID-10037746_T22", "type": "Protein", "text": [ "GCAP2" ], "offsets": [ [ 471, 476 ] ], "normalized": [] }, { "id": "PMID-10037746_T24", "type": "Enzyme", "text": [ "GC1" ], "offsets": [ [ 487, 490 ] ], "normalized": [] }, { "id": "PMID-10037746_T25", "type": "Enzyme", "text": [ "GC2" ], "offsets": [ [ 495, 498 ] ], "normalized": [] }, { "id": "PMID-10037746_T26", "type": "Ion", "text": [ "[Ca2+]free" ], "offsets": [ [ 506, 516 ] ], "normalized": [] }, { "id": "PMID-10037746_T28", "type": "Enzyme", "text": [ "GCs" ], "offsets": [ [ 529, 532 ] ], "normalized": [] }, { "id": "PMID-10037746_T29", "type": "Ion", "text": [ "[Ca2+]free" ], "offsets": [ [ 538, 548 ] ], "normalized": [] }, { "id": "PMID-10037746_T30", "type": "Protein", "text": [ "GCAP1" ], "offsets": [ [ 569, 574 ] ], "normalized": [] }, { "id": "PMID-10037746_T32", "type": "Enzyme", "text": [ "GC1" ], "offsets": [ [ 598, 601 ] ], "normalized": [] }, { "id": "PMID-10037746_T33", "type": "Protein", "text": [ "GCAP3" ], "offsets": [ [ 603, 608 ] ], "normalized": [] }, { "id": "PMID-10037746_T34", "type": "Gene", "text": [ "gene" ], "offsets": [ [ 634, 638 ] ], "normalized": [] }, { "id": "PMID-10037746_T35", "type": "Eukaryote", "text": [ "mammalian" ], "offsets": [ [ 656, 665 ] ], "normalized": [] }, { "id": "PMID-10037746_T36", "type": "Eukaryote", "text": [ "rodents" ], "offsets": [ [ 732, 739 ] ], "normalized": [] }, { "id": "PMID-10037746_T37", "type": "Eukaryote", "text": [ "amphibians" ], "offsets": [ [ 741, 751 ] ], "normalized": [] }, { "id": "PMID-10037746_T38", "type": "Eukaryote", "text": [ "lower vertebrates" ], "offsets": [ [ 757, 774 ] ], "normalized": [] }, { "id": "PMID-10037746_T39", "type": "Gene", "text": [ "GCAP3 gene" ], "offsets": [ [ 811, 821 ] ], "normalized": [] }, { "id": "PMID-10037746_T40", "type": "Gene", "text": [ "GCAP genes" ], "offsets": [ [ 856, 866 ] ], "normalized": [] }, { "id": "PMID-10037746_T41", "type": "Gene", "text": [ "GCAP1" ], "offsets": [ [ 878, 883 ] ], "normalized": [] }, { "id": "PMID-10037746_T42", "type": "Gene", "text": [ "GCAP2 genes" ], "offsets": [ [ 888, 899 ] ], "normalized": [] }, { "id": "PMID-10037746_T43", "type": "Chromosome", "text": [ "chromosome" ], "offsets": [ [ 940, 950 ] ], "normalized": [] }, { "id": "PMID-10037746_T44", "type": "Eukaryote", "text": [ "human" ], "offsets": [ [ 957, 962 ] ], "normalized": [] }, { "id": "PMID-10037746_T45", "type": "Gene", "text": [ "GCAP3 gene" ], "offsets": [ [ 968, 978 ] ], "normalized": [] }, { "id": "PMID-10037746_T46", "type": "Gene", "text": [ "gene" ], "offsets": [ [ 1025, 1029 ] ], "normalized": [] }, { "id": "PMID-10037746_T50", "type": "Protein", "text": [ "Ca2+-binding proteins" ], "offsets": [ [ 1094, 1115 ] ], "normalized": [] }, { "id": "PMID-10037746_T52", "type": "Enzyme", "text": [ "GC" ], "offsets": [ [ 1135, 1137 ] ], "normalized": [] }, { "id": "PMID-10037746_T53", "type": "Protein", "text": [ "photoreceptor" ], "offsets": [ [ 1189, 1202 ] ], "normalized": [] }, { "id": "PMID-10037746_T54", "type": "Enzyme", "text": [ "GC" ], "offsets": [ [ 1203, 1205 ] ], "normalized": [] }, { "id": "PMID-10037746_T1", "type": "Protein", "text": [ "guanylyl cyclase-activating protein" ], "offsets": [ [ 52, 87 ] ], "normalized": [] }, { "id": "PMID-10037746_T2", "type": "Protein", "text": [ "guanylyl cyclase-activating proteins" ], "offsets": [ [ 182, 218 ] ], "normalized": [] }, { "id": "PMID-10037746_T3", "type": "Chromosome", "text": [ "3q13.1" ], "offsets": [ [ 993, 999 ] ], "normalized": [] } ]

[ { "id": "PMID-10037746_E3", "type": "PositiveRegulation", "trigger": { "text": [ "stimulate" ], "offsets": [ [ 477, 486 ] ] }, "arguments": [ { "role": "hasAgent", "ref_id": "PMID-10037746_T21" }, { "role": "hasPatient", "ref_id": "PMID-10037746_T24" } ] }, { "id": "PMID-10037746_E4", "type": "NegativeRegulation", "trigger": { "text": [ "inhibit" ], "offsets": [ [ 521, 528 ] ] }, "arguments": [ { "role": "hasPatient", "ref_id": "PMID-10037746_T28" }, { "role": "hasAgent", "ref_id": "PMID-10037746_T21" } ] }, { "id": "PMID-10037746_E5", "type": "PositiveRegulation", "trigger": { "text": [ "stimulates" ], "offsets": [ [ 587, 597 ] ] }, "arguments": [ { "role": "hasAgent", "ref_id": "PMID-10037746_T30" }, { "role": "hasPatient", "ref_id": "PMID-10037746_T32" } ] }, { "id": "PMID-10037746_E6", "type": "Mutation", "trigger": { "text": [ "duplication/translocation event" ], "offsets": [ [ 1030, 1061 ] ] }, "arguments": [ { "role": "hasPatient", "ref_id": "PMID-10037746_T46" } ] }, { "id": "PMID-10037746_E8", "type": "BindingToProtein", "trigger": { "text": [ "interact" ], "offsets": [ [ 1121, 1129 ] ] }, "arguments": [ { "role": "hasPatient", "ref_id": "PMID-10037746_T52" }, { "role": "hasPatient2", "ref_id": "PMID-10037746_T50" } ] }, { "id": "PMID-10037746_E1", "type": "RegulatoryProcess", "trigger": { "text": [ "regulatory mechanisms" ], "offsets": [ [ 1163, 1184 ] ] }, "arguments": [] }, { "id": "PMID-10037746_E2", "type": "PositiveRegulation", "trigger": { "text": [ "stimulate" ], "offsets": [ [ 477, 486 ] ] }, "arguments": [ { "role": "hasAgent", "ref_id": "PMID-10037746_T22" }, { "role": "hasPatient", "ref_id": "PMID-10037746_T24" } ] }, { "id": "PMID-10037746_E7", "type": "PositiveRegulation", "trigger": { "text": [ "stimulate" ], "offsets": [ [ 477, 486 ] ] }, "arguments": [ { "role": "hasAgent", "ref_id": "PMID-10037746_T21" }, { "role": "hasPatient", "ref_id": "PMID-10037746_T25" } ] }, { "id": "PMID-10037746_E9", "type": "PositiveRegulation", "trigger": { "text": [ "stimulate" ], "offsets": [ [ 477, 486 ] ] }, "arguments": [ { "role": "hasAgent", "ref_id": "PMID-10037746_T22" }, { "role": "hasPatient", "ref_id": "PMID-10037746_T25" } ] }, { "id": "PMID-10037746_E10", "type": "NegativeRegulation", "trigger": { "text": [ "inhibit" ], "offsets": [ [ 521, 528 ] ] }, "arguments": [ { "role": "hasPatient", "ref_id": "PMID-10037746_T28" }, { "role": "hasAgent", "ref_id": "PMID-10037746_T22" } ] } ]

[]

[ { "id": "PMID-10037746_R1", "type": "fromSpecies", "arg1_id": "PMID-10037746_T5", "arg2_id": "PMID-10037746_T4", "normalized": [] }, { "id": "PMID-10037746_R2", "type": "locatedIn", "arg1_id": "PMID-10037746_T6", "arg2_id": "PMID-10037746_T5", "normalized": [] }, { "id": "PMID-10037746_R3", "type": "encodes", "arg1_id": "PMID-10037746_T34", "arg2_id": "PMID-10037746_T33", "normalized": [] }, { "id": "PMID-10037746_R4", "type": "fromSpecies", "arg1_id": "PMID-10037746_T34", "arg2_id": "PMID-10037746_T35", "normalized": [] }, { "id": "PMID-10037746_R5", "type": "fromSpecies", "arg1_id": "PMID-10037746_T43", "arg2_id": "PMID-10037746_T44", "normalized": [] }, { "id": "PMID-10037746_R6", "type": "locatedIn", "arg1_id": "PMID-10037746_T41", "arg2_id": "PMID-10037746_T43", "normalized": [] }, { "id": "PMID-10037746_R7", "type": "locatedIn", "arg1_id": "PMID-10037746_T42", "arg2_id": "PMID-10037746_T43", "normalized": [] } ]

[ { "id": "PMID-10037775__text", "type": "abstract", "text": [ "Molecular enzymology of mammalian Delta1-pyrroline-5-carboxylate synthase. Alternative splice donor utilization generates isoforms with different sensitivity to ornithine inhibition. Delta1-Pyrroline-5-carboxylate synthase (P5CS; EC not assigned), a mitochondrial inner membrane, ATP- and NADPH-dependent, bifunctional enzyme, catalyzes the reduction of glutamate to Delta1-pyrroline-5-carboxylate, a critical step in the de novo biosynthesis of proline and ornithine. We utilized published plant P5CS sequence to search the expressed sequence tag data base and cloned two full-length human P5CS cDNAs differing in length by 6 base pairs (bp) in the open reading frame. The short cDNA has a 2379-bp open reading frame encoding a protein of 793 residues; the long cDNA, generated by \"exon sliding,\" a form of alternative splicing, contains an additional 6-bp insert following bp +711 of the short form resulting in inclusion of two additional amino acids in the region predicted to be the gamma-glutamyl kinase active site of P5CS. The long form predominates in all tissues examined except gut. We also isolated the corresponding long and short murine P5CS transcripts. To confirm the identity of the putative P5CS cDNAs, we expressed both human forms in gamma-glutamyl kinase- and gamma-glutamyl phosphate reductase-deficient strains of Saccharomyces cerevisiae and showed that they conferred the proline prototrophy. Additionally, we found expression of the murine putative P5CS cDNAs conferred proline prototrophy to P5CS-deficient Chinese hamster ovary cells (CHO-K1). We utilized stable CHO-K1 cell transformants to compare the biochemical characteristics of the long and short murine P5CS isoforms. We found that both confer P5CS activity and that the short isoform is inhibited by L-ornithine with a Ki of approximately 0.25 mM. Surprisingly, the long isoform is insensitive to ornithine inhibition. Thus, the two amino acid insert in the long isoform abolishes feedback inhibition of P5CS activity by L-ornithine.\n" ], "offsets": [ [ 0, 2021 ] ] } ]

[ { "id": "PMID-10037775_T1", "type": "Eukaryote", "text": [ "mammalian" ], "offsets": [ [ 24, 33 ] ], "normalized": [] }, { "id": "PMID-10037775_T2", "type": "Enzyme", "text": [ "Delta1-pyrroline-5-carboxylate synthase" ], "offsets": [ [ 34, 73 ] ], "normalized": [] }, { "id": "PMID-10037775_T4", "type": "AminoAcid", "text": [ "ornithine" ], "offsets": [ [ 161, 170 ] ], "normalized": [] }, { "id": "PMID-10037775_T6", "type": "Enzyme", "text": [ "Delta1-Pyrroline-5-carboxylate synthase" ], "offsets": [ [ 183, 222 ] ], "normalized": [] }, { "id": "PMID-10037775_T7", "type": "Enzyme", "text": [ "P5CS" ], "offsets": [ [ 224, 228 ] ], "normalized": [] }, { "id": "PMID-10037775_T8", "type": "CellComponent", "text": [ "mitochondrial inner membrane" ], "offsets": [ [ 250, 278 ] ], "normalized": [] }, { "id": "PMID-10037775_T9", "type": "Nucleotide", "text": [ "ATP" ], "offsets": [ [ 280, 283 ] ], "normalized": [] }, { "id": "PMID-10037775_T10", "type": "Chemical", "text": [ "NADPH" ], "offsets": [ [ 289, 294 ] ], "normalized": [] }, { "id": "PMID-10037775_T11", "type": "Enzyme", "text": [ "enzyme" ], "offsets": [ [ 319, 325 ] ], "normalized": [] }, { "id": "PMID-10037775_T12", "type": "AminoAcid", "text": [ "glutamate" ], "offsets": [ [ 354, 363 ] ], "normalized": [] }, { "id": "PMID-10037775_T13", "type": "Chemical", "text": [ "Delta1-pyrroline-5-carboxylate" ], "offsets": [ [ 367, 397 ] ], "normalized": [] }, { "id": "PMID-10037775_T15", "type": "AminoAcid", "text": [ "proline" ], "offsets": [ [ 446, 453 ] ], "normalized": [] }, { "id": "PMID-10037775_T16", "type": "AminoAcid", "text": [ "ornithine" ], "offsets": [ [ 458, 467 ] ], "normalized": [] }, { "id": "PMID-10037775_T17", "type": "Eukaryote", "text": [ "plant" ], "offsets": [ [ 491, 496 ] ], "normalized": [] }, { "id": "PMID-10037775_T18", "type": "Enzyme", "text": [ "P5CS" ], "offsets": [ [ 497, 501 ] ], "normalized": [] }, { "id": "PMID-10037775_T19", "type": "Sequence", "text": [ "sequence" ], "offsets": [ [ 502, 510 ] ], "normalized": [] }, { "id": "PMID-10037775_T20", "type": "Eukaryote", "text": [ "human" ], "offsets": [ [ 585, 590 ] ], "normalized": [] }, { "id": "PMID-10037775_T21", "type": "Enzyme", "text": [ "P5CS" ], "offsets": [ [ 591, 595 ] ], "normalized": [] }, { "id": "PMID-10037775_T22", "type": "DNA", "text": [ "cDNAs" ], "offsets": [ [ 596, 601 ] ], "normalized": [] }, { "id": "PMID-10037775_T23", "type": "OpenReadingFrame", "text": [ "open reading frame" ], "offsets": [ [ 650, 668 ] ], "normalized": [] }, { "id": "PMID-10037775_T24", "type": "DNA", "text": [ "cDNA" ], "offsets": [ [ 680, 684 ] ], "normalized": [] }, { "id": "PMID-10037775_T25", "type": "OpenReadingFrame", "text": [ "open reading frame" ], "offsets": [ [ 699, 717 ] ], "normalized": [] }, { "id": "PMID-10037775_T26", "type": "Protein", "text": [ "protein" ], "offsets": [ [ 729, 736 ] ], "normalized": [] }, { "id": "PMID-10037775_T27", "type": "DNA", "text": [ "cDNA" ], "offsets": [ [ 763, 767 ] ], "normalized": [] }, { "id": "PMID-10037775_T29", "type": "AminoAcid", "text": [ "amino acids" ], "offsets": [ [ 942, 953 ] ], "normalized": [] }, { "id": "PMID-10037775_T30", "type": "ProteinSubunit", "text": [ "gamma-glutamyl kinase active site" ], "offsets": [ [ 988, 1021 ] ], "normalized": [] }, { "id": "PMID-10037775_T31", "type": "Enzyme", "text": [ "P5CS" ], "offsets": [ [ 1025, 1029 ] ], "normalized": [] }, { "id": "PMID-10037775_T32", "type": "Tissue", "text": [ "tissues" ], "offsets": [ [ 1065, 1072 ] ], "normalized": [] }, { "id": "PMID-10037775_T33", "type": "Tissue", "text": [ "gut" ], "offsets": [ [ 1089, 1092 ] ], "normalized": [] }, { "id": "PMID-10037775_T34", "type": "Eukaryote", "text": [ "murine" ], "offsets": [ [ 1144, 1150 ] ], "normalized": [] }, { "id": "PMID-10037775_T35", "type": "Enzyme", "text": [ "P5CS" ], "offsets": [ [ 1151, 1155 ] ], "normalized": [] }, { "id": "PMID-10037775_T36", "type": "Transcript", "text": [ "transcripts" ], "offsets": [ [ 1156, 1167 ] ], "normalized": [] }, { "id": "PMID-10037775_T37", "type": "Enzyme", "text": [ "P5CS" ], "offsets": [ [ 1209, 1213 ] ], "normalized": [] }, { "id": "PMID-10037775_T38", "type": "DNA", "text": [ "cDNAs" ], "offsets": [ [ 1214, 1219 ] ], "normalized": [] }, { "id": "PMID-10037775_T40", "type": "Eukaryote", "text": [ "human" ], "offsets": [ [ 1239, 1244 ] ], "normalized": [] }, { "id": "PMID-10037775_T41", "type": "Enzyme", "text": [ "gamma-glutamyl kinase" ], "offsets": [ [ 1254, 1275 ] ], "normalized": [] }, { "id": "PMID-10037775_T42", "type": "Enzyme", "text": [ "gamma-glutamyl phosphate reductase" ], "offsets": [ [ 1281, 1315 ] ], "normalized": [] }, { "id": "PMID-10037775_T43", "type": "Eukaryote", "text": [ "Saccharomyces cerevisiae" ], "offsets": [ [ 1337, 1361 ] ], "normalized": [] }, { "id": "PMID-10037775_T44", "type": "AminoAcid", "text": [ "proline" ], "offsets": [ [ 1397, 1404 ] ], "normalized": [] }, { "id": "PMID-10037775_T46", "type": "Eukaryote", "text": [ "murine" ], "offsets": [ [ 1459, 1465 ] ], "normalized": [] }, { "id": "PMID-10037775_T47", "type": "Enzyme", "text": [ "P5CS" ], "offsets": [ [ 1475, 1479 ] ], "normalized": [] }, { "id": "PMID-10037775_T48", "type": "DNA", "text": [ "cDNAs" ], "offsets": [ [ 1480, 1485 ] ], "normalized": [] }, { "id": "PMID-10037775_T49", "type": "AminoAcid", "text": [ "proline" ], "offsets": [ [ 1496, 1503 ] ], "normalized": [] }, { "id": "PMID-10037775_T50", "type": "Enzyme", "text": [ "P5CS" ], "offsets": [ [ 1519, 1523 ] ], "normalized": [] }, { "id": "PMID-10037775_T51", "type": "Cell", "text": [ "Chinese hamster ovary cells" ], "offsets": [ [ 1534, 1561 ] ], "normalized": [] }, { "id": "PMID-10037775_T52", "type": "Cell", "text": [ "CHO-K1" ], "offsets": [ [ 1563, 1569 ] ], "normalized": [] }, { "id": "PMID-10037775_T53", "type": "Cell", "text": [ "CHO-K1 cell transformants" ], "offsets": [ [ 1591, 1616 ] ], "normalized": [] }, { "id": "PMID-10037775_T54", "type": "Eukaryote", "text": [ "murine" ], "offsets": [ [ 1682, 1688 ] ], "normalized": [] }, { "id": "PMID-10037775_T55", "type": "Enzyme", "text": [ "P5CS isoforms" ], "offsets": [ [ 1689, 1702 ] ], "normalized": [] }, { "id": "PMID-10037775_T56", "type": "Enzyme", "text": [ "P5CS" ], "offsets": [ [ 1730, 1734 ] ], "normalized": [] }, { "id": "PMID-10037775_T58", "type": "AminoAcid", "text": [ "L-ornithine" ], "offsets": [ [ 1787, 1798 ] ], "normalized": [] }, { "id": "PMID-10037775_T59", "type": "AminoAcid", "text": [ "ornithine" ], "offsets": [ [ 1884, 1893 ] ], "normalized": [] }, { "id": "PMID-10037775_T64", "type": "Enzyme", "text": [ "P5CS" ], "offsets": [ [ 1991, 1995 ] ], "normalized": [] }, { "id": "PMID-10037775_T65", "type": "AminoAcid", "text": [ "L-ornithine" ], "offsets": [ [ 2008, 2019 ] ], "normalized": [] }, { "id": "PMID-10037775_T67", "type": "CatalyticActivity", "text": [ "catalyzes" ], "offsets": [ [ 327, 336 ] ], "normalized": [] }, { "id": "PMID-10037775_T71", "type": "CatalyticActivity", "text": [ "activity" ], "offsets": [ [ 1735, 1743 ] ], "normalized": [] }, { "id": "PMID-10037775_T61", "type": "AminoAcid", "text": [ "two amino acid insert" ], "offsets": [ [ 1916, 1937 ] ], "normalized": [] }, { "id": "PMID-10037775_T72", "type": "CatalyticActivity", "text": [ "activity" ], "offsets": [ [ 1996, 2004 ] ], "normalized": [] } ]

[ { "id": "PMID-10037775_E1", "type": "Splicing", "trigger": { "text": [ "Alternative splice" ], "offsets": [ [ 75, 93 ] ] }, "arguments": [] }, { "id": "PMID-10037775_E2", "type": "NegativeRegulation", "trigger": { "text": [ "inhibition" ], "offsets": [ [ 171, 181 ] ] }, "arguments": [ { "role": "hasAgent", "ref_id": "PMID-10037775_T4" } ] }, { "id": "PMID-10037775_E3", "type": "MetabolicPathway", "trigger": { "text": [ "biosynthesis" ], "offsets": [ [ 430, 442 ] ] }, "arguments": [ { "role": "hasPatient", "ref_id": "PMID-10037775_T15" } ] }, { "id": "PMID-10037775_E4", "type": "Splicing", "trigger": { "text": [ "alternative splicing" ], "offsets": [ [ 808, 828 ] ] }, "arguments": [] }, { "id": "PMID-10037775_E5", "type": "GeneExpression", "trigger": { "text": [ "expressed" ], "offsets": [ [ 1224, 1233 ] ] }, "arguments": [] }, { "id": "PMID-10037775_E6", "type": "GeneExpression", "trigger": { "text": [ "expression" ], "offsets": [ [ 1441, 1451 ] ] }, "arguments": [ { "role": "hasPatient", "ref_id": "PMID-10037775_T48" } ] }, { "id": "PMID-10037775_E7", "type": "NegativeRegulation", "trigger": { "text": [ "inhibited" ], "offsets": [ [ 1774, 1783 ] ] }, "arguments": [ { "role": "hasAgent", "ref_id": "PMID-10037775_T58" } ] }, { "id": "PMID-10037775_E8", "type": "NegativeRegulation", "trigger": { "text": [ "inhibition" ], "offsets": [ [ 1894, 1904 ] ] }, "arguments": [ { "role": "hasAgent", "ref_id": "PMID-10037775_T59" } ] }, { "id": "PMID-10037775_E9", "type": "NegativeRegulation", "trigger": { "text": [ "abolishes" ], "offsets": [ [ 1958, 1967 ] ] }, "arguments": [ { "role": "hasPatient", "ref_id": "PMID-10037775_E10" }, { "role": "hasAgent", "ref_id": "PMID-10037775_T61" } ] }, { "id": "PMID-10037775_E10", "type": "NegativeRegulation", "trigger": { "text": [ "inhibition" ], "offsets": [ [ 1977, 1987 ] ] }, "arguments": [ { "role": "hasAgent", "ref_id": "PMID-10037775_T65" }, { "role": "hasPatient", "ref_id": "PMID-10037775_T72" } ] }, { "id": "PMID-10037775_E11", "type": "ResponseProcess", "trigger": { "text": [ "sensitivity" ], "offsets": [ [ 146, 157 ] ] }, "arguments": [ { "role": "hasAgent", "ref_id": "PMID-10037775_E2" } ] }, { "id": "PMID-10037775_E12", "type": "MetabolicPathway", "trigger": { "text": [ "reduction" ], "offsets": [ [ 341, 350 ] ] }, "arguments": [ { "role": "hasAgent", "ref_id": "PMID-10037775_T12" }, { "role": "hasPatient", "ref_id": "PMID-10037775_T13" } ] }, { "id": "PMID-10037775_E13", "type": "MetabolicPathway", "trigger": { "text": [ "prototrophy" ], "offsets": [ [ 1405, 1416 ] ] }, "arguments": [ { "role": "hasPatient", "ref_id": "PMID-10037775_T44" } ] }, { "id": "PMID-10037775_E14", "type": "MetabolicPathway", "trigger": { "text": [ "prototrophy" ], "offsets": [ [ 1504, 1515 ] ] }, "arguments": [ { "role": "hasPatient", "ref_id": "PMID-10037775_T49" } ] }, { "id": "PMID-10037775_E15", "type": "MetabolicPathway", "trigger": { "text": [ "biosynthesis" ], "offsets": [ [ 430, 442 ] ] }, "arguments": [ { "role": "hasPatient", "ref_id": "PMID-10037775_T16" } ] } ]

[]

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[ { "id": "PMID-10037799__text", "type": "abstract", "text": [ "LYVE-1, a new homologue of the CD44 glycoprotein, is a lymph-specific receptor for hyaluronan. The extracellular matrix glycosaminoglycan hyaluronan (HA) is an abundant component of skin and mesenchymal tissues where it facilitates cell migration during wound healing, inflammation, and embryonic morphogenesis. Both during normal tissue homeostasis and particularly after tissue injury, HA is mobilized from these sites through lymphatic vessels to the lymph nodes where it is degraded before entering the circulation for rapid uptake by the liver. Currently, however, the identities of HA binding molecules which control this pathway are unknown. Here we describe the first such molecule, LYVE-1, which we have identified as a major receptor for HA on the lymph vessel wall. The deduced amino acid sequence of LYVE-1 predicts a 322-residue type I integral membrane polypeptide 41% similar to the CD44 HA receptor with a 212-residue extracellular domain containing a single Link module the prototypic HA binding domain of the Link protein superfamily. Like CD44, the LYVE-1 molecule binds both soluble and immobilized HA. However, unlike CD44, the LYVE-1 molecule colocalizes with HA on the luminal face of the lymph vessel wall and is completely absent from blood vessels. Hence, LYVE-1 is the first lymph-specific HA receptor to be characterized and is a uniquely powerful marker for lymph vessels themselves.\n" ], "offsets": [ [ 0, 1413 ] ] } ]

[ { "id": "PMID-10037799_T1", "type": "Protein", "text": [ "LYVE-1" ], "offsets": [ [ 0, 6 ] ], "normalized": [] }, { "id": "PMID-10037799_T2", "type": "Protein", "text": [ "CD44" ], "offsets": [ [ 31, 35 ] ], "normalized": [] }, { "id": "PMID-10037799_T3", "type": "Protein", "text": [ "glycoprotein" ], "offsets": [ [ 36, 48 ] ], "normalized": [] }, { "id": "PMID-10037799_T4", "type": "Tissue", "text": [ "lymph" ], "offsets": [ [ 55, 60 ] ], "normalized": [] }, { "id": "PMID-10037799_T5", "type": "Protein", "text": [ "receptor" ], "offsets": [ [ 70, 78 ] ], "normalized": [] }, { "id": "PMID-10037799_T6", "type": "Chemical", "text": [ "hyaluronan" ], "offsets": [ [ 83, 93 ] ], "normalized": [] }, { "id": "PMID-10037799_T7", "type": "Chemical", "text": [ "HA" ], "offsets": [ [ 150, 152 ] ], "normalized": [] }, { "id": "PMID-10037799_T9", "type": "Tissue", "text": [ "skin" ], "offsets": [ [ 182, 186 ] ], "normalized": [] }, { "id": "PMID-10037799_T10", "type": "Tissue", "text": [ "mesenchymal tissues" ], "offsets": [ [ 191, 210 ] ], "normalized": [] }, { "id": "PMID-10037799_T14", "type": "Tissue", "text": [ "tissue" ], "offsets": [ [ 373, 379 ] ], "normalized": [] }, { "id": "PMID-10037799_T15", "type": "Chemical", "text": [ "HA" ], "offsets": [ [ 388, 390 ] ], "normalized": [] }, { "id": "PMID-10037799_T17", "type": "Tissue", "text": [ "lymphatic vessels" ], "offsets": [ [ 429, 446 ] ], "normalized": [] }, { "id": "PMID-10037799_T18", "type": "Tissue", "text": [ "lymph nodes" ], "offsets": [ [ 454, 465 ] ], "normalized": [] }, { "id": "PMID-10037799_T20", "type": "Tissue", "text": [ "liver" ], "offsets": [ [ 543, 548 ] ], "normalized": [] }, { "id": "PMID-10037799_T21", "type": "Chemical", "text": [ "HA" ], "offsets": [ [ 588, 590 ] ], "normalized": [] }, { "id": "PMID-10037799_T23", "type": "MolecularEntity", "text": [ "molecules" ], "offsets": [ [ 599, 608 ] ], "normalized": [] }, { "id": "PMID-10037799_T26", "type": "Protein", "text": [ "LYVE-1" ], "offsets": [ [ 691, 697 ] ], "normalized": [] }, { "id": "PMID-10037799_T27", "type": "Protein", "text": [ "receptor" ], "offsets": [ [ 735, 743 ] ], "normalized": [] }, { "id": "PMID-10037799_T28", "type": "Chemical", "text": [ "HA" ], "offsets": [ [ 748, 750 ] ], "normalized": [] }, { "id": "PMID-10037799_T29", "type": "Tissue", "text": [ "lymph vessel wall" ], "offsets": [ [ 758, 775 ] ], "normalized": [] }, { "id": "PMID-10037799_T30", "type": "AminoAcid", "text": [ "amino acid" ], "offsets": [ [ 789, 799 ] ], "normalized": [] }, { "id": "PMID-10037799_T31", "type": "Protein", "text": [ "LYVE-1" ], "offsets": [ [ 812, 818 ] ], "normalized": [] }, { "id": "PMID-10037799_T41", "type": "Protein", "text": [ "Link protein" ], "offsets": [ [ 1027, 1039 ] ], "normalized": [] }, { "id": "PMID-10037799_T42", "type": "Protein", "text": [ "CD44" ], "offsets": [ [ 1058, 1062 ] ], "normalized": [] }, { "id": "PMID-10037799_T43", "type": "Protein", "text": [ "LYVE-1 molecule" ], "offsets": [ [ 1068, 1083 ] ], "normalized": [] }, { "id": "PMID-10037799_T45", "type": "Chemical", "text": [ "HA" ], "offsets": [ [ 1119, 1121 ] ], "normalized": [] }, { "id": "PMID-10037799_T46", "type": "Protein", "text": [ "CD44" ], "offsets": [ [ 1139, 1143 ] ], "normalized": [] }, { "id": "PMID-10037799_T47", "type": "Protein", "text": [ "LYVE-1 molecule" ], "offsets": [ [ 1149, 1164 ] ], "normalized": [] }, { "id": "PMID-10037799_T48", "type": "Chemical", "text": [ "HA" ], "offsets": [ [ 1182, 1184 ] ], "normalized": [] }, { "id": "PMID-10037799_T49", "type": "Tissue", "text": [ "lymph vessel wall" ], "offsets": [ [ 1212, 1229 ] ], "normalized": [] }, { "id": "PMID-10037799_T50", "type": "Tissue", "text": [ "blood vessels" ], "offsets": [ [ 1260, 1273 ] ], "normalized": [] }, { "id": "PMID-10037799_T51", "type": "Protein", "text": [ "LYVE-1" ], "offsets": [ [ 1282, 1288 ] ], "normalized": [] }, { "id": "PMID-10037799_T52", "type": "Tissue", "text": [ "lymph" ], "offsets": [ [ 1302, 1307 ] ], "normalized": [] }, { "id": "PMID-10037799_T53", "type": "Chemical", "text": [ "HA" ], "offsets": [ [ 1317, 1319 ] ], "normalized": [] }, { "id": "PMID-10037799_T54", "type": "Protein", "text": [ "receptor" ], "offsets": [ [ 1320, 1328 ] ], "normalized": [] }, { "id": "PMID-10037799_T55", "type": "Tissue", "text": [ "lymph vessels" ], "offsets": [ [ 1387, 1400 ] ], "normalized": [] }, { "id": "PMID-10037799_T56", "type": "Sequence", "text": [ "sequence" ], "offsets": [ [ 800, 808 ] ], "normalized": [] }, { "id": "PMID-10037799_T32", "type": "Peptide", "text": [ "type I integral membrane polypeptide" ], "offsets": [ [ 842, 878 ] ], "normalized": [] }, { "id": "PMID-10037799_T33", "type": "Protein", "text": [ "CD44 HA receptor" ], "offsets": [ [ 898, 914 ] ], "normalized": [] }, { "id": "PMID-10037799_T34", "type": "ProteinDomain", "text": [ "extracellular domain" ], "offsets": [ [ 934, 954 ] ], "normalized": [] }, { "id": "PMID-10037799_T35", "type": "ProteinDomain", "text": [ "Link module the prototypic HA binding domain" ], "offsets": [ [ 975, 1019 ] ], "normalized": [] } ]

[ { "id": "PMID-10037799_E1", "type": "CellularProcess", "trigger": { "text": [ "cell migration" ], "offsets": [ [ 232, 246 ] ] }, "arguments": [] }, { "id": "PMID-10037799_E2", "type": "DevelopmentalProcess", "trigger": { "text": [ "embryonic morphogenesis" ], "offsets": [ [ 287, 310 ] ] }, "arguments": [] }, { "id": "PMID-10037799_E3", "type": "Transport", "trigger": { "text": [ "mobilized" ], "offsets": [ [ 394, 403 ] ] }, "arguments": [ { "role": "hasPatient", "ref_id": "PMID-10037799_T15" } ] }, { "id": "PMID-10037799_E4", "type": "MetabolicPathway", "trigger": { "text": [ "degraded" ], "offsets": [ [ 478, 486 ] ] }, "arguments": [ { "role": "hasPatient", "ref_id": "PMID-10037799_T15" } ] }, { "id": "PMID-10037799_E5", "type": "Binding", "trigger": { "text": [ "binding" ], "offsets": [ [ 591, 598 ] ] }, "arguments": [ { "role": "hasAgent", "ref_id": "PMID-10037799_T23" }, { "role": "hasPatient", "ref_id": "PMID-10037799_T21" } ] }, { "id": "PMID-10037799_E6", "type": "RegulatoryProcess", "trigger": { "text": [ "control" ], "offsets": [ [ 615, 622 ] ] }, "arguments": [ { "role": "hasAgent", "ref_id": "PMID-10037799_T23" }, { "role": "hasPatient", "ref_id": "PMID-10037799_E7" } ] }, { "id": "PMID-10037799_E7", "type": "Pathway", "trigger": { "text": [ "pathway" ], "offsets": [ [ 628, 635 ] ] }, "arguments": [] }, { "id": "PMID-10037799_E9", "type": "BindingToProtein", "trigger": { "text": [ "binds" ], "offsets": [ [ 1084, 1089 ] ] }, "arguments": [ { "role": "hasPatient2", "ref_id": "PMID-10037799_T43" }, { "role": "hasPatient", "ref_id": "PMID-10037799_T45" } ] }, { "id": "PMID-10037799_E10", "type": "OrganismalProcess", "trigger": { "text": [ "tissue homeostasis" ], "offsets": [ [ 331, 349 ] ] }, "arguments": [] } ]

[]

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[ { "id": "PMID-10037815__text", "type": "abstract", "text": [ "Combining SSH and cDNA microarrays for rapid identification of differentially expressed genes. Comparing patterns of gene expression in cell lines and tissues has important applications in a variety of biological systems. In this study we have examined whether the emerging technology of cDNA microarrays will allow a high throughput analysis of expression of cDNA clones generated by suppression subtractive hybridization (SSH). A set of cDNA clones including 332 SSH inserts amplified by PCR was arrayed using robotic printing. The cDNA arrays were hybridized with fluorescent labeled probes prepared from RNA from ER-positive (MCF7 and T47D) and ER-negative (MDA-MB-231 and HBL-100) breast cancer cell lines. Ten clones were identified that were over-expressed by at least a factor of five in the ER-positive cell lines. Northern blot analysis confirmed over-expression of these 10 cDNAs. Sequence analysis identified four of these clones as cytokeratin 19, GATA-3, CD24 and glutathione-S-transferase mu-3. Of the remaining six cDNA clones, four clones matched EST sequences from two different genes and two clones were novel sequences. Flow cytometry and immunofluorescence confirmed that CD24 protein was over-expressed in the ER-positive cell lines. We conclude that SSH and microarray technology can be successfully applied to identify differentially expressed genes. This approach allowed the identification of differentially expressed genes without the need to obtain previously cloned cDNAs.\n" ], "offsets": [ [ 0, 1502 ] ] } ]

[ { "id": "PMID-10037815_T3", "type": "Gene", "text": [ "genes" ], "offsets": [ [ 88, 93 ] ], "normalized": [] }, { "id": "PMID-10037815_T5", "type": "Cell", "text": [ "cell lines" ], "offsets": [ [ 136, 146 ] ], "normalized": [] }, { "id": "PMID-10037815_T6", "type": "Tissue", "text": [ "tissues" ], "offsets": [ [ 151, 158 ] ], "normalized": [] }, { "id": "PMID-10037815_T9", "type": "DNA", "text": [ "cDNA" ], "offsets": [ [ 360, 364 ] ], "normalized": [] }, { "id": "PMID-10037815_T10", "type": "DNA", "text": [ "cDNA" ], "offsets": [ [ 439, 443 ] ], "normalized": [] }, { "id": "PMID-10037815_T12", "type": "RNA", "text": [ "RNA" ], "offsets": [ [ 608, 611 ] ], "normalized": [] }, { "id": "PMID-10037815_T13", "type": "Cell", "text": [ "breast cancer cell lines" ], "offsets": [ [ 686, 710 ] ], "normalized": [] }, { "id": "PMID-10037815_T15", "type": "Cell", "text": [ "cell lines" ], "offsets": [ [ 812, 822 ] ], "normalized": [] }, { "id": "PMID-10037815_T17", "type": "DNA", "text": [ "cDNAs" ], "offsets": [ [ 885, 890 ] ], "normalized": [] }, { "id": "PMID-10037815_T18", "type": "DNA", "text": [ "cDNA" ], "offsets": [ [ 1031, 1035 ] ], "normalized": [] }, { "id": "PMID-10037815_T19", "type": "Protein", "text": [ "CD24 protein" ], "offsets": [ [ 1193, 1205 ] ], "normalized": [] }, { "id": "PMID-10037815_T21", "type": "Cell", "text": [ "cell lines" ], "offsets": [ [ 1244, 1254 ] ], "normalized": [] }, { "id": "PMID-10037815_T23", "type": "Gene", "text": [ "genes" ], "offsets": [ [ 1368, 1373 ] ], "normalized": [] }, { "id": "PMID-10037815_T25", "type": "Gene", "text": [ "genes" ], "offsets": [ [ 1444, 1449 ] ], "normalized": [] }, { "id": "PMID-10037815_T1", "type": "ExperimentalMethod", "text": [ "SSH" ], "offsets": [ [ 10, 13 ] ], "normalized": [] }, { "id": "PMID-10037815_T27", "type": "ExpressionProfiling", "text": [ "cDNA microarrays" ], "offsets": [ [ 18, 34 ] ], "normalized": [] }, { "id": "PMID-10037815_T7", "type": "ExpressionProfiling", "text": [ "cDNA microarrays" ], "offsets": [ [ 288, 304 ] ], "normalized": [] }, { "id": "PMID-10037815_T28", "type": "ExperimentalMethod", "text": [ "SSH" ], "offsets": [ [ 424, 427 ] ], "normalized": [] }, { "id": "PMID-10037815_T11", "type": "ExpressionProfiling", "text": [ "cDNA arrays" ], "offsets": [ [ 534, 545 ] ], "normalized": [] }, { "id": "PMID-10037815_T29", "type": "Protein", "text": [ "ER" ], "offsets": [ [ 617, 619 ] ], "normalized": [] }, { "id": "PMID-10037815_T30", "type": "Protein", "text": [ "ER" ], "offsets": [ [ 800, 802 ] ], "normalized": [] }, { "id": "PMID-10037815_T31", "type": "Gene", "text": [ "cytokeratin 19" ], "offsets": [ [ 945, 959 ] ], "normalized": [] }, { "id": "PMID-10037815_T32", "type": "Gene", "text": [ "GATA-3" ], "offsets": [ [ 961, 967 ] ], "normalized": [] }, { "id": "PMID-10037815_T33", "type": "Gene", "text": [ "CD24" ], "offsets": [ [ 969, 973 ] ], "normalized": [] }, { "id": "PMID-10037815_T34", "type": "Gene", "text": [ "glutathione-S-transferase mu-3" ], "offsets": [ [ 978, 1008 ] ], "normalized": [] }, { "id": "PMID-10037815_T35", "type": "Protein", "text": [ "ER" ], "offsets": [ [ 1232, 1234 ] ], "normalized": [] }, { "id": "PMID-10037815_T36", "type": "ExperimentalMethod", "text": [ "SSH" ], "offsets": [ [ 1273, 1276 ] ], "normalized": [] }, { "id": "PMID-10037815_T37", "type": "ExpressionProfiling", "text": [ "microarray" ], "offsets": [ [ 1281, 1291 ] ], "normalized": [] }, { "id": "PMID-10037815_T26", "type": "DNA", "text": [ "cDNAs" ], "offsets": [ [ 1495, 1500 ] ], "normalized": [] } ]

[ { "id": "PMID-10037815_E2", "type": "GeneExpression", "trigger": { "text": [ "expressed" ], "offsets": [ [ 78, 87 ] ] }, "arguments": [ { "role": "hasPatient", "ref_id": "PMID-10037815_T3" } ] }, { "id": "PMID-10037815_E3", "type": "GeneExpression", "trigger": { "text": [ "gene expression" ], "offsets": [ [ 117, 132 ] ] }, "arguments": [] }, { "id": "PMID-10037815_E5", "type": "GeneExpression", "trigger": { "text": [ "expression" ], "offsets": [ [ 346, 356 ] ] }, "arguments": [ { "role": "hasPatient", "ref_id": "PMID-10037815_T9" } ] }, { "id": "PMID-10037815_E6", "type": "PositiveRegulationOfGeneExpression", "trigger": { "text": [ "over-expressed" ], "offsets": [ [ 749, 763 ] ] }, "arguments": [] }, { "id": "PMID-10037815_E7", "type": "PositiveRegulationOfGeneExpression", "trigger": { "text": [ "over-expression" ], "offsets": [ [ 857, 872 ] ] }, "arguments": [ { "role": "hasPatient", "ref_id": "PMID-10037815_T17" } ] }, { "id": "PMID-10037815_E8", "type": "PositiveRegulationOfGeneExpression", "trigger": { "text": [ "over-expressed" ], "offsets": [ [ 1210, 1224 ] ] }, "arguments": [ { "role": "hasPatient", "ref_id": "PMID-10037815_T19" } ] }, { "id": "PMID-10037815_E9", "type": "GeneExpression", "trigger": { "text": [ "expressed" ], "offsets": [ [ 1358, 1367 ] ] }, "arguments": [ { "role": "hasPatient", "ref_id": "PMID-10037815_T23" } ] }, { "id": "PMID-10037815_E10", "type": "GeneExpression", "trigger": { "text": [ "expressed" ], "offsets": [ [ 1434, 1443 ] ] }, "arguments": [ { "role": "hasPatient", "ref_id": "PMID-10037815_T25" } ] } ]

[]

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[ { "id": "PMID-10037816__text", "type": "abstract", "text": [ "Characterization of a novel mouse cDNA, ES18, involved in apoptotic cell death of T-cells. Using the modified screening approach in combination with expressed sequence tags, we have identified several novel cDNAs from mouse embryonic stem (ES) cells, whose expression is tissue-restricted and/or developmentally regulated. One of the cDNAs, ES18, is preferentially expressed in lymph node and thymus, and contains noteworthy features of transcriptional regulator. The expression of ES18 transcript was selectively regulated during the apoptosis of T-cell thymoma S49.1 induced by several stimuli. Interestingly, the ES18 transcript was differently regulated in the mutually antagonistic process, between dexamethasone- and A23187-induced cell death of T-cells. Moreover, the message level of ES18 was selectively enhanced by staurosporine, a broad protein kinase inhibitor, but not by other protein kinase inhibitors such as GF109203X and H89. In addition, ES18 transcript was induced by C2-ceramide, which is a mediator of both dexamethasone- and staurosporine-induced apoptotic signaling. We further showed that transient overexpression of ES18 in mouse T-cell lymphoma increased the apoptotic cell death. These data suggest that ES18 may be selectively involved in specific apoptotic processes in mouse T-cells.\n" ], "offsets": [ [ 0, 1315 ] ] } ]

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[ { "id": "PMID-10037816_E1", "type": "CellDeath", "trigger": { "text": [ "apoptotic cell death" ], "offsets": [ [ 58, 78 ] ] }, "arguments": [ { "role": "hasPatient", "ref_id": "PMID-10037816_T5" } ] }, { "id": "PMID-10037816_E2", "type": "GeneExpression", "trigger": { "text": [ "expression" ], "offsets": [ [ 257, 267 ] ] }, "arguments": [] }, { "id": "PMID-10037816_E3", "type": "RegulatoryProcess", "trigger": { "text": [ "regulated" ], "offsets": [ [ 312, 321 ] ] }, "arguments": [ { "role": "hasAgent", "ref_id": "PMID-10037816_E16" }, { "role": "hasPatient", "ref_id": "PMID-10037816_E2" } ] }, { "id": "PMID-10037816_E4", "type": "GeneExpression", "trigger": { "text": [ "expressed" ], "offsets": [ [ 365, 374 ] ] }, "arguments": [ { "role": "hasPatient", "ref_id": "PMID-10037816_T15" } ] }, { "id": "PMID-10037816_E5", "type": "GeneExpression", "trigger": { "text": [ "expression" ], "offsets": [ [ 468, 478 ] ] }, "arguments": [ { "role": "hasPatient", "ref_id": "PMID-10037816_T21" } ] }, { "id": "PMID-10037816_E6", "type": "RegulationOfProcess", "trigger": { "text": [ "regulated" ], "offsets": [ [ 514, 523 ] ] }, "arguments": [ { "role": "hasPatient", "ref_id": "PMID-10037816_E5" }, { "role": "hasAgent", "ref_id": "PMID-10037816_E17" } ] }, { "id": "PMID-10037816_E7", "type": "RegulatoryProcess", "trigger": { "text": [ "regulated" ], "offsets": [ [ 648, 657 ] ] }, "arguments": [ { "role": "hasPatient", "ref_id": "PMID-10037816_T26" } ] }, { "id": "PMID-10037816_E8", "type": "CellDeath", "trigger": { "text": [ "cell death" ], "offsets": [ [ 738, 748 ] ] }, "arguments": [ { "role": "hasPatient", "ref_id": "PMID-10037816_T29" } ] }, { "id": "PMID-10037816_E9", "type": "NegativeRegulation", "trigger": { "text": [ "inhibitor" ], "offsets": [ [ 863, 872 ] ] }, "arguments": [] }, { "id": "PMID-10037816_E10", "type": "NegativeRegulation", "trigger": { "text": [ "inhibitors" ], "offsets": [ [ 906, 916 ] ] }, "arguments": [] }, { "id": "PMID-10037816_E11", "type": "Increase", "trigger": { "text": [ "induced" ], "offsets": [ [ 977, 984 ] ] }, "arguments": [ { "role": "hasPatient", "ref_id": "PMID-10037816_T36" } ] }, { "id": "PMID-10037816_E12", "type": "PositiveRegulationOfGeneExpression", "trigger": { "text": [ "overexpression" ], "offsets": [ [ 1124, 1138 ] ] }, "arguments": [ { "role": "hasPatient", "ref_id": "PMID-10037816_T39" } ] }, { "id": "PMID-10037816_E13", "type": "Increase", "trigger": { "text": [ "increased" ], "offsets": [ [ 1172, 1181 ] ] }, "arguments": [ { "role": "hasPatient", "ref_id": "PMID-10037816_E14" }, { "role": "hasAgent", "ref_id": "PMID-10037816_E12" } ] }, { "id": "PMID-10037816_E14", "type": "CellDeath", "trigger": { "text": [ "apoptotic cell death" ], "offsets": [ [ 1186, 1206 ] ] }, "arguments": [] }, { "id": "PMID-10037816_E15", "type": "CellDeath", "trigger": { "text": [ "apoptotic processes" ], "offsets": [ [ 1277, 1296 ] ] }, "arguments": [] }, { "id": "PMID-10037816_E16", "type": "DevelopmentalProcess", "trigger": { "text": [ "developmentally" ], "offsets": [ [ 296, 311 ] ] }, "arguments": [] }, { "id": "PMID-10037816_E17", "type": "CellDeath", "trigger": { "text": [ "apoptosis" ], "offsets": [ [ 535, 544 ] ] }, "arguments": [ { "role": "hasPatient", "ref_id": "PMID-10037816_T10" } ] }, { "id": "PMID-10037816_E18", "type": "CellDeath", "trigger": { "text": [ "apoptotic" ], "offsets": [ [ 1070, 1079 ] ] }, "arguments": [] }, { "id": "PMID-10037816_E19", "type": "SignalingPathway", "trigger": { "text": [ "signaling" ], "offsets": [ [ 1080, 1089 ] ] }, "arguments": [ { "role": "hasPatient", "ref_id": "PMID-10037816_E18" }, { "role": "hasAgent", "ref_id": "PMID-10037816_T51" } ] }, { "id": "PMID-10037816_E20", "type": "SignalingPathway", "trigger": { "text": [ "signaling" ], "offsets": [ [ 1080, 1089 ] ] }, "arguments": [ { "role": "hasPatient", "ref_id": "PMID-10037816_E18" }, { "role": "hasAgent", "ref_id": "PMID-10037816_T50" } ] } ]

[]

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[ { "id": "PMID-10048322__text", "type": "abstract", "text": [ "Crystal structure of human muscle aldolase complexed with fructose 1,6-bisphosphate: mechanistic implications. Fructose 1,6-bisphosphate aldolase catalyzes the reversible cleavage of fructose 1,6-bisphosphate and fructose 1-phosphate to dihydroxyacetone phosphate and either glyceraldehyde 3-phosphate or glyceraldehyde, respectively. Catalysis involves the formation of a Schiff's base intermediate formed at the epsilon-amino group of Lys229. The existing apo-enzyme structure was refined using the crystallographic free-R-factor and maximum likelihood methods that have been shown to give improved structural results that are less subject to model bias. Crystals were also soaked with the natural substrate (fructose 1,6-bisphosphate), and the crystal structure of this complex has been determined to 2.8 A. The apo structure differs from the previous Brookhaven-deposited structure (1ald) in the flexible C-terminal region. This is also the region where the native and complex structures exhibit differences. The conformational changes between native and complex structure are not large, but the observed complex does not involve the full formation of the Schiff's base intermediate, and suggests a preliminary hydrogen-bonded Michaelis complex before the formation of the covalent complex.\n" ], "offsets": [ [ 0, 1295 ] ] } ]

[ { "id": "PMID-10048322_T1", "type": "Eukaryote", "text": [ "human" ], "offsets": [ [ 21, 26 ] ], "normalized": [] }, { "id": "PMID-10048322_T2", "type": "Tissue", "text": [ "muscle" ], "offsets": [ [ 27, 33 ] ], "normalized": [] }, { "id": "PMID-10048322_T3", "type": "Enzyme", "text": [ "aldolase" ], "offsets": [ [ 34, 42 ] ], "normalized": [] }, { "id": "PMID-10048322_T4", "type": "OrganicChemical", "text": [ "fructose 1,6-bisphosphate" ], "offsets": [ [ 58, 83 ] ], "normalized": [] }, { "id": "PMID-10048322_T8", "type": "OrganicChemical", "text": [ "fructose 1,6-bisphosphate" ], "offsets": [ [ 183, 208 ] ], "normalized": [] }, { "id": "PMID-10048322_T9", "type": "OrganicChemical", "text": [ "fructose 1-phosphate" ], "offsets": [ [ 213, 233 ] ], "normalized": [] }, { "id": "PMID-10048322_T10", "type": "OrganicChemical", "text": [ "dihydroxyacetone phosphate" ], "offsets": [ [ 237, 263 ] ], "normalized": [] }, { "id": "PMID-10048322_T11", "type": "OrganicChemical", "text": [ "glyceraldehyde 3-phosphate" ], "offsets": [ [ 275, 301 ] ], "normalized": [] }, { "id": "PMID-10048322_T12", "type": "OrganicChemical", "text": [ "glyceraldehyde" ], "offsets": [ [ 305, 319 ] ], "normalized": [] }, { "id": "PMID-10048322_T13", "type": "AminoAcid", "text": [ "Lys229" ], "offsets": [ [ 437, 443 ] ], "normalized": [] }, { "id": "PMID-10048322_T14", "type": "Enzyme", "text": [ "apo-enzyme" ], "offsets": [ [ 458, 468 ] ], "normalized": [] }, { "id": "PMID-10048322_T15", "type": "MolecularStructure", "text": [ "structure" ], "offsets": [ [ 469, 478 ] ], "normalized": [] }, { "id": "PMID-10048322_T16", "type": "OrganicChemical", "text": [ "fructose 1,6-bisphosphate" ], "offsets": [ [ 711, 736 ] ], "normalized": [] }, { "id": "PMID-10048322_T17", "type": "ComplexMolecularEntity", "text": [ "complex" ], "offsets": [ [ 773, 780 ] ], "normalized": [] }, { "id": "PMID-10048322_T18", "type": "MolecularStructure", "text": [ "structure" ], "offsets": [ [ 819, 828 ] ], "normalized": [] }, { "id": "PMID-10048322_T19", "type": "Conformation", "text": [ "conformational" ], "offsets": [ [ 1017, 1031 ] ], "normalized": [] }, { "id": "PMID-10048322_T5", "type": "Enzyme", "text": [ "Fructose 1,6-bisphosphate aldolase" ], "offsets": [ [ 111, 145 ] ], "normalized": [] }, { "id": "PMID-10048322_T6", "type": "CatalyticActivity", "text": [ "catalyzes" ], "offsets": [ [ 146, 155 ] ], "normalized": [] }, { "id": "PMID-10048322_T21", "type": "CatalyticActivity", "text": [ "Catalysis" ], "offsets": [ [ 335, 344 ] ], "normalized": [] }, { "id": "PMID-10048322_T22", "type": "Substrate", "text": [ "substrate" ], "offsets": [ [ 700, 709 ] ], "normalized": [] }, { "id": "PMID-10048322_T23", "type": "ComplexMolecularEntity", "text": [ "Michaelis complex" ], "offsets": [ [ 1231, 1248 ] ], "normalized": [] }, { "id": "PMID-10048322_T24", "type": "ComplexMolecularEntity", "text": [ "covalent complex" ], "offsets": [ [ 1277, 1293 ] ], "normalized": [] } ]

[ { "id": "PMID-10048322_E1", "type": "Cleavage", "trigger": { "text": [ "cleavage" ], "offsets": [ [ 171, 179 ] ] }, "arguments": [ { "role": "hasAgent", "ref_id": "PMID-10048322_T6" }, { "role": "hasPatient", "ref_id": "PMID-10048322_T8" } ] }, { "id": "PMID-10048322_E2", "type": "BindingToProtein", "trigger": { "text": [ "complexed" ], "offsets": [ [ 43, 52 ] ] }, "arguments": [ { "role": "hasPatient", "ref_id": "PMID-10048322_T3" }, { "role": "hasPatient2", "ref_id": "PMID-10048322_T4" } ] }, { "id": "PMID-10048322_E3", "type": "Cleavage", "trigger": { "text": [ "cleavage" ], "offsets": [ [ 171, 179 ] ] }, "arguments": [ { "role": "hasAgent", "ref_id": "PMID-10048322_T6" }, { "role": "hasPatient", "ref_id": "PMID-10048322_T9" } ] } ]

[]

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[ { "id": "PMID-10048323__text", "type": "abstract", "text": [ "Crystal structure of the FMN-binding domain of human cytochrome P450 reductase at 1.93 A resolution. The crystal structure of the FMN-binding domain of human NADPH-cytochrome P450 reductase (P450R-FMN), a key component in the cytochrome P450 monooxygenase system, has been determined to 1.93 A resolution and shown to be very similar both to the global fold in solution (Barsukov I et al., 1997, J Biomol NMR 10:63-75) and to the corresponding domain in the 2.6 A crystal structure of intact rat P450R (Wang M et al., 1997, Proc Nat Acad Sci USA 94:8411-8416). The crystal structure of P450R-FMN reported here confirms the overall similarity of its alpha-beta-alpha architecture to that of the bacterial flavodoxins, but reveals differences in the position, number, and length of the helices relative to the central beta-sheet. The marked similarity between P450R-FMN and flavodoxins in the interactions between the FMN and the protein, indicate a striking evolutionary conservation of the FMN binding site. The P450R-FMN molecule has an unusual surface charge distribution, leading to a very strong dipole, which may be involved in docking cytochrome P450 into place for electron transfer near the FMN. Several acidic residues near the FMN are identified by mutagenesis experiments to be important for electron transfer to P4502D6 and to cytochrome c, a clear indication of the part of the molecular surface that is likely to be involved in substrate binding. Somewhat different parts are found to be involved in binding cytochrome P450 and cytochrome c.\n" ], "offsets": [ [ 0, 1556 ] ] } ]

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[] }, { "id": "PMID-10048323_T11", "type": "Chemical", "text": [ "NADPH" ], "offsets": [ [ 158, 163 ] ], "normalized": [] }, { "id": "PMID-10048323_T12", "type": "Enzyme", "text": [ "cytochrome P450 reductase" ], "offsets": [ [ 164, 189 ] ], "normalized": [] }, { "id": "PMID-10048323_T13", "type": "Enzyme", "text": [ "P450R" ], "offsets": [ [ 191, 196 ] ], "normalized": [] }, { "id": "PMID-10048323_T14", "type": "Nucleotide", "text": [ "FMN" ], "offsets": [ [ 197, 200 ] ], "normalized": [] }, { "id": "PMID-10048323_T16", "type": "ProteinDomain", "text": [ "domain" ], "offsets": [ [ 444, 450 ] ], "normalized": [] }, { "id": "PMID-10048323_T17", "type": "Eukaryote", "text": [ "rat" ], "offsets": [ [ 492, 495 ] ], "normalized": [] }, { "id": "PMID-10048323_T18", "type": "Enzyme", "text": [ "P450R" ], "offsets": [ [ 496, 501 ] ], "normalized": [] }, { "id": "PMID-10048323_T19", "type": "ThreeDimensionalMolecularStructure", "text": [ "crystal structure" ], "offsets": [ [ 565, 582 ] ], "normalized": [] }, { "id": "PMID-10048323_T20", "type": "Enzyme", "text": [ "P450R" ], "offsets": [ [ 586, 591 ] ], "normalized": [] }, { "id": "PMID-10048323_T21", "type": "Nucleotide", "text": [ "FMN" ], "offsets": [ [ 592, 595 ] ], "normalized": [] }, { "id": "PMID-10048323_T22", "type": "MolecularStructure", "text": [ "alpha-beta-alpha architecture" ], "offsets": [ [ 649, 678 ] ], "normalized": [] }, { "id": "PMID-10048323_T23", "type": "MolecularStructure", "text": [ "helices" ], "offsets": [ [ 784, 791 ] ], "normalized": [] }, { "id": "PMID-10048323_T24", "type": "MolecularStructure", "text": [ "beta-sheet" ], "offsets": [ [ 816, 826 ] ], "normalized": [] }, { "id": "PMID-10048323_T25", "type": "Enzyme", "text": [ "P450R" ], "offsets": [ [ 858, 863 ] ], "normalized": [] }, { "id": "PMID-10048323_T26", "type": "Nucleotide", "text": [ "FMN" ], "offsets": [ [ 864, 867 ] ], "normalized": [] }, { "id": "PMID-10048323_T28", "type": "Nucleotide", "text": [ "FMN" ], "offsets": [ [ 916, 919 ] ], "normalized": [] }, { "id": "PMID-10048323_T29", "type": "Protein", "text": [ "protein" ], "offsets": [ [ 928, 935 ] ], "normalized": [] }, { "id": "PMID-10048323_T30", "type": "Nucleotide", "text": [ "FMN" ], "offsets": [ [ 990, 993 ] ], "normalized": [] }, { "id": "PMID-10048323_T31", "type": "BindingSiteOfProtein", "text": [ "binding site" ], "offsets": [ [ 994, 1006 ] ], "normalized": [] }, { "id": "PMID-10048323_T32", "type": "Enzyme", "text": [ "P450R" ], "offsets": [ [ 1012, 1017 ] ], "normalized": [] }, { "id": "PMID-10048323_T33", "type": "Nucleotide", "text": [ "FMN" ], "offsets": [ [ 1018, 1021 ] ], "normalized": [] }, { "id": "PMID-10048323_T34", "type": "Enzyme", "text": [ "cytochrome P450" ], "offsets": [ [ 1141, 1156 ] ], "normalized": [] }, { "id": "PMID-10048323_T35", "type": "Nucleotide", "text": [ "FMN" ], "offsets": [ [ 1199, 1202 ] ], "normalized": [] }, { "id": "PMID-10048323_T36", "type": "Nucleotide", "text": [ "FMN" ], "offsets": [ [ 1237, 1240 ] ], "normalized": [] }, { "id": "PMID-10048323_T37", "type": "Protein", "text": [ "cytochrome c" ], "offsets": [ [ 1339, 1351 ] ], "normalized": [] }, { "id": "PMID-10048323_T40", "type": "Protein", "text": [ "cytochrome P450" ], "offsets": [ [ 1522, 1537 ] ], "normalized": [] }, { "id": "PMID-10048323_T41", "type": "Protein", "text": [ "cytochrome c" ], "offsets": [ [ 1542, 1554 ] ], "normalized": [] }, { "id": "PMID-10048323_T42", "type": "ThreeDimensionalMolecularStructure", "text": [ "crystal structure" ], "offsets": [ [ 105, 122 ] ], "normalized": [] }, { "id": "PMID-10048323_T15", "type": "Enzyme", "text": [ "cytochrome P450 monooxygenase system" ], "offsets": [ [ 226, 262 ] ], "normalized": [] }, { "id": "PMID-10048323_T43", "type": "OrganicChemical", "text": [ "flavodoxins" ], "offsets": [ [ 704, 715 ] ], "normalized": [] }, { "id": "PMID-10048323_T44", "type": "Prokaryote", "text": [ "bacterial" ], "offsets": [ [ 694, 703 ] ], "normalized": [] }, { "id": "PMID-10048323_T45", "type": "OrganicChemical", "text": [ "flavodoxins" ], "offsets": [ [ 872, 883 ] ], "normalized": [] }, { "id": "PMID-10048323_T48", "type": "Substrate", "text": [ "substrate" ], "offsets": [ [ 1442, 1451 ] ], "normalized": [] } ]

[ { "id": "PMID-10048323_E1", "type": "BindingToProtein", "trigger": { "text": [ "binding" ], "offsets": [ [ 29, 36 ] ] }, "arguments": [ { "role": "hasPatient", "ref_id": "PMID-10048323_T4" }, { "role": "hasPatient2", "ref_id": "PMID-10048323_T2" } ] }, { "id": "PMID-10048323_E2", "type": "BindingToProtein", "trigger": { "text": [ "binding" ], "offsets": [ [ 134, 141 ] ] }, "arguments": [ { "role": "hasPatient", "ref_id": "PMID-10048323_T9" }, { "role": "hasPatient2", "ref_id": "PMID-10048323_T7" } ] }, { "id": "PMID-10048323_E3", "type": "BindingToProtein", "trigger": { "text": [ "interactions" ], "offsets": [ [ 891, 903 ] ] }, "arguments": [ { "role": "hasPatient", "ref_id": "PMID-10048323_T29" }, { "role": "hasPatient2", "ref_id": "PMID-10048323_T28" } ] }, { "id": "PMID-10048323_E4", "type": "Binding", "trigger": { "text": [ "binding" ], "offsets": [ [ 1452, 1459 ] ] }, "arguments": [ { "role": "hasPatient", "ref_id": "PMID-10048323_T48" } ] }, { "id": "PMID-10048323_E5", "type": "BindingToProtein", "trigger": { "text": [ "binding" ], "offsets": [ [ 1514, 1521 ] ] }, "arguments": [ { "role": "hasPatient", "ref_id": "PMID-10048323_T40" }, { "role": "hasPatient2", "ref_id": "PMID-10048323_T41" } ] }, { "id": "PMID-10048323_E6", "type": "MetabolicPathway", "trigger": { "text": [ "electron transfer" ], "offsets": [ [ 1172, 1189 ] ] }, "arguments": [ { "role": "hasAgent", "ref_id": "PMID-10048323_T34" } ] }, { "id": "PMID-10048323_E7", "type": "MetabolicPathway", "trigger": { "text": [ "electron transfer" ], "offsets": [ [ 1303, 1320 ] ] }, "arguments": [] } ]

[]

[ { "id": "PMID-10048323_R1", "type": "fromSpecies", "arg1_id": "PMID-10048323_T6", "arg2_id": "PMID-10048323_T5", "normalized": [] }, { "id": "PMID-10048323_R2", "type": "hasPart", "arg1_id": "PMID-10048323_T6", "arg2_id": "PMID-10048323_T4", "normalized": [] }, { "id": "PMID-10048323_R3", "type": "fromSpecies", "arg1_id": "PMID-10048323_T12", "arg2_id": "PMID-10048323_T10", "normalized": [] }, { "id": "PMID-10048323_R4", "type": "hasPart", "arg1_id": "PMID-10048323_T12", "arg2_id": "PMID-10048323_T9", "normalized": [] }, { "id": "PMID-10048323_R5", "type": "fromSpecies", "arg1_id": "PMID-10048323_T18", "arg2_id": "PMID-10048323_T17", "normalized": [] }, { "id": "PMID-10048323_R7", "type": "hasPart", "arg1_id": "PMID-10048323_T18", "arg2_id": "PMID-10048323_T16", "normalized": [] }, { "id": "PMID-10048323_R8", "type": "fromSpecies", "arg1_id": "PMID-10048323_T43", "arg2_id": "PMID-10048323_T44", "normalized": [] } ]

[ { "id": "PMID-10049357__text", "type": "abstract", "text": [ "Ski is a component of the histone deacetylase complex required for transcriptional repression by Mad and thyroid hormone receptor. The N-CoR/SMRT complex containing mSin3 and histone deacetylase (HDAC) mediates transcriptional repression by nuclear hormone receptors and Mad. The proteins encoded by the ski proto-oncogene family directly bind to N-CoR/SMRT and mSin3A, and forms a complex with HDAC. c-Ski and its related gene product Sno are required for transcriptional repression by Mad and thyroid hormone receptor (TRbeta). The oncogenic form, v-Ski, which lacks the mSin3A-binding domain, acts in a dominant-negative fashion, and abrogates transcriptional repression by Mad and TRbeta. In ski-deficient mouse embryos, the ornithine decarboxylase gene, whose expression is normally repressed by Mad-Max, is expressed ectopically. These results show that Ski is a component of the HDAC complex and that Ski is required for the transcriptional repression mediated by this complex. The involvement of c-Ski in the HDAC complex indicates that the function of the HDAC complex is important for oncogenesis.\n" ], "offsets": [ [ 0, 1108 ] ] } ]

[ { "id": "PMID-10049357_T1", "type": "Protein", "text": [ "Ski" ], "offsets": [ [ 0, 3 ] ], "normalized": [] }, { "id": "PMID-10049357_T2", "type": "Enzyme", "text": [ "histone deacetylase complex" ], "offsets": [ [ 26, 53 ] ], "normalized": [] }, { "id": "PMID-10049357_T6", "type": "Protein", "text": [ "Mad" ], "offsets": [ [ 97, 100 ] ], "normalized": [] }, { "id": "PMID-10049357_T9", "type": "ProteinComplex", "text": [ "N-CoR/SMRT complex" ], "offsets": [ [ 135, 153 ] ], "normalized": [] }, { "id": "PMID-10049357_T10", "type": "Protein", "text": [ "mSin3" ], "offsets": [ [ 165, 170 ] ], "normalized": [] }, { "id": "PMID-10049357_T11", "type": "Enzyme", "text": [ "histone deacetylase" ], "offsets": [ [ 175, 194 ] ], "normalized": [] }, { "id": "PMID-10049357_T13", "type": "Enzyme", "text": [ "HDAC" ], "offsets": [ [ 196, 200 ] ], "normalized": [] }, { "id": "PMID-10049357_T20", "type": "Protein", "text": [ "Mad" ], "offsets": [ [ 271, 274 ] ], "normalized": [] }, { "id": "PMID-10049357_T21", "type": "Protein", "text": [ "proteins" ], "offsets": [ [ 280, 288 ] ], "normalized": [] }, { "id": "PMID-10049357_T22", "type": "Gene", "text": [ "ski proto-oncogene" ], "offsets": [ [ 304, 322 ] ], "normalized": [] }, { "id": "PMID-10049357_T24", "type": "Protein", "text": [ "N-CoR/SMRT" ], "offsets": [ [ 347, 357 ] ], "normalized": [] }, { "id": "PMID-10049357_T25", "type": "Protein", "text": [ "mSin3A" ], "offsets": [ [ 362, 368 ] ], "normalized": [] }, { "id": "PMID-10049357_T26", "type": "ProteinComplex", "text": [ "complex" ], "offsets": [ [ 382, 389 ] ], "normalized": [] }, { "id": "PMID-10049357_T27", "type": "Enzyme", "text": [ "HDAC" ], "offsets": [ [ 395, 399 ] ], "normalized": [] }, { "id": "PMID-10049357_T28", "type": "Protein", "text": [ "c-Ski" ], "offsets": [ [ 401, 406 ] ], "normalized": [] }, { "id": "PMID-10049357_T29", "type": "GeneProduct", "text": [ "gene product" ], "offsets": [ [ 423, 435 ] ], "normalized": [] }, { "id": "PMID-10049357_T30", "type": "Protein", "text": [ "Sno" ], "offsets": [ [ 436, 439 ] ], "normalized": [] }, { "id": "PMID-10049357_T33", "type": "Protein", "text": [ "Mad" ], "offsets": [ [ 487, 490 ] ], "normalized": [] }, { "id": "PMID-10049357_T36", "type": "Protein", "text": [ "TRbeta" ], "offsets": [ [ 521, 527 ] ], "normalized": [] }, { "id": "PMID-10049357_T37", "type": "Protein", "text": [ "v-Ski" ], "offsets": [ [ 550, 555 ] ], "normalized": [] }, { "id": "PMID-10049357_T38", "type": "Protein", "text": [ "mSin3A" ], "offsets": [ [ 573, 579 ] ], "normalized": [] }, { "id": "PMID-10049357_T40", "type": "ProteinDomain", "text": [ "domain" ], "offsets": [ [ 588, 594 ] ], "normalized": [] }, { "id": "PMID-10049357_T44", "type": "Protein", "text": [ "Mad" ], "offsets": [ [ 677, 680 ] ], "normalized": [] }, { "id": "PMID-10049357_T45", "type": "Protein", "text": [ "TRbeta" ], "offsets": [ [ 685, 691 ] ], "normalized": [] }, { "id": "PMID-10049357_T46", "type": "Gene", "text": [ "ski" ], "offsets": [ [ 696, 699 ] ], "normalized": [] }, { "id": "PMID-10049357_T47", "type": "Eukaryote", "text": [ "mouse" ], "offsets": [ [ 710, 715 ] ], "normalized": [] }, { "id": "PMID-10049357_T48", "type": "LivingEntity", "text": [ "embryos" ], "offsets": [ [ 716, 723 ] ], "normalized": [] }, { "id": "PMID-10049357_T49", "type": "Enzyme", "text": [ "ornithine decarboxylase" ], "offsets": [ [ 729, 752 ] ], "normalized": [] }, { "id": "PMID-10049357_T50", "type": "Gene", "text": [ "gene" ], "offsets": [ [ 753, 757 ] ], "normalized": [] }, { "id": "PMID-10049357_T53", "type": "Protein", "text": [ "Mad" ], "offsets": [ [ 801, 804 ] ], "normalized": [] }, { "id": "PMID-10049357_T54", "type": "Protein", "text": [ "Max" ], "offsets": [ [ 805, 808 ] ], "normalized": [] }, { "id": "PMID-10049357_T56", "type": "Protein", "text": [ "Ski" ], "offsets": [ [ 860, 863 ] ], "normalized": [] }, { "id": "PMID-10049357_T57", "type": "Enzyme", "text": [ "HDAC complex" ], "offsets": [ [ 886, 898 ] ], "normalized": [] }, { "id": "PMID-10049357_T58", "type": "Protein", "text": [ "Ski" ], "offsets": [ [ 908, 911 ] ], "normalized": [] }, { "id": "PMID-10049357_T62", "type": "ProteinComplex", "text": [ "this complex" ], "offsets": [ [ 971, 983 ] ], "normalized": [] }, { "id": "PMID-10049357_T63", "type": "Protein", "text": [ "c-Ski" ], "offsets": [ [ 1004, 1009 ] ], "normalized": [] }, { "id": "PMID-10049357_T64", "type": "Enzyme", "text": [ "HDAC complex" ], "offsets": [ [ 1017, 1029 ] ], "normalized": [] }, { "id": "PMID-10049357_T65", "type": "Enzyme", "text": [ "HDAC complex" ], "offsets": [ [ 1065, 1077 ] ], "normalized": [] }, { "id": "PMID-10049357_T4", "type": "Protein", "text": [ "thyroid hormone receptor" ], "offsets": [ [ 105, 129 ] ], "normalized": [] }, { "id": "PMID-10049357_T7", "type": "Protein", "text": [ "nuclear hormone receptors" ], "offsets": [ [ 241, 266 ] ], "normalized": [] }, { "id": "PMID-10049357_T12", "type": "Protein", "text": [ "thyroid hormone receptor" ], "offsets": [ [ 495, 519 ] ], "normalized": [] } ]

[ { "id": "PMID-10049357_E3", "type": "RegulatoryProcess", "trigger": { "text": [ "mediates" ], "offsets": [ [ 202, 210 ] ] }, "arguments": [ { "role": "hasAgent", "ref_id": "PMID-10049357_T9" }, { "role": "hasPatient", "ref_id": "PMID-10049357_E2" } ] }, { "id": "PMID-10049357_E6", "type": "BindingToProtein", "trigger": { "text": [ "bind" ], "offsets": [ [ 339, 343 ] ] }, "arguments": [ { "role": "hasPatient", "ref_id": "PMID-10049357_T24" }, { "role": "hasPatient2", "ref_id": "PMID-10049357_T25" }, { "role": "hasPatient3", "ref_id": "PMID-10049357_T21" } ] }, { "id": "PMID-10049357_E9", "type": "BindingToProtein", "trigger": { "text": [ "binding" ], "offsets": [ [ 580, 587 ] ] }, "arguments": [ { "role": "hasPatient", "ref_id": "PMID-10049357_T38" }, { "role": "hasPatient2", "ref_id": "PMID-10049357_T40" } ] }, { "id": "PMID-10049357_E10", "type": "NegativeRegulation", "trigger": { "text": [ "abrogates" ], "offsets": [ [ 637, 646 ] ] }, "arguments": [ { "role": "hasAgent", "ref_id": "PMID-10049357_T37" }, { "role": "hasPatient", "ref_id": "PMID-10049357_E5" } ] }, { "id": "PMID-10049357_E13", "type": "GeneExpression", "trigger": { "text": [ "expression" ], "offsets": [ [ 765, 775 ] ] }, "arguments": [ { "role": "hasPatient", "ref_id": "PMID-10049357_T49" } ] }, { "id": "PMID-10049357_E14", "type": "NegativeRegulation", "trigger": { "text": [ "repressed" ], "offsets": [ [ 788, 797 ] ] }, "arguments": [ { "role": "hasPatient", "ref_id": "PMID-10049357_E13" }, { "role": "hasAgent", "ref_id": "PMID-10049357_T53" } ] }, { "id": "PMID-10049357_E15", "type": "GeneExpression", "trigger": { "text": [ "expressed" ], "offsets": [ [ 813, 822 ] ] }, "arguments": [ { "role": "hasPatient", "ref_id": "PMID-10049357_T49" } ] }, { "id": "PMID-10049357_E18", "type": "RegulatoryProcess", "trigger": { "text": [ "mediated" ], "offsets": [ [ 959, 967 ] ] }, "arguments": [ { "role": "hasAgent", "ref_id": "PMID-10049357_T62" }, { "role": "hasPatient", "ref_id": "PMID-10049357_E7" } ] }, { "id": "PMID-10049357_E1", "type": "NegativeRegulationOfTranscription", "trigger": { "text": [ "transcriptional repression" ], "offsets": [ [ 67, 93 ] ] }, "arguments": [ { "role": "hasAgent", "ref_id": "PMID-10049357_T6" } ] }, { "id": "PMID-10049357_E2", "type": "NegativeRegulationOfTranscription", "trigger": { "text": [ "transcriptional repression" ], "offsets": [ [ 211, 237 ] ] }, "arguments": [ { "role": "hasAgent", "ref_id": "PMID-10049357_T7" } ] }, { "id": "PMID-10049357_E4", "type": "NegativeRegulationOfTranscription", "trigger": { "text": [ "transcriptional repression" ], "offsets": [ [ 457, 483 ] ] }, "arguments": [ { "role": "hasAgent", "ref_id": "PMID-10049357_T33" } ] }, { "id": "PMID-10049357_E5", "type": "NegativeRegulationOfTranscription", "trigger": { "text": [ "transcriptional repression" ], "offsets": [ [ 647, 673 ] ] }, "arguments": [ { "role": "hasAgent", "ref_id": "PMID-10049357_T44" } ] }, { "id": "PMID-10049357_E7", "type": "NegativeRegulationOfTranscription", "trigger": { "text": [ "transcriptional repression" ], "offsets": [ [ 932, 958 ] ] }, "arguments": [] }, { "id": "PMID-10049357_E8", "type": "NegativeRegulationOfTranscription", "trigger": { "text": [ "transcriptional repression" ], "offsets": [ [ 67, 93 ] ] }, "arguments": [ { "role": "hasAgent", "ref_id": "PMID-10049357_T4" } ] }, { "id": "PMID-10049357_E11", "type": "NegativeRegulationOfTranscription", "trigger": { "text": [ "transcriptional repression" ], "offsets": [ [ 211, 237 ] ] }, "arguments": [ { "role": "hasAgent", "ref_id": "PMID-10049357_T20" } ] }, { "id": "PMID-10049357_E12", "type": "NegativeRegulationOfTranscription", "trigger": { "text": [ "transcriptional repression" ], "offsets": [ [ 457, 483 ] ] }, "arguments": [ { "role": "hasAgent", "ref_id": "PMID-10049357_T12" } ] }, { "id": "PMID-10049357_E16", "type": "NegativeRegulationOfTranscription", "trigger": { "text": [ "transcriptional repression" ], "offsets": [ [ 647, 673 ] ] }, "arguments": [ { "role": "hasAgent", "ref_id": "PMID-10049357_T45" } ] }, { "id": "PMID-10049357_E17", "type": "NegativeRegulation", "trigger": { "text": [ "repressed" ], "offsets": [ [ 788, 797 ] ] }, "arguments": [ { "role": "hasPatient", "ref_id": "PMID-10049357_E13" }, { "role": "hasAgent", "ref_id": "PMID-10049357_T54" } ] }, { "id": "PMID-10049357_E19", "type": "NegativeRegulation", "trigger": { "text": [ "abrogates" ], "offsets": [ [ 637, 646 ] ] }, "arguments": [ { "role": "hasAgent", "ref_id": "PMID-10049357_T37" }, { "role": "hasPatient", "ref_id": "PMID-10049357_E16" } ] }, { "id": "PMID-10049357_E20", "type": "RegulatoryProcess", "trigger": { "text": [ "mediates" ], "offsets": [ [ 202, 210 ] ] }, "arguments": [ { "role": "hasAgent", "ref_id": "PMID-10049357_T9" }, { "role": "hasPatient", "ref_id": "PMID-10049357_E11" } ] } ]

[]

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[ { "id": "PMID-10049579__text", "type": "abstract", "text": [ "Cloning and characterization of two cytoplasmic dynein intermediate chain genes in mouse and human. Cytoplasmic dynein is a large multisubunit microtubule-based motor protein, which mediates movement of numerous intracellular organelles. We report here the identification of the human homologue of cytoplasmic dynein intermediate chain 1 gene (DNCI1) located on human chromosome 7q21.3-q22.1. The mouse orthologue (Dnci1) was identified along with another highly related gene, Dnci2, and their RNA in situ expression patterns were examined during mouse embryogenesis. Dnci1 was found to have a highly restricted expression domain in the developing forebrain as well as the peripheral nervous system (PNS), while Dnci2 displayed a broad expression profile throughout the entire central nervous system and most of the PNS. A dynamic expression profile was also found for Dnci2 in the developing mouse limb bud. The data presented here provide a framework for the further analysis of the functional role of Dnci1 and Dnci2 in mouse and DNCI1 in human.\n" ], "offsets": [ [ 0, 1049 ] ] } ]

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[]

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[ { "id": "PMID-10049581__text", "type": "abstract", "text": [ "Identification and characterization of the human homologue (RAI2) of a mouse retinoic acid-induced gene in Xp22. We have identified a novel human gene during studies of a 1.3-Mb region of Xp22 between DXS418 and DXS999. A PAC contig spanning the region was constructed, sequenced, and analyzed by gene and exon prediction programs and by homology searches. Further investigation of predicted exons from PAC clone 389A20 led to the identification of a single-exon gene, designated RAI2 (retinoic acid-induced 2). RAI2 mapped 28 kb centromeric to marker DXS7996, between DXS7996 and DXS7997, and was transcribed from centromere to telomere. Northern blot analysis and reverse transcription-polymerase chain reaction analysis revealed expression of a 2.5-kb transcript in four fetal tissues (brain, lung, kidney, and heart) and eight adult tissues (heart, brain, placenta, lung, skeletal muscle, kidney, pancreas, and retina) but not in fetal or adult liver. The 530-amino-acid protein (57 kDa predicted mass) displays 94% homology with a mouse retinoic acid-induced gene product and contains a novel proline-rich (39%) domain of 68 amino acids. Retinoic acid is involved in vertebrate anteroposterior axis formation and cellular differentiation and has been shown to modulate gene expression controlling early embryonal development, suggesting a developmental role for RAI2. RAI2 remains a candidate gene for diseases mapping to the Xp22 region.\n" ], "offsets": [ [ 0, 1444 ] ] } ]

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"offsets": [ [ 306, 310 ] ], "normalized": [] }, { "id": "PMID-10049581_T12", "type": "Exon", "text": [ "exons" ], "offsets": [ [ 392, 397 ] ], "normalized": [] }, { "id": "PMID-10049581_T13", "type": "Exon", "text": [ "exon" ], "offsets": [ [ 458, 462 ] ], "normalized": [] }, { "id": "PMID-10049581_T14", "type": "Gene", "text": [ "gene" ], "offsets": [ [ 463, 467 ] ], "normalized": [] }, { "id": "PMID-10049581_T15", "type": "Gene", "text": [ "RAI2" ], "offsets": [ [ 480, 484 ] ], "normalized": [] }, { "id": "PMID-10049581_T16", "type": "Gene", "text": [ "retinoic acid-induced 2" ], "offsets": [ [ 486, 509 ] ], "normalized": [] }, { "id": "PMID-10049581_T17", "type": "Gene", "text": [ "RAI2" ], "offsets": [ [ 512, 516 ] ], "normalized": [] }, { "id": "PMID-10049581_T20", "type": "Transcript", "text": [ "transcript" ], "offsets": [ [ 755, 765 ] ], "normalized": [] }, { "id": "PMID-10049581_T21", "type": "Tissue", "text": [ "fetal tissues" ], "offsets": [ [ 774, 787 ] ], "normalized": [] }, { "id": "PMID-10049581_T22", "type": "Tissue", "text": [ "brain" ], "offsets": [ [ 789, 794 ] ], "normalized": [] }, { "id": "PMID-10049581_T23", "type": "Tissue", "text": [ "lung" ], "offsets": [ [ 796, 800 ] ], "normalized": [] }, { "id": "PMID-10049581_T24", "type": "Tissue", "text": [ "kidney" ], "offsets": [ [ 802, 808 ] ], "normalized": [] }, { "id": "PMID-10049581_T25", "type": "Tissue", "text": [ "heart" ], "offsets": [ [ 814, 819 ] ], "normalized": [] }, { "id": "PMID-10049581_T26", "type": "Tissue", "text": [ "adult tissues" ], "offsets": [ [ 831, 844 ] ], "normalized": [] }, { "id": "PMID-10049581_T27", "type": "Tissue", "text": [ "heart" ], "offsets": [ [ 846, 851 ] ], "normalized": [] }, { "id": "PMID-10049581_T28", "type": "Tissue", "text": [ "brain" ], "offsets": [ [ 853, 858 ] ], "normalized": [] }, { "id": "PMID-10049581_T29", "type": "Tissue", "text": [ "placenta" ], "offsets": [ [ 860, 868 ] ], "normalized": [] }, { "id": "PMID-10049581_T30", "type": "Tissue", "text": [ "lung" ], "offsets": [ [ 870, 874 ] ], "normalized": [] }, { "id": "PMID-10049581_T31", "type": "Tissue", "text": [ "skeletal muscle" ], "offsets": [ [ 876, 891 ] ], "normalized": [] }, { "id": "PMID-10049581_T32", "type": "Tissue", "text": [ "kidney" ], "offsets": [ [ 893, 899 ] ], "normalized": [] }, { "id": "PMID-10049581_T33", "type": "Tissue", "text": [ "pancreas" ], "offsets": [ [ 901, 909 ] ], "normalized": [] }, { "id": "PMID-10049581_T34", "type": "Tissue", "text": [ "retina" ], "offsets": [ [ 915, 921 ] ], "normalized": [] }, { "id": "PMID-10049581_T35", "type": "Tissue", "text": [ "adult liver" ], "offsets": [ [ 943, 954 ] ], "normalized": [] }, { "id": "PMID-10049581_T36", "type": "AminoAcid", "text": [ "amino-acid" ], "offsets": [ [ 964, 974 ] ], "normalized": [] }, { "id": "PMID-10049581_T37", "type": "Protein", "text": [ "protein" ], "offsets": [ [ 975, 982 ] ], "normalized": [] }, { "id": "PMID-10049581_T38", "type": "Eukaryote", "text": [ "mouse" ], "offsets": [ [ 1036, 1041 ] ], "normalized": [] }, { "id": "PMID-10049581_T40", "type": "GeneProduct", "text": [ "gene product" ], "offsets": [ [ 1064, 1076 ] ], "normalized": [] }, { "id": "PMID-10049581_T41", "type": "ProteinDomain", "text": [ "domain" ], "offsets": [ [ 1117, 1123 ] ], "normalized": [] }, { "id": "PMID-10049581_T42", "type": "AminoAcid", "text": [ "amino acids" ], "offsets": [ [ 1130, 1141 ] ], "normalized": [] }, { "id": "PMID-10049581_T43", "type": "Chemical", "text": [ "Retinoic acid" ], "offsets": [ [ 1143, 1156 ] ], "normalized": [] }, { "id": "PMID-10049581_T46", "type": "Gene", "text": [ "RAI2" ], "offsets": [ [ 1367, 1371 ] ], "normalized": [] }, { "id": "PMID-10049581_T47", "type": "Gene", "text": [ "RAI2" ], "offsets": [ [ 1373, 1377 ] ], "normalized": [] }, { "id": "PMID-10049581_T48", "type": "Gene", "text": [ "gene" ], "offsets": [ [ 1398, 1402 ] ], "normalized": [] }, { "id": "PMID-10049581_T49", "type": "Chromosome", "text": [ "Xp22" ], "offsets": [ [ 1431, 1435 ] ], "normalized": [] }, { "id": "PMID-10049581_T51", "type": "SequenceHomologyAnalysis", "text": [ "homology searches" ], "offsets": [ [ 338, 355 ] ], "normalized": [] }, { "id": "PMID-10049581_T4", "type": "Gene", "text": [ "retinoic acid-induced gene" ], "offsets": [ [ 77, 103 ] ], "normalized": [] }, { "id": "PMID-10049581_T5", "type": "Gene", "text": [ "retinoic acid-induced" ], "offsets": [ [ 1042, 1063 ] ], "normalized": [] } ]

[ { "id": "PMID-10049581_E1", "type": "Transcription", "trigger": { "text": [ "transcribed" ], "offsets": [ [ 598, 609 ] ] }, "arguments": [] }, { "id": "PMID-10049581_E2", "type": "GeneExpression", "trigger": { "text": [ "expression" ], "offsets": [ [ 732, 742 ] ] }, "arguments": [ { "role": "hasPatient", "ref_id": "PMID-10049581_T20" } ] }, { "id": "PMID-10049581_E3", "type": "RegulatoryProcess", "trigger": { "text": [ "modulate" ], "offsets": [ [ 1265, 1273 ] ] }, "arguments": [ { "role": "hasPatient", "ref_id": "PMID-10049581_E4" } ] }, { "id": "PMID-10049581_E4", "type": "GeneExpression", "trigger": { "text": [ "gene expression" ], "offsets": [ [ 1274, 1289 ] ] }, "arguments": [] }, { "id": "PMID-10049581_E5", "type": "DevelopmentalProcess", "trigger": { "text": [ "vertebrate anteroposterior axis formation" ], "offsets": [ [ 1172, 1213 ] ] }, "arguments": [] }, { "id": "PMID-10049581_E6", "type": "CellDifferentiation", "trigger": { "text": [ "cellular differentiation" ], "offsets": [ [ 1218, 1242 ] ] }, "arguments": [] }, { "id": "PMID-10049581_E7", "type": "RegulatoryProcess", "trigger": { "text": [ "controlling early" ], "offsets": [ [ 1290, 1307 ] ] }, "arguments": [ { "role": "hasAgent", "ref_id": "PMID-10049581_E4" }, { "role": "hasPatient", "ref_id": "PMID-10049581_E8" } ] }, { "id": "PMID-10049581_E8", "type": "DevelopmentalProcess", "trigger": { "text": [ "embryonal development" ], "offsets": [ [ 1308, 1329 ] ] }, "arguments": [] }, { "id": "PMID-10049581_E9", "type": "Disease", "trigger": { "text": [ "diseases" ], "offsets": [ [ 1407, 1415 ] ] }, "arguments": [] } ]

[]

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[ { "id": "PMID-10049584__text", "type": "abstract", "text": [ "GPR56, a novel secretin-like human G-protein-coupled receptor gene. A novel gene product, GPR56, with homology to the seven transmembrane-domain receptor superfamily, has been cloned by PCR amplification using degenerate oligonucleotide primers and subsequent screening of a human heart cDNA library. The isolated 2.8-kb cDNA clone encodes a protein of 693 amino acids that shows highest identity (32%) to HE6, a member of a subclass of the class B secretin-like G-protein-coupled receptors. Northern analysis of various human tissues revealed a wide distribution of the transcript with highest levels found in thyroid gland, brain, and heart. In situ hybridization analysis of human thyroid gland as well as rat heart and brain tissue confirms these results and identifies the hippocampus and hypothalamic nuclei as brain areas with particularly high expression of GPR56 mRNA. The high level of mRNA expression, its wide distribution, and the mucin-like extracellular domain of the receptor protein suggest a possible role for this receptor in cell-cell interaction processes. The human gene for GPR56 has been isolated and its exon-intron structure determined. The total length of the human GPR56 gene is approximately 15 kb, and it consists of 13 exons. Fluorescence in situ hybridization, PCR analysis of somatic cell hybrids, and interspecific mouse backcross mapping have localized the genes to human chromosome 16q13 and mouse chromosome 8.\n" ], "offsets": [ [ 0, 1448 ] ] } ]

[ { "id": "PMID-10049584_T1", "type": "Gene", "text": [ "GPR56" ], "offsets": [ [ 0, 5 ] ], "normalized": [] }, { "id": "PMID-10049584_T2", "type": "Protein", "text": [ "secretin" ], "offsets": [ [ 15, 23 ] ], "normalized": [] }, { "id": "PMID-10049584_T3", "type": "Eukaryote", "text": [ "human" ], "offsets": [ [ 29, 34 ] ], "normalized": [] }, { "id": "PMID-10049584_T7", "type": "GeneProduct", "text": [ "gene product" ], "offsets": [ [ 76, 88 ] ], "normalized": [] }, { "id": "PMID-10049584_T8", "type": "Protein", "text": [ "GPR56" ], "offsets": [ [ 90, 95 ] ], "normalized": [] }, { "id": "PMID-10049584_T11", "type": "Eukaryote", "text": [ "human" ], "offsets": [ [ 275, 280 ] ], "normalized": [] }, { "id": "PMID-10049584_T12", "type": "Tissue", "text": [ "heart" ], "offsets": [ [ 281, 286 ] ], "normalized": [] }, { "id": "PMID-10049584_T13", "type": "DNA", "text": [ "cDNA" ], "offsets": [ [ 287, 291 ] ], "normalized": [] }, { "id": "PMID-10049584_T14", "type": "DNA", "text": [ "cDNA" ], "offsets": [ [ 321, 325 ] ], "normalized": [] }, { "id": "PMID-10049584_T15", "type": "Protein", "text": [ "protein" ], "offsets": [ [ 342, 349 ] ], "normalized": [] }, { "id": "PMID-10049584_T16", "type": "AminoAcid", "text": [ "amino acids" ], "offsets": [ [ 357, 368 ] ], "normalized": [] }, { "id": "PMID-10049584_T17", "type": "Protein", "text": [ "HE6" ], "offsets": [ [ 406, 409 ] ], "normalized": [] }, { "id": "PMID-10049584_T21", "type": "Eukaryote", "text": [ "human" ], "offsets": [ [ 521, 526 ] ], "normalized": [] }, { "id": "PMID-10049584_T22", "type": "Tissue", "text": [ "tissues" ], "offsets": [ [ 527, 534 ] ], "normalized": [] }, { "id": "PMID-10049584_T23", "type": "Transcript", "text": [ "transcript" ], "offsets": [ [ 571, 581 ] ], "normalized": [] }, { "id": "PMID-10049584_T24", "type": "Tissue", "text": [ "thyroid gland" ], "offsets": [ [ 611, 624 ] ], "normalized": [] }, { "id": "PMID-10049584_T25", "type": "Tissue", "text": [ "brain" ], "offsets": [ [ 626, 631 ] ], "normalized": [] }, { "id": "PMID-10049584_T26", "type": "Tissue", "text": [ "heart" ], "offsets": [ [ 637, 642 ] ], "normalized": [] }, { "id": "PMID-10049584_T27", "type": "Eukaryote", "text": [ "human" ], "offsets": [ [ 678, 683 ] ], "normalized": [] }, { "id": "PMID-10049584_T28", "type": "Tissue", "text": [ "thyroid gland" ], "offsets": [ [ 684, 697 ] ], "normalized": [] }, { "id": "PMID-10049584_T29", "type": "Eukaryote", "text": [ "rat" ], "offsets": [ [ 709, 712 ] ], "normalized": [] }, { "id": "PMID-10049584_T30", "type": "Tissue", "text": [ "heart" ], "offsets": [ [ 713, 718 ] ], "normalized": [] }, { "id": "PMID-10049584_T31", "type": "Tissue", "text": [ "brain tissue" ], "offsets": [ [ 723, 735 ] ], "normalized": [] }, { "id": "PMID-10049584_T32", "type": "Tissue", "text": [ "hippocampus" ], "offsets": [ [ 778, 789 ] ], "normalized": [] }, { "id": "PMID-10049584_T33", "type": "Tissue", "text": [ "hypothalamic nuclei" ], "offsets": [ [ 794, 813 ] ], "normalized": [] }, { "id": "PMID-10049584_T34", "type": "Tissue", "text": [ "brain areas" ], "offsets": [ [ 817, 828 ] ], "normalized": [] }, { "id": "PMID-10049584_T36", "type": "Protein", "text": [ "GPR56" ], "offsets": [ [ 866, 871 ] ], "normalized": [] }, { "id": "PMID-10049584_T37", "type": "MessengerRNA", "text": [ "mRNA" ], "offsets": [ [ 872, 876 ] ], "normalized": [] }, { "id": "PMID-10049584_T38", "type": "MessengerRNA", "text": [ "mRNA" ], "offsets": [ [ 896, 900 ] ], "normalized": [] }, { "id": "PMID-10049584_T40", "type": "Protein", "text": [ "mucin" ], "offsets": [ [ 944, 949 ] ], "normalized": [] }, { "id": "PMID-10049584_T41", "type": "ProteinDomain", "text": [ "extracellular domain" ], "offsets": [ [ 955, 975 ] ], "normalized": [] }, { "id": "PMID-10049584_T42", "type": "Protein", "text": [ "receptor protein" ], "offsets": [ [ 983, 999 ] ], "normalized": [] }, { "id": "PMID-10049584_T43", "type": "Protein", "text": [ "receptor" ], "offsets": [ [ 1033, 1041 ] ], "normalized": [] }, { "id": "PMID-10049584_T47", "type": "Eukaryote", "text": [ "human" ], "offsets": [ [ 1082, 1087 ] ], "normalized": [] }, { "id": "PMID-10049584_T48", "type": "Gene", "text": [ "gene" ], "offsets": [ [ 1088, 1092 ] ], "normalized": [] }, { "id": "PMID-10049584_T49", "type": "Protein", "text": [ "GPR56" ], "offsets": [ [ 1097, 1102 ] ], "normalized": [] }, { "id": "PMID-10049584_T50", "type": "Exon", "text": [ "exon" ], "offsets": [ [ 1129, 1133 ] ], "normalized": [] }, { "id": "PMID-10049584_T51", "type": "Intron", "text": [ "intron" ], "offsets": [ [ 1134, 1140 ] ], "normalized": [] }, { "id": "PMID-10049584_T52", "type": "Eukaryote", "text": [ "human" ], "offsets": [ [ 1187, 1192 ] ], "normalized": [] }, { "id": "PMID-10049584_T53", "type": "Gene", "text": [ "GPR56 gene" ], "offsets": [ [ 1193, 1203 ] ], "normalized": [] }, { "id": "PMID-10049584_T54", "type": "Exon", "text": [ "exons" ], "offsets": [ [ 1250, 1255 ] ], "normalized": [] }, { "id": "PMID-10049584_T55", "type": "Cell", "text": [ "somatic cell" ], "offsets": [ [ 1309, 1321 ] ], "normalized": [] }, { "id": "PMID-10049584_T56", "type": "Eukaryote", "text": [ "mouse" ], "offsets": [ [ 1349, 1354 ] ], "normalized": [] }, { "id": "PMID-10049584_T57", "type": "Gene", "text": [ "genes" ], "offsets": [ [ 1392, 1397 ] ], "normalized": [] }, { "id": "PMID-10049584_T58", "type": "Eukaryote", "text": [ "human" ], "offsets": [ [ 1401, 1406 ] ], "normalized": [] }, { "id": "PMID-10049584_T59", "type": "Chromosome", "text": [ "chromosome" ], "offsets": [ [ 1407, 1417 ] ], "normalized": [] }, { "id": "PMID-10049584_T60", "type": "Eukaryote", "text": [ "mouse" ], "offsets": [ [ 1428, 1433 ] ], "normalized": [] }, { "id": "PMID-10049584_T61", "type": "Chromosome", "text": [ "chromosome" ], "offsets": [ [ 1434, 1444 ] ], "normalized": [] }, { "id": "PMID-10049584_T4", "type": "Gene", "text": [ "G-protein-coupled receptor gene" ], "offsets": [ [ 35, 66 ] ], "normalized": [] }, { "id": "PMID-10049584_T5", "type": "Protein", "text": [ "seven transmembrane-domain receptor" ], "offsets": [ [ 118, 153 ] ], "normalized": [] }, { "id": "PMID-10049584_T6", "type": "Protein", "text": [ "class B secretin-like G-protein-coupled receptors" ], "offsets": [ [ 441, 490 ] ], "normalized": [] } ]

[ { "id": "PMID-10049584_E2", "type": "TranscriptionOfGene", "trigger": { "text": [ "expression" ], "offsets": [ [ 901, 911 ] ] }, "arguments": [ { "role": "hasPatient", "ref_id": "PMID-10049584_T38" } ] }, { "id": "PMID-10049584_E1", "type": "PositiveRegulationOfTranscriptionOfGene", "trigger": { "text": [ "high expression" ], "offsets": [ [ 847, 862 ] ] }, "arguments": [ { "role": "hasPatient", "ref_id": "PMID-10049584_T37" } ] }, { "id": "PMID-10049584_E4", "type": "Increase", "trigger": { "text": [ "high level" ], "offsets": [ [ 882, 892 ] ] }, "arguments": [ { "role": "hasPatient", "ref_id": "PMID-10049584_E2" } ] }, { "id": "PMID-10049584_E3", "type": "CellularProcess", "trigger": { "text": [ "cell-cell interaction processes" ], "offsets": [ [ 1045, 1076 ] ] }, "arguments": [] } ]

[]

[ { "id": "PMID-10049584_R3", "type": "fromSpecies", "arg1_id": "PMID-10049584_T12", "arg2_id": "PMID-10049584_T11", "normalized": [] }, { "id": "PMID-10049584_R4", "type": "locatedIn", "arg1_id": "PMID-10049584_T13", "arg2_id": "PMID-10049584_T12", "normalized": [] }, { "id": "PMID-10049584_R5", "type": "encodes", "arg1_id": "PMID-10049584_T14", "arg2_id": "PMID-10049584_T15", "normalized": [] }, { "id": "PMID-10049584_R6", "type": "hasPart", "arg1_id": "PMID-10049584_T15", "arg2_id": "PMID-10049584_T16", "normalized": [] }, { "id": "PMID-10049584_R7", "type": "fromSpecies", "arg1_id": "PMID-10049584_T22", "arg2_id": "PMID-10049584_T21", "normalized": [] }, { "id": "PMID-10049584_R8", "type": "locatedIn", "arg1_id": "PMID-10049584_T23", "arg2_id": "PMID-10049584_T24", "normalized": [] }, { "id": "PMID-10049584_R9", "type": "locatedIn", "arg1_id": "PMID-10049584_T23", "arg2_id": "PMID-10049584_T25", "normalized": [] }, { "id": "PMID-10049584_R10", "type": "locatedIn", "arg1_id": "PMID-10049584_T23", "arg2_id": "PMID-10049584_T26", "normalized": [] }, { "id": "PMID-10049584_R11", "type": "fromSpecies", "arg1_id": "PMID-10049584_T28", "arg2_id": "PMID-10049584_T27", "normalized": [] }, { "id": "PMID-10049584_R12", "type": "fromSpecies", "arg1_id": "PMID-10049584_T30", "arg2_id": "PMID-10049584_T29", "normalized": [] }, { "id": "PMID-10049584_R13", "type": "fromSpecies", "arg1_id": "PMID-10049584_T31", "arg2_id": "PMID-10049584_T29", "normalized": [] }, { "id": "PMID-10049584_R17", "type": "encodes", "arg1_id": "PMID-10049584_T37", "arg2_id": "PMID-10049584_T36", "normalized": [] }, { "id": "PMID-10049584_R18", "type": "hasPart", "arg1_id": "PMID-10049584_T42", "arg2_id": "PMID-10049584_T41", "normalized": [] }, { "id": "PMID-10049584_R19", "type": "encodes", "arg1_id": "PMID-10049584_T48", "arg2_id": "PMID-10049584_T49", "normalized": [] }, { "id": "PMID-10049584_R20", "type": "fromSpecies", "arg1_id": "PMID-10049584_T48", "arg2_id": "PMID-10049584_T47", "normalized": [] }, { "id": "PMID-10049584_R21", "type": "hasPart", "arg1_id": "PMID-10049584_T53", "arg2_id": "PMID-10049584_T54", "normalized": [] }, { "id": "PMID-10049584_R22", "type": "fromSpecies", "arg1_id": "PMID-10049584_T53", "arg2_id": "PMID-10049584_T52", "normalized": [] }, { "id": "PMID-10049584_R23", "type": "locatedIn", "arg1_id": "PMID-10049584_T57", "arg2_id": "PMID-10049584_T59", "normalized": [] }, { "id": "PMID-10049584_R24", "type": "locatedIn", "arg1_id": "PMID-10049584_T57", "arg2_id": "PMID-10049584_T61", "normalized": [] }, { "id": "PMID-10049584_R25", "type": "fromSpecies", "arg1_id": "PMID-10049584_T59", "arg2_id": "PMID-10049584_T58", "normalized": [] }, { "id": "PMID-10049584_R26", "type": "fromSpecies", "arg1_id": "PMID-10049584_T61", "arg2_id": "PMID-10049584_T60", "normalized": [] }, { "id": "PMID-10049584_R1", "type": "fromSpecies", "arg1_id": "PMID-10049584_T4", "arg2_id": "PMID-10049584_T3", "normalized": [] }, { "id": "PMID-10049584_R16", "type": "hasPart", "arg1_id": "PMID-10049584_T48", "arg2_id": "PMID-10049584_T50", "normalized": [] }, { "id": "PMID-10049584_R27", "type": "hasPart", "arg1_id": "PMID-10049584_T48", "arg2_id": "PMID-10049584_T51", "normalized": [] } ]

[ { "id": "PMID-10049693__text", "type": "abstract", "text": [ "The LIM proteins FHL1 and FHL3 are expressed differently in skeletal muscle. We have determined the complete mRNA sequence of FHL3 (formerly SLIM2). We have confirmed that it is a member of the family of LIM proteins that share a similar secondary protein structure, renamed as Four-and-a-Half-LIM domain (or FHL) proteins in accordance with this structure. The \"half-LIM\" domain is a single zinc finger domain that may represent a subfamily of LIM domains and defines this particular family of LIM proteins. The distribution of FHL mRNA expression within a variety of murine tissues is complex. Both FHL1 and FHL3 were expressed in a number of skeletal muscles while FHL2 was expressed at high levels in cardiac muscle. Localisation of FHL3 to human chromosome 1 placed this gene in the proximity of, but not overlapping with, alleles associated with muscle diseases. FHL1 and FHL3 mRNAs were reciprocally expressed in the murine C2C12 skeletal muscle cell line and this suggested that the pattern of expression was linked to key events in myogenesis.\n" ], "offsets": [ [ 0, 1053 ] ] } ]

[ { "id": "PMID-10049693_T1", "type": "Protein", "text": [ "LIM proteins" ], "offsets": [ [ 4, 16 ] ], "normalized": [] }, { "id": "PMID-10049693_T2", "type": "Protein", "text": [ "FHL1" ], "offsets": [ [ 17, 21 ] ], "normalized": [] }, { "id": "PMID-10049693_T3", "type": "Protein", "text": [ "FHL3" ], "offsets": [ [ 26, 30 ] ], "normalized": [] }, { "id": "PMID-10049693_T5", "type": "Tissue", "text": [ "skeletal muscle" ], "offsets": [ [ 60, 75 ] ], "normalized": [] }, { "id": "PMID-10049693_T6", "type": "MessengerRNA", "text": [ "mRNA" ], "offsets": [ [ 109, 113 ] ], "normalized": [] }, { "id": "PMID-10049693_T7", "type": "Protein", "text": [ "FHL3" ], "offsets": [ [ 126, 130 ] ], "normalized": [] }, { "id": "PMID-10049693_T8", "type": "Protein", "text": [ "SLIM2" ], "offsets": [ [ 141, 146 ] ], "normalized": [] }, { "id": "PMID-10049693_T9", "type": "Protein", "text": [ "LIM proteins" ], "offsets": [ [ 204, 216 ] ], "normalized": [] }, { "id": "PMID-10049693_T11", "type": "ProteinDomain", "text": [ "Four-and-a-Half-LIM domain" ], "offsets": [ [ 278, 304 ] ], "normalized": [] }, { "id": "PMID-10049693_T12", "type": "ProteinDomain", "text": [ "FHL" ], "offsets": [ [ 309, 312 ] ], "normalized": [] }, { "id": "PMID-10049693_T13", "type": "Protein", "text": [ "proteins" ], "offsets": [ [ 314, 322 ] ], "normalized": [] }, { "id": "PMID-10049693_T16", "type": "ZincCoordinatingDomain", "text": [ "zinc finger domain" ], "offsets": [ [ 392, 410 ] ], "normalized": [] }, { "id": "PMID-10049693_T17", "type": "ProteinDomain", "text": [ "LIM domains" ], "offsets": [ [ 445, 456 ] ], "normalized": [] }, { "id": "PMID-10049693_T18", "type": "Protein", "text": [ "LIM proteins" ], "offsets": [ [ 495, 507 ] ], "normalized": [] }, { "id": "PMID-10049693_T19", "type": "Protein", "text": [ "FHL" ], "offsets": [ [ 529, 532 ] ], "normalized": [] }, { "id": "PMID-10049693_T20", "type": "MessengerRNA", "text": [ "mRNA" ], "offsets": [ [ 533, 537 ] ], "normalized": [] }, { "id": "PMID-10049693_T22", "type": "Eukaryote", "text": [ "murine" ], "offsets": [ [ 569, 575 ] ], "normalized": [] }, { "id": "PMID-10049693_T23", "type": "Tissue", "text": [ "tissues" ], "offsets": [ [ 576, 583 ] ], "normalized": [] }, { "id": "PMID-10049693_T24", "type": "Protein", "text": [ "FHL1" ], "offsets": [ [ 601, 605 ] ], "normalized": [] }, { "id": "PMID-10049693_T25", "type": "Protein", "text": [ "FHL3" ], "offsets": [ [ 610, 614 ] ], "normalized": [] }, { "id": "PMID-10049693_T27", "type": "Tissue", "text": [ "skeletal muscles" ], "offsets": [ [ 645, 661 ] ], "normalized": [] }, { "id": "PMID-10049693_T28", "type": "Protein", "text": [ "FHL2" ], "offsets": [ [ 668, 672 ] ], "normalized": [] }, { "id": "PMID-10049693_T30", "type": "Tissue", "text": [ "cardiac muscle" ], "offsets": [ [ 705, 719 ] ], "normalized": [] }, { "id": "PMID-10049693_T31", "type": "Gene", "text": [ "FHL3" ], "offsets": [ [ 737, 741 ] ], "normalized": [] }, { "id": "PMID-10049693_T32", "type": "Eukaryote", "text": [ "human" ], "offsets": [ [ 745, 750 ] ], "normalized": [] }, { "id": "PMID-10049693_T33", "type": "Chromosome", "text": [ "chromosome" ], "offsets": [ [ 751, 761 ] ], "normalized": [] }, { "id": "PMID-10049693_T34", "type": "Gene", "text": [ "gene" ], "offsets": [ [ 776, 780 ] ], "normalized": [] }, { "id": "PMID-10049693_T37", "type": "Protein", "text": [ "FHL1" ], "offsets": [ [ 869, 873 ] ], "normalized": [] }, { "id": "PMID-10049693_T38", "type": "Protein", "text": [ "FHL3" ], "offsets": [ [ 878, 882 ] ], "normalized": [] }, { "id": "PMID-10049693_T39", "type": "MessengerRNA", "text": [ "mRNAs" ], "offsets": [ [ 883, 888 ] ], "normalized": [] }, { "id": "PMID-10049693_T41", "type": "Eukaryote", "text": [ "murine" ], "offsets": [ [ 924, 930 ] ], "normalized": [] }, { "id": "PMID-10049693_T42", "type": "Cell", "text": [ "C2C12" ], "offsets": [ [ 931, 936 ] ], "normalized": [] }, { "id": "PMID-10049693_T10", "type": "MolecularStructure", "text": [ "secondary protein structure" ], "offsets": [ [ 238, 265 ] ], "normalized": [] }, { "id": "PMID-10049693_T14", "type": "ProteinDomain", "text": [ "\"half-LIM\" domain" ], "offsets": [ [ 362, 379 ] ], "normalized": [] }, { "id": "PMID-10049693_T35", "type": "Cell", "text": [ "skeletal muscle cell line" ], "offsets": [ [ 937, 962 ] ], "normalized": [] } ]

[ { "id": "PMID-10049693_E1", "type": "GeneExpression", "trigger": { "text": [ "expressed" ], "offsets": [ [ 35, 44 ] ] }, "arguments": [ { "role": "hasPatient", "ref_id": "PMID-10049693_T2" } ] }, { "id": "PMID-10049693_E2", "type": "TranscriptionOfGene", "trigger": { "text": [ "expression" ], "offsets": [ [ 538, 548 ] ] }, "arguments": [ { "role": "hasPatient", "ref_id": "PMID-10049693_T20" } ] }, { "id": "PMID-10049693_E3", "type": "GeneExpression", "trigger": { "text": [ "expressed" ], "offsets": [ [ 620, 629 ] ] }, "arguments": [ { "role": "hasPatient", "ref_id": "PMID-10049693_T24" } ] }, { "id": "PMID-10049693_E4", "type": "GeneExpression", "trigger": { "text": [ "expressed" ], "offsets": [ [ 677, 686 ] ] }, "arguments": [ { "role": "hasPatient", "ref_id": "PMID-10049693_T28" } ] }, { "id": "PMID-10049693_E7", "type": "TranscriptionOfGene", "trigger": { "text": [ "expressed" ], "offsets": [ [ 907, 916 ] ] }, "arguments": [ { "role": "hasPatient", "ref_id": "PMID-10049693_T39" } ] }, { "id": "PMID-10049693_E8", "type": "GeneExpression", "trigger": { "text": [ "expression" ], "offsets": [ [ 1002, 1012 ] ] }, "arguments": [] }, { "id": "PMID-10049693_E9", "type": "CellularDevelopmentalProcess", "trigger": { "text": [ "myogenesis" ], "offsets": [ [ 1041, 1051 ] ] }, "arguments": [] }, { "id": "PMID-10049693_E5", "type": "Disease", "trigger": { "text": [ "muscle diseases" ], "offsets": [ [ 852, 867 ] ] }, "arguments": [] }, { "id": "PMID-10049693_E6", "type": "GeneExpression", "trigger": { "text": [ "expressed" ], "offsets": [ [ 35, 44 ] ] }, "arguments": [ { "role": "hasPatient", "ref_id": "PMID-10049693_T3" } ] }, { "id": "PMID-10049693_E10", "type": "GeneExpression", "trigger": { "text": [ "expressed" ], "offsets": [ [ 620, 629 ] ] }, "arguments": [ { "role": "hasPatient", "ref_id": "PMID-10049693_T25" } ] } ]

[]

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[ { "id": "PMID-10049739__text", "type": "abstract", "text": [ "Molecular cloning and characterization of two novel human renal organic anion transporters (hOAT1 and hOAT3). The cloned organic anion transporters from rat, mouse, and winter flounder (rOAT1, mOAT1, fROAT) mediate the coupled exchange of alpha-ketoglutarate with multiple organic anions, including p-aminohippurate (PAH). We have isolated two novel gene products from human kidney which bear significant homology to the known OATs and belong to the amphiphilic solute facilitator (ASF) family. The cDNAs, hOAT1 and hOAT3, encode for 550- and 568-amino-acid residue proteins, respectively. hOAT1 and hOAT3 mRNAs are expressed strongly in kidney and weakly in brain. Both genes map to chromosome 11 region q11.7. PAH uptake by Xenopus laevis oocytes injected with hOAT1 mRNA is increased 100-fold compared to water-injected oocytes. PAH uptake is chloride dependent and is not further increased by preincubation of oocytes in 5 mM glutarate. Uptake of PAH is inhibited by probenicid, alpha-ketoglutarate, bumetanide, furosemide, and losartan, but not by salicylate, urate, choline, amilioride, and hydrochlorothiazide.\n" ], "offsets": [ [ 0, 1118 ] ] } ]

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"PMID-10049739_T9", "type": "Eukaryote", "text": [ "winter flounder" ], "offsets": [ [ 169, 184 ] ], "normalized": [] }, { "id": "PMID-10049739_T10", "type": "Protein", "text": [ "rOAT1" ], "offsets": [ [ 186, 191 ] ], "normalized": [] }, { "id": "PMID-10049739_T11", "type": "Protein", "text": [ "mOAT1" ], "offsets": [ [ 193, 198 ] ], "normalized": [] }, { "id": "PMID-10049739_T12", "type": "Protein", "text": [ "fROAT" ], "offsets": [ [ 200, 205 ] ], "normalized": [] }, { "id": "PMID-10049739_T14", "type": "Chemical", "text": [ "alpha-ketoglutarate" ], "offsets": [ [ 239, 258 ] ], "normalized": [] }, { "id": "PMID-10049739_T15", "type": "Chemical", "text": [ "p-aminohippurate" ], "offsets": [ [ 299, 315 ] ], "normalized": [] }, { "id": "PMID-10049739_T16", "type": "Chemical", "text": [ "PAH" ], "offsets": [ [ 317, 320 ] ], "normalized": [] }, { "id": "PMID-10049739_T17", "type": "GeneProduct", "text": [ "gene products" ], "offsets": [ [ 350, 363 ] ], "normalized": [] }, { "id": "PMID-10049739_T18", "type": "Eukaryote", "text": [ "human" ], "offsets": [ [ 369, 374 ] ], "normalized": [] }, { "id": "PMID-10049739_T19", "type": "Tissue", "text": [ "kidney" ], "offsets": [ [ 375, 381 ] ], "normalized": [] }, { "id": "PMID-10049739_T20", "type": "Protein", "text": [ "OATs" ], "offsets": [ [ 427, 431 ] ], "normalized": [] }, { "id": "PMID-10049739_T21", "type": "DNA", "text": [ "cDNAs" ], "offsets": [ [ 499, 504 ] ], "normalized": [] }, { "id": "PMID-10049739_T22", "type": "Gene", "text": [ "hOAT1" ], "offsets": [ [ 506, 511 ] ], "normalized": [] }, { "id": "PMID-10049739_T23", "type": "Gene", "text": [ "hOAT3" ], "offsets": [ [ 516, 521 ] ], "normalized": [] }, { "id": "PMID-10049739_T24", "type": "AminoAcid", "text": [ "amino-acid" ], "offsets": [ [ 547, 557 ] ], "normalized": [] }, { "id": "PMID-10049739_T25", "type": "Protein", "text": [ "proteins" ], "offsets": [ [ 566, 574 ] ], "normalized": [] }, { "id": "PMID-10049739_T26", "type": "Gene", "text": [ "hOAT1" ], "offsets": [ [ 590, 595 ] ], "normalized": [] }, { "id": "PMID-10049739_T27", "type": "Gene", "text": [ "hOAT3" ], "offsets": [ [ 600, 605 ] ], "normalized": [] }, { "id": "PMID-10049739_T28", "type": "MessengerRNA", "text": [ "mRNAs" ], "offsets": [ [ 606, 611 ] ], "normalized": [] }, { "id": "PMID-10049739_T30", "type": "Tissue", "text": [ "kidney" ], "offsets": [ [ 638, 644 ] ], "normalized": [] }, { "id": "PMID-10049739_T31", "type": "Tissue", "text": [ "brain" ], "offsets": [ [ 659, 664 ] ], "normalized": [] }, { "id": "PMID-10049739_T32", "type": "Chromosome", "text": [ "chromosome" ], "offsets": [ [ 684, 694 ] ], "normalized": [] }, { "id": "PMID-10049739_T33", "type": "Chemical", "text": [ "PAH" ], "offsets": [ [ 712, 715 ] ], "normalized": [] }, { "id": "PMID-10049739_T34", "type": "Gene", "text": [ "hOAT1" ], "offsets": [ [ 763, 768 ] ], "normalized": [] }, { "id": "PMID-10049739_T35", "type": "MessengerRNA", "text": [ "mRNA" ], "offsets": [ [ 769, 773 ] ], "normalized": [] }, { "id": "PMID-10049739_T36", "type": "Chemical", "text": [ "PAH" ], "offsets": [ [ 832, 835 ] ], "normalized": [] }, { "id": "PMID-10049739_T37", "type": "Chemical", "text": [ "PAH" ], "offsets": [ [ 951, 954 ] ], "normalized": [] }, { "id": "PMID-10049739_T39", "type": "Chemical", "text": [ "probenicid" ], "offsets": [ [ 971, 981 ] ], "normalized": [] }, { "id": "PMID-10049739_T40", "type": "Chemical", "text": [ "alpha-ketoglutarate" ], "offsets": [ [ 983, 1002 ] ], "normalized": [] }, { "id": "PMID-10049739_T41", "type": "Chemical", "text": [ "bumetanide" ], "offsets": [ [ 1004, 1014 ] ], "normalized": [] }, { "id": "PMID-10049739_T42", "type": "Chemical", "text": [ "furosemide" ], "offsets": [ [ 1016, 1026 ] ], "normalized": [] }, { "id": "PMID-10049739_T43", "type": "Chemical", "text": [ "losartan" ], "offsets": [ [ 1032, 1040 ] ], "normalized": [] }, { "id": "PMID-10049739_T44", "type": "Chemical", "text": [ "salicylate" ], "offsets": [ [ 1053, 1063 ] ], "normalized": [] }, { "id": "PMID-10049739_T45", "type": "Chemical", "text": [ "urate" ], "offsets": [ [ 1065, 1070 ] ], "normalized": [] }, { "id": "PMID-10049739_T46", "type": "Chemical", "text": [ "choline" ], "offsets": [ [ 1072, 1079 ] ], "normalized": [] }, { "id": "PMID-10049739_T47", "type": "Chemical", "text": [ "amilioride" ], "offsets": [ [ 1081, 1091 ] ], "normalized": [] }, { "id": "PMID-10049739_T48", "type": "Chemical", "text": [ "hydrochlorothiazide" ], "offsets": [ [ 1097, 1116 ] ], "normalized": [] }, { "id": "PMID-10049739_T49", "type": "Ion", "text": [ "organic anions" ], "offsets": [ [ 273, 287 ] ], "normalized": [] }, { "id": "PMID-10049739_T51", "type": "Protein", "text": [ "amphiphilic solute facilitator" ], "offsets": [ [ 450, 480 ] ], "normalized": [] }, { "id": "PMID-10049739_T52", "type": "Protein", "text": [ "ASF" ], "offsets": [ [ 482, 485 ] ], "normalized": [] }, { "id": "PMID-10049739_T53", "type": "Gene", "text": [ "genes" ], "offsets": [ [ 671, 676 ] ], "normalized": [] }, { "id": "PMID-10049739_T54", "type": "Eukaryote", "text": [ "Xenopus laevis" ], "offsets": [ [ 726, 740 ] ], "normalized": [] }, { "id": "PMID-10049739_T55", "type": "Cell", "text": [ "oocytes" ], "offsets": [ [ 741, 748 ] ], "normalized": [] }, { "id": "PMID-10049739_T57", "type": "Cell", "text": [ "oocytes" ], "offsets": [ [ 823, 830 ] ], "normalized": [] } ]

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[]

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[ { "id": "PMID-10049767__text", "type": "abstract", "text": [ "X11L2, a new member of the X11 protein family, interacts with Alzheimer's beta-amyloid precursor protein. We screened proteins for interaction with Alzheimer's beta-amyloid precursor protein (APP) and cloned a new member of the X11 protein family, X11L2. The PID/PTB element of X11L2 protein interacted with the intracellular domain of APP by GST binding assay, and in vivo interaction was confirmed by coimmunoprecipitation from cell extracts overexpressing APP and HA-tagged X11L2. This gene encoded 575 amino acids and the deduced amino acid sequence was highly homologous to rat Mint3. Three protein-protein interaction domains, a PID/PTB and two PDZ elements, were conserved among the X11 protein family, and the N-terminal region of X11L2 protein had several putative SH3 binding motifs, PXXP. Unlike other members of the X11 protein family, X11L2 mRNA was expressed in various tissues.\n" ], "offsets": [ [ 0, 893 ] ] } ]

[ { "id": "PMID-10049767_T1", "type": "Protein", "text": [ "X11L2" ], "offsets": [ [ 0, 5 ] ], "normalized": [] }, { "id": "PMID-10049767_T2", "type": "Protein", "text": [ "X11 protein" ], "offsets": [ [ 27, 38 ] ], "normalized": [] }, { "id": "PMID-10049767_T4", "type": "Protein", "text": [ "beta-amyloid precursor protein" ], "offsets": [ [ 74, 104 ] ], "normalized": [] }, { "id": "PMID-10049767_T5", "type": "Protein", "text": [ "proteins" ], "offsets": [ [ 118, 126 ] ], "normalized": [] }, { "id": "PMID-10049767_T7", "type": "Protein", "text": [ "beta-amyloid precursor protein" ], "offsets": [ [ 160, 190 ] ], "normalized": [] }, { "id": "PMID-10049767_T8", "type": "Protein", "text": [ "APP" ], "offsets": [ [ 192, 195 ] ], "normalized": [] }, { "id": "PMID-10049767_T9", "type": "Protein", "text": [ "X11 protein" ], "offsets": [ [ 228, 239 ] ], "normalized": [] }, { "id": "PMID-10049767_T10", "type": "Protein", "text": [ "X11L2" ], "offsets": [ [ 248, 253 ] ], "normalized": [] }, { "id": "PMID-10049767_T11", "type": "Protein", "text": [ "X11L2 protein" ], "offsets": [ [ 278, 291 ] ], "normalized": [] }, { "id": "PMID-10049767_T14", "type": "Protein", "text": [ "APP" ], "offsets": [ [ 336, 339 ] ], "normalized": [] }, { "id": "PMID-10049767_T17", "type": "Protein", "text": [ "APP" ], "offsets": [ [ 459, 462 ] ], "normalized": [] }, { "id": "PMID-10049767_T18", "type": "Protein", "text": [ "X11L2" ], "offsets": [ [ 477, 482 ] ], "normalized": [] }, { "id": "PMID-10049767_T19", "type": "Gene", "text": [ "gene" ], "offsets": [ [ 489, 493 ] ], "normalized": [] }, { "id": "PMID-10049767_T20", "type": "AminoAcid", "text": [ "amino acids" ], "offsets": [ [ 506, 517 ] ], "normalized": [] }, { "id": "PMID-10049767_T21", "type": "AminoAcid", "text": [ "amino acid" ], "offsets": [ [ 534, 544 ] ], "normalized": [] }, { "id": "PMID-10049767_T22", "type": "Eukaryote", "text": [ "rat" ], "offsets": [ [ 579, 582 ] ], "normalized": [] }, { "id": "PMID-10049767_T23", "type": "Protein", "text": [ "Mint3" ], "offsets": [ [ 583, 588 ] ], "normalized": [] }, { "id": "PMID-10049767_T27", "type": "ProteinDomain", "text": [ "domains" ], "offsets": [ [ 624, 631 ] ], "normalized": [] }, { "id": "PMID-10049767_T28", "type": "Protein", "text": [ "X11 protein" ], "offsets": [ [ 690, 701 ] ], "normalized": [] }, { "id": "PMID-10049767_T29", "type": "Protein", "text": [ "X11L2 protein" ], "offsets": [ [ 739, 752 ] ], "normalized": [] }, { "id": "PMID-10049767_T30", "type": "ProteinDomain", "text": [ "SH3" ], "offsets": [ [ 774, 777 ] ], "normalized": [] }, { "id": "PMID-10049767_T32", "type": "ProteinDomain", "text": [ "motifs" ], "offsets": [ [ 786, 792 ] ], "normalized": [] }, { "id": "PMID-10049767_T33", "type": "ProteinDomain", "text": [ "PXXP" ], "offsets": [ [ 794, 798 ] ], "normalized": [] }, { "id": "PMID-10049767_T34", "type": "Protein", "text": [ "X11 protein" ], "offsets": [ [ 828, 839 ] ], "normalized": [] }, { "id": "PMID-10049767_T35", "type": "Protein", "text": [ "X11L2" ], "offsets": [ [ 848, 853 ] ], "normalized": [] }, { "id": "PMID-10049767_T36", "type": "MessengerRNA", "text": [ "mRNA" ], "offsets": [ [ 854, 858 ] ], "normalized": [] }, { "id": "PMID-10049767_T38", "type": "Tissue", "text": [ "tissues" ], "offsets": [ [ 884, 891 ] ], "normalized": [] }, { "id": "PMID-10049767_T41", "type": "ProteinDomain", "text": [ "PID/PTB element" ], "offsets": [ [ 259, 274 ] ], "normalized": [] }, { "id": "PMID-10049767_T13", "type": "ProteinDomain", "text": [ "intracellular domain" ], "offsets": [ [ 312, 332 ] ], "normalized": [] }, { "id": "PMID-10049767_T25", "type": "ProteinDomain", "text": [ "PID/PTB" ], "offsets": [ [ 635, 642 ] ], "normalized": [] }, { "id": "PMID-10049767_T26", "type": "ProteinDomain", "text": [ "PDZ elements" ], "offsets": [ [ 651, 663 ] ], "normalized": [] } ]

[ { "id": "PMID-10049767_E1", "type": "BindingToProtein", "trigger": { "text": [ "interacts" ], "offsets": [ [ 47, 56 ] ] }, "arguments": [ { "role": "hasPatient", "ref_id": "PMID-10049767_T4" }, { "role": "hasPatient2", "ref_id": "PMID-10049767_T1" } ] }, { "id": "PMID-10049767_E2", "type": "BindingToProtein", "trigger": { "text": [ "interaction" ], "offsets": [ [ 131, 142 ] ] }, "arguments": [ { "role": "hasPatient", "ref_id": "PMID-10049767_T7" }, { "role": "hasPatient2", "ref_id": "PMID-10049767_T5" } ] }, { "id": "PMID-10049767_E3", "type": "BindingToProtein", "trigger": { "text": [ "interacted" ], "offsets": [ [ 292, 302 ] ] }, "arguments": [ { "role": "hasPatient", "ref_id": "PMID-10049767_T41" }, { "role": "hasPatient2", "ref_id": "PMID-10049767_T13" } ] }, { "id": "PMID-10049767_E4", "type": "BindingToProtein", "trigger": { "text": [ "interaction" ], "offsets": [ [ 374, 385 ] ] }, "arguments": [] }, { "id": "PMID-10049767_E5", "type": "GeneExpression", "trigger": { "text": [ "overexpressing" ], "offsets": [ [ 444, 458 ] ] }, "arguments": [ { "role": "hasPatient", "ref_id": "PMID-10049767_T17" } ] }, { "id": "PMID-10049767_E7", "type": "BindingToProtein", "trigger": { "text": [ "binding" ], "offsets": [ [ 778, 785 ] ] }, "arguments": [ { "role": "hasPatient", "ref_id": "PMID-10049767_T32" }, { "role": "hasPatient2", "ref_id": "PMID-10049767_T30" } ] }, { "id": "PMID-10049767_E8", "type": "TranscriptionOfGene", "trigger": { "text": [ "expressed" ], "offsets": [ [ 863, 872 ] ] }, "arguments": [ { "role": "hasPatient", "ref_id": "PMID-10049767_T36" } ] }, { "id": "PMID-10049767_E9", "type": "Disease", "trigger": { "text": [ "Alzheimer's" ], "offsets": [ [ 62, 73 ] ] }, "arguments": [] }, { "id": "PMID-10049767_E10", "type": "Disease", "trigger": { "text": [ "Alzheimer's" ], "offsets": [ [ 148, 159 ] ] }, "arguments": [] }, { "id": "PMID-10049767_E6", "type": "BindingOfProteinToProteinBindingSiteOfProtein", "trigger": { "text": [ "protein-protein interaction" ], "offsets": [ [ 596, 623 ] ] }, "arguments": [] }, { "id": "PMID-10049767_E11", "type": "GeneExpression", "trigger": { "text": [ "overexpressing" ], "offsets": [ [ 444, 458 ] ] }, "arguments": [ { "role": "hasPatient", "ref_id": "PMID-10049767_T18" } ] } ]

[]

[ { "id": "PMID-10049767_R2", "type": "encodes", "arg1_id": "PMID-10049767_T19", "arg2_id": "PMID-10049767_T20", "normalized": [] }, { "id": "PMID-10049767_R3", "type": "fromSpecies", "arg1_id": "PMID-10049767_T23", "arg2_id": "PMID-10049767_T22", "normalized": [] }, { "id": "PMID-10049767_R4", "type": "encodes", "arg1_id": "PMID-10049767_T36", "arg2_id": "PMID-10049767_T35", "normalized": [] }, { "id": "PMID-10049767_R6", "type": "hasPart", "arg1_id": "PMID-10049767_T11", "arg2_id": "PMID-10049767_T41", "normalized": [] }, { "id": "PMID-10049767_R1", "type": "hasPart", "arg1_id": "PMID-10049767_T14", "arg2_id": "PMID-10049767_T13", "normalized": [] }, { "id": "PMID-10049767_R7", "type": "hasPart", "arg1_id": "PMID-10049767_T28", "arg2_id": "PMID-10049767_T25", "normalized": [] }, { "id": "PMID-10049767_R8", "type": "hasPart", "arg1_id": "PMID-10049767_T28", "arg2_id": "PMID-10049767_T26", "normalized": [] } ]

[ { "id": "PMID-10049768__text", "type": "abstract", "text": [ "An antisense transcript to SMAD5 expressed in fetal and tumor tissues. SMAD5, a transducer of TGF-beta/BMP inhibitory signals and a tumor suppressor candidate, localizes to the region of invariant loss in human myeloid neoplasms, on chromosome 5q31.1. Recent evidence indicates a gene-dosage effect along the TGF-beta/BMP signaling pathways. We have identified a novel transcript designated DAMS, whose 3' exonic sequences contain in part an alternate 5' exon of SMAD5, in the antisense orientation. Expressed sequenced tags (ESTs) for DAMS are found in fetal tissues (heart, adrenal glands, and total fetus) and pancreatic tumor cDNA libraries. In contrast to SMAD5, DAMS expression is not readily detectable in adult and fetal tissues. Semiquantitative PCR suggests that the stoichiometry between SMAD5 and DAMS transcripts ranges between 15 and 120 in normal and malignant hematopoietic cells. The findings raise the possibility that DAMS may be a fail-safe mechanism for precise regulation of SMAD5 transcript levels that may be critical in maintaining normal homeostasis.\n" ], "offsets": [ [ 0, 1077 ] ] } ]

[ { "id": "PMID-10049768_T2", "type": "Protein", "text": [ "SMAD5" ], "offsets": [ [ 27, 32 ] ], "normalized": [] }, { "id": "PMID-10049768_T5", "type": "Tissue", "text": [ "tumor tissues" ], "offsets": [ [ 56, 69 ] ], "normalized": [] }, { "id": "PMID-10049768_T6", "type": "Protein", "text": [ "SMAD5" ], "offsets": [ [ 71, 76 ] ], "normalized": [] }, { "id": "PMID-10049768_T7", "type": "Protein", "text": [ "TGF-beta/BMP" ], "offsets": [ [ 94, 106 ] ], "normalized": [] }, { "id": "PMID-10049768_T8", "type": "Eukaryote", "text": [ "human" ], "offsets": [ [ 205, 210 ] ], "normalized": [] }, { "id": "PMID-10049768_T9", "type": "Chromosome", "text": [ "chromosome" ], "offsets": [ [ 233, 243 ] ], "normalized": [] }, { "id": "PMID-10049768_T10", "type": "Gene", "text": [ "gene" ], "offsets": [ [ 280, 284 ] ], "normalized": [] }, { "id": "PMID-10049768_T12", "type": "Protein", "text": [ "TGF-beta/BMP" ], "offsets": [ [ 309, 321 ] ], "normalized": [] }, { "id": "PMID-10049768_T14", "type": "Transcript", "text": [ "transcript" ], "offsets": [ [ 369, 379 ] ], "normalized": [] }, { "id": "PMID-10049768_T15", "type": "Protein", "text": [ "DAMS" ], "offsets": [ [ 391, 395 ] ], "normalized": [] }, { "id": "PMID-10049768_T16", "type": "Exon", "text": [ "exon" ], "offsets": [ [ 455, 459 ] ], "normalized": [] }, { "id": "PMID-10049768_T17", "type": "Protein", "text": [ "SMAD5" ], "offsets": [ [ 463, 468 ] ], "normalized": [] }, { "id": "PMID-10049768_T18", "type": "Protein", "text": [ "DAMS" ], "offsets": [ [ 536, 540 ] ], "normalized": [] }, { "id": "PMID-10049768_T19", "type": "Tissue", "text": [ "fetal tissues" ], "offsets": [ [ 554, 567 ] ], "normalized": [] }, { "id": "PMID-10049768_T20", "type": "Tissue", "text": [ "heart" ], "offsets": [ [ 569, 574 ] ], "normalized": [] }, { "id": "PMID-10049768_T21", "type": "Tissue", "text": [ "adrenal glands" ], "offsets": [ [ 576, 590 ] ], "normalized": [] }, { "id": "PMID-10049768_T22", "type": "Tissue", "text": [ "total fetus" ], "offsets": [ [ 596, 607 ] ], "normalized": [] }, { "id": "PMID-10049768_T23", "type": "DNA", "text": [ "cDNA" ], "offsets": [ [ 630, 634 ] ], "normalized": [] }, { "id": "PMID-10049768_T24", "type": "Protein", "text": [ "SMAD5" ], "offsets": [ [ 661, 666 ] ], "normalized": [] }, { "id": "PMID-10049768_T25", "type": "Protein", "text": [ "DAMS" ], "offsets": [ [ 668, 672 ] ], "normalized": [] }, { "id": "PMID-10049768_T29", "type": "Protein", "text": [ "SMAD5" ], "offsets": [ [ 799, 804 ] ], "normalized": [] }, { "id": "PMID-10049768_T30", "type": "Protein", "text": [ "DAMS" ], "offsets": [ [ 809, 813 ] ], "normalized": [] }, { "id": "PMID-10049768_T31", "type": "Transcript", "text": [ "transcripts" ], "offsets": [ [ 814, 825 ] ], "normalized": [] }, { "id": "PMID-10049768_T33", "type": "Protein", "text": [ "DAMS" ], "offsets": [ [ 937, 941 ] ], "normalized": [] }, { "id": "PMID-10049768_T35", "type": "Protein", "text": [ "SMAD5" ], "offsets": [ [ 997, 1002 ] ], "normalized": [] }, { "id": "PMID-10049768_T36", "type": "Transcript", "text": [ "transcript" ], "offsets": [ [ 1003, 1013 ] ], "normalized": [] }, { "id": "PMID-10049768_T1", "type": "AntisenseRNA", "text": [ "antisense transcript" ], "offsets": [ [ 3, 23 ] ], "normalized": [] }, { "id": "PMID-10049768_T4", "type": "Tissue", "text": [ "fetal" ], "offsets": [ [ 46, 51 ] ], "normalized": [] }, { "id": "PMID-10049768_T38", "type": "Protein", "text": [ "tumor suppressor" ], "offsets": [ [ 132, 148 ] ], "normalized": [] }, { "id": "PMID-10049768_T40", "type": "Exon", "text": [ "3' exonic sequences" ], "offsets": [ [ 403, 422 ] ], "normalized": [] }, { "id": "PMID-10049768_T41", "type": "Tissue", "text": [ "pancreatic tumor" ], "offsets": [ [ 613, 629 ] ], "normalized": [] }, { "id": "PMID-10049768_T27", "type": "Tissue", "text": [ "adult and fetal tissues" ], "offsets": [ [ 713, 736 ] ], "normalized": [] }, { "id": "PMID-10049768_T28", "type": "Cell", "text": [ "hematopoietic cells" ], "offsets": [ [ 876, 895 ] ], "normalized": [] } ]

[ { "id": "PMID-10049768_E1", "type": "Transcription", "trigger": { "text": [ "expressed" ], "offsets": [ [ 33, 42 ] ] }, "arguments": [ { "role": "hasPatient", "ref_id": "PMID-10049768_T1" } ] }, { "id": "PMID-10049768_E2", "type": "RegulationOfGeneExpression", "trigger": { "text": [ "dosage effect" ], "offsets": [ [ 285, 298 ] ] }, "arguments": [ { "role": "hasPatient", "ref_id": "PMID-10049768_T10" } ] }, { "id": "PMID-10049768_E3", "type": "SignalingPathway", "trigger": { "text": [ "signaling pathways" ], "offsets": [ [ 322, 340 ] ] }, "arguments": [] }, { "id": "PMID-10049768_E4", "type": "GeneExpression", "trigger": { "text": [ "expression" ], "offsets": [ [ 673, 683 ] ] }, "arguments": [ { "role": "hasPatient", "ref_id": "PMID-10049768_T25" } ] }, { "id": "PMID-10049768_E5", "type": "RegulatoryProcess", "trigger": { "text": [ "regulation" ], "offsets": [ [ 983, 993 ] ] }, "arguments": [ { "role": "hasAgent", "ref_id": "PMID-10049768_T33" }, { "role": "hasPatient", "ref_id": "PMID-10049768_T36" } ] }, { "id": "PMID-10049768_E6", "type": "SignalingPathway", "trigger": { "text": [ "inhibitory signals" ], "offsets": [ [ 107, 125 ] ] }, "arguments": [] }, { "id": "PMID-10049768_E7", "type": "Disease", "trigger": { "text": [ "myeloid neoplasms" ], "offsets": [ [ 211, 228 ] ] }, "arguments": [] }, { "id": "PMID-10049768_E8", "type": "CellHomeostasis", "trigger": { "text": [ "homeostasis" ], "offsets": [ [ 1064, 1075 ] ] }, "arguments": [] }, { "id": "PMID-10049768_E9", "type": "Maintenance", "trigger": { "text": [ "maintaining" ], "offsets": [ [ 1045, 1056 ] ] }, "arguments": [ { "role": "hasAgent", "ref_id": "PMID-10049768_T36" }, { "role": "hasPatient", "ref_id": "PMID-10049768_E8" } ] } ]

[]

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[ { "id": "PMID-10049774__text", "type": "abstract", "text": [ "Cloning of BRAK, a novel divergent CXC chemokine preferentially expressed in normal versus malignant cells. Chemokines are a family of related proteins that regulate leukocyte infiltration into inflamed tissue and play important roles in many disease processes. Chemokines are divided into two major groups, CC or CXC, based on their sequence around the amino terminal cysteines. We report the PCR cloning of a novel human chemokine termed BRAK for its initial isolation from breast and kidney cells. This novel chemokine is distantly related to other CXC chemokines (30% identity with MIP-2alpha and beta) and shares several biological activities. BRAK is expressed ubiquitously and highly in normal tissue. However, it was expressed in only 2 of 18 cancer cell lines. BRAK is located on human chromosome 5q31.\n" ], "offsets": [ [ 0, 812 ] ] } ]

[ { "id": "PMID-10049774_T1", "type": "Protein", "text": [ "BRAK" ], "offsets": [ [ 11, 15 ] ], "normalized": [] }, { "id": "PMID-10049774_T2", "type": "Protein", "text": [ "CXC chemokine" ], "offsets": [ [ 35, 48 ] ], "normalized": [] }, { "id": "PMID-10049774_T4", "type": "Cell", "text": [ "malignant cells" ], "offsets": [ [ 91, 106 ] ], "normalized": [] }, { "id": "PMID-10049774_T5", "type": "Protein", "text": [ "Chemokines" ], "offsets": [ [ 108, 118 ] ], "normalized": [] }, { "id": "PMID-10049774_T6", "type": "Protein", "text": [ "proteins" ], "offsets": [ [ 143, 151 ] ], "normalized": [] }, { "id": "PMID-10049774_T8", "type": "Cell", "text": [ "leukocyte" ], "offsets": [ [ 166, 175 ] ], "normalized": [] }, { "id": "PMID-10049774_T10", "type": "Tissue", "text": [ "tissue" ], "offsets": [ [ 203, 209 ] ], "normalized": [] }, { "id": "PMID-10049774_T12", "type": "Protein", "text": [ "Chemokines" ], "offsets": [ [ 262, 272 ] ], "normalized": [] }, { "id": "PMID-10049774_T13", "type": "Eukaryote", "text": [ "human" ], "offsets": [ [ 417, 422 ] ], "normalized": [] }, { "id": "PMID-10049774_T14", "type": "Protein", "text": [ "chemokine" ], "offsets": [ [ 423, 432 ] ], "normalized": [] }, { "id": "PMID-10049774_T15", "type": "Protein", "text": [ "BRAK" ], "offsets": [ [ 440, 444 ] ], "normalized": [] }, { "id": "PMID-10049774_T16", "type": "Tissue", "text": [ "breast" ], "offsets": [ [ 476, 482 ] ], "normalized": [] }, { "id": "PMID-10049774_T17", "type": "Tissue", "text": [ "kidney" ], "offsets": [ [ 487, 493 ] ], "normalized": [] }, { "id": "PMID-10049774_T18", "type": "Cell", "text": [ "cells" ], "offsets": [ [ 494, 499 ] ], "normalized": [] }, { "id": "PMID-10049774_T19", "type": "Protein", "text": [ "chemokine" ], "offsets": [ [ 512, 521 ] ], "normalized": [] }, { "id": "PMID-10049774_T20", "type": "Protein", "text": [ "CXC chemokines" ], "offsets": [ [ 552, 566 ] ], "normalized": [] }, { "id": "PMID-10049774_T21", "type": "Protein", "text": [ "BRAK" ], "offsets": [ [ 649, 653 ] ], "normalized": [] }, { "id": "PMID-10049774_T23", "type": "Tissue", "text": [ "tissue" ], "offsets": [ [ 701, 707 ] ], "normalized": [] }, { "id": "PMID-10049774_T26", "type": "Protein", "text": [ "BRAK" ], "offsets": [ [ 770, 774 ] ], "normalized": [] }, { "id": "PMID-10049774_T27", "type": "Eukaryote", "text": [ "human" ], "offsets": [ [ 789, 794 ] ], "normalized": [] }, { "id": "PMID-10049774_T28", "type": "Chromosome", "text": [ "chromosome" ], "offsets": [ [ 795, 805 ] ], "normalized": [] }, { "id": "PMID-10049774_T29", "type": "Cell", "text": [ "normal" ], "offsets": [ [ 77, 83 ] ], "normalized": [] }, { "id": "PMID-10049774_T30", "type": "Protein", "text": [ "CC" ], "offsets": [ [ 308, 310 ] ], "normalized": [] }, { "id": "PMID-10049774_T31", "type": "Protein", "text": [ "CXC" ], "offsets": [ [ 314, 317 ] ], "normalized": [] }, { "id": "PMID-10049774_T32", "type": "Sequence", "text": [ "sequence" ], "offsets": [ [ 334, 342 ] ], "normalized": [] }, { "id": "PMID-10049774_T33", "type": "AminoAcid", "text": [ "cysteines" ], "offsets": [ [ 369, 378 ] ], "normalized": [] }, { "id": "PMID-10049774_T34", "type": "Protein", "text": [ "MIP-2alpha and beta" ], "offsets": [ [ 586, 605 ] ], "normalized": [] }, { "id": "PMID-10049774_T25", "type": "Cell", "text": [ "cancer cell lines" ], "offsets": [ [ 751, 768 ] ], "normalized": [] } ]

[ { "id": "PMID-10049774_E1", "type": "GeneExpression", "trigger": { "text": [ "expressed" ], "offsets": [ [ 64, 73 ] ] }, "arguments": [ { "role": "hasPatient", "ref_id": "PMID-10049774_T2" } ] }, { "id": "PMID-10049774_E2", "type": "RegulatoryProcess", "trigger": { "text": [ "regulate" ], "offsets": [ [ 157, 165 ] ] }, "arguments": [ { "role": "hasAgent", "ref_id": "PMID-10049774_T5" }, { "role": "hasPatient", "ref_id": "PMID-10049774_E3" } ] }, { "id": "PMID-10049774_E3", "type": "Localization", "trigger": { "text": [ "infiltration" ], "offsets": [ [ 176, 188 ] ] }, "arguments": [ { "role": "hasPatient", "ref_id": "PMID-10049774_T8" } ] }, { "id": "PMID-10049774_E4", "type": "Disease", "trigger": { "text": [ "disease processes" ], "offsets": [ [ 243, 260 ] ] }, "arguments": [] }, { "id": "PMID-10049774_E5", "type": "GeneExpression", "trigger": { "text": [ "expressed" ], "offsets": [ [ 657, 666 ] ] }, "arguments": [ { "role": "hasPatient", "ref_id": "PMID-10049774_T21" } ] }, { "id": "PMID-10049774_E6", "type": "GeneExpression", "trigger": { "text": [ "expressed" ], "offsets": [ [ 725, 734 ] ] }, "arguments": [] } ]

[]

[ { "id": "PMID-10049774_R2", "type": "fromSpecies", "arg1_id": "PMID-10049774_T14", "arg2_id": "PMID-10049774_T13", "normalized": [] }, { "id": "PMID-10049774_R3", "type": "locatedIn", "arg1_id": "PMID-10049774_T15", "arg2_id": "PMID-10049774_T18", "normalized": [] }, { "id": "PMID-10049774_R8", "type": "fromSpecies", "arg1_id": "PMID-10049774_T28", "arg2_id": "PMID-10049774_T27", "normalized": [] }, { "id": "PMID-10049774_R4", "type": "locatedIn", "arg1_id": "PMID-10049774_T18", "arg2_id": "PMID-10049774_T16", "normalized": [] }, { "id": "PMID-10049774_R5", "type": "locatedIn", "arg1_id": "PMID-10049774_T18", "arg2_id": "PMID-10049774_T17", "normalized": [] }, { "id": "PMID-10049774_R10", "type": "locatedIn", "arg1_id": "PMID-10049774_T26", "arg2_id": "PMID-10049774_T28", "normalized": [] } ]

[ { "id": "PMID-10049777__text", "type": "abstract", "text": [ "Cloning and characterization of a cDNA encoding a novel fibroblast growth factor preferentially expressed in human heart. A novel human fibroblast growth factor (hFGF), which shows 75% sequence homology with fibroblast growth factor-9, was isolated in random sequencing of a human heart cDNA library. The full-length sequence is 928 bp, the encoded protein is composed of 168 amino acid residues, and its pI value and molecular weight were estimated to be 8.13 and 19.1 kDa, respectively. RT-PCR using Marathon human heart cDNA shows that the coding region is approximately 507 bp. Southern hybridization showed a single band which indicates that this is a single copy gene. Northern hybridization done on a human multiple tissues blot showed that the gene is preferentially expressed in human heart, very weakly detectable in human brain and not detectable in 18 other different human tissues.\n" ], "offsets": [ [ 0, 895 ] ] } ]

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[ { "id": "PMID-10049777_E1", "type": "GeneExpression", "trigger": { "text": [ "expressed" ], "offsets": [ [ 96, 105 ] ] }, "arguments": [ { "role": "hasPatient", "ref_id": "PMID-10049777_T1" } ] }, { "id": "PMID-10049777_E2", "type": "GeneExpression", "trigger": { "text": [ "expressed" ], "offsets": [ [ 775, 784 ] ] }, "arguments": [ { "role": "hasPatient", "ref_id": "PMID-10049777_T24" } ] } ]

[]

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[ { "id": "PMID-10049785__text", "type": "abstract", "text": [ "Human phenylalanyl-tRNA synthetase: cloning, characterization of the deduced amino acid sequences in terms of the structural domains and coordinately regulated expression of the alpha and beta subunits in chronic myeloid leukemia cells. Unlike the catalytic alpha-subunit, the beta-subunit of heterodimeric (alphabeta)2 phenylalanyl-tRNA synthetase (PheRS) has no invariant functional amino acids directly involved in the aminoacylation process as it is evident from the crystal structure of the T. thermophilus enzyme complexed with tRNAPhe. Having no catalytic function, the prokaryotic beta-subunit comprises OB-, RNP-, SH3-, and DNA-binding-like domains involved in a variety of biological functions in other proteins. It was shown that the mRNA of the human alpha-subunit overexpressed in the tumorigenic versus the nontumorigenic variant of the same acute-phase chronic myeloid leukemia cell line (CML). We cloned, sequenced, and expressed human PheRS. The layout of the human sequence indicates that the general tRNA binding mode and anticodon recognition differ between prokaryotes and eukaryotes for the phenylalanine system. Northern blot hybridization analysis from malignant and normal human tissues enabled us to assess the relative expression levels of the alpha- and beta-subunits independently, in view of the additional cellular role proposed for the beta-subunit in tumorigenic events. The levels of mRNA corresponding to the alpha- and beta-subunits were remarkably similar in all cell types and tissues examined, thus indicating the implication of the entire (alphabeta)2 heterodimer in tumorigenic events.\n" ], "offsets": [ [ 0, 1627 ] ] } ]

[ { "id": "PMID-10049785_T1", "type": "Eukaryote", "text": [ "Human" ], "offsets": [ [ 0, 5 ] ], "normalized": [] }, { "id": "PMID-10049785_T2", "type": "Enzyme", "text": [ "phenylalanyl-tRNA synthetase" ], "offsets": [ [ 6, 34 ] ], "normalized": [] }, { "id": "PMID-10049785_T3", "type": "AminoAcid", "text": [ "amino acid" ], "offsets": [ [ 77, 87 ] ], "normalized": [] }, { "id": "PMID-10049785_T4", "type": "ProteinDomain", "text": [ "structural domains" ], "offsets": [ [ 114, 132 ] ], "normalized": [] }, { "id": "PMID-10049785_T7", "type": "ProteinSubunit", "text": [ "alpha and beta subunits" ], "offsets": [ [ 178, 201 ] ], "normalized": [] }, { "id": "PMID-10049785_T9", "type": "Cell", "text": [ "chronic myeloid leukemia cells" ], "offsets": [ [ 205, 235 ] ], "normalized": [] }, { "id": "PMID-10049785_T10", "type": "ProteinSubunit", "text": [ "alpha-subunit" ], "offsets": [ [ 258, 271 ] ], "normalized": [] }, { "id": "PMID-10049785_T11", "type": "ProteinSubunit", "text": [ "beta-subunit" ], "offsets": [ [ 277, 289 ] ], "normalized": [] }, { "id": "PMID-10049785_T14", "type": "AminoAcid", "text": [ "amino acids" ], "offsets": [ [ 385, 396 ] ], "normalized": [] }, { "id": "PMID-10049785_T15", "type": "Prokaryote", "text": [ "T. thermophilus" ], "offsets": [ [ 496, 511 ] ], "normalized": [] }, { "id": "PMID-10049785_T16", "type": "Enzyme", "text": [ "enzyme" ], "offsets": [ [ 512, 518 ] ], "normalized": [] }, { "id": "PMID-10049785_T17", "type": "tRNA", "text": [ "tRNAPhe" ], "offsets": [ [ 534, 541 ] ], "normalized": [] }, { "id": "PMID-10049785_T18", "type": "Prokaryote", "text": [ "prokaryotic" ], "offsets": [ [ 577, 588 ] ], "normalized": [] }, { "id": "PMID-10049785_T19", "type": "ProteinSubunit", "text": [ "beta-subunit" ], "offsets": [ [ 589, 601 ] ], "normalized": [] }, { "id": "PMID-10049785_T22", "type": "ProteinDomain", "text": [ "domains" ], "offsets": [ [ 650, 657 ] ], "normalized": [] }, { "id": "PMID-10049785_T23", "type": "Protein", "text": [ "proteins" ], "offsets": [ [ 713, 721 ] ], "normalized": [] }, { "id": "PMID-10049785_T24", "type": "MessengerRNA", "text": [ "mRNA" ], "offsets": [ [ 745, 749 ] ], "normalized": [] }, { "id": "PMID-10049785_T25", "type": "Eukaryote", "text": [ "human" ], "offsets": [ [ 757, 762 ] ], "normalized": [] }, { "id": "PMID-10049785_T26", "type": "ProteinSubunit", "text": [ "alpha-subunit" ], "offsets": [ [ 763, 776 ] ], "normalized": [] }, { "id": "PMID-10049785_T28", "type": "Cell", "text": [ "CML" ], "offsets": [ [ 904, 907 ] ], "normalized": [] }, { "id": "PMID-10049785_T32", "type": "Eukaryote", "text": [ "human" ], "offsets": [ [ 946, 951 ] ], "normalized": [] }, { "id": "PMID-10049785_T33", "type": "Enzyme", "text": [ "PheRS" ], "offsets": [ [ 952, 957 ] ], "normalized": [] }, { "id": "PMID-10049785_T34", "type": "Eukaryote", "text": [ "human" ], "offsets": [ [ 977, 982 ] ], "normalized": [] }, { "id": "PMID-10049785_T35", "type": "tRNA", "text": [ "tRNA" ], "offsets": [ [ 1019, 1023 ] ], "normalized": [] }, { "id": "PMID-10049785_T37", "type": "Prokaryote", "text": [ "prokaryotes" ], "offsets": [ [ 1078, 1089 ] ], "normalized": [] }, { "id": "PMID-10049785_T38", "type": "Eukaryote", "text": [ "eukaryotes" ], "offsets": [ [ 1094, 1104 ] ], "normalized": [] }, { "id": "PMID-10049785_T39", "type": "AminoAcid", "text": [ "phenylalanine" ], "offsets": [ [ 1113, 1126 ] ], "normalized": [] }, { "id": "PMID-10049785_T40", "type": "Eukaryote", "text": [ "human" ], "offsets": [ [ 1198, 1203 ] ], "normalized": [] }, { "id": "PMID-10049785_T41", "type": "Tissue", "text": [ "tissues" ], "offsets": [ [ 1204, 1211 ] ], "normalized": [] }, { "id": "PMID-10049785_T43", "type": "ProteinSubunit", "text": [ "alpha- and beta-subunits" ], "offsets": [ [ 1271, 1295 ] ], "normalized": [] }, { "id": "PMID-10049785_T46", "type": "ProteinSubunit", "text": [ "beta-subunit" ], "offsets": [ [ 1368, 1380 ] ], "normalized": [] }, { "id": "PMID-10049785_T47", "type": "MessengerRNA", "text": [ "mRNA" ], "offsets": [ [ 1418, 1422 ] ], "normalized": [] }, { "id": "PMID-10049785_T48", "type": "ProteinSubunit", "text": [ "alpha- and beta-subunits" ], "offsets": [ [ 1444, 1468 ] ], "normalized": [] }, { "id": "PMID-10049785_T50", "type": "Cell", "text": [ "cell" ], "offsets": [ [ 1500, 1504 ] ], "normalized": [] }, { "id": "PMID-10049785_T51", "type": "Tissue", "text": [ "tissues" ], "offsets": [ [ 1515, 1522 ] ], "normalized": [] }, { "id": "PMID-10049785_T52", "type": "Sequence", "text": [ "sequences" ], "offsets": [ [ 88, 97 ] ], "normalized": [] }, { "id": "PMID-10049785_T8", "type": "CatalyticActivity", "text": [ "catalytic" ], "offsets": [ [ 248, 257 ] ], "normalized": [] }, { "id": "PMID-10049785_T12", "type": "Enzyme", "text": [ "PheRS" ], "offsets": [ [ 350, 355 ] ], "normalized": [] }, { "id": "PMID-10049785_T45", "type": "Protein", "text": [ "(alphabeta)2" ], "offsets": [ [ 1579, 1591 ] ], "normalized": [] } ]

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[]

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[ { "id": "PMID-10049787__text", "type": "abstract", "text": [ "Parathyroid hormone-regulated production of stem cell factor in human osteoblasts and osteoblast-like cells. We investigated stem cell factor (SCF) expression in osteoblasts because mast cells, which occur ectopically in hyperparathyroid bone, are induced by SCF. Nontransformed osteoblasts and Saos2 or MG63 cells expressed SCF in response to PTH. Western analysis showed only large, cell-associated isoforms, Mrs approximately 40-48 kD. Transfection of MG63 cells with plasmids expressing antisense SCF mRNA eliminated immunoreactive SCF. Sequencing osteoblast SCF cDNAs showed that exon 6 was omitted. mRNAs without exon 6 produce membrane-associated SCF isoforms in rodents, suggesting that human SCFs are processed similarly. The major osteoblastic SCF mRNA, approximately 5 kB, was augmented by PTH. Neither protein or mRNA was increased by vitamin D, however, 6-7 kB transcripts were predominant in other tissues but not detectable in osteoblasts. We conclude that osteoblasts express SCF in response to PTH, with mRNA and protein processing differences relative to other cells. SCF stimulates osteoclasts, suggesting that PTH-induced osteoblastic SCF functions to accelerate bone turnover. Mast cells may occur due to SCF overexpression at extreme PTH levels.\n" ], "offsets": [ [ 0, 1268 ] ] } ]

[ { "id": "PMID-10049787_T1", "type": "Peptide", "text": [ "Parathyroid hormone" ], "offsets": [ [ 0, 19 ] ], "normalized": [] }, { "id": "PMID-10049787_T3", "type": "Protein", "text": [ "stem cell factor" ], "offsets": [ [ 44, 60 ] ], "normalized": [] }, { "id": "PMID-10049787_T4", "type": "Eukaryote", "text": [ "human" ], "offsets": [ [ 64, 69 ] ], "normalized": [] }, { "id": "PMID-10049787_T5", "type": "Cell", "text": [ "osteoblasts" ], "offsets": [ [ 70, 81 ] ], "normalized": [] }, { "id": "PMID-10049787_T6", "type": "Cell", "text": [ "osteoblast-like cells" ], "offsets": [ [ 86, 107 ] ], "normalized": [] }, { "id": "PMID-10049787_T7", "type": "Protein", "text": [ "stem cell factor" ], "offsets": [ [ 125, 141 ] ], "normalized": [] }, { "id": "PMID-10049787_T8", "type": "Protein", "text": [ "SCF" ], "offsets": [ [ 143, 146 ] ], "normalized": [] }, { "id": "PMID-10049787_T10", "type": "Cell", "text": [ "osteoblasts" ], "offsets": [ [ 162, 173 ] ], "normalized": [] }, { "id": "PMID-10049787_T11", "type": "Cell", "text": [ "mast cells" ], "offsets": [ [ 182, 192 ] ], "normalized": [] }, { "id": "PMID-10049787_T12", "type": "Protein", "text": [ "SCF" ], "offsets": [ [ 259, 262 ] ], "normalized": [] }, { "id": "PMID-10049787_T13", "type": "Cell", "text": [ "osteoblasts" ], "offsets": [ [ 279, 290 ] ], "normalized": [] }, { "id": "PMID-10049787_T14", "type": "Cell", "text": [ "Saos2" ], "offsets": [ [ 295, 300 ] ], "normalized": [] }, { "id": "PMID-10049787_T15", "type": "Cell", "text": [ "MG63 cells" ], "offsets": [ [ 304, 314 ] ], "normalized": [] }, { "id": "PMID-10049787_T17", "type": "Protein", "text": [ "SCF" ], "offsets": [ [ 325, 328 ] ], "normalized": [] }, { "id": "PMID-10049787_T18", "type": "Peptide", "text": [ "PTH" ], "offsets": [ [ 344, 347 ] ], "normalized": [] }, { "id": "PMID-10049787_T19", "type": "Cell", "text": [ "cell" ], "offsets": [ [ 385, 389 ] ], "normalized": [] }, { "id": "PMID-10049787_T20", "type": "Cell", "text": [ "MG63 cells" ], "offsets": [ [ 455, 465 ] ], "normalized": [] }, { "id": "PMID-10049787_T25", "type": "Protein", "text": [ "SCF" ], "offsets": [ [ 536, 539 ] ], "normalized": [] }, { "id": "PMID-10049787_T26", "type": "Cell", "text": [ "osteoblast" ], "offsets": [ [ 552, 562 ] ], "normalized": [] }, { "id": "PMID-10049787_T27", "type": "Protein", "text": [ "SCF" ], "offsets": [ [ 563, 566 ] ], "normalized": [] }, { "id": "PMID-10049787_T28", "type": "DNA", "text": [ "cDNAs" ], "offsets": [ [ 567, 572 ] ], "normalized": [] }, { "id": "PMID-10049787_T29", "type": "MessengerRNA", "text": [ "mRNAs" ], "offsets": [ [ 605, 610 ] ], "normalized": [] }, { "id": "PMID-10049787_T30", "type": "Protein", "text": [ "SCF isoforms" ], "offsets": [ [ 654, 666 ] ], "normalized": [] }, { "id": "PMID-10049787_T31", "type": "Eukaryote", "text": [ "rodents" ], "offsets": [ [ 670, 677 ] ], "normalized": [] }, { "id": "PMID-10049787_T32", "type": "Eukaryote", "text": [ "human" ], "offsets": [ [ 695, 700 ] ], "normalized": [] }, { "id": "PMID-10049787_T33", "type": "Protein", "text": [ "SCFs" ], "offsets": [ [ 701, 705 ] ], "normalized": [] }, { "id": "PMID-10049787_T34", "type": "Cell", "text": [ "osteoblastic" ], "offsets": [ [ 741, 753 ] ], "normalized": [] }, { "id": "PMID-10049787_T35", "type": "Protein", "text": [ "SCF" ], "offsets": [ [ 754, 757 ] ], "normalized": [] }, { "id": "PMID-10049787_T36", "type": "MessengerRNA", "text": [ "mRNA" ], "offsets": [ [ 758, 762 ] ], "normalized": [] }, { "id": "PMID-10049787_T37", "type": "Peptide", "text": [ "PTH" ], "offsets": [ [ 801, 804 ] ], "normalized": [] }, { "id": "PMID-10049787_T38", "type": "Protein", "text": [ "protein" ], "offsets": [ [ 814, 821 ] ], "normalized": [] }, { "id": "PMID-10049787_T39", "type": "MessengerRNA", "text": [ "mRNA" ], "offsets": [ [ 825, 829 ] ], "normalized": [] }, { "id": "PMID-10049787_T40", "type": "Chemical", "text": [ "vitamin D" ], "offsets": [ [ 847, 856 ] ], "normalized": [] }, { "id": "PMID-10049787_T41", "type": "Transcript", "text": [ "transcripts" ], "offsets": [ [ 874, 885 ] ], "normalized": [] }, { "id": "PMID-10049787_T42", "type": "Tissue", "text": [ "tissues" ], "offsets": [ [ 912, 919 ] ], "normalized": [] }, { "id": "PMID-10049787_T43", "type": "Cell", "text": [ "osteoblasts" ], "offsets": [ [ 942, 953 ] ], "normalized": [] }, { "id": "PMID-10049787_T44", "type": "Cell", "text": [ "osteoblasts" ], "offsets": [ [ 972, 983 ] ], "normalized": [] }, { "id": "PMID-10049787_T46", "type": "Protein", "text": [ "SCF" ], "offsets": [ [ 992, 995 ] ], "normalized": [] }, { "id": "PMID-10049787_T47", "type": "Peptide", "text": [ "PTH" ], "offsets": [ [ 1011, 1014 ] ], "normalized": [] }, { "id": "PMID-10049787_T48", "type": "MessengerRNA", "text": [ "mRNA" ], "offsets": [ [ 1021, 1025 ] ], "normalized": [] }, { "id": "PMID-10049787_T49", "type": "Protein", "text": [ "protein" ], "offsets": [ [ 1030, 1037 ] ], "normalized": [] }, { "id": "PMID-10049787_T50", "type": "Cell", "text": [ "cells" ], "offsets": [ [ 1079, 1084 ] ], "normalized": [] }, { "id": "PMID-10049787_T51", "type": "Protein", "text": [ "SCF" ], "offsets": [ [ 1086, 1089 ] ], "normalized": [] }, { "id": "PMID-10049787_T53", "type": "Cell", "text": [ "osteoclasts" ], "offsets": [ [ 1101, 1112 ] ], "normalized": [] }, { "id": "PMID-10049787_T54", "type": "Peptide", "text": [ "PTH" ], "offsets": [ [ 1130, 1133 ] ], "normalized": [] }, { "id": "PMID-10049787_T55", "type": "Cell", "text": [ "osteoblastic" ], "offsets": [ [ 1142, 1154 ] ], "normalized": [] }, { "id": "PMID-10049787_T56", "type": "Protein", "text": [ "SCF" ], "offsets": [ [ 1155, 1158 ] ], "normalized": [] }, { "id": "PMID-10049787_T57", "type": "Cell", "text": [ "Mast cells" ], "offsets": [ [ 1198, 1208 ] ], "normalized": [] }, { "id": "PMID-10049787_T58", "type": "Protein", "text": [ "SCF" ], "offsets": [ [ 1226, 1229 ] ], "normalized": [] }, { "id": "PMID-10049787_T60", "type": "Peptide", "text": [ "PTH" ], "offsets": [ [ 1256, 1259 ] ], "normalized": [] }, { "id": "PMID-10049787_T22", "type": "AntisenseRNA", "text": [ "antisense SCF mRNA" ], "offsets": [ [ 491, 509 ] ], "normalized": [] }, { "id": "PMID-10049787_T23", "type": "Exon", "text": [ "exon 6" ], "offsets": [ [ 619, 625 ] ], "normalized": [] }, { "id": "PMID-10049787_T63", "type": "CellComponent", "text": [ "membrane" ], "offsets": [ [ 634, 642 ] ], "normalized": [] } ]

[ { "id": "PMID-10049787_E1", "type": "RegulatoryProcess", "trigger": { "text": [ "regulated" ], "offsets": [ [ 20, 29 ] ] }, "arguments": [ { "role": "hasAgent", "ref_id": "PMID-10049787_T1" }, { "role": "hasPatient", "ref_id": "PMID-10049787_E9" } ] }, { "id": "PMID-10049787_E2", "type": "GeneExpression", "trigger": { "text": [ "expression" ], "offsets": [ [ 148, 158 ] ] }, "arguments": [ { "role": "hasPatient", "ref_id": "PMID-10049787_T7" } ] }, { "id": "PMID-10049787_E3", "type": "GeneExpression", "trigger": { "text": [ "expressed" ], "offsets": [ [ 315, 324 ] ] }, "arguments": [ { "role": "hasPatient", "ref_id": "PMID-10049787_T17" } ] }, { "id": "PMID-10049787_E4", "type": "GeneExpression", "trigger": { "text": [ "expressing" ], "offsets": [ [ 480, 490 ] ] }, "arguments": [ { "role": "hasPatient", "ref_id": "PMID-10049787_T22" } ] }, { "id": "PMID-10049787_E5", "type": "NegativeRegulation", "trigger": { "text": [ "eliminated" ], "offsets": [ [ 510, 520 ] ] }, "arguments": [ { "role": "hasAgent", "ref_id": "PMID-10049787_E4" }, { "role": "hasPatient", "ref_id": "PMID-10049787_T25" } ] }, { "id": "PMID-10049787_E6", "type": "GeneExpression", "trigger": { "text": [ "express" ], "offsets": [ [ 984, 991 ] ] }, "arguments": [ { "role": "hasAgent", "ref_id": "PMID-10049787_T47" }, { "role": "hasPatient", "ref_id": "PMID-10049787_T46" } ] }, { "id": "PMID-10049787_E7", "type": "PositiveRegulation", "trigger": { "text": [ "stimulates" ], "offsets": [ [ 1090, 1100 ] ] }, "arguments": [ { "role": "hasAgent", "ref_id": "PMID-10049787_T51" }, { "role": "hasPatient", "ref_id": "PMID-10049787_T53" } ] }, { "id": "PMID-10049787_E8", "type": "PositiveRegulationOfGeneExpression", "trigger": { "text": [ "overexpression" ], "offsets": [ [ 1230, 1244 ] ] }, "arguments": [ { "role": "hasPatient", "ref_id": "PMID-10049787_T58" } ] }, { "id": "PMID-10049787_E9", "type": "ProteinBiosynthesis", "trigger": { "text": [ "production" ], "offsets": [ [ 30, 40 ] ] }, "arguments": [ { "role": "hasPatient", "ref_id": "PMID-10049787_T3" } ] }, { "id": "PMID-10049787_E10", "type": "ResponseProcess", "trigger": { "text": [ "response" ], "offsets": [ [ 332, 340 ] ] }, "arguments": [ { "role": "hasAgent", "ref_id": "PMID-10049787_T18" }, { "role": "hasPatient", "ref_id": "PMID-10049787_E3" } ] }, { "id": "PMID-10049787_E11", "type": "MetabolicPathway", "trigger": { "text": [ "bone turnover" ], "offsets": [ [ 1183, 1196 ] ] }, "arguments": [ { "role": "hasAgent", "ref_id": "PMID-10049787_T56" } ] } ]

[]

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[ { "id": "PMID-10049942__text", "type": "abstract", "text": [ "NKp44, a triggering receptor involved in tumor cell lysis by activated human natural killer cells, is a novel member of the immunoglobulin superfamily. Surface receptors involved in natural killer (NK) cell triggering during the process of tumor cell lysis have recently been identified. Of these receptors, NKp44 is selectively expressed by IL-2- activated NK cells and may contribute to the increased efficiency of activated NK cells to mediate tumor cell lysis. Here we describe the molecular cloning of NKp44. Analysis of the cloned cDNA indicated that NKp44 is a novel transmembrane glycoprotein belonging to the Immunoglobulin superfamily characterized by a single extracellular V-type domain. The charged amino acid lysine in the transmembrane region may be involved in the association of NKp44 with the signal transducing molecule killer activating receptor-associated polypeptide (KARAP)/DAP12. These molecules were found to be crucial for the surface expression of NKp44. In agreement with data of NKp44 surface expression, the NKp44 transcripts were strictly confined to activated NK cells and to a minor subset of TCR-gamma/delta+ T lymphocytes. Unlike genes coding for other receptors involved in NK cell triggering or inhibition, the NKp44 gene is on human chromosome 6.\n" ], "offsets": [ [ 0, 1285 ] ] } ]

[ { "id": "PMID-10049942_T1", "type": "Protein", "text": [ "NKp44" ], "offsets": [ [ 0, 5 ] ], "normalized": [] }, { "id": "PMID-10049942_T2", "type": "Protein", "text": [ "receptor" ], "offsets": [ [ 20, 28 ] ], "normalized": [] }, { "id": "PMID-10049942_T5", "type": "Eukaryote", "text": [ "human" ], "offsets": [ [ 71, 76 ] ], "normalized": [] }, { "id": "PMID-10049942_T6", "type": "Cell", "text": [ "natural killer cells" ], "offsets": [ [ 77, 97 ] ], "normalized": [] }, { "id": "PMID-10049942_T7", "type": "Protein", "text": [ "immunoglobulin" ], "offsets": [ [ 124, 138 ] ], "normalized": [] }, { "id": "PMID-10049942_T8", "type": "Protein", "text": [ "receptors" ], "offsets": [ [ 160, 169 ] ], "normalized": [] }, { "id": "PMID-10049942_T10", "type": "Cell", "text": [ "NK" ], "offsets": [ [ 198, 200 ] ], "normalized": [] }, { "id": "PMID-10049942_T13", "type": "Protein", "text": [ "receptors" ], "offsets": [ [ 297, 306 ] ], "normalized": [] }, { "id": "PMID-10049942_T14", "type": "Protein", "text": [ "NKp44" ], "offsets": [ [ 308, 313 ] ], "normalized": [] }, { "id": "PMID-10049942_T16", "type": "Protein", "text": [ "IL-2" ], "offsets": [ [ 342, 346 ] ], "normalized": [] }, { "id": "PMID-10049942_T18", "type": "Cell", "text": [ "NK cells" ], "offsets": [ [ 358, 366 ] ], "normalized": [] }, { "id": "PMID-10049942_T20", "type": "Cell", "text": [ "NK cells" ], "offsets": [ [ 427, 435 ] ], "normalized": [] }, { "id": "PMID-10049942_T24", "type": "Protein", "text": [ "NKp44" ], "offsets": [ [ 507, 512 ] ], "normalized": [] }, { "id": "PMID-10049942_T25", "type": "DNA", "text": [ "cDNA" ], "offsets": [ [ 537, 541 ] ], "normalized": [] }, { "id": "PMID-10049942_T26", "type": "Protein", "text": [ "NKp44" ], "offsets": [ [ 557, 562 ] ], "normalized": [] }, { "id": "PMID-10049942_T27", "type": "Protein", "text": [ "glycoprotein" ], "offsets": [ [ 588, 600 ] ], "normalized": [] }, { "id": "PMID-10049942_T28", "type": "Protein", "text": [ "Immunoglobulin" ], "offsets": [ [ 618, 632 ] ], "normalized": [] }, { "id": "PMID-10049942_T29", "type": "ProteinDomain", "text": [ "V-type domain" ], "offsets": [ [ 685, 698 ] ], "normalized": [] }, { "id": "PMID-10049942_T31", "type": "Protein", "text": [ "NKp44" ], "offsets": [ [ 796, 801 ] ], "normalized": [] }, { "id": "PMID-10049942_T35", "type": "Protein", "text": [ "NKp44" ], "offsets": [ [ 975, 980 ] ], "normalized": [] }, { "id": "PMID-10049942_T36", "type": "Protein", "text": [ "NKp44" ], "offsets": [ [ 1008, 1013 ] ], "normalized": [] }, { "id": "PMID-10049942_T38", "type": "Protein", "text": [ "NKp44" ], "offsets": [ [ 1038, 1043 ] ], "normalized": [] }, { "id": "PMID-10049942_T39", "type": "Transcript", "text": [ "transcripts" ], "offsets": [ [ 1044, 1055 ] ], "normalized": [] }, { "id": "PMID-10049942_T41", "type": "Cell", "text": [ "NK cells" ], "offsets": [ [ 1092, 1100 ] ], "normalized": [] }, { "id": "PMID-10049942_T42", "type": "Cell", "text": [ "T lymphocytes" ], "offsets": [ [ 1143, 1156 ] ], "normalized": [] }, { "id": "PMID-10049942_T43", "type": "Gene", "text": [ "genes" ], "offsets": [ [ 1165, 1170 ] ], "normalized": [] }, { "id": "PMID-10049942_T44", "type": "Protein", "text": [ "receptors" ], "offsets": [ [ 1188, 1197 ] ], "normalized": [] }, { "id": "PMID-10049942_T45", "type": "Cell", "text": [ "NK cell" ], "offsets": [ [ 1210, 1217 ] ], "normalized": [] }, { "id": "PMID-10049942_T47", "type": "Protein", "text": [ "NKp44" ], "offsets": [ [ 1248, 1253 ] ], "normalized": [] }, { "id": "PMID-10049942_T48", "type": "Gene", "text": [ "gene" ], "offsets": [ [ 1254, 1258 ] ], "normalized": [] }, { "id": "PMID-10049942_T49", "type": "Eukaryote", "text": [ "human" ], "offsets": [ [ 1265, 1270 ] ], "normalized": [] }, { "id": "PMID-10049942_T50", "type": "Chromosome", "text": [ "chromosome" ], "offsets": [ [ 1271, 1281 ] ], "normalized": [] }, { "id": "PMID-10049942_T23", "type": "AminoAcid", "text": [ "charged amino acid lysine" ], "offsets": [ [ 704, 729 ] ], "normalized": [] }, { "id": "PMID-10049942_T30", "type": "CellComponent", "text": [ "transmembrane region" ], "offsets": [ [ 737, 757 ] ], "normalized": [] }, { "id": "PMID-10049942_T33", "type": "Protein", "text": [ "(KARAP)/DAP12" ], "offsets": [ [ 889, 902 ] ], "normalized": [] }, { "id": "PMID-10049942_T53", "type": "Protein", "text": [ "TCR-gamma/delta" ], "offsets": [ [ 1126, 1141 ] ], "normalized": [] } ]

[ { "id": "PMID-10049942_E1", "type": "PositiveRegulation", "trigger": { "text": [ "activated" ], "offsets": [ [ 61, 70 ] ] }, "arguments": [ { "role": "hasPatient", "ref_id": "PMID-10049942_T6" } ] }, { "id": "PMID-10049942_E2", "type": "GeneExpression", "trigger": { "text": [ "expressed" ], "offsets": [ [ 329, 338 ] ] }, "arguments": [ { "role": "hasPatient", "ref_id": "PMID-10049942_T14" } ] }, { "id": "PMID-10049942_E3", "type": "PositiveRegulation", "trigger": { "text": [ "activated" ], "offsets": [ [ 348, 357 ] ] }, "arguments": [ { "role": "hasAgent", "ref_id": "PMID-10049942_T16" }, { "role": "hasPatient", "ref_id": "PMID-10049942_T18" } ] }, { "id": "PMID-10049942_E4", "type": "PositiveRegulation", "trigger": { "text": [ "activated" ], "offsets": [ [ 417, 426 ] ] }, "arguments": [ { "role": "hasPatient", "ref_id": "PMID-10049942_T20" } ] }, { "id": "PMID-10049942_E5", "type": "RegulatoryProcess", "trigger": { "text": [ "mediate" ], "offsets": [ [ 439, 446 ] ] }, "arguments": [ { "role": "hasPatient", "ref_id": "PMID-10049942_E6" } ] }, { "id": "PMID-10049942_E8", "type": "GeneExpression", "trigger": { "text": [ "expression" ], "offsets": [ [ 961, 971 ] ] }, "arguments": [ { "role": "hasPatient", "ref_id": "PMID-10049942_T35" } ] }, { "id": "PMID-10049942_E9", "type": "GeneExpression", "trigger": { "text": [ "expression" ], "offsets": [ [ 1022, 1032 ] ] }, "arguments": [ { "role": "hasPatient", "ref_id": "PMID-10049942_T36" } ] }, { "id": "PMID-10049942_E10", "type": "PositiveRegulation", "trigger": { "text": [ "activated" ], "offsets": [ [ 1082, 1091 ] ] }, "arguments": [ { "role": "hasPatient", "ref_id": "PMID-10049942_T41" } ] }, { "id": "PMID-10049942_E11", "type": "NegativeRegulation", "trigger": { "text": [ "inhibition" ], "offsets": [ [ 1232, 1242 ] ] }, "arguments": [ { "role": "hasPatient", "ref_id": "PMID-10049942_T45" } ] }, { "id": "PMID-10049942_E12", "type": "CellDeath", "trigger": { "text": [ "tumor cell lysis" ], "offsets": [ [ 41, 57 ] ] }, "arguments": [] }, { "id": "PMID-10049942_E13", "type": "CellDeath", "trigger": { "text": [ "tumor cell lysis" ], "offsets": [ [ 240, 256 ] ] }, "arguments": [] }, { "id": "PMID-10049942_E6", "type": "CellDeath", "trigger": { "text": [ "tumor cell lysis" ], "offsets": [ [ 447, 463 ] ] }, "arguments": [] }, { "id": "PMID-10049942_E14", "type": "BindingToProtein", "trigger": { "text": [ "association" ], "offsets": [ [ 781, 792 ] ] }, "arguments": [ { "role": "hasPatient", "ref_id": "PMID-10049942_T31" }, { "role": "hasPatient2", "ref_id": "PMID-10049942_T33" } ] }, { "id": "PMID-10049942_E15", "type": "SignalingPathway", "trigger": { "text": [ "signal transducing" ], "offsets": [ [ 811, 829 ] ] }, "arguments": [] }, { "id": "PMID-10049942_E7", "type": "PositiveRegulation", "trigger": { "text": [ "triggering" ], "offsets": [ [ 1218, 1228 ] ] }, "arguments": [ { "role": "hasPatient", "ref_id": "PMID-10049942_T45" } ] } ]

[]

[ { "id": "PMID-10049942_R2", "type": "fromSpecies", "arg1_id": "PMID-10049942_T6", "arg2_id": "PMID-10049942_T5", "normalized": [] }, { "id": "PMID-10049942_R3", "type": "locatedIn", "arg1_id": "PMID-10049942_T8", "arg2_id": "PMID-10049942_T10", "normalized": [] }, { "id": "PMID-10049942_R5", "type": "encodes", "arg1_id": "PMID-10049942_T39", "arg2_id": "PMID-10049942_T38", "normalized": [] }, { "id": "PMID-10049942_R6", "type": "locatedIn", "arg1_id": "PMID-10049942_T39", "arg2_id": "PMID-10049942_T41", "normalized": [] }, { "id": "PMID-10049942_R7", "type": "encodes", "arg1_id": "PMID-10049942_T43", "arg2_id": "PMID-10049942_T44", "normalized": [] }, { "id": "PMID-10049942_R9", "type": "encodes", "arg1_id": "PMID-10049942_T48", "arg2_id": "PMID-10049942_T47", "normalized": [] }, { "id": "PMID-10049942_R10", "type": "locatedIn", "arg1_id": "PMID-10049942_T48", "arg2_id": "PMID-10049942_T50", "normalized": [] }, { "id": "PMID-10049942_R11", "type": "fromSpecies", "arg1_id": "PMID-10049942_T50", "arg2_id": "PMID-10049942_T49", "normalized": [] }, { "id": "PMID-10049942_R1", "type": "locatedIn", "arg1_id": "PMID-10049942_T23", "arg2_id": "PMID-10049942_T30", "normalized": [] } ]

[ { "id": "PMID-10050887__text", "type": "abstract", "text": [ "Nuclear and nucleolar targeting of human ribosomal protein S25: common features shared with HIV-1 regulatory proteins. The nuclear and nucleolar targeting properties of human ribosomal protein S25 (RPS25) were analysed by the expression of epitope-tagged RPS25 cDNAs in Cos-1 cells. The tagged RPS25 was localized to the cell nucleus, with a strong predominance in the nucleolus. At the amino terminus of RPS25, two stretches of highly basic residues juxtapose. This configuration shares common features with the nucleolar targeting signals (NOS) of lentiviral RNA-binding transactivators, including human immunodeficiency viruses' (HIV) Rev proteins. Deletion and site-directed mutational analyses demonstrated that the first NOS-like stretch is dispensable for both nuclear and nucleolar localization of RPS25, and that the nuclear targeting signal is located within the second NOS-like stretch. It has also been suggested that a set of continuous basic residues and the total number of basic residues should be required for nucleolar targeting. Signal-mediated nuclear/nucleolar targeting was further characterized by the construction and expression of a variety of chimeric constructs, utilizing three different backbones with RPS25 cDNA fragments. Immunofluorescence analyses demonstrated a 17 residue peptide of RPS25 as a potential nuclear/nucleolar targeting signal. The identified peptide signal may belong to a putative subclass of NOS, characterized by compact structure, together with lentiviral RNA-binding transactivators.\n" ], "offsets": [ [ 0, 1537 ] ] } ]

[ { "id": "PMID-10050887_T2", "type": "Eukaryote", "text": [ "human" ], "offsets": [ [ 35, 40 ] ], "normalized": [] }, { "id": "PMID-10050887_T6", "type": "Virus", "text": [ "HIV-1" ], "offsets": [ [ 92, 97 ] ], "normalized": [] }, { "id": "PMID-10050887_T7", "type": "Protein", "text": [ "regulatory proteins" ], "offsets": [ [ 98, 117 ] ], "normalized": [] }, { "id": "PMID-10050887_T9", "type": "Eukaryote", "text": [ "human" ], "offsets": [ [ 169, 174 ] ], "normalized": [] }, { "id": "PMID-10050887_T13", "type": "Protein", "text": [ "RPS25" ], "offsets": [ [ 198, 203 ] ], "normalized": [] }, { "id": "PMID-10050887_T15", "type": "Protein", "text": [ "RPS25" ], "offsets": [ [ 255, 260 ] ], "normalized": [] }, { "id": "PMID-10050887_T16", "type": "DNA", "text": [ "cDNAs" ], "offsets": [ [ 261, 266 ] ], "normalized": [] }, { "id": "PMID-10050887_T17", "type": "Cell", "text": [ "Cos-1 cells" ], "offsets": [ [ 270, 281 ] ], "normalized": [] }, { "id": "PMID-10050887_T18", "type": "Protein", "text": [ "RPS25" ], "offsets": [ [ 294, 299 ] ], "normalized": [] }, { "id": "PMID-10050887_T19", "type": "Cell", "text": [ "cell" ], "offsets": [ [ 321, 325 ] ], "normalized": [] }, { "id": "PMID-10050887_T20", "type": "Nucleus", "text": [ "nucleus" ], "offsets": [ [ 326, 333 ] ], "normalized": [] }, { "id": "PMID-10050887_T21", "type": "Nucleus", "text": [ "nucleolus" ], "offsets": [ [ 369, 378 ] ], "normalized": [] }, { "id": "PMID-10050887_T22", "type": "Protein", "text": [ "RPS25" ], "offsets": [ [ 405, 410 ] ], "normalized": [] }, { "id": "PMID-10050887_T23", "type": "Peptide", "text": [ "nucleolar targeting signals" ], "offsets": [ [ 513, 540 ] ], "normalized": [] }, { "id": "PMID-10050887_T24", "type": "Peptide", "text": [ "NOS" ], "offsets": [ [ 542, 545 ] ], "normalized": [] }, { "id": "PMID-10050887_T25", "type": "RNA", "text": [ "RNA" ], "offsets": [ [ 561, 564 ] ], "normalized": [] }, { "id": "PMID-10050887_T27", "type": "TranscriptionActivator", "text": [ "transactivators" ], "offsets": [ [ 573, 588 ] ], "normalized": [] }, { "id": "PMID-10050887_T28", "type": "Virus", "text": [ "human immunodeficiency viruses'" ], "offsets": [ [ 600, 631 ] ], "normalized": [] }, { "id": "PMID-10050887_T29", "type": "Virus", "text": [ "HIV" ], "offsets": [ [ 633, 636 ] ], "normalized": [] }, { "id": "PMID-10050887_T30", "type": "Protein", "text": [ "Rev proteins" ], "offsets": [ [ 638, 650 ] ], "normalized": [] }, { "id": "PMID-10050887_T31", "type": "Peptide", "text": [ "NOS" ], "offsets": [ [ 727, 730 ] ], "normalized": [] }, { "id": "PMID-10050887_T33", "type": "Protein", "text": [ "RPS25" ], "offsets": [ [ 806, 811 ] ], "normalized": [] }, { "id": "PMID-10050887_T34", "type": "Peptide", "text": [ "nuclear targeting signal" ], "offsets": [ [ 826, 850 ] ], "normalized": [] }, { "id": "PMID-10050887_T35", "type": "Peptide", "text": [ "NOS" ], "offsets": [ [ 880, 883 ] ], "normalized": [] }, { "id": "PMID-10050887_T36", "type": "Nucleus", "text": [ "nucleolar" ], "offsets": [ [ 1027, 1036 ] ], "normalized": [] }, { "id": "PMID-10050887_T39", "type": "Protein", "text": [ "RPS25" ], "offsets": [ [ 1231, 1236 ] ], "normalized": [] }, { "id": "PMID-10050887_T40", "type": "DNA", "text": [ "cDNA" ], "offsets": [ [ 1237, 1241 ] ], "normalized": [] }, { "id": "PMID-10050887_T41", "type": "Peptide", "text": [ "peptide" ], "offsets": [ [ 1307, 1314 ] ], "normalized": [] }, { "id": "PMID-10050887_T42", "type": "Protein", "text": [ "RPS25" ], "offsets": [ [ 1318, 1323 ] ], "normalized": [] }, { "id": "PMID-10050887_T43", "type": "Peptide", "text": [ "peptide" ], "offsets": [ [ 1390, 1397 ] ], "normalized": [] }, { "id": "PMID-10050887_T44", "type": "Peptide", "text": [ "NOS" ], "offsets": [ [ 1442, 1445 ] ], "normalized": [] }, { "id": "PMID-10050887_T45", "type": "RNA", "text": [ "RNA" ], "offsets": [ [ 1508, 1511 ] ], "normalized": [] }, { "id": "PMID-10050887_T47", "type": "TranscriptionActivator", "text": [ "transactivators" ], "offsets": [ [ 1520, 1535 ] ], "normalized": [] }, { "id": "PMID-10050887_T3", "type": "Protein", "text": [ "ribosomal protein S25" ], "offsets": [ [ 41, 62 ] ], "normalized": [] }, { "id": "PMID-10050887_T5", "type": "Protein", "text": [ "ribosomal protein S25" ], "offsets": [ [ 175, 196 ] ], "normalized": [] }, { "id": "PMID-10050887_T8", "type": "Virus", "text": [ "lentiviral" ], "offsets": [ [ 550, 560 ] ], "normalized": [] }, { "id": "PMID-10050887_T11", "type": "Nucleus", "text": [ "nuclear and nucleolar" ], "offsets": [ [ 768, 789 ] ], "normalized": [] }, { "id": "PMID-10050887_T1", "type": "Nucleus", "text": [ "Nuclear and nucleolar" ], "offsets": [ [ 0, 21 ] ], "normalized": [] }, { "id": "PMID-10050887_T4", "type": "Nucleus", "text": [ "nuclear and nucleolar" ], "offsets": [ [ 123, 144 ] ], "normalized": [] }, { "id": "PMID-10050887_T49", "type": "Nucleus", "text": [ "nuclear/nucleolar" ], "offsets": [ [ 1064, 1081 ] ], "normalized": [] }, { "id": "PMID-10050887_T51", "type": "Peptide", "text": [ "Signal" ], "offsets": [ [ 1048, 1054 ] ], "normalized": [] }, { "id": "PMID-10050887_T52", "type": "Virus", "text": [ "lentiviral" ], "offsets": [ [ 1497, 1507 ] ], "normalized": [] } ]

[ { "id": "PMID-10050887_E1", "type": "GeneExpression", "trigger": { "text": [ "expression" ], "offsets": [ [ 226, 236 ] ] }, "arguments": [ { "role": "hasPatient", "ref_id": "PMID-10050887_T16" } ] }, { "id": "PMID-10050887_E2", "type": "BindingToRNA", "trigger": { "text": [ "binding" ], "offsets": [ [ 565, 572 ] ] }, "arguments": [ { "role": "hasPatient", "ref_id": "PMID-10050887_T25" }, { "role": "hasPatient2", "ref_id": "PMID-10050887_T27" } ] }, { "id": "PMID-10050887_E3", "type": "RegulatoryProcess", "trigger": { "text": [ "mediated" ], "offsets": [ [ 1055, 1063 ] ] }, "arguments": [ { "role": "hasPatient", "ref_id": "PMID-10050887_E10" }, { "role": "hasAgent", "ref_id": "PMID-10050887_T51" } ] }, { "id": "PMID-10050887_E4", "type": "GeneExpression", "trigger": { "text": [ "expression" ], "offsets": [ [ 1142, 1152 ] ] }, "arguments": [ { "role": "hasPatient", "ref_id": "PMID-10050887_T40" } ] }, { "id": "PMID-10050887_E5", "type": "BindingToRNA", "trigger": { "text": [ "binding" ], "offsets": [ [ 1512, 1519 ] ] }, "arguments": [ { "role": "hasPatient", "ref_id": "PMID-10050887_T45" }, { "role": "hasPatient2", "ref_id": "PMID-10050887_T47" } ] }, { "id": "PMID-10050887_E8", "type": "Localization", "trigger": { "text": [ "localization" ], "offsets": [ [ 790, 802 ] ] }, "arguments": [ { "role": "hasPatient", "ref_id": "PMID-10050887_T33" } ] }, { "id": "PMID-10050887_E9", "type": "ProteinTargeting", "trigger": { "text": [ "targeting" ], "offsets": [ [ 1037, 1046 ] ] }, "arguments": [] }, { "id": "PMID-10050887_E6", "type": "ProteinTargeting", "trigger": { "text": [ "targeting" ], "offsets": [ [ 22, 31 ] ] }, "arguments": [ { "role": "hasPatient", "ref_id": "PMID-10050887_T3" } ] }, { "id": "PMID-10050887_E7", "type": "ProteinTargeting", "trigger": { "text": [ "targeting" ], "offsets": [ [ 145, 154 ] ] }, "arguments": [ { "role": "hasPatient", "ref_id": "PMID-10050887_T5" } ] }, { "id": "PMID-10050887_E10", "type": "ProteinTargeting", "trigger": { "text": [ "targeting" ], "offsets": [ [ 1082, 1091 ] ] }, "arguments": [] } ]

[]

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[ { "id": "PMID-10050892__text", "type": "abstract", "text": [ "Ma1, a novel neuron- and testis-specific protein, is recognized by the serum of patients with paraneoplastic neurological disorders. The identification of antineuronal antibodies has facilitated the diagnosis of paraneoplastic neurological disorders and the early detection of the associated tumours. It has also led to the cloning of possibly important neuron-specific proteins. In this study we wanted to identify novel antineuronal antibodies in the sera of patients with paraneoplastic neurological disorders and to clone the corresponding antigens. Serological studies of 1705 sera from patients with suspected paraneoplastic neurological disorders resulted in the identification of four patients with antibodies that reacted with 37 and 40 kDa neuronal proteins (anti-Ma antibodies). Three patients had brainstem and cerebellar dysfunction, and one had dysphagia and motor weakness. Autopsy of two patients showed loss of Purkinje cells, Bergmann gliosis and deep cerebellar white matter inflammatory infiltrates. Extensive neuronal degeneration, gliosis and infiltrates mainly composed of CD8+ T cells were also found in the brainstem of one patient. In normal human and rat tissues, the anti-Ma antibodies reacted exclusively with neurons and with testicular germ cells; the reaction was mainly with subnuclear elements (including the nucleoli) and to a lesser degree the cytoplasm. Anti-Ma antibodies also reacted with the cancers (breast, colon and parotid) available from three anti-Ma patients, but not with 66 other tumours of varying histological types. Preincubation of tissues with any of the anti-Ma sera abrogated the reactivity of the other anti-Ma immunoglobulins. Probing of a human complementary DNA library with anti-Ma serum resulted in the cloning of a gene that encodes a novel 37 kDa protein (Mal). Recombinant Mal was specifically recognized by the four anti-Ma sera but not by 337 control sera, including those from 52 normal individuals, 179 cancer patients without paraneoplastic neurological symptoms, 96 patients with paraneoplastic syndromes and 10 patients with non-cancer-related neurological disorders. The expression of Mal mRNA is highly restricted to the brain and testis. Subsequent analysis suggested that Mal is likely to be a phosphoprotein. Our study demonstrates that some patients with paraneoplastic neurological disorders develop antibodies against Mal, a new member of an expanding family of 'brain/testis' proteins.\n" ], "offsets": [ [ 0, 2467 ] ] } ]

[ { "id": "PMID-10050892_T1", "type": "Protein", "text": [ "Ma1" ], "offsets": [ [ 0, 3 ] ], "normalized": [] }, { "id": "PMID-10050892_T2", "type": "Tissue", "text": [ "neuron" ], "offsets": [ [ 13, 19 ] ], "normalized": [] }, { "id": "PMID-10050892_T3", "type": "Tissue", "text": [ "testis" ], "offsets": [ [ 25, 31 ] ], "normalized": [] }, { "id": "PMID-10050892_T4", "type": "Protein", "text": [ "protein" ], "offsets": [ [ 41, 48 ] ], "normalized": [] }, { "id": "PMID-10050892_T6", "type": "Protein", "text": [ "antibodies" ], "offsets": [ [ 168, 178 ] ], "normalized": [] }, { "id": "PMID-10050892_T8", "type": "Tissue", "text": [ "neuron" ], "offsets": [ [ 354, 360 ] ], "normalized": [] }, { "id": "PMID-10050892_T9", "type": "Protein", "text": [ "proteins" ], "offsets": [ [ 370, 378 ] ], "normalized": [] }, { "id": "PMID-10050892_T10", "type": "Protein", "text": [ "antibodies" ], "offsets": [ [ 435, 445 ] ], "normalized": [] }, { "id": "PMID-10050892_T13", "type": "Protein", "text": [ "antibodies" ], "offsets": [ [ 707, 717 ] ], "normalized": [] }, { "id": "PMID-10050892_T14", "type": "Protein", "text": [ "proteins" ], "offsets": [ [ 759, 767 ] ], "normalized": [] }, { "id": "PMID-10050892_T15", "type": "Protein", "text": [ "antibodies" ], "offsets": [ [ 777, 787 ] ], "normalized": [] }, { "id": "PMID-10050892_T16", "type": "Cell", "text": [ "Purkinje cells" ], "offsets": [ [ 928, 942 ] ], "normalized": [] }, { "id": "PMID-10050892_T17", "type": "Cell", "text": [ "T cells" ], "offsets": [ [ 1101, 1108 ] ], "normalized": [] }, { "id": "PMID-10050892_T18", "type": "Tissue", "text": [ "brainstem" ], "offsets": [ [ 1132, 1141 ] ], "normalized": [] }, { "id": "PMID-10050892_T19", "type": "Eukaryote", "text": [ "human" ], "offsets": [ [ 1168, 1173 ] ], "normalized": [] }, { "id": "PMID-10050892_T20", "type": "Eukaryote", "text": [ "rat" ], "offsets": [ [ 1178, 1181 ] ], "normalized": [] }, { "id": "PMID-10050892_T21", "type": "Tissue", "text": [ "tissues" ], "offsets": [ [ 1182, 1189 ] ], "normalized": [] }, { "id": "PMID-10050892_T22", "type": "Protein", "text": [ "antibodies" ], "offsets": [ [ 1203, 1213 ] ], "normalized": [] }, { "id": "PMID-10050892_T23", "type": "Tissue", "text": [ "neurons" ], "offsets": [ [ 1239, 1246 ] ], "normalized": [] }, { "id": "PMID-10050892_T24", "type": "Tissue", "text": [ "testicular" ], "offsets": [ [ 1256, 1266 ] ], "normalized": [] }, { "id": "PMID-10050892_T25", "type": "Cell", "text": [ "germ cells" ], "offsets": [ [ 1267, 1277 ] ], "normalized": [] }, { "id": "PMID-10050892_T26", "type": "Nucleus", "text": [ "nucleoli" ], "offsets": [ [ 1343, 1351 ] ], "normalized": [] }, { "id": "PMID-10050892_T27", "type": "CellComponent", "text": [ "cytoplasm" ], "offsets": [ [ 1380, 1389 ] ], "normalized": [] }, { "id": "PMID-10050892_T28", "type": "Protein", "text": [ "antibodies" ], "offsets": [ [ 1399, 1409 ] ], "normalized": [] }, { "id": "PMID-10050892_T29", "type": "Tissue", "text": [ "breast" ], "offsets": [ [ 1441, 1447 ] ], "normalized": [] }, { "id": "PMID-10050892_T30", "type": "Tissue", "text": [ "colon" ], "offsets": [ [ 1449, 1454 ] ], "normalized": [] }, { "id": "PMID-10050892_T31", "type": "Tissue", "text": [ "parotid" ], "offsets": [ [ 1459, 1466 ] ], "normalized": [] }, { "id": "PMID-10050892_T32", "type": "Tissue", "text": [ "tissues" ], "offsets": [ [ 1585, 1592 ] ], "normalized": [] }, { "id": "PMID-10050892_T34", "type": "Protein", "text": [ "immunoglobulins" ], "offsets": [ [ 1668, 1683 ] ], "normalized": [] }, { "id": "PMID-10050892_T35", "type": "Eukaryote", "text": [ "human" ], "offsets": [ [ 1698, 1703 ] ], "normalized": [] }, { "id": "PMID-10050892_T36", "type": "DNA", "text": [ "complementary DNA" ], "offsets": [ [ 1704, 1721 ] ], "normalized": [] }, { "id": "PMID-10050892_T37", "type": "Gene", "text": [ "gene" ], "offsets": [ [ 1778, 1782 ] ], "normalized": [] }, { "id": "PMID-10050892_T38", "type": "Protein", "text": [ "protein" ], "offsets": [ [ 1811, 1818 ] ], "normalized": [] }, { "id": "PMID-10050892_T39", "type": "Protein", "text": [ "Mal" ], "offsets": [ [ 1820, 1823 ] ], "normalized": [] }, { "id": "PMID-10050892_T40", "type": "Protein", "text": [ "Recombinant Mal" ], "offsets": [ [ 1826, 1841 ] ], "normalized": [] }, { "id": "PMID-10050892_T45", "type": "MessengerRNA", "text": [ "mRNA" ], "offsets": [ [ 2162, 2166 ] ], "normalized": [] }, { "id": "PMID-10050892_T46", "type": "Tissue", "text": [ "brain" ], "offsets": [ [ 2195, 2200 ] ], "normalized": [] }, { "id": "PMID-10050892_T47", "type": "Tissue", "text": [ "testis" ], "offsets": [ [ 2205, 2211 ] ], "normalized": [] }, { "id": "PMID-10050892_T48", "type": "Protein", "text": [ "Mal" ], "offsets": [ [ 2248, 2251 ] ], "normalized": [] }, { "id": "PMID-10050892_T49", "type": "Protein", "text": [ "phosphoprotein" ], "offsets": [ [ 2270, 2284 ] ], "normalized": [] }, { "id": "PMID-10050892_T51", "type": "Protein", "text": [ "antibodies" ], "offsets": [ [ 2379, 2389 ] ], "normalized": [] }, { "id": "PMID-10050892_T52", "type": "Protein", "text": [ "Mal" ], "offsets": [ [ 2398, 2401 ] ], "normalized": [] }, { "id": "PMID-10050892_T53", "type": "Tissue", "text": [ "'brain/testis'" ], "offsets": [ [ 2442, 2456 ] ], "normalized": [] }, { "id": "PMID-10050892_T54", "type": "Protein", "text": [ "proteins" ], "offsets": [ [ 2457, 2465 ] ], "normalized": [] }, { "id": "PMID-10050892_T65", "type": "Protein", "text": [ "CD8" ], "offsets": [ [ 1096, 1099 ] ], "normalized": [] }, { "id": "PMID-10050892_T66", "type": "Nucleus", "text": [ "subnuclear elements" ], "offsets": [ [ 1308, 1327 ] ], "normalized": [] }, { "id": "PMID-10050892_T69", "type": "Protein", "text": [ "Mal" ], "offsets": [ [ 2158, 2161 ] ], "normalized": [] } ]

[ { "id": "PMID-10050892_E1", "type": "Disease", "trigger": { "text": [ "paraneoplastic neurological disorders" ], "offsets": [ [ 94, 131 ] ] }, "arguments": [] }, { "id": "PMID-10050892_E2", "type": "Disease", "trigger": { "text": [ "paraneoplastic neurological disorders" ], "offsets": [ [ 212, 249 ] ] }, "arguments": [] }, { "id": "PMID-10050892_E3", "type": "Disease", "trigger": { "text": [ "paraneoplastic neurological disorders" ], "offsets": [ [ 475, 512 ] ] }, "arguments": [] }, { "id": "PMID-10050892_E4", "type": "Disease", "trigger": { "text": [ "paraneoplastic neurological disorders" ], "offsets": [ [ 616, 653 ] ] }, "arguments": [] }, { "id": "PMID-10050892_E5", "type": "NegativeRegulation", "trigger": { "text": [ "abrogated" ], "offsets": [ [ 1622, 1631 ] ] }, "arguments": [] }, { "id": "PMID-10050892_E6", "type": "Disease", "trigger": { "text": [ "paraneoplastic neurological symptoms" ], "offsets": [ [ 1996, 2032 ] ] }, "arguments": [] }, { "id": "PMID-10050892_E7", "type": "Disease", "trigger": { "text": [ "paraneoplastic syndromes" ], "offsets": [ [ 2051, 2075 ] ] }, "arguments": [] }, { "id": "PMID-10050892_E8", "type": "Disease", "trigger": { "text": [ "neurological disorders" ], "offsets": [ [ 2116, 2138 ] ] }, "arguments": [] }, { "id": "PMID-10050892_E9", "type": "TranscriptionOfGene", "trigger": { "text": [ "expression" ], "offsets": [ [ 2144, 2154 ] ] }, "arguments": [ { "role": "hasPatient", "ref_id": "PMID-10050892_T45" } ] }, { "id": "PMID-10050892_E10", "type": "Disease", "trigger": { "text": [ "paraneoplastic neurological disorders" ], "offsets": [ [ 2333, 2370 ] ] }, "arguments": [] }, { "id": "PMID-10050892_E11", "type": "Disease", "trigger": { "text": [ "tumours" ], "offsets": [ [ 292, 299 ] ] }, "arguments": [] }, { "id": "PMID-10050892_E12", "type": "Disease", "trigger": { "text": [ "brainstem and cerebellar dysfunction" ], "offsets": [ [ 809, 845 ] ] }, "arguments": [] }, { "id": "PMID-10050892_E13", "type": "Disease", "trigger": { "text": [ "dysphagia" ], "offsets": [ [ 859, 868 ] ] }, "arguments": [] }, { "id": "PMID-10050892_E14", "type": "Disease", "trigger": { "text": [ "motor weakness" ], "offsets": [ [ 873, 887 ] ] }, "arguments": [] }, { "id": "PMID-10050892_E15", "type": "Decrease", "trigger": { "text": [ "loss" ], "offsets": [ [ 920, 924 ] ] }, "arguments": [ { "role": "hasPatient", "ref_id": "PMID-10050892_T16" } ] }, { "id": "PMID-10050892_E16", "type": "Disease", "trigger": { "text": [ "deep cerebellar white matter inflammatory infiltrates" ], "offsets": [ [ 965, 1018 ] ] }, "arguments": [] }, { "id": "PMID-10050892_E17", "type": "Disease", "trigger": { "text": [ "Bergmann gliosis" ], "offsets": [ [ 944, 960 ] ] }, "arguments": [] }, { "id": "PMID-10050892_E18", "type": "Disease", "trigger": { "text": [ "Extensive neuronal degeneration" ], "offsets": [ [ 1020, 1051 ] ] }, "arguments": [] }, { "id": "PMID-10050892_E19", "type": "Disease", "trigger": { "text": [ "gliosis" ], "offsets": [ [ 1053, 1060 ] ] }, "arguments": [] }, { "id": "PMID-10050892_E20", "type": "Disease", "trigger": { "text": [ "infiltrates" ], "offsets": [ [ 1065, 1076 ] ] }, "arguments": [] }, { "id": "PMID-10050892_E21", "type": "Disease", "trigger": { "text": [ "cancers" ], "offsets": [ [ 1432, 1439 ] ] }, "arguments": [] }, { "id": "PMID-10050892_E22", "type": "Disease", "trigger": { "text": [ "tumours" ], "offsets": [ [ 1529, 1536 ] ] }, "arguments": [] } ]

[]

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[ { "id": "PMID-10051328__text", "type": "abstract", "text": [ "Chromosomal localization of three human genes encoding bone morphogenetic protein receptors. Bone morphogenetic proteins (BMPs) are members of the TGF-beta superfamily that play a pivotal role in bone formation during embryogenesis and fracture repair. BMP signaling occurs via hetero-oligomeric serine/threonine kinase complexes of BMP type I (BMPR-IA or BMPR-IB) and type II receptors (BMPR-II). BMPR-IA and IB are closely related receptors, with sequence differences conserved between different species, suggesting that they serve distinct functions. Here we report the cDNA cloning of human BMPR1B and the chromosomal localization of all three BMPR genes. Using somatic cell hybrid and FISH analyses, the BMPR1A, BMPR1B, and BMPR2 genes were assigned to 10q23, 4q22-24, and 2q33-34, respectively. A processed BMPR1A pseudogene was mapped to 6q23.\n" ], "offsets": [ [ 0, 851 ] ] } ]

[ { "id": "PMID-10051328_T1", "type": "Chromosome", "text": [ "Chromosomal" ], "offsets": [ [ 0, 11 ] ], "normalized": [] }, { "id": "PMID-10051328_T2", "type": "Eukaryote", "text": [ "human" ], "offsets": [ [ 34, 39 ] ], "normalized": [] }, { "id": "PMID-10051328_T3", "type": "Gene", "text": [ "genes" ], "offsets": [ [ 40, 45 ] ], "normalized": [] }, { "id": "PMID-10051328_T6", "type": "Protein", "text": [ "Bone morphogenetic proteins" ], "offsets": [ [ 93, 120 ] ], "normalized": [] }, { "id": "PMID-10051328_T7", "type": "Protein", "text": [ "BMPs" ], "offsets": [ [ 122, 126 ] ], "normalized": [] }, { "id": "PMID-10051328_T8", "type": "Protein", "text": [ "TGF-beta" ], "offsets": [ [ 147, 155 ] ], "normalized": [] }, { "id": "PMID-10051328_T11", "type": "Protein", "text": [ "BMP" ], "offsets": [ [ 253, 256 ] ], "normalized": [] }, { "id": "PMID-10051328_T12", "type": "Enzyme", "text": [ "serine/threonine kinase complexes" ], "offsets": [ [ 296, 329 ] ], "normalized": [] }, { "id": "PMID-10051328_T13", "type": "Protein", "text": [ "BMP type I" ], "offsets": [ [ 333, 343 ] ], "normalized": [] }, { "id": "PMID-10051328_T14", "type": "Protein", "text": [ "BMPR-IA" ], "offsets": [ [ 345, 352 ] ], "normalized": [] }, { "id": "PMID-10051328_T15", "type": "Protein", "text": [ "BMPR-IB" ], "offsets": [ [ 356, 363 ] ], "normalized": [] }, { "id": "PMID-10051328_T16", "type": "Protein", "text": [ "type II receptors" ], "offsets": [ [ 369, 386 ] ], "normalized": [] }, { "id": "PMID-10051328_T17", "type": "Protein", "text": [ "BMPR-II" ], "offsets": [ [ 388, 395 ] ], "normalized": [] }, { "id": "PMID-10051328_T18", "type": "Protein", "text": [ "BMPR-IA" ], "offsets": [ [ 398, 405 ] ], "normalized": [] }, { "id": "PMID-10051328_T19", "type": "Protein", "text": [ "IB" ], "offsets": [ [ 410, 412 ] ], "normalized": [] }, { "id": "PMID-10051328_T20", "type": "Protein", "text": [ "receptors" ], "offsets": [ [ 433, 442 ] ], "normalized": [] }, { "id": "PMID-10051328_T21", "type": "DNA", "text": [ "cDNA" ], "offsets": [ [ 573, 577 ] ], "normalized": [] }, { "id": "PMID-10051328_T22", "type": "Eukaryote", "text": [ "human" ], "offsets": [ [ 589, 594 ] ], "normalized": [] }, { "id": "PMID-10051328_T23", "type": "Protein", "text": [ "BMPR1B" ], "offsets": [ [ 595, 601 ] ], "normalized": [] }, { "id": "PMID-10051328_T24", "type": "Chromosome", "text": [ "chromosomal" ], "offsets": [ [ 610, 621 ] ], "normalized": [] }, { "id": "PMID-10051328_T25", "type": "Gene", "text": [ "BMPR genes" ], "offsets": [ [ 648, 658 ] ], "normalized": [] }, { "id": "PMID-10051328_T26", "type": "Gene", "text": [ "BMPR1A" ], "offsets": [ [ 709, 715 ] ], "normalized": [] }, { "id": "PMID-10051328_T27", "type": "Gene", "text": [ "BMPR1B" ], "offsets": [ [ 717, 723 ] ], "normalized": [] }, { "id": "PMID-10051328_T28", "type": "Gene", "text": [ "BMPR2 genes" ], "offsets": [ [ 729, 740 ] ], "normalized": [] }, { "id": "PMID-10051328_T29", "type": "Gene", "text": [ "BMPR1A pseudogene" ], "offsets": [ [ 813, 830 ] ], "normalized": [] }, { "id": "PMID-10051328_T4", "type": "Protein", "text": [ "bone morphogenetic protein receptors" ], "offsets": [ [ 55, 91 ] ], "normalized": [] } ]

[ { "id": "PMID-10051328_E1", "type": "DevelopmentalProcess", "trigger": { "text": [ "bone formation" ], "offsets": [ [ 196, 210 ] ] }, "arguments": [] }, { "id": "PMID-10051328_E2", "type": "DevelopmentalProcess", "trigger": { "text": [ "embryogenesis" ], "offsets": [ [ 218, 231 ] ] }, "arguments": [] }, { "id": "PMID-10051328_E3", "type": "SignalingPathway", "trigger": { "text": [ "signaling" ], "offsets": [ [ 257, 266 ] ] }, "arguments": [] }, { "id": "PMID-10051328_E4", "type": "OrganismalProcess", "trigger": { "text": [ "fracture repair" ], "offsets": [ [ 236, 251 ] ] }, "arguments": [] } ]

[]

[ { "id": "PMID-10051328_R2", "type": "fromSpecies", "arg1_id": "PMID-10051328_T3", "arg2_id": "PMID-10051328_T2", "normalized": [] }, { "id": "PMID-10051328_R3", "type": "hasPart", "arg1_id": "PMID-10051328_T13", "arg2_id": "PMID-10051328_T12", "normalized": [] }, { "id": "PMID-10051328_R4", "type": "hasPart", "arg1_id": "PMID-10051328_T16", "arg2_id": "PMID-10051328_T12", "normalized": [] }, { "id": "PMID-10051328_R5", "type": "encodes", "arg1_id": "PMID-10051328_T21", "arg2_id": "PMID-10051328_T23", "normalized": [] }, { "id": "PMID-10051328_R6", "type": "fromSpecies", "arg1_id": "PMID-10051328_T23", "arg2_id": "PMID-10051328_T22", "normalized": [] }, { "id": "PMID-10051328_R7", "type": "locatedIn", "arg1_id": "PMID-10051328_T25", "arg2_id": "PMID-10051328_T24", "normalized": [] }, { "id": "PMID-10051328_R1", "type": "encodes", "arg1_id": "PMID-10051328_T3", "arg2_id": "PMID-10051328_T4", "normalized": [] } ]

[ { "id": "PMID-10051403__text", "type": "abstract", "text": [ "Genomic structure, chromosomal mapping, and expression pattern of human DCAMKL1 (KIAA0369), a homologue of DCX (XLIS). Human DCAMKL1, also known as KIAA0369, is a homologue of DCX (Xq22. 3), a gene associated with X-linked lissencephaly and subcortical band heterotopia. This suggests that DCAMKL1 may play a role in neuronal migration. The gene also shows similarity to Ca2+/calmodulin-dependent protein kinases. We have determined its genomic structure, regional mapping, and expression pattern in human tissues. DCAMKL1 consists of at least 18 exons ranging from 58 to 3359 bp in length. We have characterized the exon/intron borders, and primers were designed to amplify each individual exon for mutation analysis. DCAMKL1 was mapped to chromosome 13q13 by fluorescence in situ hybridization. Northern blot analysis showed DCAMKL1 to be predominantly expressed in human fetal brain as a major transcript of about 5.8 kb.\n" ], "offsets": [ [ 0, 925 ] ] } ]

[ { "id": "PMID-10051403_T1", "type": "Chromosome", "text": [ "chromosomal" ], "offsets": [ [ 19, 30 ] ], "normalized": [] }, { "id": "PMID-10051403_T3", "type": "Eukaryote", "text": [ "human" ], "offsets": [ [ 66, 71 ] ], "normalized": [] }, { "id": "PMID-10051403_T4", "type": "Gene", "text": [ "DCAMKL1" ], "offsets": [ [ 72, 79 ] ], "normalized": [] }, { "id": "PMID-10051403_T5", "type": "Gene", "text": [ "KIAA0369" ], "offsets": [ [ 81, 89 ] ], "normalized": [] }, { "id": "PMID-10051403_T6", "type": "Gene", "text": [ "DCX" ], "offsets": [ [ 107, 110 ] ], "normalized": [] }, { "id": "PMID-10051403_T7", "type": "Gene", "text": [ "XLIS" ], "offsets": [ [ 112, 116 ] ], "normalized": [] }, { "id": "PMID-10051403_T8", "type": "Eukaryote", "text": [ "Human" ], "offsets": [ [ 119, 124 ] ], "normalized": [] }, { "id": "PMID-10051403_T9", "type": "Gene", "text": [ "DCAMKL1" ], "offsets": [ [ 125, 132 ] ], "normalized": [] }, { "id": "PMID-10051403_T10", "type": "Gene", "text": [ "KIAA0369" ], "offsets": [ [ 148, 156 ] ], "normalized": [] }, { "id": "PMID-10051403_T11", "type": "Gene", "text": [ "DCX" ], "offsets": [ [ 176, 179 ] ], "normalized": [] }, { "id": "PMID-10051403_T12", "type": "Gene", "text": [ "gene" ], "offsets": [ [ 193, 197 ] ], "normalized": [] }, { "id": "PMID-10051403_T13", "type": "Gene", "text": [ "DCAMKL1" ], "offsets": [ [ 290, 297 ] ], "normalized": [] }, { "id": "PMID-10051403_T15", "type": "Gene", "text": [ "gene" ], "offsets": [ [ 341, 345 ] ], "normalized": [] }, { "id": "PMID-10051403_T16", "type": "ProteinComplex", "text": [ "Ca2+/calmodulin" ], "offsets": [ [ 371, 386 ] ], "normalized": [] }, { "id": "PMID-10051403_T17", "type": "Enzyme", "text": [ "protein kinases" ], "offsets": [ [ 397, 412 ] ], "normalized": [] }, { "id": "PMID-10051403_T19", "type": "Eukaryote", "text": [ "human" ], "offsets": [ [ 500, 505 ] ], "normalized": [] }, { "id": "PMID-10051403_T20", "type": "Tissue", "text": [ "tissues" ], "offsets": [ [ 506, 513 ] ], "normalized": [] }, { "id": "PMID-10051403_T21", "type": "Gene", "text": [ "DCAMKL1" ], "offsets": [ [ 515, 522 ] ], "normalized": [] }, { "id": "PMID-10051403_T22", "type": "Exon", "text": [ "exons" ], "offsets": [ [ 547, 552 ] ], "normalized": [] }, { "id": "PMID-10051403_T23", "type": "Exon", "text": [ "exon" ], "offsets": [ [ 691, 695 ] ], "normalized": [] }, { "id": "PMID-10051403_T25", "type": "Gene", "text": [ "DCAMKL1" ], "offsets": [ [ 719, 726 ] ], "normalized": [] }, { "id": "PMID-10051403_T26", "type": "Chromosome", "text": [ "chromosome" ], "offsets": [ [ 741, 751 ] ], "normalized": [] }, { "id": "PMID-10051403_T27", "type": "Gene", "text": [ "DCAMKL1" ], "offsets": [ [ 827, 834 ] ], "normalized": [] }, { "id": "PMID-10051403_T29", "type": "Eukaryote", "text": [ "human" ], "offsets": [ [ 868, 873 ] ], "normalized": [] }, { "id": "PMID-10051403_T30", "type": "Tissue", "text": [ "fetal brain" ], "offsets": [ [ 874, 885 ] ], "normalized": [] }, { "id": "PMID-10051403_T31", "type": "Transcript", "text": [ "transcript" ], "offsets": [ [ 897, 907 ] ], "normalized": [] } ]

[ { "id": "PMID-10051403_E1", "type": "GeneExpression", "trigger": { "text": [ "expression" ], "offsets": [ [ 44, 54 ] ] }, "arguments": [ { "role": "hasPatient", "ref_id": "PMID-10051403_T4" } ] }, { "id": "PMID-10051403_E2", "type": "CellularProcess", "trigger": { "text": [ "neuronal migration" ], "offsets": [ [ 317, 335 ] ] }, "arguments": [] }, { "id": "PMID-10051403_E3", "type": "GeneExpression", "trigger": { "text": [ "expression" ], "offsets": [ [ 478, 488 ] ] }, "arguments": [] }, { "id": "PMID-10051403_E4", "type": "Mutation", "trigger": { "text": [ "mutation" ], "offsets": [ [ 700, 708 ] ] }, "arguments": [] }, { "id": "PMID-10051403_E5", "type": "GeneExpression", "trigger": { "text": [ "expressed" ], "offsets": [ [ 855, 864 ] ] }, "arguments": [ { "role": "hasPatient", "ref_id": "PMID-10051403_T27" } ] }, { "id": "PMID-10051403_E6", "type": "Disease", "trigger": { "text": [ "X-linked lissencephaly" ], "offsets": [ [ 214, 236 ] ] }, "arguments": [] }, { "id": "PMID-10051403_E7", "type": "Disease", "trigger": { "text": [ "subcortical band heterotopia" ], "offsets": [ [ 241, 269 ] ] }, "arguments": [] } ]

[]

[ { "id": "PMID-10051403_R1", "type": "fromSpecies", "arg1_id": "PMID-10051403_T4", "arg2_id": "PMID-10051403_T3", "normalized": [] }, { "id": "PMID-10051403_R2", "type": "fromSpecies", "arg1_id": "PMID-10051403_T9", "arg2_id": "PMID-10051403_T8", "normalized": [] }, { "id": "PMID-10051403_R4", "type": "fromSpecies", "arg1_id": "PMID-10051403_T20", "arg2_id": "PMID-10051403_T19", "normalized": [] }, { "id": "PMID-10051403_R5", "type": "hasPart", "arg1_id": "PMID-10051403_T21", "arg2_id": "PMID-10051403_T22", "normalized": [] }, { "id": "PMID-10051403_R6", "type": "locatedIn", "arg1_id": "PMID-10051403_T25", "arg2_id": "PMID-10051403_T26", "normalized": [] }, { "id": "PMID-10051403_R8", "type": "fromSpecies", "arg1_id": "PMID-10051403_T30", "arg2_id": "PMID-10051403_T29", "normalized": [] } ]

[ { "id": "PMID-10051404__text", "type": "abstract", "text": [ "Structure and chromosomal assignment of the sterol 12alpha-hydroxylase gene (CYP8B1) in human and mouse: eukaryotic cytochrome P-450 gene devoid of introns. Sterol 12alpha-hydroxylase (CYP8B1) is a hepatic cytochrome P-450 that controls the ratio of cholic acid over chenodeoxycholic acid in bile and thus controls the solubility of cholesterol. Both the human and the mouse CYP8B1 complementary DNA and gene were cloned and structurally characterized. Surprisingly, the genomic DNA from both species was found to lack introns. The major transcript of the human gene was estimated to be 3950 bp, and the putative promoter region was estimated to be at least 1360 bp. The murine structural gene was found to span approximately 3 kb. By using FISH and radiation hybrid mapping techniques, the human CYP8B1 gene was located to chromosome 3p21.3-p22, whereas FISH mapped the murine counterpart to chromosome 9qF4, a region that is homologous to the third human chromosome. The results from the chromosome mapping and Southern blotting indicated that the gene is present in a single copy. Transcription of the mouse and human CYP8B1 genes was initiated from a position situated 51 and 35 bases, respectively, downstream of a consensus TATA box. A homology of 21% for the promoter regions of mouse and human may indicate differences in transcriptional regulation. Although a potent induction of CYP8B1 mRNA was observed upon starvation of mice, the mechanism behind this effect was not revealed by analysis of the promoter for potential cis-acting elements. In the human promoter, several possible cis-acting regions were identified but none of them could be directly related to bile acid metabolism. After transfection of COS cells with the human coding region, mRNA and enzymatic activity for the 12alpha-hydroxylase were identified. This is the first mammalian cytochrome P-450 gene reported to lack introns. The importance of this structural feature for evolution and gene regulation is discussed.\n" ], "offsets": [ [ 0, 1996 ] ] } ]

[ { "id": "PMID-10051404_T1", "type": "Chromosome", "text": [ "chromosomal" ], "offsets": [ [ 14, 25 ] ], "normalized": [] }, { "id": "PMID-10051404_T2", "type": "Gene", "text": [ "sterol 12alpha-hydroxylase gene" ], "offsets": [ [ 44, 75 ] ], "normalized": [] }, { "id": "PMID-10051404_T3", "type": "Gene", "text": [ "CYP8B1" ], "offsets": [ [ 77, 83 ] ], "normalized": [] }, { "id": "PMID-10051404_T4", "type": "Eukaryote", "text": [ "human" ], "offsets": [ [ 88, 93 ] ], "normalized": [] }, { "id": "PMID-10051404_T5", "type": "Eukaryote", "text": [ "mouse" ], "offsets": [ [ 98, 103 ] ], "normalized": [] }, { "id": "PMID-10051404_T6", "type": "Eukaryote", "text": [ "eukaryotic" ], "offsets": [ [ 105, 115 ] ], "normalized": [] }, { "id": "PMID-10051404_T8", "type": "Enzyme", "text": [ "Sterol 12alpha-hydroxylase" ], "offsets": [ [ 157, 183 ] ], "normalized": [] }, { "id": "PMID-10051404_T9", "type": "Enzyme", "text": [ "CYP8B1" ], "offsets": [ [ 185, 191 ] ], "normalized": [] }, { "id": "PMID-10051404_T12", "type": "Eukaryote", "text": [ "human" ], "offsets": [ [ 355, 360 ] ], "normalized": [] }, { "id": "PMID-10051404_T13", "type": "Eukaryote", "text": [ "mouse" ], "offsets": [ [ 369, 374 ] ], "normalized": [] }, { "id": "PMID-10051404_T14", "type": "Gene", "text": [ "CYP8B1" ], "offsets": [ [ 375, 381 ] ], "normalized": [] }, { "id": "PMID-10051404_T15", "type": "DNA", "text": [ "complementary DNA" ], "offsets": [ [ 382, 399 ] ], "normalized": [] }, { "id": "PMID-10051404_T16", "type": "Gene", "text": [ "gene" ], "offsets": [ [ 404, 408 ] ], "normalized": [] }, { "id": "PMID-10051404_T17", "type": "DNA", "text": [ "genomic DNA" ], "offsets": [ [ 471, 482 ] ], "normalized": [] }, { "id": "PMID-10051404_T18", "type": "Intron", "text": [ "introns" ], "offsets": [ [ 519, 526 ] ], "normalized": [] }, { "id": "PMID-10051404_T19", "type": "Transcript", "text": [ "transcript" ], "offsets": [ [ 538, 548 ] ], "normalized": [] }, { "id": "PMID-10051404_T20", "type": "Eukaryote", "text": [ "human" ], "offsets": [ [ 556, 561 ] ], "normalized": [] }, { "id": "PMID-10051404_T21", "type": "Gene", "text": [ "gene" ], "offsets": [ [ 562, 566 ] ], "normalized": [] }, { "id": "PMID-10051404_T22", "type": "Promoter", "text": [ "promoter" ], "offsets": [ [ 613, 621 ] ], "normalized": [] }, { "id": "PMID-10051404_T23", "type": "Eukaryote", "text": [ "murine" ], "offsets": [ [ 671, 677 ] ], "normalized": [] }, { "id": "PMID-10051404_T24", "type": "Gene", "text": [ "gene" ], "offsets": [ [ 689, 693 ] ], "normalized": [] }, { "id": "PMID-10051404_T25", "type": "Eukaryote", "text": [ "human" ], "offsets": [ [ 791, 796 ] ], "normalized": [] }, { "id": "PMID-10051404_T26", "type": "Gene", "text": [ "CYP8B1 gene" ], "offsets": [ [ 797, 808 ] ], "normalized": [] }, { "id": "PMID-10051404_T27", "type": "Chromosome", "text": [ "chromosome" ], "offsets": [ [ 824, 834 ] ], "normalized": [] }, { "id": "PMID-10051404_T28", "type": "Eukaryote", "text": [ "murine" ], "offsets": [ [ 871, 877 ] ], "normalized": [] }, { "id": "PMID-10051404_T29", "type": "Chromosome", "text": [ "chromosome" ], "offsets": [ [ 893, 903 ] ], "normalized": [] }, { "id": "PMID-10051404_T30", "type": "Eukaryote", "text": [ "human" ], "offsets": [ [ 951, 956 ] ], "normalized": [] }, { "id": "PMID-10051404_T31", "type": "Chromosome", "text": [ "chromosome" ], "offsets": [ [ 957, 967 ] ], "normalized": [] }, { "id": "PMID-10051404_T32", "type": "Chromosome", "text": [ "chromosome" ], "offsets": [ [ 990, 1000 ] ], "normalized": [] }, { "id": "PMID-10051404_T33", "type": "Gene", "text": [ "gene" ], "offsets": [ [ 1050, 1054 ] ], "normalized": [] }, { "id": "PMID-10051404_T35", "type": "Eukaryote", "text": [ "mouse" ], "offsets": [ [ 1105, 1110 ] ], "normalized": [] }, { "id": "PMID-10051404_T36", "type": "Eukaryote", "text": [ "human" ], "offsets": [ [ 1115, 1120 ] ], "normalized": [] }, { "id": "PMID-10051404_T37", "type": "Gene", "text": [ "CYP8B1 genes" ], "offsets": [ [ 1121, 1133 ] ], "normalized": [] }, { "id": "PMID-10051404_T38", "type": "Promoter", "text": [ "promoter" ], "offsets": [ [ 1266, 1274 ] ], "normalized": [] }, { "id": "PMID-10051404_T39", "type": "Eukaryote", "text": [ "mouse" ], "offsets": [ [ 1286, 1291 ] ], "normalized": [] }, { "id": "PMID-10051404_T40", "type": "Eukaryote", "text": [ "human" ], "offsets": [ [ 1296, 1301 ] ], "normalized": [] }, { "id": "PMID-10051404_T43", "type": "Gene", "text": [ "CYP8B1" ], "offsets": [ [ 1389, 1395 ] ], "normalized": [] }, { "id": "PMID-10051404_T44", "type": "MessengerRNA", "text": [ "mRNA" ], "offsets": [ [ 1396, 1400 ] ], "normalized": [] }, { "id": "PMID-10051404_T45", "type": "Eukaryote", "text": [ "mice" ], "offsets": [ [ 1433, 1437 ] ], "normalized": [] }, { "id": "PMID-10051404_T46", "type": "Promoter", "text": [ "promoter" ], "offsets": [ [ 1508, 1516 ] ], "normalized": [] }, { "id": "PMID-10051404_T47", "type": "Eukaryote", "text": [ "human" ], "offsets": [ [ 1559, 1564 ] ], "normalized": [] }, { "id": "PMID-10051404_T48", "type": "Promoter", "text": [ "promoter" ], "offsets": [ [ 1565, 1573 ] ], "normalized": [] }, { "id": "PMID-10051404_T49", "type": "Cell", "text": [ "COS cells" ], "offsets": [ [ 1717, 1726 ] ], "normalized": [] }, { "id": "PMID-10051404_T50", "type": "Eukaryote", "text": [ "human" ], "offsets": [ [ 1736, 1741 ] ], "normalized": [] }, { "id": "PMID-10051404_T51", "type": "MessengerRNA", "text": [ "mRNA" ], "offsets": [ [ 1757, 1761 ] ], "normalized": [] }, { "id": "PMID-10051404_T52", "type": "Enzyme", "text": [ "12alpha-hydroxylase" ], "offsets": [ [ 1793, 1812 ] ], "normalized": [] }, { "id": "PMID-10051404_T53", "type": "Eukaryote", "text": [ "mammalian" ], "offsets": [ [ 1848, 1857 ] ], "normalized": [] }, { "id": "PMID-10051404_T55", "type": "Gene", "text": [ "gene" ], "offsets": [ [ 1966, 1970 ] ], "normalized": [] }, { "id": "PMID-10051404_T7", "type": "Gene", "text": [ "cytochrome P-450 gene" ], "offsets": [ [ 116, 137 ] ], "normalized": [] }, { "id": "PMID-10051404_T57", "type": "Intron", "text": [ "introns" ], "offsets": [ [ 148, 155 ] ], "normalized": [] }, { "id": "PMID-10051404_T58", "type": "Tissue", "text": [ "hepatic" ], "offsets": [ [ 198, 205 ] ], "normalized": [] }, { "id": "PMID-10051404_T59", "type": "Protein", "text": [ "cytochrome P-450" ], "offsets": [ [ 206, 222 ] ], "normalized": [] }, { "id": "PMID-10051404_T60", "type": "OrganicChemical", "text": [ "cholic acid" ], "offsets": [ [ 250, 261 ] ], "normalized": [] }, { "id": "PMID-10051404_T61", "type": "OrganicChemical", "text": [ "chenodeoxycholic acid" ], "offsets": [ [ 267, 288 ] ], "normalized": [] }, { "id": "PMID-10051404_T62", "type": "Lipid", "text": [ "cholesterol" ], "offsets": [ [ 333, 344 ] ], "normalized": [] }, { "id": "PMID-10051404_T63", "type": "TATAbox", "text": [ "TATA box" ], "offsets": [ [ 1230, 1238 ] ], "normalized": [] }, { "id": "PMID-10051404_T42", "type": "RegulatoryDNARegion", "text": [ "cis-acting elements" ], "offsets": [ [ 1531, 1550 ] ], "normalized": [] }, { "id": "PMID-10051404_T65", "type": "RegulatoryDNARegion", "text": [ "cis-acting regions" ], "offsets": [ [ 1592, 1610 ] ], "normalized": [] }, { "id": "PMID-10051404_T67", "type": "ProteinCodingRegion", "text": [ "coding region" ], "offsets": [ [ 1742, 1755 ] ], "normalized": [] }, { "id": "PMID-10051404_T68", "type": "CatalyticActivity", "text": [ "enzymatic activity" ], "offsets": [ [ 1766, 1784 ] ], "normalized": [] }, { "id": "PMID-10051404_T54", "type": "Gene", "text": [ "cytochrome P-450 gene" ], "offsets": [ [ 1858, 1879 ] ], "normalized": [] }, { "id": "PMID-10051404_T69", "type": "Intron", "text": [ "introns" ], "offsets": [ [ 1897, 1904 ] ], "normalized": [] } ]

[ { "id": "PMID-10051404_E1", "type": "RegulatoryProcess", "trigger": { "text": [ "controls" ], "offsets": [ [ 228, 236 ] ] }, "arguments": [ { "role": "hasAgent", "ref_id": "PMID-10051404_T8" } ] }, { "id": "PMID-10051404_E2", "type": "RegulatoryProcess", "trigger": { "text": [ "controls" ], "offsets": [ [ 306, 314 ] ] }, "arguments": [] }, { "id": "PMID-10051404_E3", "type": "Transcription", "trigger": { "text": [ "Transcription" ], "offsets": [ [ 1084, 1097 ] ] }, "arguments": [ { "role": "hasPatient", "ref_id": "PMID-10051404_T37" } ] }, { "id": "PMID-10051404_E6", "type": "RegulatoryProcess", "trigger": { "text": [ "regulation" ], "offsets": [ [ 1971, 1981 ] ] }, "arguments": [ { "role": "hasPatient", "ref_id": "PMID-10051404_T55" } ] }, { "id": "PMID-10051404_E7", "type": "TranscriptionInitiation", "trigger": { "text": [ "initiated" ], "offsets": [ [ 1138, 1147 ] ] }, "arguments": [ { "role": "hasPatient", "ref_id": "PMID-10051404_E3" } ] }, { "id": "PMID-10051404_E4", "type": "RegulationOfTranscription", "trigger": { "text": [ "transcriptional regulation" ], "offsets": [ [ 1330, 1356 ] ] }, "arguments": [] }, { "id": "PMID-10051404_E5", "type": "MetabolicPathway", "trigger": { "text": [ "bile acid metabolism" ], "offsets": [ [ 1673, 1693 ] ] }, "arguments": [] } ]

[]

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[ { "id": "PMID-10051426__text", "type": "abstract", "text": [ "Three distinct anti-allergic drugs, amlexanox, cromolyn and tranilast, bind to S100A12 and S100A13 of the S100 protein family. To investigate the roles of calcium-binding proteins in degranulation, we used three anti-allergic drugs, amlexanox, cromolyn and tranilast, which inhibit IgE-mediated degranulation of mast cells, as molecular probes in affinity chromatography. All of these drugs, which have different structures but similar function, scarcely bound to calmodulin in bovine lung extract, but bound to the same kinds of calcium-binding proteins, such as the 10-kDa proteins isolated in this study, calcyphosine and annexins I-V. The 10-kDa proteins obtained on three drug-coupled resins and on phenyl-Sepharose were analysed by reversed-phase HPLC. It was found that two characteristic 10-kDa proteins, one polar and one less polar, were bound with all three drugs, although S100A2 (S100L), of the S100 family, was bound with phenyl-Sepharose. The cDNA and deduced amino acid sequence proved our major polar protein to be identical with the calcium-binding protein in bovine amniotic fluid (CAAF1, S100A12). The cDNA and deduced amino acid sequence of the less-polar protein shared 95% homology with human and mouse S100A13. In addition, it was demonstrated that the native S100A12 and recombinant S100A12 and S100A13 bind to immobilized amlexanox. On the basis of these findings, we speculate that the three anti-allergic drugs might inhibit degranulation by binding with S100A12 and S100A13.\n" ], "offsets": [ [ 0, 1504 ] ] } ]

[ { "id": "PMID-10051426_T2", "type": "Protein", "text": [ "S100 protein" ], "offsets": [ [ 106, 118 ] ], "normalized": [] }, { "id": "PMID-10051426_T3", "type": "Ion", "text": [ "calcium" ], "offsets": [ [ 155, 162 ] ], "normalized": [] }, { "id": "PMID-10051426_T5", "type": "Protein", "text": [ "proteins" ], "offsets": [ [ 171, 179 ] ], "normalized": [] }, { "id": "PMID-10051426_T8", "type": "Protein", "text": [ "IgE" ], "offsets": [ [ 282, 285 ] ], "normalized": [] }, { "id": "PMID-10051426_T11", "type": "Cell", "text": [ "mast cells" ], "offsets": [ [ 312, 322 ] ], "normalized": [] }, { "id": "PMID-10051426_T13", "type": "Protein", "text": [ "calmodulin" ], "offsets": [ [ 464, 474 ] ], "normalized": [] }, { "id": "PMID-10051426_T14", "type": "Eukaryote", "text": [ "bovine" ], "offsets": [ [ 478, 484 ] ], "normalized": [] }, { "id": "PMID-10051426_T18", "type": "Protein", "text": [ "calcium-binding proteins" ], "offsets": [ [ 530, 554 ] ], "normalized": [] }, { "id": "PMID-10051426_T19", "type": "Protein", "text": [ "proteins" ], "offsets": [ [ 575, 583 ] ], "normalized": [] }, { "id": "PMID-10051426_T20", "type": "Protein", "text": [ "proteins" ], "offsets": [ [ 650, 658 ] ], "normalized": [] }, { "id": "PMID-10051426_T21", "type": "Protein", "text": [ "proteins" ], "offsets": [ [ 803, 811 ] ], "normalized": [] }, { "id": "PMID-10051426_T24", "type": "DNA", "text": [ "cDNA" ], "offsets": [ [ 958, 962 ] ], "normalized": [] }, { "id": "PMID-10051426_T25", "type": "AminoAcid", "text": [ "amino acid" ], "offsets": [ [ 975, 985 ] ], "normalized": [] }, { "id": "PMID-10051426_T26", "type": "Protein", "text": [ "protein" ], "offsets": [ [ 1018, 1025 ] ], "normalized": [] }, { "id": "PMID-10051426_T29", "type": "Protein", "text": [ "calcium-binding protein" ], "offsets": [ [ 1051, 1074 ] ], "normalized": [] }, { "id": "PMID-10051426_T30", "type": "Eukaryote", "text": [ "bovine" ], "offsets": [ [ 1078, 1084 ] ], "normalized": [] }, { "id": "PMID-10051426_T31", "type": "DNA", "text": [ "cDNA" ], "offsets": [ [ 1122, 1126 ] ], "normalized": [] }, { "id": "PMID-10051426_T32", "type": "AminoAcid", "text": [ "amino acid" ], "offsets": [ [ 1139, 1149 ] ], "normalized": [] }, { "id": "PMID-10051426_T33", "type": "Protein", "text": [ "protein" ], "offsets": [ [ 1177, 1184 ] ], "normalized": [] }, { "id": "PMID-10051426_T34", "type": "Eukaryote", "text": [ "human" ], "offsets": [ [ 1210, 1215 ] ], "normalized": [] }, { "id": "PMID-10051426_T35", "type": "Eukaryote", "text": [ "mouse" ], "offsets": [ [ 1220, 1225 ] ], "normalized": [] }, { "id": "PMID-10051426_T40", "type": "Chemical", "text": [ "anti-allergic drugs" ], "offsets": [ [ 15, 34 ] ], "normalized": [] }, { "id": "PMID-10051426_T41", "type": "Protein", "text": [ "S100A12" ], "offsets": [ [ 79, 86 ] ], "normalized": [] }, { "id": "PMID-10051426_T42", "type": "Protein", "text": [ "S100A13" ], "offsets": [ [ 91, 98 ] ], "normalized": [] }, { "id": "PMID-10051426_T43", "type": "Chemical", "text": [ "anti-allergic drugs" ], "offsets": [ [ 212, 231 ] ], "normalized": [] }, { "id": "PMID-10051426_T44", "type": "Tissue", "text": [ "lung" ], "offsets": [ [ 485, 489 ] ], "normalized": [] }, { "id": "PMID-10051426_T45", "type": "Protein", "text": [ "calcyphosine" ], "offsets": [ [ 608, 620 ] ], "normalized": [] }, { "id": "PMID-10051426_T46", "type": "Protein", "text": [ "annexins I-V" ], "offsets": [ [ 625, 637 ] ], "normalized": [] }, { "id": "PMID-10051426_T47", "type": "Chemical", "text": [ "drugs" ], "offsets": [ [ 869, 874 ] ], "normalized": [] }, { "id": "PMID-10051426_T48", "type": "Protein", "text": [ "S100A2 (S100L)" ], "offsets": [ [ 885, 899 ] ], "normalized": [] }, { "id": "PMID-10051426_T49", "type": "Protein", "text": [ "S100" ], "offsets": [ [ 908, 912 ] ], "normalized": [] }, { "id": "PMID-10051426_T50", "type": "Sequence", "text": [ "sequence" ], "offsets": [ [ 986, 994 ] ], "normalized": [] }, { "id": "PMID-10051426_T51", "type": "Protein", "text": [ "CAAF1" ], "offsets": [ [ 1101, 1106 ] ], "normalized": [] }, { "id": "PMID-10051426_T52", "type": "Protein", "text": [ "S100A12" ], "offsets": [ [ 1108, 1115 ] ], "normalized": [] }, { "id": "PMID-10051426_T53", "type": "Sequence", "text": [ "sequence" ], "offsets": [ [ 1150, 1158 ] ], "normalized": [] }, { "id": "PMID-10051426_T54", "type": "Protein", "text": [ "S100A13" ], "offsets": [ [ 1226, 1233 ] ], "normalized": [] }, { "id": "PMID-10051426_T55", "type": "Protein", "text": [ "S100A12" ], "offsets": [ [ 1284, 1291 ] ], "normalized": [] }, { "id": "PMID-10051426_T56", "type": "Protein", "text": [ "S100A12" ], "offsets": [ [ 1308, 1315 ] ], "normalized": [] }, { "id": "PMID-10051426_T57", "type": "Protein", "text": [ "S100A13" ], "offsets": [ [ 1320, 1327 ] ], "normalized": [] }, { "id": "PMID-10051426_T58", "type": "Chemical", "text": [ "anti-allergic drugs" ], "offsets": [ [ 1419, 1438 ] ], "normalized": [] }, { "id": "PMID-10051426_T59", "type": "Protein", "text": [ "S100A12" ], "offsets": [ [ 1483, 1490 ] ], "normalized": [] }, { "id": "PMID-10051426_T60", "type": "Protein", "text": [ "S100A13" ], "offsets": [ [ 1495, 1502 ] ], "normalized": [] }, { "id": "PMID-10051426_T16", "type": "Chemical", "text": [ "amlexanox" ], "offsets": [ [ 36, 45 ] ], "normalized": [] }, { "id": "PMID-10051426_T17", "type": "Chemical", "text": [ "cromolyn" ], "offsets": [ [ 47, 55 ] ], "normalized": [] }, { "id": "PMID-10051426_T27", "type": "Chemical", "text": [ "tranilast" ], "offsets": [ [ 60, 69 ] ], "normalized": [] } ]

[ { "id": "PMID-10051426_E1", "type": "BindingToProtein", "trigger": { "text": [ "bind" ], "offsets": [ [ 71, 75 ] ] }, "arguments": [ { "role": "hasPatient", "ref_id": "PMID-10051426_T41" }, { "role": "hasPatient2", "ref_id": "PMID-10051426_T42" }, { "role": "hasPatient3", "ref_id": "PMID-10051426_T40" } ] }, { "id": "PMID-10051426_E2", "type": "BindingToProtein", "trigger": { "text": [ "binding" ], "offsets": [ [ 163, 170 ] ] }, "arguments": [ { "role": "hasPatient2", "ref_id": "PMID-10051426_T5" }, { "role": "hasPatient", "ref_id": "PMID-10051426_T3" } ] }, { "id": "PMID-10051426_E3", "type": "CellularProcess", "trigger": { "text": [ "degranulation" ], "offsets": [ [ 183, 196 ] ] }, "arguments": [] }, { "id": "PMID-10051426_E4", "type": "NegativeRegulation", "trigger": { "text": [ "inhibit" ], "offsets": [ [ 274, 281 ] ] }, "arguments": [ { "role": "hasPatient", "ref_id": "PMID-10051426_E6" } ] }, { "id": "PMID-10051426_E5", "type": "RegulatoryProcess", "trigger": { "text": [ "mediated" ], "offsets": [ [ 286, 294 ] ] }, "arguments": [ { "role": "hasAgent", "ref_id": "PMID-10051426_T8" }, { "role": "hasPatient", "ref_id": "PMID-10051426_E6" } ] }, { "id": "PMID-10051426_E6", "type": "CellularProcess", "trigger": { "text": [ "degranulation" ], "offsets": [ [ 295, 308 ] ] }, "arguments": [] }, { "id": "PMID-10051426_E7", "type": "BindingToProtein", "trigger": { "text": [ "bound" ], "offsets": [ [ 455, 460 ] ] }, "arguments": [ { "role": "hasPatient", "ref_id": "PMID-10051426_T13" } ] }, { "id": "PMID-10051426_E8", "type": "BindingToProtein", "trigger": { "text": [ "bound" ], "offsets": [ [ 503, 508 ] ] }, "arguments": [ { "role": "hasPatient", "ref_id": "PMID-10051426_T18" } ] }, { "id": "PMID-10051426_E10", "type": "BindingToProtein", "trigger": { "text": [ "bound" ], "offsets": [ [ 848, 853 ] ] }, "arguments": [ { "role": "hasPatient", "ref_id": "PMID-10051426_T21" }, { "role": "hasPatient2", "ref_id": "PMID-10051426_T47" } ] }, { "id": "PMID-10051426_E11", "type": "BindingToProtein", "trigger": { "text": [ "bound" ], "offsets": [ [ 925, 930 ] ] }, "arguments": [ { "role": "hasPatient", "ref_id": "PMID-10051426_T48" } ] }, { "id": "PMID-10051426_E13", "type": "BindingToProtein", "trigger": { "text": [ "bind" ], "offsets": [ [ 1328, 1332 ] ] }, "arguments": [ { "role": "hasPatient", "ref_id": "PMID-10051426_T55" }, { "role": "hasPatient2", "ref_id": "PMID-10051426_T56" }, { "role": "hasPatient3", "ref_id": "PMID-10051426_T57" } ] }, { "id": "PMID-10051426_E14", "type": "NegativeRegulation", "trigger": { "text": [ "inhibit" ], "offsets": [ [ 1445, 1452 ] ] }, "arguments": [ { "role": "hasPatient", "ref_id": "PMID-10051426_E15" }, { "role": "hasAgent", "ref_id": "PMID-10051426_T58" } ] }, { "id": "PMID-10051426_E15", "type": "CellularProcess", "trigger": { "text": [ "degranulation" ], "offsets": [ [ 1453, 1466 ] ] }, "arguments": [] }, { "id": "PMID-10051426_E16", "type": "BindingToProtein", "trigger": { "text": [ "binding" ], "offsets": [ [ 1470, 1477 ] ] }, "arguments": [ { "role": "hasPatient", "ref_id": "PMID-10051426_T59" }, { "role": "hasPatient2", "ref_id": "PMID-10051426_T60" }, { "role": "hasPatient3", "ref_id": "PMID-10051426_T58" } ] } ]

[]

[ { "id": "PMID-10051426_R3", "type": "fromSpecies", "arg1_id": "PMID-10051426_T29", "arg2_id": "PMID-10051426_T30", "normalized": [] }, { "id": "PMID-10051426_R2", "type": "locatedIn", "arg1_id": "PMID-10051426_T13", "arg2_id": "PMID-10051426_T44", "normalized": [] }, { "id": "PMID-10051426_R4", "type": "fromSpecies", "arg1_id": "PMID-10051426_T44", "arg2_id": "PMID-10051426_T14", "normalized": [] }, { "id": "PMID-10051426_R5", "type": "fromSpecies", "arg1_id": "PMID-10051426_T54", "arg2_id": "PMID-10051426_T35", "normalized": [] }, { "id": "PMID-10051426_R6", "type": "fromSpecies", "arg1_id": "PMID-10051426_T54", "arg2_id": "PMID-10051426_T34", "normalized": [] } ]

[ { "id": "PMID-10199402__text", "type": "abstract", "text": [ "Active transcriptional repression by the Rb-E2F complex mediates G1 arrest triggered by p16INK4a, TGFbeta, and contact inhibition. Rb inhibits progression from G1 to S phase of the cell cycle. It associates with a number of cellular proteins; however, the nature of these interactions and their relative significance in cell cycle regulation are still unclear. We present evidence that Rb must normally interact with the E2F family of transcription factors to arrest cells in G1, and that this arrest results from active transcriptional repression by the Rb-E2F complex, not from inactivation of E2F. Thus, a major role of E2F in cell cycle regulation is assembly of this repressor complex. We demonstrate that active repression by Rb-E2F mediates the G1 arrest triggered by TGFbeta, p16INK4a, and contact inhibition.\n" ], "offsets": [ [ 0, 818 ] ] } ]

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"CellCyclePhase", "trigger": { "text": [ "G1" ], "offsets": [ [ 160, 162 ] ] }, "arguments": [] }, { "id": "PMID-10199402_E11", "type": "CellCyclePhase", "trigger": { "text": [ "S phase" ], "offsets": [ [ 166, 173 ] ] }, "arguments": [] }, { "id": "PMID-10199402_E12", "type": "CellCycle", "trigger": { "text": [ "cell cycle" ], "offsets": [ [ 181, 191 ] ] }, "arguments": [] }, { "id": "PMID-10199402_E13", "type": "BindingToProtein", "trigger": { "text": [ "interactions" ], "offsets": [ [ 272, 284 ] ] }, "arguments": [] }, { "id": "PMID-10199402_E14", "type": "CellCycle", "trigger": { "text": [ "cell cycle" ], "offsets": [ [ 320, 330 ] ] }, "arguments": [] }, { "id": "PMID-10199402_E15", "type": "RegulatoryProcess", "trigger": { "text": [ "regulation" ], "offsets": [ [ 331, 341 ] ] }, "arguments": [ { "role": "hasPatient", "ref_id": "PMID-10199402_E14" } ] }, { "id": "PMID-10199402_E16", "type": "BindingOfTFToTFBindingSiteOfProtein", "trigger": { "text": [ "interact" ], "offsets": [ [ 403, 411 ] ] }, "arguments": [ { "role": "hasAgent2", "ref_id": "PMID-10199402_T24" }, { "role": "hasPatient", "ref_id": "PMID-10199402_T22" } ] }, { "id": "PMID-10199402_E17", "type": "CellCyclePhaseTransition", "trigger": { "text": [ "arrest" ], "offsets": [ [ 460, 466 ] ] }, "arguments": [ { "role": "hasPatient", "ref_id": "PMID-10199402_T27" }, { "role": "hasAgent", "ref_id": "PMID-10199402_E16" } ] }, { "id": "PMID-10199402_E18", "type": "CellCyclePhase", "trigger": { "text": [ "G1" ], "offsets": [ [ 476, 478 ] ] }, "arguments": [] }, { "id": "PMID-10199402_E19", "type": "CellCyclePhaseTransition", "trigger": { "text": [ "arrest" ], "offsets": [ [ 494, 500 ] ] }, "arguments": [ { "role": "hasAgent", "ref_id": "PMID-10199402_E4" } ] }, { "id": "PMID-10199402_E22", "type": "NegativeRegulation", "trigger": { "text": [ "inactivation" ], "offsets": [ [ 580, 592 ] ] }, "arguments": [] }, { "id": "PMID-10199402_E23", "type": "CellCycle", "trigger": { "text": [ "cell cycle" ], "offsets": [ [ 630, 640 ] ] }, "arguments": [] }, { "id": "PMID-10199402_E24", "type": "RegulatoryProcess", "trigger": { "text": [ "regulation" ], "offsets": [ [ 641, 651 ] ] }, "arguments": [ { "role": "hasPatient", "ref_id": "PMID-10199402_E23" } ] }, { "id": "PMID-10199402_E25", "type": "NegativeRegulation", "trigger": { "text": [ "repression" ], "offsets": [ [ 718, 728 ] ] }, "arguments": [ { "role": "hasAgent", "ref_id": "PMID-10199402_T40" }, { "role": "hasPatient", "ref_id": "PMID-10199402_E26" } ] }, { "id": "PMID-10199402_E26", "type": "RegulatoryProcess", "trigger": { "text": [ "mediates" ], "offsets": [ [ 739, 747 ] ] }, "arguments": [ { "role": "hasPatient", "ref_id": "PMID-10199402_E5" } ] }, { "id": "PMID-10199402_E29", "type": "PositiveRegulation", "trigger": { "text": [ "triggered" ], "offsets": [ [ 762, 771 ] ] }, "arguments": [ { "role": "hasAgent", "ref_id": "PMID-10199402_T45" } ] }, { "id": "PMID-10199402_E30", "type": "NegativeRegulation", "trigger": { "text": [ "inhibition" ], "offsets": [ [ 806, 816 ] ] }, "arguments": [] }, { "id": "PMID-10199402_E1", "type": "NegativeRegulationOfTranscription", "trigger": { "text": [ "transcriptional repression" ], "offsets": [ [ 7, 33 ] ] }, "arguments": [ { "role": "hasAgent", "ref_id": "PMID-10199402_T3" }, { "role": "hasPatient", "ref_id": "PMID-10199402_E3" } ] }, { "id": "PMID-10199402_E2", "type": "CellCyclePhaseTransition", "trigger": { "text": [ "G1 arrest" ], "offsets": [ [ 65, 74 ] ] }, "arguments": [ { "role": "hasAgent", "ref_id": "PMID-10199402_E6" } ] }, { "id": "PMID-10199402_E4", "type": "NegativeRegulationOfTranscription", "trigger": { "text": [ "transcriptional repression" ], "offsets": [ [ 521, 547 ] ] }, "arguments": [ { "role": "hasAgent", "ref_id": "PMID-10199402_T32" } ] }, { "id": "PMID-10199402_E5", "type": "CellCyclePhaseTransition", "trigger": { "text": [ "G1 arrest" ], "offsets": [ [ 752, 761 ] ] }, "arguments": [ { "role": "hasAgent", "ref_id": "PMID-10199402_E29" } ] }, { "id": "PMID-10199402_E20", "type": "PositiveRegulation", "trigger": { "text": [ "triggered" ], "offsets": [ [ 75, 84 ] ] }, "arguments": [ { "role": "hasAgent", "ref_id": "PMID-10199402_T9" } ] }, { "id": "PMID-10199402_E21", "type": "PositiveRegulation", "trigger": { "text": [ "triggered" ], "offsets": [ [ 75, 84 ] ] }, "arguments": [ { "role": "hasAgent", "ref_id": "PMID-10199402_E7" } ] }, { "id": "PMID-10199402_E27", "type": "PositiveRegulation", "trigger": { "text": [ "triggered" ], "offsets": [ [ 762, 771 ] ] }, "arguments": [ { "role": "hasAgent", "ref_id": "PMID-10199402_T46" } ] }, { "id": "PMID-10199402_E28", "type": "PositiveRegulation", "trigger": { "text": [ "triggered" ], "offsets": [ [ 762, 771 ] ] }, "arguments": [ { "role": "hasAgent", "ref_id": "PMID-10199402_E30" } ] }, { "id": "PMID-10199402_E31", "type": "CellCyclePhaseTransition", "trigger": { "text": [ "G1 arrest" ], "offsets": [ [ 65, 74 ] ] }, "arguments": [ { "role": "hasAgent", "ref_id": "PMID-10199402_E20" } ] }, { "id": "PMID-10199402_E32", "type": "CellCyclePhaseTransition", "trigger": { "text": [ "G1 arrest" ], "offsets": [ [ 65, 74 ] ] }, "arguments": [ { "role": "hasAgent", "ref_id": "PMID-10199402_E21" } ] }, { "id": "PMID-10199402_E33", "type": "RegulatoryProcess", "trigger": { "text": [ "mediates" ], "offsets": [ [ 56, 64 ] ] }, "arguments": [ { "role": "hasPatient", "ref_id": "PMID-10199402_E31" } ] }, { "id": "PMID-10199402_E34", "type": "RegulatoryProcess", "trigger": { "text": [ "mediates" ], "offsets": [ [ 56, 64 ] ] }, "arguments": [ { "role": "hasPatient", "ref_id": "PMID-10199402_E32" } ] }, { "id": "PMID-10199402_E35", "type": "NegativeRegulationOfTranscription", "trigger": { "text": [ "transcriptional repression" ], "offsets": [ [ 7, 33 ] ] }, "arguments": [ { "role": "hasAgent", "ref_id": "PMID-10199402_T3" }, { "role": "hasPatient", "ref_id": "PMID-10199402_E33" } ] }, { "id": "PMID-10199402_E36", "type": "NegativeRegulationOfTranscription", "trigger": { "text": [ "transcriptional repression" ], "offsets": [ [ 7, 33 ] ] }, "arguments": [ { "role": "hasAgent", "ref_id": "PMID-10199402_T3" }, { "role": "hasPatient", "ref_id": "PMID-10199402_E34" } ] }, { "id": "PMID-10199402_E37", "type": "CellCyclePhaseTransition", "trigger": { "text": [ "G1 arrest" ], "offsets": [ [ 752, 761 ] ] }, "arguments": [ { "role": "hasAgent", "ref_id": "PMID-10199402_E27" } ] }, { "id": "PMID-10199402_E38", "type": "CellCyclePhaseTransition", "trigger": { "text": [ "G1 arrest" ], "offsets": [ [ 752, 761 ] ] }, "arguments": [ { "role": "hasAgent", "ref_id": "PMID-10199402_E28" } ] }, { "id": "PMID-10199402_E39", "type": "RegulatoryProcess", "trigger": { "text": [ "mediates" ], "offsets": [ [ 739, 747 ] ] }, "arguments": [ { "role": "hasPatient", "ref_id": "PMID-10199402_E37" } ] }, { "id": "PMID-10199402_E40", "type": "RegulatoryProcess", "trigger": { "text": [ "mediates" ], "offsets": [ [ 739, 747 ] ] }, "arguments": [ { "role": "hasPatient", "ref_id": "PMID-10199402_E38" } ] }, { "id": "PMID-10199402_E41", "type": "NegativeRegulation", "trigger": { "text": [ "repression" ], "offsets": [ [ 718, 728 ] ] }, "arguments": [ { "role": "hasAgent", "ref_id": "PMID-10199402_T40" }, { "role": "hasPatient", "ref_id": "PMID-10199402_E39" } ] }, { "id": "PMID-10199402_E42", "type": "NegativeRegulation", "trigger": { "text": [ "repression" ], "offsets": [ [ 718, 728 ] ] }, "arguments": [ { "role": "hasAgent", "ref_id": "PMID-10199402_T40" }, { "role": "hasPatient", "ref_id": "PMID-10199402_E40" } ] } ]

[]

[ { "id": "PMID-10199402_R1", "type": "locatedIn", "arg1_id": "PMID-10199402_T18", "arg2_id": "PMID-10199402_T17", "normalized": [] } ]

[ { "id": "PMID-10200294__text", "type": "abstract", "text": [ "A novel lipopolysaccharide-induced transcription factor regulating tumor necrosis factor alpha gene expression: molecular cloning, sequencing, characterization, and chromosomal assignment. Lipopolysaccharide (LPS) is a potent stimulator of monocytes and macrophages, causing secretion of tumor necrosis factor alpha (TNF-alpha) and other inflammatory mediators. Given the deleterious effects to the host of TNF-alpha, it has been postulated that TNF-alpha gene expression must be tightly regulated. The nature of the nuclear factor(s) that control TNF-alpha gene transcription in humans remains obscure, although NF-kappaB has been suggested. Our previous studies pertaining to macrophage response to LPS identified a novel DNA-binding domain located from -550 to -487 in the human TNF-alpha promoter that contains transcriptional activity, but lacks any known NF-kappaB-binding sites. We have used this DNA fragment to isolate and purify a 60-kDa protein binding to this fragment and obtained its amino-terminal sequence, which was used to design degenerate probes to screen a cDNA library from THP-1 cells. A novel cDNA clone (1.8 kb) was isolated and fully sequenced. Characterization of this cDNA clone revealed that its induction was dependent on LPS activation of THP-1 cells; hence, the name LPS-induced TNF-alpha factor (LITAF). Inhibition of LITAF mRNA expression in THP-1 cells resulted in a reduction of TNF-alpha transcripts. In addition, high level of expression of LITAF mRNA was observed predominantly in the placenta, peripheral blood leukocytes, lymph nodes, and the spleen. Finally, chromosomal localization using fluorescence in situ hybridization revealed that LITAF mapped to chromosome 16p12-16p13.3. Together, these findings suggest that LITAF plays an important role in the activation of the human TNF-alpha gene and proposes a new mechanism to control TNF-alpha gene expression.\n" ], "offsets": [ [ 0, 1904 ] ] } ]

[ { "id": "PMID-10200294_T1", "type": "OrganicChemical", "text": [ "lipopolysaccharide" ], "offsets": [ [ 8, 26 ] ], "normalized": [] }, { "id": "PMID-10200294_T3", "type": "TranscriptionFactor", "text": [ "transcription factor" ], "offsets": [ [ 35, 55 ] ], "normalized": [] }, { "id": "PMID-10200294_T5", "type": "Protein", "text": [ "tumor necrosis factor alpha" ], "offsets": [ [ 67, 94 ] ], "normalized": [] }, { "id": "PMID-10200294_T7", "type": "OrganicChemical", "text": [ "Lipopolysaccharide" ], "offsets": [ [ 189, 207 ] ], "normalized": [] }, { "id": "PMID-10200294_T8", "type": "OrganicChemical", "text": [ "LPS" ], "offsets": [ [ 209, 212 ] ], "normalized": [] }, { "id": "PMID-10200294_T10", "type": "Cell", "text": [ "monocytes" ], "offsets": [ [ 240, 249 ] ], "normalized": [] }, { "id": "PMID-10200294_T11", "type": "Cell", "text": [ "macrophages" ], "offsets": [ [ 254, 265 ] ], "normalized": [] }, { "id": "PMID-10200294_T12", "type": "Protein", "text": [ "TNF-alpha" ], "offsets": [ [ 317, 326 ] ], "normalized": [] }, { "id": "PMID-10200294_T14", "type": "MolecularEntity", "text": [ "inflammatory mediators" ], "offsets": [ [ 338, 360 ] ], "normalized": [] }, { "id": "PMID-10200294_T15", "type": "Protein", "text": [ "TNF-alpha" ], "offsets": [ [ 407, 416 ] ], "normalized": [] }, { "id": "PMID-10200294_T16", "type": "Protein", "text": [ "TNF-alpha" ], "offsets": [ [ 446, 455 ] ], "normalized": [] }, { "id": "PMID-10200294_T19", "type": "Protein", "text": [ "nuclear factor(s)" ], "offsets": [ [ 517, 534 ] ], "normalized": [] }, { "id": "PMID-10200294_T21", "type": "Gene", "text": [ "TNF-alpha gene" ], "offsets": [ [ 548, 562 ] ], "normalized": [] }, { "id": "PMID-10200294_T23", "type": "Eukaryote", "text": [ "humans" ], "offsets": [ [ 580, 586 ] ], "normalized": [] }, { "id": "PMID-10200294_T24", "type": "Protein", "text": [ "NF-kappaB" ], "offsets": [ [ 613, 622 ] ], "normalized": [] }, { "id": "PMID-10200294_T25", "type": "Cell", "text": [ "macrophage" ], "offsets": [ [ 678, 688 ] ], "normalized": [] }, { "id": "PMID-10200294_T27", "type": "OrganicChemical", "text": [ "LPS" ], "offsets": [ [ 701, 704 ] ], "normalized": [] }, { "id": "PMID-10200294_T28", "type": "DNABindingDomainOfProtein", "text": [ "DNA-binding domain" ], "offsets": [ [ 724, 742 ] ], "normalized": [] }, { "id": "PMID-10200294_T29", "type": "Eukaryote", "text": [ "human" ], "offsets": [ [ 776, 781 ] ], "normalized": [] }, { "id": "PMID-10200294_T30", "type": "Gene", "text": [ "TNF-alpha" ], "offsets": [ [ 782, 791 ] ], "normalized": [] }, { "id": "PMID-10200294_T31", "type": "Promoter", "text": [ "promoter" ], "offsets": [ [ 792, 800 ] ], "normalized": [] }, { "id": "PMID-10200294_T33", "type": "Protein", "text": [ "NF-kappaB" ], "offsets": [ [ 861, 870 ] ], "normalized": [] }, { "id": "PMID-10200294_T34", "type": "BindingSiteOfProtein", "text": [ "binding sites" ], "offsets": [ [ 871, 884 ] ], "normalized": [] }, { "id": "PMID-10200294_T35", "type": "DNAFragment", "text": [ "DNA fragment" ], "offsets": [ [ 904, 916 ] ], "normalized": [] }, { "id": "PMID-10200294_T36", "type": "Protein", "text": [ "protein" ], "offsets": [ [ 948, 955 ] ], "normalized": [] }, { "id": "PMID-10200294_T38", "type": "DNAFragment", "text": [ "fragment" ], "offsets": [ [ 972, 980 ] ], "normalized": [] }, { "id": "PMID-10200294_T39", "type": "DNA", "text": [ "cDNA library" ], "offsets": [ [ 1078, 1090 ] ], "normalized": [] }, { "id": "PMID-10200294_T40", "type": "Cell", "text": [ "THP-1 cells" ], "offsets": [ [ 1096, 1107 ] ], "normalized": [] }, { "id": "PMID-10200294_T41", "type": "DNA", "text": [ "cDNA clone" ], "offsets": [ [ 1117, 1127 ] ], "normalized": [] }, { "id": "PMID-10200294_T42", "type": "DNA", "text": [ "cDNA clone" ], "offsets": [ [ 1196, 1206 ] ], "normalized": [] }, { "id": "PMID-10200294_T44", "type": "OrganicChemical", "text": [ "LPS" ], "offsets": [ [ 1252, 1255 ] ], "normalized": [] }, { "id": "PMID-10200294_T46", "type": "Cell", "text": [ "THP-1 cells" ], "offsets": [ [ 1270, 1281 ] ], "normalized": [] }, { "id": "PMID-10200294_T47", "type": "Protein", "text": [ "LPS-induced TNF-alpha factor" ], "offsets": [ [ 1299, 1327 ] ], "normalized": [] }, { "id": "PMID-10200294_T48", "type": "Protein", "text": [ "LITAF" ], "offsets": [ [ 1329, 1334 ] ], "normalized": [] }, { "id": "PMID-10200294_T50", "type": "Protein", "text": [ "LITAF" ], "offsets": [ [ 1351, 1356 ] ], "normalized": [] }, { "id": "PMID-10200294_T51", "type": "MessengerRNA", "text": [ "mRNA" ], "offsets": [ [ 1357, 1361 ] ], "normalized": [] }, { "id": "PMID-10200294_T53", "type": "Cell", "text": [ "THP-1 cells" ], "offsets": [ [ 1376, 1387 ] ], "normalized": [] }, { "id": "PMID-10200294_T55", "type": "Protein", "text": [ "TNF-alpha" ], "offsets": [ [ 1415, 1424 ] ], "normalized": [] }, { "id": "PMID-10200294_T56", "type": "Transcript", "text": [ "transcripts" ], "offsets": [ [ 1425, 1436 ] ], "normalized": [] }, { "id": "PMID-10200294_T58", "type": "Protein", "text": [ "LITAF" ], "offsets": [ [ 1479, 1484 ] ], "normalized": [] }, { "id": "PMID-10200294_T59", "type": "MessengerRNA", "text": [ "mRNA" ], "offsets": [ [ 1485, 1489 ] ], "normalized": [] }, { "id": "PMID-10200294_T60", "type": "Tissue", "text": [ "placenta" ], "offsets": [ [ 1524, 1532 ] ], "normalized": [] }, { "id": "PMID-10200294_T61", "type": "Cell", "text": [ "peripheral blood leukocytes" ], "offsets": [ [ 1534, 1561 ] ], "normalized": [] }, { "id": "PMID-10200294_T62", "type": "Tissue", "text": [ "lymph nodes" ], "offsets": [ [ 1563, 1574 ] ], "normalized": [] }, { "id": "PMID-10200294_T63", "type": "Tissue", "text": [ "spleen" ], "offsets": [ [ 1584, 1590 ] ], "normalized": [] }, { "id": "PMID-10200294_T64", "type": "Chromosome", "text": [ "chromosomal" ], "offsets": [ [ 1601, 1612 ] ], "normalized": [] }, { "id": "PMID-10200294_T66", "type": "Gene", "text": [ "LITAF" ], "offsets": [ [ 1681, 1686 ] ], "normalized": [] }, { "id": "PMID-10200294_T67", "type": "Chromosome", "text": [ "chromosome 16p12-16p13.3" ], "offsets": [ [ 1697, 1721 ] ], "normalized": [] }, { "id": "PMID-10200294_T68", "type": "Protein", "text": [ "LITAF" ], "offsets": [ [ 1761, 1766 ] ], "normalized": [] }, { "id": "PMID-10200294_T70", "type": "Eukaryote", "text": [ "human" ], "offsets": [ [ 1816, 1821 ] ], "normalized": [] }, { "id": "PMID-10200294_T71", "type": "Gene", "text": [ "TNF-alpha gene" ], "offsets": [ [ 1822, 1836 ] ], "normalized": [] }, { "id": "PMID-10200294_T73", "type": "Protein", "text": [ "TNF-alpha" ], "offsets": [ [ 1877, 1886 ] ], "normalized": [] }, { "id": "PMID-10200294_T32", "type": "TranscriptionFactorActivity", "text": [ "transcriptional activity" ], "offsets": [ [ 815, 839 ] ], "normalized": [] } ]

[ { "id": "PMID-10200294_E1", "type": "PositiveRegulation", "trigger": { "text": [ "induced" ], "offsets": [ [ 27, 34 ] ] }, "arguments": [ { "role": "hasAgent", "ref_id": "PMID-10200294_T1" }, { "role": "hasPatient", "ref_id": "PMID-10200294_T3" } ] }, { "id": "PMID-10200294_E2", "type": "RegulatoryProcess", "trigger": { "text": [ "regulating" ], "offsets": [ [ 56, 66 ] ] }, "arguments": [ { "role": "hasAgent", "ref_id": "PMID-10200294_T3" }, { "role": "hasPatient", "ref_id": "PMID-10200294_E3" } ] }, { "id": "PMID-10200294_E3", "type": "GeneExpression", "trigger": { "text": [ "gene expression" ], "offsets": [ [ 95, 110 ] ] }, "arguments": [ { "role": "hasPatient", "ref_id": "PMID-10200294_T5" } ] }, { "id": "PMID-10200294_E4", "type": "GeneExpression", "trigger": { "text": [ "gene expression" ], "offsets": [ [ 456, 471 ] ] }, "arguments": [ { "role": "hasPatient", "ref_id": "PMID-10200294_T16" } ] }, { "id": "PMID-10200294_E5", "type": "RegulatoryProcess", "trigger": { "text": [ "regulated" ], "offsets": [ [ 488, 497 ] ] }, "arguments": [ { "role": "hasPatient", "ref_id": "PMID-10200294_E4" } ] }, { "id": "PMID-10200294_E6", "type": "RegulatoryProcess", "trigger": { "text": [ "control" ], "offsets": [ [ 540, 547 ] ] }, "arguments": [ { "role": "hasAgent", "ref_id": "PMID-10200294_T19" }, { "role": "hasPatient", "ref_id": "PMID-10200294_E7" } ] }, { "id": "PMID-10200294_E7", "type": "Transcription", "trigger": { "text": [ "transcription" ], "offsets": [ [ 563, 576 ] ] }, "arguments": [ { "role": "hasPatient", "ref_id": "PMID-10200294_T21" } ] }, { "id": "PMID-10200294_E8", "type": "ResponseProcess", "trigger": { "text": [ "response" ], "offsets": [ [ 689, 697 ] ] }, "arguments": [ { "role": "hasPatient2", "ref_id": "PMID-10200294_T25" }, { "role": "hasAgent", "ref_id": "PMID-10200294_T27" } ] }, { "id": "PMID-10200294_E10", "type": "BindingOfProteinToDNA", "trigger": { "text": [ "binding" ], "offsets": [ [ 956, 963 ] ] }, "arguments": [ { "role": "hasAgent", "ref_id": "PMID-10200294_T36" }, { "role": "hasPatient", "ref_id": "PMID-10200294_T38" } ] }, { "id": "PMID-10200294_E11", "type": "Increase", "trigger": { "text": [ "induction" ], "offsets": [ [ 1225, 1234 ] ] }, "arguments": [ { "role": "hasPatient", "ref_id": "PMID-10200294_T42" }, { "role": "hasAgent", "ref_id": "PMID-10200294_E12" } ] }, { "id": "PMID-10200294_E12", "type": "PositiveRegulation", "trigger": { "text": [ "activation" ], "offsets": [ [ 1256, 1266 ] ] }, "arguments": [ { "role": "hasPatient2", "ref_id": "PMID-10200294_T46" }, { "role": "hasAgent", "ref_id": "PMID-10200294_T44" } ] }, { "id": "PMID-10200294_E13", "type": "NegativeRegulation", "trigger": { "text": [ "Inhibition" ], "offsets": [ [ 1337, 1347 ] ] }, "arguments": [ { "role": "hasPatient", "ref_id": "PMID-10200294_E14" } ] }, { "id": "PMID-10200294_E14", "type": "TranscriptionOfGene", "trigger": { "text": [ "expression" ], "offsets": [ [ 1362, 1372 ] ] }, "arguments": [ { "role": "hasPatient", "ref_id": "PMID-10200294_T51" } ] }, { "id": "PMID-10200294_E15", "type": "Decrease", "trigger": { "text": [ "reduction" ], "offsets": [ [ 1402, 1411 ] ] }, "arguments": [ { "role": "hasPatient", "ref_id": "PMID-10200294_T56" }, { "role": "hasAgent", "ref_id": "PMID-10200294_E13" } ] }, { "id": "PMID-10200294_E18", "type": "PositiveRegulation", "trigger": { "text": [ "activation" ], "offsets": [ [ 1798, 1808 ] ] }, "arguments": [ { "role": "hasPatient", "ref_id": "PMID-10200294_T71" } ] }, { "id": "PMID-10200294_E19", "type": "RegulatoryProcess", "trigger": { "text": [ "control" ], "offsets": [ [ 1869, 1876 ] ] }, "arguments": [ { "role": "hasPatient", "ref_id": "PMID-10200294_E20" } ] }, { "id": "PMID-10200294_E20", "type": "GeneExpression", "trigger": { "text": [ "gene expression" ], "offsets": [ [ 1887, 1902 ] ] }, "arguments": [ { "role": "hasPatient", "ref_id": "PMID-10200294_T73" } ] }, { "id": "PMID-10200294_E21", "type": "PositiveRegulation", "trigger": { "text": [ "stimulator" ], "offsets": [ [ 226, 236 ] ] }, "arguments": [ { "role": "hasAgent", "ref_id": "PMID-10200294_T7" }, { "role": "hasPatient", "ref_id": "PMID-10200294_T10" } ] }, { "id": "PMID-10200294_E22", "type": "Transport", "trigger": { "text": [ "secretion" ], "offsets": [ [ 275, 284 ] ] }, "arguments": [ { "role": "hasPatient", "ref_id": "PMID-10200294_T12" } ] }, { "id": "PMID-10200294_E9", "type": "PositiveRegulationOfTranscriptionOfGene", "trigger": { "text": [ "high level of expression" ], "offsets": [ [ 1451, 1475 ] ] }, "arguments": [ { "role": "hasPatient", "ref_id": "PMID-10200294_T59" } ] }, { "id": "PMID-10200294_E16", "type": "PositiveRegulation", "trigger": { "text": [ "stimulator" ], "offsets": [ [ 226, 236 ] ] }, "arguments": [ { "role": "hasAgent", "ref_id": "PMID-10200294_T7" }, { "role": "hasPatient", "ref_id": "PMID-10200294_T11" } ] }, { "id": "PMID-10200294_E17", "type": "Transport", "trigger": { "text": [ "secretion" ], "offsets": [ [ 275, 284 ] ] }, "arguments": [ { "role": "hasPatient", "ref_id": "PMID-10200294_T14" } ] } ]

[]

[ { "id": "PMID-10200294_R1", "type": "fromSpecies", "arg1_id": "PMID-10200294_T30", "arg2_id": "PMID-10200294_T29", "normalized": [] }, { "id": "PMID-10200294_R2", "type": "hasPart", "arg1_id": "PMID-10200294_T30", "arg2_id": "PMID-10200294_T31", "normalized": [] }, { "id": "PMID-10200294_R7", "type": "encodes", "arg1_id": "PMID-10200294_T51", "arg2_id": "PMID-10200294_T50", "normalized": [] }, { "id": "PMID-10200294_R14", "type": "encodes", "arg1_id": "PMID-10200294_T59", "arg2_id": "PMID-10200294_T58", "normalized": [] }, { "id": "PMID-10200294_R16", "type": "locatedIn", "arg1_id": "PMID-10200294_T66", "arg2_id": "PMID-10200294_T67", "normalized": [] }, { "id": "PMID-10200294_R17", "type": "fromSpecies", "arg1_id": "PMID-10200294_T71", "arg2_id": "PMID-10200294_T70", "normalized": [] }, { "id": "PMID-10200294_R3", "type": "locatedIn", "arg1_id": "PMID-10200294_T39", "arg2_id": "PMID-10200294_T40", "normalized": [] }, { "id": "PMID-10200294_R4", "type": "encodes", "arg1_id": "PMID-10200294_T56", "arg2_id": "PMID-10200294_T55", "normalized": [] } ]

[ { "id": "PMID-10209036__text", "type": "abstract", "text": [ "SHP2-interacting transmembrane adaptor protein (SIT), a novel disulfide-linked dimer regulating human T cell activation. T lymphocytes express several low molecular weight transmembrane adaptor proteins that recruit src homology (SH)2 domain-containing intracellular molecules to the cell membrane via tyrosine-based signaling motifs. We describe here a novel molecule of this group termed SIT (SHP2 interacting transmembrane adaptor protein). SIT is a disulfide-linked homodimeric glycoprotein that is expressed in lymphocytes. After tyrosine phosphorylation by src and possibly syk protein tyrosine kinases SIT recruits the SH2 domain-containing tyrosine phosphatase SHP2 via an immunoreceptor tyrosine-based inhibition motif. Overexpression of SIT in Jurkat cells downmodulates T cell receptor- and phytohemagglutinin-mediated activation of the nuclear factor of activated T cells (NF-AT) by interfering with signaling processes that are probably located upstream of activation of phospholipase C. However, binding of SHP2 to SIT is not required for inhibition of NF-AT induction, suggesting that SIT not only regulates NF-AT activity but also controls NF-AT unrelated pathways of T cell activation involving SHP2.\n" ], "offsets": [ [ 0, 1218 ] ] } ]

[ { "id": "PMID-10209036_T2", "type": "Protein", "text": [ "SIT" ], "offsets": [ [ 48, 51 ] ], "normalized": [] }, { "id": "PMID-10209036_T4", "type": "Eukaryote", "text": [ "human" ], "offsets": [ [ 96, 101 ] ], "normalized": [] }, { "id": "PMID-10209036_T5", "type": "Cell", "text": [ "T cell" ], "offsets": [ [ 102, 108 ] ], "normalized": [] }, { "id": "PMID-10209036_T7", "type": "Cell", "text": [ "T lymphocytes" ], "offsets": [ [ 121, 134 ] ], "normalized": [] }, { "id": "PMID-10209036_T9", "type": "Protein", "text": [ "transmembrane adaptor proteins" ], "offsets": [ [ 172, 202 ] ], "normalized": [] }, { "id": "PMID-10209036_T12", "type": "MolecularEntity", "text": [ "molecules" ], "offsets": [ [ 267, 276 ] ], "normalized": [] }, { "id": "PMID-10209036_T13", "type": "CellComponent", "text": [ "cell membrane" ], "offsets": [ [ 284, 297 ] ], "normalized": [] }, { "id": "PMID-10209036_T15", "type": "ProteinDomain", "text": [ "motifs" ], "offsets": [ [ 327, 333 ] ], "normalized": [] }, { "id": "PMID-10209036_T16", "type": "Protein", "text": [ "SIT" ], "offsets": [ [ 390, 393 ] ], "normalized": [] }, { "id": "PMID-10209036_T18", "type": "Protein", "text": [ "SIT" ], "offsets": [ [ 444, 447 ] ], "normalized": [] }, { "id": "PMID-10209036_T21", "type": "Cell", "text": [ "lymphocytes" ], "offsets": [ [ 516, 527 ] ], "normalized": [] }, { "id": "PMID-10209036_T22", "type": "AminoAcid", "text": [ "tyrosine" ], "offsets": [ [ 535, 543 ] ], "normalized": [] }, { "id": "PMID-10209036_T24", "type": "Protein", "text": [ "src" ], "offsets": [ [ 563, 566 ] ], "normalized": [] }, { "id": "PMID-10209036_T28", "type": "Protein", "text": [ "SIT" ], "offsets": [ [ 609, 612 ] ], "normalized": [] }, { "id": "PMID-10209036_T33", "type": "Enzyme", "text": [ "SHP2" ], "offsets": [ [ 669, 673 ] ], "normalized": [] }, { "id": "PMID-10209036_T34", "type": "AminoAcid", "text": [ "tyrosine" ], "offsets": [ [ 696, 704 ] ], "normalized": [] }, { "id": "PMID-10209036_T35", "type": "ProteinDomain", "text": [ "inhibition motif" ], "offsets": [ [ 711, 727 ] ], "normalized": [] }, { "id": "PMID-10209036_T37", "type": "Protein", "text": [ "SIT" ], "offsets": [ [ 747, 750 ] ], "normalized": [] }, { "id": "PMID-10209036_T38", "type": "Cell", "text": [ "Jurkat cells" ], "offsets": [ [ 754, 766 ] ], "normalized": [] }, { "id": "PMID-10209036_T40", "type": "Cell", "text": [ "T cell" ], "offsets": [ [ 781, 787 ] ], "normalized": [] }, { "id": "PMID-10209036_T41", "type": "Protein", "text": [ "receptor" ], "offsets": [ [ 788, 796 ] ], "normalized": [] }, { "id": "PMID-10209036_T42", "type": "Protein", "text": [ "phytohemagglutinin" ], "offsets": [ [ 802, 820 ] ], "normalized": [] }, { "id": "PMID-10209036_T46", "type": "Protein", "text": [ "NF-AT" ], "offsets": [ [ 885, 890 ] ], "normalized": [] }, { "id": "PMID-10209036_T50", "type": "Enzyme", "text": [ "phospholipase C" ], "offsets": [ [ 984, 999 ] ], "normalized": [] }, { "id": "PMID-10209036_T52", "type": "Protein", "text": [ "SHP2" ], "offsets": [ [ 1021, 1025 ] ], "normalized": [] }, { "id": "PMID-10209036_T53", "type": "Protein", "text": [ "SIT" ], "offsets": [ [ 1029, 1032 ] ], "normalized": [] }, { "id": "PMID-10209036_T55", "type": "Protein", "text": [ "NF-AT" ], "offsets": [ [ 1067, 1072 ] ], "normalized": [] }, { "id": "PMID-10209036_T57", "type": "Protein", "text": [ "SIT" ], "offsets": [ [ 1100, 1103 ] ], "normalized": [] }, { "id": "PMID-10209036_T59", "type": "Protein", "text": [ "NF-AT" ], "offsets": [ [ 1123, 1128 ] ], "normalized": [] }, { "id": "PMID-10209036_T61", "type": "Protein", "text": [ "NF-AT" ], "offsets": [ [ 1156, 1161 ] ], "normalized": [] }, { "id": "PMID-10209036_T63", "type": "Cell", "text": [ "T cell" ], "offsets": [ [ 1184, 1190 ] ], "normalized": [] }, { "id": "PMID-10209036_T65", "type": "Protein", "text": [ "SHP2" ], "offsets": [ [ 1212, 1216 ] ], "normalized": [] }, { "id": "PMID-10209036_T11", "type": "ProteinDomain", "text": [ "(SH)2 domain" ], "offsets": [ [ 229, 241 ] ], "normalized": [] }, { "id": "PMID-10209036_T66", "type": "Protein", "text": [ "glycoprotein" ], "offsets": [ [ 482, 494 ] ], "normalized": [] }, { "id": "PMID-10209036_T25", "type": "Enzyme", "text": [ "syk protein tyrosine kinases" ], "offsets": [ [ 580, 608 ] ], "normalized": [] }, { "id": "PMID-10209036_T26", "type": "Enzyme", "text": [ "SH2 domain-containing tyrosine phosphatase" ], "offsets": [ [ 626, 668 ] ], "normalized": [] }, { "id": "PMID-10209036_T27", "type": "Protein", "text": [ "immunoreceptor" ], "offsets": [ [ 681, 695 ] ], "normalized": [] } ]

[ { "id": "PMID-10209036_E1", "type": "RegulatoryProcess", "trigger": { "text": [ "regulating" ], "offsets": [ [ 85, 95 ] ] }, "arguments": [ { "role": "hasPatient", "ref_id": "PMID-10209036_E2" }, { "role": "hasAgent", "ref_id": "PMID-10209036_T2" } ] }, { "id": "PMID-10209036_E2", "type": "PositiveRegulation", "trigger": { "text": [ "activation" ], "offsets": [ [ 109, 119 ] ] }, "arguments": [ { "role": "hasPatient", "ref_id": "PMID-10209036_T5" } ] }, { "id": "PMID-10209036_E3", "type": "GeneExpression", "trigger": { "text": [ "express" ], "offsets": [ [ 135, 142 ] ] }, "arguments": [ { "role": "hasPatient", "ref_id": "PMID-10209036_T9" } ] }, { "id": "PMID-10209036_E4", "type": "Localization", "trigger": { "text": [ "recruit" ], "offsets": [ [ 208, 215 ] ] }, "arguments": [ { "role": "hasAgent", "ref_id": "PMID-10209036_T9" }, { "role": "hasPatient", "ref_id": "PMID-10209036_T12" } ] }, { "id": "PMID-10209036_E5", "type": "GeneExpression", "trigger": { "text": [ "expressed" ], "offsets": [ [ 503, 512 ] ] }, "arguments": [ { "role": "hasPatient", "ref_id": "PMID-10209036_T18" } ] }, { "id": "PMID-10209036_E6", "type": "Phosphorylation", "trigger": { "text": [ "phosphorylation" ], "offsets": [ [ 544, 559 ] ] }, "arguments": [ { "role": "hasAgent", "ref_id": "PMID-10209036_T24" }, { "role": "hasPatient", "ref_id": "PMID-10209036_T22" } ] }, { "id": "PMID-10209036_E7", "type": "Localization", "trigger": { "text": [ "recruits" ], "offsets": [ [ 613, 621 ] ] }, "arguments": [ { "role": "hasAgent", "ref_id": "PMID-10209036_T28" }, { "role": "hasPatient", "ref_id": "PMID-10209036_T26" } ] }, { "id": "PMID-10209036_E9", "type": "PositiveRegulationOfGeneExpression", "trigger": { "text": [ "Overexpression" ], "offsets": [ [ 729, 743 ] ] }, "arguments": [ { "role": "hasPatient", "ref_id": "PMID-10209036_T37" } ] }, { "id": "PMID-10209036_E10", "type": "Decrease", "trigger": { "text": [ "downmodulates" ], "offsets": [ [ 767, 780 ] ] }, "arguments": [ { "role": "hasAgent", "ref_id": "PMID-10209036_E9" }, { "role": "hasPatient", "ref_id": "PMID-10209036_E12" } ] }, { "id": "PMID-10209036_E11", "type": "RegulatoryProcess", "trigger": { "text": [ "mediated" ], "offsets": [ [ 821, 829 ] ] }, "arguments": [ { "role": "hasPatient", "ref_id": "PMID-10209036_E12" }, { "role": "hasAgent", "ref_id": "PMID-10209036_T41" } ] }, { "id": "PMID-10209036_E12", "type": "PositiveRegulation", "trigger": { "text": [ "activation" ], "offsets": [ [ 830, 840 ] ] }, "arguments": [ { "role": "hasPatient", "ref_id": "PMID-10209036_T46" } ] }, { "id": "PMID-10209036_E13", "type": "Affecting", "trigger": { "text": [ "interfering" ], "offsets": [ [ 895, 906 ] ] }, "arguments": [ { "role": "hasAgent", "ref_id": "PMID-10209036_E14" } ] }, { "id": "PMID-10209036_E14", "type": "SignalingPathway", "trigger": { "text": [ "signaling processes" ], "offsets": [ [ 912, 931 ] ] }, "arguments": [] }, { "id": "PMID-10209036_E15", "type": "PositiveRegulation", "trigger": { "text": [ "activation" ], "offsets": [ [ 970, 980 ] ] }, "arguments": [ { "role": "hasPatient", "ref_id": "PMID-10209036_T50" } ] }, { "id": "PMID-10209036_E16", "type": "BindingToProtein", "trigger": { "text": [ "binding" ], "offsets": [ [ 1010, 1017 ] ] }, "arguments": [ { "role": "hasPatient", "ref_id": "PMID-10209036_T53" }, { "role": "hasPatient2", "ref_id": "PMID-10209036_T52" } ] }, { "id": "PMID-10209036_E17", "type": "NegativeRegulation", "trigger": { "text": [ "inhibition" ], "offsets": [ [ 1053, 1063 ] ] }, "arguments": [ { "role": "hasPatient", "ref_id": "PMID-10209036_E18" } ] }, { "id": "PMID-10209036_E18", "type": "Increase", "trigger": { "text": [ "induction" ], "offsets": [ [ 1073, 1082 ] ] }, "arguments": [ { "role": "hasPatient", "ref_id": "PMID-10209036_T55" } ] }, { "id": "PMID-10209036_E19", "type": "RegulatoryProcess", "trigger": { "text": [ "regulates" ], "offsets": [ [ 1113, 1122 ] ] }, "arguments": [ { "role": "hasAgent", "ref_id": "PMID-10209036_T57" }, { "role": "hasPatient", "ref_id": "PMID-10209036_T59" } ] }, { "id": "PMID-10209036_E20", "type": "RegulatoryProcess", "trigger": { "text": [ "controls" ], "offsets": [ [ 1147, 1155 ] ] }, "arguments": [ { "role": "hasAgent", "ref_id": "PMID-10209036_T57" }, { "role": "hasPatient", "ref_id": "PMID-10209036_E21" } ] }, { "id": "PMID-10209036_E21", "type": "SignalingPathway", "trigger": { "text": [ "pathways" ], "offsets": [ [ 1172, 1180 ] ] }, "arguments": [] }, { "id": "PMID-10209036_E22", "type": "PositiveRegulation", "trigger": { "text": [ "activation" ], "offsets": [ [ 1191, 1201 ] ] }, "arguments": [ { "role": "hasPatient", "ref_id": "PMID-10209036_T63" } ] }, { "id": "PMID-10209036_E23", "type": "SignalingPathway", "trigger": { "text": [ "tyrosine-based signaling" ], "offsets": [ [ 302, 326 ] ] }, "arguments": [] }, { "id": "PMID-10209036_E24", "type": "Homodimerization", "trigger": { "text": [ "homodimeric" ], "offsets": [ [ 470, 481 ] ] }, "arguments": [ { "role": "hasPatient", "ref_id": "PMID-10209036_T66" } ] }, { "id": "PMID-10209036_E8", "type": "RegulatoryProcess", "trigger": { "text": [ "mediated" ], "offsets": [ [ 821, 829 ] ] }, "arguments": [ { "role": "hasPatient", "ref_id": "PMID-10209036_E12" }, { "role": "hasAgent", "ref_id": "PMID-10209036_T42" } ] } ]

[]

[ { "id": "PMID-10209036_R1", "type": "fromSpecies", "arg1_id": "PMID-10209036_T5", "arg2_id": "PMID-10209036_T4", "normalized": [] }, { "id": "PMID-10209036_R8", "type": "locatedIn", "arg1_id": "PMID-10209036_T41", "arg2_id": "PMID-10209036_T40", "normalized": [] }, { "id": "PMID-10209036_R3", "type": "hasPart", "arg1_id": "PMID-10209036_T12", "arg2_id": "PMID-10209036_T11", "normalized": [] } ]

[ { "id": "PMID-10329626__text", "type": "abstract", "text": [ "Rel/NF-kappaB can trigger the Notch signaling pathway by inducing the expression of Jagged1, a ligand for Notch receptors. Jagged1 belongs to the DSL family of ligands for Notch receptors that control the proliferation and differentiation of various cell lineages. However, little is known about the transcription factors that regulate its expression. Here, we show that Jagged1 is a Rel/NF-kappaB-responsive gene. Both c-Rel and RelA induced jagged1 gene expression, whereas a mutant defective for transactivation did not. Importantly, jagged1 transcripts were also upregulated by endogenous NF-kappaB activation and this effect was inhibited by a dominant mutant of IkappaBalpha, a physiological inhibitor of NF-kappaB. Cell surface expression of Jagged1 in c-Rel-expressing cell monolayers led to a functional interaction with lymphocytes expressing the Notch1/TAN-1 receptor. This correlated with the initiation of signaling downstream of Notch, as evidenced by increased levels of HES-1 transcripts in co-cultivated T cells and of CD23 transcripts in co-cultivated B cells. Consistent with its Rel/NF-kappaB-dependent induction, Jagged1 was found to be highly expressed in splenic B cells where c-Rel is expressed constitutively. These results demonstrate that c-Rel can trigger the Notch signaling pathway in neighboring cells by inducing jagged1 gene expression, and suggest a role for Jagged1 in B-cell activation, differentiation or function. These findings also highlight the potential for an interplay between the Notch and NF-kappaB signaling pathways in the immune system.\n" ], "offsets": [ [ 0, 1586 ] ] } ]

[ { "id": "PMID-10329626_T1", "type": "Protein", "text": [ "Rel/NF-kappaB" ], "offsets": [ [ 0, 13 ] ], "normalized": [] }, { "id": "PMID-10329626_T3", "type": "Protein", "text": [ "Notch" ], "offsets": [ [ 30, 35 ] ], "normalized": [] }, { "id": "PMID-10329626_T7", "type": "Ligand", "text": [ "Jagged1" ], "offsets": [ [ 84, 91 ] ], "normalized": [] }, { "id": "PMID-10329626_T8", "type": "Ligand", "text": [ "ligand" ], "offsets": [ [ 95, 101 ] ], "normalized": [] }, { "id": "PMID-10329626_T11", "type": "Ligand", "text": [ "Jagged1" ], "offsets": [ [ 123, 130 ] ], "normalized": [] }, { "id": "PMID-10329626_T12", "type": "Ligand", "text": [ "DSL family" ], "offsets": [ [ 146, 156 ] ], "normalized": [] }, { "id": "PMID-10329626_T13", "type": "Ligand", "text": [ "ligands" ], "offsets": [ [ 160, 167 ] ], "normalized": [] }, { "id": "PMID-10329626_T19", "type": "Cell", "text": [ "cell lineages" ], "offsets": [ [ 250, 263 ] ], "normalized": [] }, { "id": "PMID-10329626_T20", "type": "TranscriptionFactor", "text": [ "transcription factors" ], "offsets": [ [ 300, 321 ] ], "normalized": [] }, { "id": "PMID-10329626_T23", "type": "Ligand", "text": [ "Jagged1" ], "offsets": [ [ 371, 378 ] ], "normalized": [] }, { "id": "PMID-10329626_T24", "type": "Protein", "text": [ "Rel/NF-kappaB" ], "offsets": [ [ 384, 397 ] ], "normalized": [] }, { "id": "PMID-10329626_T25", "type": "Gene", "text": [ "gene" ], "offsets": [ [ 409, 413 ] ], "normalized": [] }, { "id": "PMID-10329626_T26", "type": "Protein", "text": [ "c-Rel" ], "offsets": [ [ 420, 425 ] ], "normalized": [] }, { "id": "PMID-10329626_T27", "type": "Protein", "text": [ "RelA" ], "offsets": [ [ 430, 434 ] ], "normalized": [] }, { "id": "PMID-10329626_T29", "type": "Ligand", "text": [ "jagged1" ], "offsets": [ [ 443, 450 ] ], "normalized": [] }, { "id": "PMID-10329626_T31", "type": "Ligand", "text": [ "jagged1" ], "offsets": [ [ 537, 544 ] ], "normalized": [] }, { "id": "PMID-10329626_T32", "type": "Transcript", "text": [ "transcripts" ], "offsets": [ [ 545, 556 ] ], "normalized": [] }, { "id": "PMID-10329626_T34", "type": "Protein", "text": [ "NF-kappaB" ], "offsets": [ [ 593, 602 ] ], "normalized": [] }, { "id": "PMID-10329626_T37", "type": "Protein", "text": [ "IkappaBalpha" ], "offsets": [ [ 668, 680 ] ], "normalized": [] }, { "id": "PMID-10329626_T39", "type": "Protein", "text": [ "NF-kappaB" ], "offsets": [ [ 711, 720 ] ], "normalized": [] }, { "id": "PMID-10329626_T40", "type": "CellComponent", "text": [ "Cell surface" ], "offsets": [ [ 722, 734 ] ], "normalized": [] }, { "id": "PMID-10329626_T42", "type": "Ligand", "text": [ "Jagged1" ], "offsets": [ [ 749, 756 ] ], "normalized": [] }, { "id": "PMID-10329626_T43", "type": "Protein", "text": [ "c-Rel" ], "offsets": [ [ 760, 765 ] ], "normalized": [] }, { "id": "PMID-10329626_T45", "type": "Cell", "text": [ "cell" ], "offsets": [ [ 777, 781 ] ], "normalized": [] }, { "id": "PMID-10329626_T47", "type": "Cell", "text": [ "lymphocytes" ], "offsets": [ [ 830, 841 ] ], "normalized": [] }, { "id": "PMID-10329626_T53", "type": "Protein", "text": [ "Notch" ], "offsets": [ [ 943, 948 ] ], "normalized": [] }, { "id": "PMID-10329626_T55", "type": "Protein", "text": [ "HES-1" ], "offsets": [ [ 986, 991 ] ], "normalized": [] }, { "id": "PMID-10329626_T56", "type": "Transcript", "text": [ "transcripts" ], "offsets": [ [ 992, 1003 ] ], "normalized": [] }, { "id": "PMID-10329626_T57", "type": "Cell", "text": [ "T cells" ], "offsets": [ [ 1021, 1028 ] ], "normalized": [] }, { "id": "PMID-10329626_T58", "type": "Protein", "text": [ "CD23" ], "offsets": [ [ 1036, 1040 ] ], "normalized": [] }, { "id": "PMID-10329626_T59", "type": "Transcript", "text": [ "transcripts" ], "offsets": [ [ 1041, 1052 ] ], "normalized": [] }, { "id": "PMID-10329626_T60", "type": "Cell", "text": [ "B cells" ], "offsets": [ [ 1070, 1077 ] ], "normalized": [] }, { "id": "PMID-10329626_T61", "type": "Protein", "text": [ "Rel/NF-kappaB" ], "offsets": [ [ 1099, 1112 ] ], "normalized": [] }, { "id": "PMID-10329626_T63", "type": "Ligand", "text": [ "Jagged1" ], "offsets": [ [ 1134, 1141 ] ], "normalized": [] }, { "id": "PMID-10329626_T65", "type": "Tissue", "text": [ "splenic" ], "offsets": [ [ 1178, 1185 ] ], "normalized": [] }, { "id": "PMID-10329626_T66", "type": "Cell", "text": [ "B cells" ], "offsets": [ [ 1186, 1193 ] ], "normalized": [] }, { "id": "PMID-10329626_T67", "type": "Protein", "text": [ "c-Rel" ], "offsets": [ [ 1200, 1205 ] ], "normalized": [] }, { "id": "PMID-10329626_T69", "type": "Protein", "text": [ "c-Rel" ], "offsets": [ [ 1266, 1271 ] ], "normalized": [] }, { "id": "PMID-10329626_T71", "type": "Protein", "text": [ "Notch" ], "offsets": [ [ 1288, 1293 ] ], "normalized": [] }, { "id": "PMID-10329626_T74", "type": "Ligand", "text": [ "jagged1" ], "offsets": [ [ 1345, 1352 ] ], "normalized": [] }, { "id": "PMID-10329626_T76", "type": "Ligand", "text": [ "Jagged1" ], "offsets": [ [ 1393, 1400 ] ], "normalized": [] }, { "id": "PMID-10329626_T77", "type": "Cell", "text": [ "B-cell" ], "offsets": [ [ 1404, 1410 ] ], "normalized": [] }, { "id": "PMID-10329626_T80", "type": "Protein", "text": [ "Notch" ], "offsets": [ [ 1525, 1530 ] ], "normalized": [] }, { "id": "PMID-10329626_T81", "type": "Protein", "text": [ "NF-kappaB" ], "offsets": [ [ 1535, 1544 ] ], "normalized": [] }, { "id": "PMID-10329626_T9", "type": "Protein", "text": [ "Notch receptors" ], "offsets": [ [ 106, 121 ] ], "normalized": [] }, { "id": "PMID-10329626_T10", "type": "Protein", "text": [ "Notch receptors" ], "offsets": [ [ 172, 187 ] ], "normalized": [] }, { "id": "PMID-10329626_T15", "type": "MutantProtein", "text": [ "dominant mutant" ], "offsets": [ [ 649, 664 ] ], "normalized": [] }, { "id": "PMID-10329626_T49", "type": "Protein", "text": [ "Notch1/TAN-1 receptor" ], "offsets": [ [ 857, 878 ] ], "normalized": [] } ]

[ { "id": "PMID-10329626_E1", "type": "PositiveRegulation", "trigger": { "text": [ "trigger" ], "offsets": [ [ 18, 25 ] ] }, "arguments": [ { "role": "hasAgent", "ref_id": "PMID-10329626_T1" }, { "role": "hasPatient", "ref_id": "PMID-10329626_E2" } ] }, { "id": "PMID-10329626_E2", "type": "SignalingPathway", "trigger": { "text": [ "signaling pathway" ], "offsets": [ [ 36, 53 ] ] }, "arguments": [] }, { "id": "PMID-10329626_E3", "type": "Increase", "trigger": { "text": [ "inducing" ], "offsets": [ [ 57, 65 ] ] }, "arguments": [ { "role": "hasPatient", "ref_id": "PMID-10329626_E4" }, { "role": "hasAgent", "ref_id": "PMID-10329626_T1" } ] }, { "id": "PMID-10329626_E4", "type": "GeneExpression", "trigger": { "text": [ "expression" ], "offsets": [ [ 70, 80 ] ] }, "arguments": [ { "role": "hasPatient", "ref_id": "PMID-10329626_T7" } ] }, { "id": "PMID-10329626_E5", "type": "RegulatoryProcess", "trigger": { "text": [ "control" ], "offsets": [ [ 193, 200 ] ] }, "arguments": [ { "role": "hasAgent", "ref_id": "PMID-10329626_T12" }, { "role": "hasPatient", "ref_id": "PMID-10329626_E6" } ] }, { "id": "PMID-10329626_E6", "type": "CellGrowth", "trigger": { "text": [ "proliferation" ], "offsets": [ [ 205, 218 ] ] }, "arguments": [] }, { "id": "PMID-10329626_E7", "type": "CellDifferentiation", "trigger": { "text": [ "differentiation" ], "offsets": [ [ 223, 238 ] ] }, "arguments": [] }, { "id": "PMID-10329626_E8", "type": "RegulatoryProcess", "trigger": { "text": [ "regulate" ], "offsets": [ [ 327, 335 ] ] }, "arguments": [ { "role": "hasAgent", "ref_id": "PMID-10329626_T20" }, { "role": "hasPatient", "ref_id": "PMID-10329626_E9" } ] }, { "id": "PMID-10329626_E9", "type": "GeneExpression", "trigger": { "text": [ "expression" ], "offsets": [ [ 340, 350 ] ] }, "arguments": [] }, { "id": "PMID-10329626_E10", "type": "PositiveRegulation", "trigger": { "text": [ "induced" ], "offsets": [ [ 435, 442 ] ] }, "arguments": [ { "role": "hasPatient", "ref_id": "PMID-10329626_E11" }, { "role": "hasAgent", "ref_id": "PMID-10329626_T26" } ] }, { "id": "PMID-10329626_E11", "type": "GeneExpression", "trigger": { "text": [ "gene expression" ], "offsets": [ [ 451, 466 ] ] }, "arguments": [ { "role": "hasPatient", "ref_id": "PMID-10329626_T29" } ] }, { "id": "PMID-10329626_E12", "type": "Increase", "trigger": { "text": [ "upregulated" ], "offsets": [ [ 567, 578 ] ] }, "arguments": [ { "role": "hasAgent", "ref_id": "PMID-10329626_E13" }, { "role": "hasPatient", "ref_id": "PMID-10329626_T32" } ] }, { "id": "PMID-10329626_E13", "type": "PositiveRegulation", "trigger": { "text": [ "activation" ], "offsets": [ [ 603, 613 ] ] }, "arguments": [ { "role": "hasAgent", "ref_id": "PMID-10329626_T34" } ] }, { "id": "PMID-10329626_E14", "type": "NegativeRegulation", "trigger": { "text": [ "inhibited" ], "offsets": [ [ 634, 643 ] ] }, "arguments": [ { "role": "hasPatient", "ref_id": "PMID-10329626_E12" }, { "role": "hasAgent", "ref_id": "PMID-10329626_T15" } ] }, { "id": "PMID-10329626_E15", "type": "NegativeRegulation", "trigger": { "text": [ "inhibitor" ], "offsets": [ [ 698, 707 ] ] }, "arguments": [ { "role": "hasAgent", "ref_id": "PMID-10329626_T37" }, { "role": "hasPatient", "ref_id": "PMID-10329626_T39" } ] }, { "id": "PMID-10329626_E16", "type": "GeneExpression", "trigger": { "text": [ "expression" ], "offsets": [ [ 735, 745 ] ] }, "arguments": [ { "role": "hasPatient", "ref_id": "PMID-10329626_T42" } ] }, { "id": "PMID-10329626_E17", "type": "GeneExpression", "trigger": { "text": [ "expressing" ], "offsets": [ [ 766, 776 ] ] }, "arguments": [ { "role": "hasPatient", "ref_id": "PMID-10329626_T43" } ] }, { "id": "PMID-10329626_E18", "type": "CellularProcess", "trigger": { "text": [ "interaction" ], "offsets": [ [ 813, 824 ] ] }, "arguments": [ { "role": "hasAgent", "ref_id": "PMID-10329626_E16" }, { "role": "hasPatient", "ref_id": "PMID-10329626_T47" } ] }, { "id": "PMID-10329626_E19", "type": "GeneExpression", "trigger": { "text": [ "expressing" ], "offsets": [ [ 842, 852 ] ] }, "arguments": [ { "role": "hasPatient", "ref_id": "PMID-10329626_T49" } ] }, { "id": "PMID-10329626_E20", "type": "PositiveRegulation", "trigger": { "text": [ "initiation" ], "offsets": [ [ 905, 915 ] ] }, "arguments": [ { "role": "hasPatient", "ref_id": "PMID-10329626_E21" } ] }, { "id": "PMID-10329626_E21", "type": "SignalingPathway", "trigger": { "text": [ "signaling" ], "offsets": [ [ 919, 928 ] ] }, "arguments": [ { "role": "hasAgent", "ref_id": "PMID-10329626_T53" } ] }, { "id": "PMID-10329626_E22", "type": "Increase", "trigger": { "text": [ "increased" ], "offsets": [ [ 966, 975 ] ] }, "arguments": [ { "role": "hasPatient", "ref_id": "PMID-10329626_T56" } ] }, { "id": "PMID-10329626_E23", "type": "Increase", "trigger": { "text": [ "induction" ], "offsets": [ [ 1123, 1132 ] ] }, "arguments": [ { "role": "hasAgent", "ref_id": "PMID-10329626_T61" } ] }, { "id": "PMID-10329626_E24", "type": "GeneExpression", "trigger": { "text": [ "expressed" ], "offsets": [ [ 1165, 1174 ] ] }, "arguments": [ { "role": "hasPatient", "ref_id": "PMID-10329626_T63" } ] }, { "id": "PMID-10329626_E25", "type": "GeneExpression", "trigger": { "text": [ "expressed" ], "offsets": [ [ 1209, 1218 ] ] }, "arguments": [ { "role": "hasPatient", "ref_id": "PMID-10329626_T67" } ] }, { "id": "PMID-10329626_E26", "type": "PositiveRegulation", "trigger": { "text": [ "trigger" ], "offsets": [ [ 1276, 1283 ] ] }, "arguments": [ { "role": "hasAgent", "ref_id": "PMID-10329626_T69" }, { "role": "hasPatient", "ref_id": "PMID-10329626_E27" } ] }, { "id": "PMID-10329626_E27", "type": "SignalingPathway", "trigger": { "text": [ "signaling pathway" ], "offsets": [ [ 1294, 1311 ] ] }, "arguments": [] }, { "id": "PMID-10329626_E28", "type": "Increase", "trigger": { "text": [ "inducing" ], "offsets": [ [ 1336, 1344 ] ] }, "arguments": [ { "role": "hasPatient", "ref_id": "PMID-10329626_E29" } ] }, { "id": "PMID-10329626_E29", "type": "GeneExpression", "trigger": { "text": [ "gene expression" ], "offsets": [ [ 1353, 1368 ] ] }, "arguments": [ { "role": "hasPatient", "ref_id": "PMID-10329626_T74" } ] }, { "id": "PMID-10329626_E30", "type": "PositiveRegulation", "trigger": { "text": [ "activation" ], "offsets": [ [ 1411, 1421 ] ] }, "arguments": [ { "role": "hasPatient", "ref_id": "PMID-10329626_T77" } ] }, { "id": "PMID-10329626_E31", "type": "CellDifferentiation", "trigger": { "text": [ "differentiation" ], "offsets": [ [ 1423, 1438 ] ] }, "arguments": [] }, { "id": "PMID-10329626_E32", "type": "SignalingPathway", "trigger": { "text": [ "signaling pathways" ], "offsets": [ [ 1545, 1563 ] ] }, "arguments": [] }, { "id": "PMID-10329626_E33", "type": "ResponseProcess", "trigger": { "text": [ "responsive" ], "offsets": [ [ 398, 408 ] ] }, "arguments": [ { "role": "hasAgent", "ref_id": "PMID-10329626_T24" }, { "role": "hasPatient", "ref_id": "PMID-10329626_T23" } ] }, { "id": "PMID-10329626_E34", "type": "RegulatoryProcess", "trigger": { "text": [ "control" ], "offsets": [ [ 193, 200 ] ] }, "arguments": [ { "role": "hasAgent", "ref_id": "PMID-10329626_T12" }, { "role": "hasPatient", "ref_id": "PMID-10329626_E7" } ] }, { "id": "PMID-10329626_E35", "type": "PositiveRegulation", "trigger": { "text": [ "induced" ], "offsets": [ [ 435, 442 ] ] }, "arguments": [ { "role": "hasPatient", "ref_id": "PMID-10329626_E11" }, { "role": "hasAgent", "ref_id": "PMID-10329626_T27" } ] }, { "id": "PMID-10329626_E36", "type": "Increase", "trigger": { "text": [ "increased" ], "offsets": [ [ 966, 975 ] ] }, "arguments": [ { "role": "hasPatient", "ref_id": "PMID-10329626_T59" } ] } ]

[]

[ { "id": "PMID-10329626_R4", "type": "encodes", "arg1_id": "PMID-10329626_T32", "arg2_id": "PMID-10329626_T31", "normalized": [] }, { "id": "PMID-10329626_R11", "type": "encodes", "arg1_id": "PMID-10329626_T56", "arg2_id": "PMID-10329626_T55", "normalized": [] }, { "id": "PMID-10329626_R12", "type": "locatedIn", "arg1_id": "PMID-10329626_T56", "arg2_id": "PMID-10329626_T57", "normalized": [] }, { "id": "PMID-10329626_R13", "type": "encodes", "arg1_id": "PMID-10329626_T59", "arg2_id": "PMID-10329626_T58", "normalized": [] }, { "id": "PMID-10329626_R14", "type": "locatedIn", "arg1_id": "PMID-10329626_T59", "arg2_id": "PMID-10329626_T60", "normalized": [] }, { "id": "PMID-10329626_R16", "type": "locatedIn", "arg1_id": "PMID-10329626_T66", "arg2_id": "PMID-10329626_T65", "normalized": [] } ]

[ { "id": "PMID-10426995__text", "type": "abstract", "text": [ "Host defense mechanisms triggered by microbial lipoproteins through toll-like receptors. The generation of cell-mediated immunity against many infectious pathogens involves the production of interleukin-12 (IL-12), a key signal of the innate immune system. Yet, for many pathogens, the molecules that induce IL-12 production by macrophages and the mechanisms by which they do so remain undefined. Here it is shown that microbial lipoproteins are potent stimulators of IL-12 production by human macrophages, and that induction is mediated by Toll-like receptors (TLRs). Several lipoproteins stimulated TLR-dependent transcription of inducible nitric oxide synthase and the production of nitric oxide, a powerful microbicidal pathway. Activation of TLRs by microbial lipoproteins may initiate innate defense mechanisms against infectious pathogens.\n" ], "offsets": [ [ 0, 847 ] ] } ]

[ { "id": "PMID-10426995_T2", "type": "Microorganism", "text": [ "microbial" ], "offsets": [ [ 37, 46 ] ], "normalized": [] }, { "id": "PMID-10426995_T3", "type": "Protein", "text": [ "lipoproteins" ], "offsets": [ [ 47, 59 ] ], "normalized": [] }, { "id": "PMID-10426995_T4", "type": "Protein", "text": [ "toll-like receptors" ], "offsets": [ [ 68, 87 ] ], "normalized": [] }, { "id": "PMID-10426995_T5", "type": "Cell", "text": [ "cell" ], "offsets": [ [ 107, 111 ] ], "normalized": [] }, { "id": "PMID-10426995_T8", "type": "Protein", "text": [ "interleukin-12" ], "offsets": [ [ 191, 205 ] ], "normalized": [] }, { "id": "PMID-10426995_T9", "type": "Protein", "text": [ "IL-12" ], "offsets": [ [ 207, 212 ] ], "normalized": [] }, { "id": "PMID-10426995_T11", "type": "Protein", "text": [ "IL-12" ], "offsets": [ [ 308, 313 ] ], "normalized": [] }, { "id": "PMID-10426995_T13", "type": "Cell", "text": [ "macrophages" ], "offsets": [ [ 328, 339 ] ], "normalized": [] }, { "id": "PMID-10426995_T14", "type": "Microorganism", "text": [ "microbial" ], "offsets": [ [ 419, 428 ] ], "normalized": [] }, { "id": "PMID-10426995_T15", "type": "Protein", "text": [ "lipoproteins" ], "offsets": [ [ 429, 441 ] ], "normalized": [] }, { "id": "PMID-10426995_T17", "type": "Protein", "text": [ "IL-12" ], "offsets": [ [ 468, 473 ] ], "normalized": [] }, { "id": "PMID-10426995_T19", "type": "Eukaryote", "text": [ "human" ], "offsets": [ [ 488, 493 ] ], "normalized": [] }, { "id": "PMID-10426995_T20", "type": "Cell", "text": [ "macrophages" ], "offsets": [ [ 494, 505 ] ], "normalized": [] }, { "id": "PMID-10426995_T23", "type": "Protein", "text": [ "Toll-like receptors" ], "offsets": [ [ 541, 560 ] ], "normalized": [] }, { "id": "PMID-10426995_T24", "type": "Protein", "text": [ "TLRs" ], "offsets": [ [ 562, 566 ] ], "normalized": [] }, { "id": "PMID-10426995_T25", "type": "Protein", "text": [ "lipoproteins" ], "offsets": [ [ 577, 589 ] ], "normalized": [] }, { "id": "PMID-10426995_T27", "type": "Protein", "text": [ "TLR" ], "offsets": [ [ 601, 604 ] ], "normalized": [] }, { "id": "PMID-10426995_T32", "type": "Chemical", "text": [ "nitric oxide" ], "offsets": [ [ 686, 698 ] ], "normalized": [] }, { "id": "PMID-10426995_T35", "type": "Protein", "text": [ "TLRs" ], "offsets": [ [ 747, 751 ] ], "normalized": [] }, { "id": "PMID-10426995_T36", "type": "Microorganism", "text": [ "microbial" ], "offsets": [ [ 755, 764 ] ], "normalized": [] }, { "id": "PMID-10426995_T37", "type": "Protein", "text": [ "lipoproteins" ], "offsets": [ [ 765, 777 ] ], "normalized": [] }, { "id": "PMID-10426995_T29", "type": "Enzyme", "text": [ "nitric oxide synthase" ], "offsets": [ [ 642, 663 ] ], "normalized": [] } ]

[ { "id": "PMID-10426995_E1", "type": "PositiveRegulation", "trigger": { "text": [ "triggered" ], "offsets": [ [ 24, 33 ] ] }, "arguments": [ { "role": "hasAgent", "ref_id": "PMID-10426995_T3" }, { "role": "hasPatient", "ref_id": "PMID-10426995_E15" } ] }, { "id": "PMID-10426995_E2", "type": "RegulatoryProcess", "trigger": { "text": [ "mediated" ], "offsets": [ [ 112, 120 ] ] }, "arguments": [ { "role": "hasAgent2", "ref_id": "PMID-10426995_T5" }, { "role": "hasPatient", "ref_id": "PMID-10426995_E16" } ] }, { "id": "PMID-10426995_E3", "type": "ProteinBiosynthesis", "trigger": { "text": [ "production" ], "offsets": [ [ 177, 187 ] ] }, "arguments": [ { "role": "hasPatient", "ref_id": "PMID-10426995_T8" } ] }, { "id": "PMID-10426995_E4", "type": "Increase", "trigger": { "text": [ "induce" ], "offsets": [ [ 301, 307 ] ] }, "arguments": [ { "role": "hasPatient", "ref_id": "PMID-10426995_E5" } ] }, { "id": "PMID-10426995_E5", "type": "ProteinBiosynthesis", "trigger": { "text": [ "production" ], "offsets": [ [ 314, 324 ] ] }, "arguments": [ { "role": "hasPatient", "ref_id": "PMID-10426995_T11" }, { "role": "hasAgent", "ref_id": "PMID-10426995_T13" } ] }, { "id": "PMID-10426995_E6", "type": "ProteinBiosynthesis", "trigger": { "text": [ "production" ], "offsets": [ [ 474, 484 ] ] }, "arguments": [ { "role": "hasAgent", "ref_id": "PMID-10426995_T20" }, { "role": "hasPatient", "ref_id": "PMID-10426995_T17" } ] }, { "id": "PMID-10426995_E7", "type": "Increase", "trigger": { "text": [ "induction" ], "offsets": [ [ 516, 525 ] ] }, "arguments": [] }, { "id": "PMID-10426995_E8", "type": "RegulatoryProcess", "trigger": { "text": [ "mediated" ], "offsets": [ [ 529, 537 ] ] }, "arguments": [ { "role": "hasAgent", "ref_id": "PMID-10426995_T23" }, { "role": "hasPatient", "ref_id": "PMID-10426995_E7" } ] }, { "id": "PMID-10426995_E9", "type": "Increase", "trigger": { "text": [ "stimulated" ], "offsets": [ [ 590, 600 ] ] }, "arguments": [ { "role": "hasAgent", "ref_id": "PMID-10426995_T25" }, { "role": "hasPatient", "ref_id": "PMID-10426995_E10" } ] }, { "id": "PMID-10426995_E10", "type": "Transcription", "trigger": { "text": [ "transcription" ], "offsets": [ [ 615, 628 ] ] }, "arguments": [ { "role": "hasPatient", "ref_id": "PMID-10426995_T29" } ] }, { "id": "PMID-10426995_E11", "type": "Producing", "trigger": { "text": [ "production" ], "offsets": [ [ 672, 682 ] ] }, "arguments": [ { "role": "hasPatient", "ref_id": "PMID-10426995_T32" } ] }, { "id": "PMID-10426995_E12", "type": "PositiveRegulation", "trigger": { "text": [ "Activation" ], "offsets": [ [ 733, 743 ] ] }, "arguments": [ { "role": "hasAgent", "ref_id": "PMID-10426995_T37" }, { "role": "hasPatient", "ref_id": "PMID-10426995_T35" } ] }, { "id": "PMID-10426995_E13", "type": "PositiveRegulation", "trigger": { "text": [ "initiate" ], "offsets": [ [ 782, 790 ] ] }, "arguments": [ { "role": "hasAgent", "ref_id": "PMID-10426995_E12" }, { "role": "hasPatient", "ref_id": "PMID-10426995_E14" } ] }, { "id": "PMID-10426995_E14", "type": "ResponseProcess", "trigger": { "text": [ "innate defense mechanisms" ], "offsets": [ [ 791, 816 ] ] }, "arguments": [] }, { "id": "PMID-10426995_E15", "type": "ResponseProcess", "trigger": { "text": [ "Host defense mechanisms" ], "offsets": [ [ 0, 23 ] ] }, "arguments": [] }, { "id": "PMID-10426995_E16", "type": "CellularProcess", "trigger": { "text": [ "immunity" ], "offsets": [ [ 121, 129 ] ] }, "arguments": [] }, { "id": "PMID-10426995_E17", "type": "Increase", "trigger": { "text": [ "stimulators" ], "offsets": [ [ 453, 464 ] ] }, "arguments": [ { "role": "hasAgent", "ref_id": "PMID-10426995_T15" }, { "role": "hasPatient", "ref_id": "PMID-10426995_E6" } ] }, { "id": "PMID-10426995_E18", "type": "Pathway", "trigger": { "text": [ "microbicidal pathway" ], "offsets": [ [ 711, 731 ] ] }, "arguments": [] }, { "id": "PMID-10426995_E19", "type": "Increase", "trigger": { "text": [ "stimulated" ], "offsets": [ [ 590, 600 ] ] }, "arguments": [ { "role": "hasAgent", "ref_id": "PMID-10426995_T25" }, { "role": "hasPatient", "ref_id": "PMID-10426995_E11" } ] } ]

[]

[ { "id": "PMID-10426995_R1", "type": "locatedIn", "arg1_id": "PMID-10426995_T3", "arg2_id": "PMID-10426995_T2", "normalized": [] }, { "id": "PMID-10426995_R3", "type": "locatedIn", "arg1_id": "PMID-10426995_T15", "arg2_id": "PMID-10426995_T14", "normalized": [] }, { "id": "PMID-10426995_R4", "type": "fromSpecies", "arg1_id": "PMID-10426995_T20", "arg2_id": "PMID-10426995_T19", "normalized": [] }, { "id": "PMID-10426995_R5", "type": "locatedIn", "arg1_id": "PMID-10426995_T37", "arg2_id": "PMID-10426995_T36", "normalized": [] } ]

[ { "id": "PMID-10426996__text", "type": "abstract", "text": [ "Cell activation and apoptosis by bacterial lipoproteins through toll-like receptor-2. Apoptosis is implicated in the generation and resolution of inflammation in response to bacterial pathogens. All bacterial pathogens produce lipoproteins (BLPs), which trigger the innate immune response. BLPs were found to induce apoptosis in THP-1 monocytic cells through human Toll-like receptor-2 (hTLR2). BLPs also initiated apoptosis in an epithelial cell line transfected with hTLR2. In addition, BLPs stimulated nuclear factor-kappaB, a transcriptional activator of multiple host defense genes, and activated the respiratory burst through hTLR2. Thus, hTLR2 is a molecular link between microbial products, apoptosis, and host defense mechanisms.\n" ], "offsets": [ [ 0, 739 ] ] } ]

[ { "id": "PMID-10426996_T1", "type": "Cell", "text": [ "Cell" ], "offsets": [ [ 0, 4 ] ], "normalized": [] }, { "id": "PMID-10426996_T4", "type": "Prokaryote", "text": [ "bacterial" ], "offsets": [ [ 33, 42 ] ], "normalized": [] }, { "id": "PMID-10426996_T5", "type": "Protein", "text": [ "lipoproteins" ], "offsets": [ [ 43, 55 ] ], "normalized": [] }, { "id": "PMID-10426996_T6", "type": "Protein", "text": [ "toll-like receptor-2" ], "offsets": [ [ 64, 84 ] ], "normalized": [] }, { "id": "PMID-10426996_T14", "type": "Protein", "text": [ "lipoproteins" ], "offsets": [ [ 227, 239 ] ], "normalized": [] }, { "id": "PMID-10426996_T15", "type": "Protein", "text": [ "BLPs" ], "offsets": [ [ 241, 245 ] ], "normalized": [] }, { "id": "PMID-10426996_T18", "type": "Protein", "text": [ "BLPs" ], "offsets": [ [ 290, 294 ] ], "normalized": [] }, { "id": "PMID-10426996_T21", "type": "Cell", "text": [ "THP-1 monocytic cells" ], "offsets": [ [ 329, 350 ] ], "normalized": [] }, { "id": "PMID-10426996_T22", "type": "Eukaryote", "text": [ "human" ], "offsets": [ [ 359, 364 ] ], "normalized": [] }, { "id": "PMID-10426996_T23", "type": "Protein", "text": [ "Toll-like receptor-2" ], "offsets": [ [ 365, 385 ] ], "normalized": [] }, { "id": "PMID-10426996_T24", "type": "Protein", "text": [ "hTLR2" ], "offsets": [ [ 387, 392 ] ], "normalized": [] }, { "id": "PMID-10426996_T25", "type": "Protein", "text": [ "BLPs" ], "offsets": [ [ 395, 399 ] ], "normalized": [] }, { "id": "PMID-10426996_T28", "type": "Cell", "text": [ "epithelial cell line" ], "offsets": [ [ 431, 451 ] ], "normalized": [] }, { "id": "PMID-10426996_T29", "type": "Protein", "text": [ "hTLR2" ], "offsets": [ [ 469, 474 ] ], "normalized": [] }, { "id": "PMID-10426996_T30", "type": "Protein", "text": [ "BLPs" ], "offsets": [ [ 489, 493 ] ], "normalized": [] }, { "id": "PMID-10426996_T32", "type": "TranscriptionActivator", "text": [ "nuclear factor-kappaB" ], "offsets": [ [ 505, 526 ] ], "normalized": [] }, { "id": "PMID-10426996_T33", "type": "TranscriptionActivator", "text": [ "transcriptional activator" ], "offsets": [ [ 530, 555 ] ], "normalized": [] }, { "id": "PMID-10426996_T34", "type": "Gene", "text": [ "genes" ], "offsets": [ [ 581, 586 ] ], "normalized": [] }, { "id": "PMID-10426996_T37", "type": "Protein", "text": [ "hTLR2" ], "offsets": [ [ 632, 637 ] ], "normalized": [] }, { "id": "PMID-10426996_T38", "type": "Protein", "text": [ "hTLR2" ], "offsets": [ [ 645, 650 ] ], "normalized": [] }, { "id": "PMID-10426996_T39", "type": "Microorganism", "text": [ "microbial" ], "offsets": [ [ 679, 688 ] ], "normalized": [] }, { "id": "PMID-10426996_T9", "type": "Prokaryote", "text": [ "bacterial pathogens" ], "offsets": [ [ 174, 193 ] ], "normalized": [] }, { "id": "PMID-10426996_T10", "type": "Prokaryote", "text": [ "bacterial pathogens" ], "offsets": [ [ 199, 218 ] ], "normalized": [] } ]

[ { "id": "PMID-10426996_E1", "type": "PositiveRegulation", "trigger": { "text": [ "activation" ], "offsets": [ [ 5, 15 ] ] }, "arguments": [ { "role": "hasPatient", "ref_id": "PMID-10426996_T1" } ] }, { "id": "PMID-10426996_E2", "type": "CellDeath", "trigger": { "text": [ "apoptosis" ], "offsets": [ [ 20, 29 ] ] }, "arguments": [] }, { "id": "PMID-10426996_E3", "type": "CellDeath", "trigger": { "text": [ "Apoptosis" ], "offsets": [ [ 86, 95 ] ] }, "arguments": [] }, { "id": "PMID-10426996_E4", "type": "ResponseProcess", "trigger": { "text": [ "response" ], "offsets": [ [ 162, 170 ] ] }, "arguments": [ { "role": "hasPatient", "ref_id": "PMID-10426996_E3" }, { "role": "hasAgent", "ref_id": "PMID-10426996_T9" } ] }, { "id": "PMID-10426996_E5", "type": "Producing", "trigger": { "text": [ "produce" ], "offsets": [ [ 219, 226 ] ] }, "arguments": [ { "role": "hasPatient", "ref_id": "PMID-10426996_T14" }, { "role": "hasAgent", "ref_id": "PMID-10426996_T10" } ] }, { "id": "PMID-10426996_E6", "type": "PositiveRegulation", "trigger": { "text": [ "trigger" ], "offsets": [ [ 254, 261 ] ] }, "arguments": [ { "role": "hasPatient", "ref_id": "PMID-10426996_E7" }, { "role": "hasAgent", "ref_id": "PMID-10426996_T14" } ] }, { "id": "PMID-10426996_E7", "type": "ResponseProcess", "trigger": { "text": [ "immune response" ], "offsets": [ [ 273, 288 ] ] }, "arguments": [] }, { "id": "PMID-10426996_E8", "type": "PositiveRegulation", "trigger": { "text": [ "induce" ], "offsets": [ [ 309, 315 ] ] }, "arguments": [ { "role": "hasAgent", "ref_id": "PMID-10426996_T18" }, { "role": "hasPatient", "ref_id": "PMID-10426996_E9" } ] }, { "id": "PMID-10426996_E9", "type": "CellDeath", "trigger": { "text": [ "apoptosis" ], "offsets": [ [ 316, 325 ] ] }, "arguments": [] }, { "id": "PMID-10426996_E10", "type": "PositiveRegulation", "trigger": { "text": [ "initiated" ], "offsets": [ [ 405, 414 ] ] }, "arguments": [ { "role": "hasAgent", "ref_id": "PMID-10426996_T25" }, { "role": "hasPatient", "ref_id": "PMID-10426996_E11" } ] }, { "id": "PMID-10426996_E11", "type": "CellDeath", "trigger": { "text": [ "apoptosis" ], "offsets": [ [ 415, 424 ] ] }, "arguments": [] }, { "id": "PMID-10426996_E12", "type": "Increase", "trigger": { "text": [ "stimulated" ], "offsets": [ [ 494, 504 ] ] }, "arguments": [ { "role": "hasAgent", "ref_id": "PMID-10426996_T30" }, { "role": "hasPatient", "ref_id": "PMID-10426996_T32" } ] }, { "id": "PMID-10426996_E13", "type": "PositiveRegulation", "trigger": { "text": [ "activated" ], "offsets": [ [ 592, 601 ] ] }, "arguments": [ { "role": "hasAgent", "ref_id": "PMID-10426996_T30" }, { "role": "hasPatient", "ref_id": "PMID-10426996_E14" } ] }, { "id": "PMID-10426996_E14", "type": "CellularMetabolicProcess", "trigger": { "text": [ "respiratory burst" ], "offsets": [ [ 606, 623 ] ] }, "arguments": [] }, { "id": "PMID-10426996_E15", "type": "Producing", "trigger": { "text": [ "products" ], "offsets": [ [ 689, 697 ] ] }, "arguments": [] }, { "id": "PMID-10426996_E16", "type": "CellDeath", "trigger": { "text": [ "apoptosis" ], "offsets": [ [ 699, 708 ] ] }, "arguments": [] }, { "id": "PMID-10426996_E17", "type": "ResponseProcess", "trigger": { "text": [ "host defense mechanisms" ], "offsets": [ [ 714, 737 ] ] }, "arguments": [] }, { "id": "PMID-10426996_E18", "type": "ResponseProcess", "trigger": { "text": [ "host defense" ], "offsets": [ [ 568, 580 ] ] }, "arguments": [] } ]

[]

[ { "id": "PMID-10426996_R4", "type": "fromSpecies", "arg1_id": "PMID-10426996_T23", "arg2_id": "PMID-10426996_T22", "normalized": [] }, { "id": "PMID-10426996_R6", "type": "locatedIn", "arg1_id": "PMID-10426996_T29", "arg2_id": "PMID-10426996_T28", "normalized": [] }, { "id": "PMID-10426996_R1", "type": "fromSpecies", "arg1_id": "PMID-10426996_T5", "arg2_id": "PMID-10426996_T4", "normalized": [] } ]

[ { "id": "PMID-10428808__text", "type": "abstract", "text": [ "Isolation and characterization of ARA160 as the first androgen receptor N-terminal-associated coactivator in human prostate cells. The androgen receptor (AR) is a member of the steroid receptor superfamily that may require coactivators for proper or maximal transactivation. Using a purified AR N-terminal peptide as a probe to screen the human testis expression library, we identified an androgen-enhanced AR N-terminal-associated protein ARA160, which consists of 1,093 amino acids with an apparent molecular mass of 160 kDa. Sequence comparison in GenBank(TM) reveals that ARA160 shares an identical sequence with a HIV-1 TATA element modulatory factor, TMF. The far-Western blotting and co-immunoprecipitation assays demonstrate that the AR can interact directly with ARA160/TMF. Affinity gel pull-down and mammalian two-hybrid assays further suggest androgen can enhance significantly the interaction between AR and ARA160. Transient transfection assays demonstrated that ARA160 might function as a coactivator for AR-mediated transactivation in human prostate cancer PC-3 cells. Our data further suggest that this AR N-terminal coactivator can function cooperatively with AR C-terminal coactivator, ARA70, in PC-3 cells. Together, our data demonstrate that ARA160 might represent the first identified androgen-enhanced N-terminal coactivator for the AR.\n" ], "offsets": [ [ 0, 1360 ] ] } ]

[ { "id": "PMID-10428808_T1", "type": "Protein", "text": [ "ARA160" ], "offsets": [ [ 34, 40 ] ], "normalized": [] }, { "id": "PMID-10428808_T4", "type": "Eukaryote", "text": [ "human" ], "offsets": [ [ 109, 114 ] ], "normalized": [] }, { "id": "PMID-10428808_T5", "type": "Cell", "text": [ "prostate cells" ], "offsets": [ [ 115, 129 ] ], "normalized": [] }, { "id": "PMID-10428808_T6", "type": "Protein", "text": [ "androgen receptor" ], "offsets": [ [ 135, 152 ] ], "normalized": [] }, { "id": "PMID-10428808_T7", "type": "Protein", "text": [ "AR" ], "offsets": [ [ 154, 156 ] ], "normalized": [] }, { "id": "PMID-10428808_T8", "type": "Protein", "text": [ "steroid receptor superfamily" ], "offsets": [ [ 177, 205 ] ], "normalized": [] }, { "id": "PMID-10428808_T9", "type": "Protein", "text": [ "coactivators" ], "offsets": [ [ 223, 235 ] ], "normalized": [] }, { "id": "PMID-10428808_T11", "type": "Protein", "text": [ "AR" ], "offsets": [ [ 292, 294 ] ], "normalized": [] }, { "id": "PMID-10428808_T12", "type": "Peptide", "text": [ "peptide" ], "offsets": [ [ 306, 313 ] ], "normalized": [] }, { "id": "PMID-10428808_T13", "type": "Eukaryote", "text": [ "human" ], "offsets": [ [ 339, 344 ] ], "normalized": [] }, { "id": "PMID-10428808_T14", "type": "Tissue", "text": [ "testis" ], "offsets": [ [ 345, 351 ] ], "normalized": [] }, { "id": "PMID-10428808_T15", "type": "OrganicChemical", "text": [ "androgen" ], "offsets": [ [ 389, 397 ] ], "normalized": [] }, { "id": "PMID-10428808_T19", "type": "AminoAcid", "text": [ "amino acids" ], "offsets": [ [ 472, 483 ] ], "normalized": [] }, { "id": "PMID-10428808_T20", "type": "Protein", "text": [ "ARA160" ], "offsets": [ [ 576, 582 ] ], "normalized": [] }, { "id": "PMID-10428808_T21", "type": "Virus", "text": [ "HIV-1" ], "offsets": [ [ 619, 624 ] ], "normalized": [] }, { "id": "PMID-10428808_T24", "type": "TranscriptionRegulator", "text": [ "TMF" ], "offsets": [ [ 657, 660 ] ], "normalized": [] }, { "id": "PMID-10428808_T25", "type": "Protein", "text": [ "AR" ], "offsets": [ [ 742, 744 ] ], "normalized": [] }, { "id": "PMID-10428808_T27", "type": "Protein", "text": [ "ARA160/TMF" ], "offsets": [ [ 772, 782 ] ], "normalized": [] }, { "id": "PMID-10428808_T28", "type": "Eukaryote", "text": [ "mammalian" ], "offsets": [ [ 811, 820 ] ], "normalized": [] }, { "id": "PMID-10428808_T29", "type": "OrganicChemical", "text": [ "androgen" ], "offsets": [ [ 855, 863 ] ], "normalized": [] }, { "id": "PMID-10428808_T32", "type": "Protein", "text": [ "AR" ], "offsets": [ [ 914, 916 ] ], "normalized": [] }, { "id": "PMID-10428808_T33", "type": "Protein", "text": [ "ARA160" ], "offsets": [ [ 921, 927 ] ], "normalized": [] }, { "id": "PMID-10428808_T34", "type": "Protein", "text": [ "ARA160" ], "offsets": [ [ 977, 983 ] ], "normalized": [] }, { "id": "PMID-10428808_T35", "type": "Protein", "text": [ "coactivator" ], "offsets": [ [ 1004, 1015 ] ], "normalized": [] }, { "id": "PMID-10428808_T36", "type": "Protein", "text": [ "AR" ], "offsets": [ [ 1020, 1022 ] ], "normalized": [] }, { "id": "PMID-10428808_T39", "type": "Eukaryote", "text": [ "human" ], "offsets": [ [ 1051, 1056 ] ], "normalized": [] }, { "id": "PMID-10428808_T40", "type": "Cell", "text": [ "prostate cancer PC-3 cells" ], "offsets": [ [ 1057, 1083 ] ], "normalized": [] }, { "id": "PMID-10428808_T46", "type": "Protein", "text": [ "ARA70" ], "offsets": [ [ 1205, 1210 ] ], "normalized": [] }, { "id": "PMID-10428808_T47", "type": "Cell", "text": [ "PC-3 cells" ], "offsets": [ [ 1215, 1225 ] ], "normalized": [] }, { "id": "PMID-10428808_T48", "type": "Protein", "text": [ "ARA160" ], "offsets": [ [ 1263, 1269 ] ], "normalized": [] }, { "id": "PMID-10428808_T49", "type": "OrganicChemical", "text": [ "androgen" ], "offsets": [ [ 1307, 1315 ] ], "normalized": [] }, { "id": "PMID-10428808_T52", "type": "Protein", "text": [ "AR" ], "offsets": [ [ 1356, 1358 ] ], "normalized": [] }, { "id": "PMID-10428808_T2", "type": "Protein", "text": [ "androgen receptor N-terminal-associated coactivator" ], "offsets": [ [ 54, 105 ] ], "normalized": [] }, { "id": "PMID-10428808_T10", "type": "Protein", "text": [ "AR N-terminal-associated protein ARA160" ], "offsets": [ [ 407, 446 ] ], "normalized": [] }, { "id": "PMID-10428808_T17", "type": "TranscriptionRegulator", "text": [ "TATA element modulatory factor" ], "offsets": [ [ 625, 655 ] ], "normalized": [] }, { "id": "PMID-10428808_T18", "type": "Sequence", "text": [ "sequence" ], "offsets": [ [ 603, 611 ] ], "normalized": [] }, { "id": "PMID-10428808_T22", "type": "Protein", "text": [ "AR N-terminal coactivator" ], "offsets": [ [ 1120, 1145 ] ], "normalized": [] }, { "id": "PMID-10428808_T23", "type": "Function", "text": [ "function" ], "offsets": [ [ 1150, 1158 ] ], "normalized": [] }, { "id": "PMID-10428808_T41", "type": "Protein", "text": [ "AR C-terminal coactivator" ], "offsets": [ [ 1178, 1203 ] ], "normalized": [] }, { "id": "PMID-10428808_T42", "type": "Protein", "text": [ "N-terminal coactivator" ], "offsets": [ [ 1325, 1347 ] ], "normalized": [] } ]

[ { "id": "PMID-10428808_E2", "type": "Increase", "trigger": { "text": [ "enhanced" ], "offsets": [ [ 398, 406 ] ] }, "arguments": [ { "role": "hasAgent", "ref_id": "PMID-10428808_T15" }, { "role": "hasPatient", "ref_id": "PMID-10428808_T10" } ] }, { "id": "PMID-10428808_E3", "type": "BindingToProtein", "trigger": { "text": [ "interact" ], "offsets": [ [ 749, 757 ] ] }, "arguments": [ { "role": "hasPatient", "ref_id": "PMID-10428808_T27" }, { "role": "hasPatient2", "ref_id": "PMID-10428808_T25" } ] }, { "id": "PMID-10428808_E4", "type": "Increase", "trigger": { "text": [ "enhance" ], "offsets": [ [ 868, 875 ] ] }, "arguments": [ { "role": "hasAgent", "ref_id": "PMID-10428808_T29" }, { "role": "hasPatient", "ref_id": "PMID-10428808_E5" } ] }, { "id": "PMID-10428808_E5", "type": "BindingToProtein", "trigger": { "text": [ "interaction" ], "offsets": [ [ 894, 905 ] ] }, "arguments": [ { "role": "hasPatient", "ref_id": "PMID-10428808_T32" }, { "role": "hasPatient2", "ref_id": "PMID-10428808_T33" } ] }, { "id": "PMID-10428808_E6", "type": "RegulatoryProcess", "trigger": { "text": [ "mediated" ], "offsets": [ [ 1023, 1031 ] ] }, "arguments": [ { "role": "hasPatient", "ref_id": "PMID-10428808_E7" }, { "role": "hasAgent", "ref_id": "PMID-10428808_T36" } ] }, { "id": "PMID-10428808_E7", "type": "SignalingPathway", "trigger": { "text": [ "transactivation" ], "offsets": [ [ 1032, 1047 ] ] }, "arguments": [] }, { "id": "PMID-10428808_E9", "type": "Increase", "trigger": { "text": [ "enhanced" ], "offsets": [ [ 1316, 1324 ] ] }, "arguments": [ { "role": "hasAgent", "ref_id": "PMID-10428808_T49" }, { "role": "hasPatient", "ref_id": "PMID-10428808_T42" } ] }, { "id": "PMID-10428808_E1", "type": "SignalingPathway", "trigger": { "text": [ "transactivation" ], "offsets": [ [ 258, 273 ] ] }, "arguments": [ { "role": "hasAgent", "ref_id": "PMID-10428808_T6" } ] }, { "id": "PMID-10428808_E8", "type": "RegulatoryProcess", "trigger": { "text": [ "mediated" ], "offsets": [ [ 1023, 1031 ] ] }, "arguments": [ { "role": "hasPatient", "ref_id": "PMID-10428808_E7" }, { "role": "hasAgent", "ref_id": "PMID-10428808_T34" } ] } ]

[]

[ { "id": "PMID-10428808_R3", "type": "fromSpecies", "arg1_id": "PMID-10428808_T5", "arg2_id": "PMID-10428808_T4", "normalized": [] }, { "id": "PMID-10428808_R4", "type": "hasPart", "arg1_id": "PMID-10428808_T11", "arg2_id": "PMID-10428808_T12", "normalized": [] }, { "id": "PMID-10428808_R5", "type": "fromSpecies", "arg1_id": "PMID-10428808_T14", "arg2_id": "PMID-10428808_T13", "normalized": [] }, { "id": "PMID-10428808_R10", "type": "fromSpecies", "arg1_id": "PMID-10428808_T40", "arg2_id": "PMID-10428808_T39", "normalized": [] }, { "id": "PMID-10428808_R2", "type": "locatedIn", "arg1_id": "PMID-10428808_T2", "arg2_id": "PMID-10428808_T5", "normalized": [] }, { "id": "PMID-10428808_R1", "type": "fromSpecies", "arg1_id": "PMID-10428808_T17", "arg2_id": "PMID-10428808_T21", "normalized": [] }, { "id": "PMID-10428808_R6", "type": "hasPart", "arg1_id": "PMID-10428808_T20", "arg2_id": "PMID-10428808_T18", "normalized": [] }, { "id": "PMID-10428808_R7", "type": "hasPart", "arg1_id": "PMID-10428808_T17", "arg2_id": "PMID-10428808_T18", "normalized": [] }, { "id": "PMID-10428808_R8", "type": "locatedIn", "arg1_id": "PMID-10428808_T23", "arg2_id": "PMID-10428808_T47", "normalized": [] } ]

[ { "id": "PMID-10805756__text", "type": "abstract", "text": [ "Phosphorylation of SOX9 by cyclic AMP-dependent protein kinase A enhances SOX9's ability to transactivate a Col2a1 chondrocyte-specific enhancer. Sox9 is a high-mobility-group domain-containing transcription factor required for chondrocyte differentiation and cartilage formation. We used a yeast two-hybrid method based on Son of Sevenless (SOS) recruitment to screen a chondrocyte cDNA library and found that the catalytic subunit of cyclic AMP (cAMP)-dependent protein kinase A (PKA-Calpha) interacted specifically with SOX9. Next we found that two consensus PKA phosphorylation sites within SOX9 could be phosphorylated by PKA in vitro and that SOX9 could be phosphorylated by PKA-Calpha in vivo. In COS-7 cells cotransfected with PKA-Calpha and SOX9 expression plasmids, PKA enhanced the phosphorylation of wild-type SOX9 but did not affect phosphorylation of a SOX9 protein in which the two PKA phosphorylation sites (S(64) and S(211)) were mutated. Using a phosphospecific antibody that specifically recognized SOX9 phosphorylated at serine 211, one of the two PKA phosphorylation sites, we demonstrated that addition of cAMP to chondrocytes strongly increased the phosphorylation of endogenous Sox9. In addition, immunohistochemistry of mouse embryo hind legs showed that Sox9 phosphorylated at serine 211 was principally localized in the prehypertrophic zone of the growth plate, corresponding to the major site of expression of the parathyroid hormone-related peptide (PTHrP) receptor. Since cAMP has previously been shown to effectively increase the mRNA levels of Col2a1 and other specific markers of chondrocyte differentiation in culture, we then asked whether PKA phosphorylation could modulate the activity of SOX9. Addition of 8-bromo-cAMP to chondrocytes in culture increased the activity of a transiently transfected SOX9-dependent 48-bp Col2a1 chondrocyte-specific enhancer; similarly, cotransfection of PKA-Calpha increased the activity of this enhancer. Mutations of the two PKA phosphorylation consensus sites of SOX9 markedly decreased the PKA-Calpha activation of this enhancer by SOX9. PKA phosphorylation and the mutations in the consensus PKA phosphorylation sites of SOX9 did not alter its nuclear localization. In vitro phosphorylation of SOX9 by PKA resulted in more efficient DNA binding. We conclude that SOX9 is a target of cAMP signaling and that phosphorylation of SOX9 by PKA enhances its transcriptional and DNA-binding activity. Because PTHrP signaling is mediated by cAMP, our results support the hypothesis that Sox9 is a target of PTHrP signaling in the growth plate and that the increased activity of Sox9 might mediate the effect of PTHrP in maintaining the cells as nonhypertrophic chondrocytes.\n" ], "offsets": [ [ 0, 2741 ] ] } ]

[ { "id": "PMID-10805756_T2", "type": "TranscriptionFactor", "text": [ "SOX9" ], "offsets": [ [ 19, 23 ] ], "normalized": [] }, { "id": "PMID-10805756_T3", "type": "SecondMessenger", "text": [ "cyclic AMP" ], "offsets": [ [ 27, 37 ] ], "normalized": [] }, { "id": "PMID-10805756_T4", "type": "Enzyme", "text": [ "protein kinase A" ], "offsets": [ [ 48, 64 ] ], "normalized": [] }, { "id": "PMID-10805756_T6", "type": "TranscriptionFactor", "text": [ "SOX9's" ], "offsets": [ [ 74, 80 ] ], "normalized": [] }, { "id": "PMID-10805756_T8", "type": "Gene", "text": [ "Col2a1" ], "offsets": [ [ 108, 114 ] ], "normalized": [] }, { "id": "PMID-10805756_T9", "type": "Cell", "text": [ "chondrocyte" ], "offsets": [ [ 115, 126 ] ], "normalized": [] }, { "id": "PMID-10805756_T10", "type": "Enhancer", "text": [ "enhancer" ], "offsets": [ [ 136, 144 ] ], "normalized": [] }, { "id": "PMID-10805756_T11", "type": "TranscriptionFactor", "text": [ "Sox9" ], "offsets": [ [ 146, 150 ] ], "normalized": [] }, { "id": "PMID-10805756_T16", "type": "Protein", "text": [ "Son of Sevenless" ], "offsets": [ [ 324, 340 ] ], "normalized": [] }, { "id": "PMID-10805756_T18", "type": "Cell", "text": [ "chondrocyte" ], "offsets": [ [ 371, 382 ] ], "normalized": [] }, { "id": "PMID-10805756_T19", "type": "DNA", "text": [ "cDNA library" ], "offsets": [ [ 383, 395 ] ], "normalized": [] }, { "id": "PMID-10805756_T20", "type": "ProteinSubunit", "text": [ "subunit" ], "offsets": [ [ 425, 432 ] ], "normalized": [] }, { "id": "PMID-10805756_T22", "type": "SecondMessenger", "text": [ "cAMP" ], "offsets": [ [ 448, 452 ] ], "normalized": [] }, { "id": "PMID-10805756_T23", "type": "Enzyme", "text": [ "protein kinase A" ], "offsets": [ [ 464, 480 ] ], "normalized": [] }, { "id": "PMID-10805756_T24", "type": "Enzyme", "text": [ "PKA-Calpha" ], "offsets": [ [ 482, 492 ] ], "normalized": [] }, { "id": "PMID-10805756_T26", "type": "TranscriptionFactor", "text": [ "SOX9" ], "offsets": [ [ 523, 527 ] ], "normalized": [] }, { "id": "PMID-10805756_T27", "type": "Enzyme", "text": [ "PKA" ], "offsets": [ [ 562, 565 ] ], "normalized": [] }, { "id": "PMID-10805756_T29", "type": "AminoAcid", "text": [ "sites" ], "offsets": [ [ 582, 587 ] ], "normalized": [] }, { "id": "PMID-10805756_T30", "type": "TranscriptionFactor", "text": [ "SOX9" ], "offsets": [ [ 595, 599 ] ], "normalized": [] }, { "id": "PMID-10805756_T32", "type": "Enzyme", "text": [ "PKA" ], "offsets": [ [ 627, 630 ] ], "normalized": [] }, { "id": "PMID-10805756_T33", "type": "TranscriptionFactor", "text": [ "SOX9" ], "offsets": [ [ 649, 653 ] ], "normalized": [] }, { "id": "PMID-10805756_T35", "type": "Enzyme", "text": [ "PKA-Calpha" ], "offsets": [ [ 681, 691 ] ], "normalized": [] }, { "id": "PMID-10805756_T36", "type": "Cell", "text": [ "COS-7 cells" ], "offsets": [ [ 704, 715 ] ], "normalized": [] }, { "id": "PMID-10805756_T37", "type": "Enzyme", "text": [ "PKA-Calpha" ], "offsets": [ [ 735, 745 ] ], "normalized": [] }, { "id": "PMID-10805756_T38", "type": "TranscriptionFactor", "text": [ "SOX9" ], "offsets": [ [ 750, 754 ] ], "normalized": [] }, { "id": "PMID-10805756_T40", "type": "DNA", "text": [ "plasmids" ], "offsets": [ [ 766, 774 ] ], "normalized": [] }, { "id": "PMID-10805756_T41", "type": "Enzyme", "text": [ "PKA" ], "offsets": [ [ 776, 779 ] ], "normalized": [] }, { "id": "PMID-10805756_T44", "type": "TranscriptionFactor", "text": [ "wild-type SOX9" ], "offsets": [ [ 812, 826 ] ], "normalized": [] }, { "id": "PMID-10805756_T45", "type": "TranscriptionFactor", "text": [ "SOX9" ], "offsets": [ [ 1018, 1022 ] ], "normalized": [] }, { "id": "PMID-10805756_T47", "type": "AminoAcid", "text": [ "serine 211" ], "offsets": [ [ 1041, 1051 ] ], "normalized": [] }, { "id": "PMID-10805756_T48", "type": "Enzyme", "text": [ "PKA" ], "offsets": [ [ 1068, 1071 ] ], "normalized": [] }, { "id": "PMID-10805756_T50", "type": "AminoAcid", "text": [ "sites" ], "offsets": [ [ 1088, 1093 ] ], "normalized": [] }, { "id": "PMID-10805756_T51", "type": "SecondMessenger", "text": [ "cAMP" ], "offsets": [ [ 1128, 1132 ] ], "normalized": [] }, { "id": "PMID-10805756_T52", "type": "Cell", "text": [ "chondrocytes" ], "offsets": [ [ 1136, 1148 ] ], "normalized": [] }, { "id": "PMID-10805756_T55", "type": "TranscriptionFactor", "text": [ "Sox9" ], "offsets": [ [ 1202, 1206 ] ], "normalized": [] }, { "id": "PMID-10805756_T56", "type": "Eukaryote", "text": [ "mouse" ], "offsets": [ [ 1245, 1250 ] ], "normalized": [] }, { "id": "PMID-10805756_T57", "type": "Tissue", "text": [ "embryo hind legs" ], "offsets": [ [ 1251, 1267 ] ], "normalized": [] }, { "id": "PMID-10805756_T58", "type": "TranscriptionFactor", "text": [ "Sox9" ], "offsets": [ [ 1280, 1284 ] ], "normalized": [] }, { "id": "PMID-10805756_T60", "type": "AminoAcid", "text": [ "serine 211" ], "offsets": [ [ 1303, 1313 ] ], "normalized": [] }, { "id": "PMID-10805756_T62", "type": "CellComponent", "text": [ "prehypertrophic zone" ], "offsets": [ [ 1347, 1367 ] ], "normalized": [] }, { "id": "PMID-10805756_T67", "type": "SecondMessenger", "text": [ "cAMP" ], "offsets": [ [ 1502, 1506 ] ], "normalized": [] }, { "id": "PMID-10805756_T69", "type": "MessengerRNA", "text": [ "mRNA" ], "offsets": [ [ 1561, 1565 ] ], "normalized": [] }, { "id": "PMID-10805756_T70", "type": "Protein", "text": [ "Col2a1" ], "offsets": [ [ 1576, 1582 ] ], "normalized": [] }, { "id": "PMID-10805756_T71", "type": "MolecularEntity", "text": [ "specific markers" ], "offsets": [ [ 1593, 1609 ] ], "normalized": [] }, { "id": "PMID-10805756_T73", "type": "Enzyme", "text": [ "PKA" ], "offsets": [ [ 1675, 1678 ] ], "normalized": [] }, { "id": "PMID-10805756_T76", "type": "TranscriptionFactor", "text": [ "SOX9" ], "offsets": [ [ 1726, 1730 ] ], "normalized": [] }, { "id": "PMID-10805756_T77", "type": "SecondMessenger", "text": [ "8-bromo-cAMP" ], "offsets": [ [ 1744, 1756 ] ], "normalized": [] }, { "id": "PMID-10805756_T78", "type": "Cell", "text": [ "chondrocytes" ], "offsets": [ [ 1760, 1772 ] ], "normalized": [] }, { "id": "PMID-10805756_T80", "type": "TranscriptionFactor", "text": [ "SOX9" ], "offsets": [ [ 1836, 1840 ] ], "normalized": [] }, { "id": "PMID-10805756_T81", "type": "Gene", "text": [ "Col2a1" ], "offsets": [ [ 1857, 1863 ] ], "normalized": [] }, { "id": "PMID-10805756_T82", "type": "Cell", "text": [ "chondrocyte" ], "offsets": [ [ 1864, 1875 ] ], "normalized": [] }, { "id": "PMID-10805756_T83", "type": "Enhancer", "text": [ "enhancer" ], "offsets": [ [ 1885, 1893 ] ], "normalized": [] }, { "id": "PMID-10805756_T84", "type": "Enzyme", "text": [ "PKA-Calpha" ], "offsets": [ [ 1924, 1934 ] ], "normalized": [] }, { "id": "PMID-10805756_T86", "type": "Enhancer", "text": [ "this enhancer" ], "offsets": [ [ 1961, 1974 ] ], "normalized": [] }, { "id": "PMID-10805756_T88", "type": "Enzyme", "text": [ "PKA" ], "offsets": [ [ 1997, 2000 ] ], "normalized": [] }, { "id": "PMID-10805756_T90", "type": "AminoAcid", "text": [ "sites" ], "offsets": [ [ 2027, 2032 ] ], "normalized": [] }, { "id": "PMID-10805756_T91", "type": "TranscriptionFactor", "text": [ "SOX9" ], "offsets": [ [ 2036, 2040 ] ], "normalized": [] }, { "id": "PMID-10805756_T93", "type": "Enzyme", "text": [ "PKA-Calpha" ], "offsets": [ [ 2064, 2074 ] ], "normalized": [] }, { "id": "PMID-10805756_T95", "type": "Enhancer", "text": [ "this enhancer" ], "offsets": [ [ 2089, 2102 ] ], "normalized": [] }, { "id": "PMID-10805756_T96", "type": "TranscriptionFactor", "text": [ "SOX9" ], "offsets": [ [ 2106, 2110 ] ], "normalized": [] }, { "id": "PMID-10805756_T97", "type": "Enzyme", "text": [ "PKA" ], "offsets": [ [ 2112, 2115 ] ], "normalized": [] }, { "id": "PMID-10805756_T99", "type": "Protein", "text": [ "SOX9" ], "offsets": [ [ 2196, 2200 ] ], "normalized": [] }, { "id": "PMID-10805756_T100", "type": "Nucleus", "text": [ "nuclear" ], "offsets": [ [ 2219, 2226 ] ], "normalized": [] }, { "id": "PMID-10805756_T103", "type": "TranscriptionFactor", "text": [ "SOX9" ], "offsets": [ [ 2269, 2273 ] ], "normalized": [] }, { "id": "PMID-10805756_T104", "type": "Enzyme", "text": [ "PKA" ], "offsets": [ [ 2277, 2280 ] ], "normalized": [] }, { "id": "PMID-10805756_T105", "type": "DNA", "text": [ "DNA" ], "offsets": [ [ 2308, 2311 ] ], "normalized": [] }, { "id": "PMID-10805756_T107", "type": "TranscriptionFactor", "text": [ "SOX9" ], "offsets": [ [ 2338, 2342 ] ], "normalized": [] }, { "id": "PMID-10805756_T108", "type": "SecondMessenger", "text": [ "cAMP" ], "offsets": [ [ 2358, 2362 ] ], "normalized": [] }, { "id": "PMID-10805756_T111", "type": "TranscriptionFactor", "text": [ "SOX9" ], "offsets": [ [ 2401, 2405 ] ], "normalized": [] }, { "id": "PMID-10805756_T112", "type": "Enzyme", "text": [ "PKA" ], "offsets": [ [ 2409, 2412 ] ], "normalized": [] }, { "id": "PMID-10805756_T114", "type": "TranscriptionFactor", "text": [ "its" ], "offsets": [ [ 2422, 2425 ] ], "normalized": [] }, { "id": "PMID-10805756_T116", "type": "DNA", "text": [ "DNA" ], "offsets": [ [ 2446, 2449 ] ], "normalized": [] }, { "id": "PMID-10805756_T118", "type": "Peptide", "text": [ "PTHrP" ], "offsets": [ [ 2476, 2481 ] ], "normalized": [] }, { "id": "PMID-10805756_T121", "type": "SecondMessenger", "text": [ "cAMP" ], "offsets": [ [ 2507, 2511 ] ], "normalized": [] }, { "id": "PMID-10805756_T122", "type": "TranscriptionFactor", "text": [ "Sox9" ], "offsets": [ [ 2553, 2557 ] ], "normalized": [] }, { "id": "PMID-10805756_T123", "type": "Peptide", "text": [ "PTHrP" ], "offsets": [ [ 2573, 2578 ] ], "normalized": [] }, { "id": "PMID-10805756_T125", "type": "Tissue", "text": [ "growth plate" ], "offsets": [ [ 2596, 2608 ] ], "normalized": [] }, { "id": "PMID-10805756_T127", "type": "TranscriptionFactorActivity", "text": [ "activity" ], "offsets": [ [ 2632, 2640 ] ], "normalized": [] }, { "id": "PMID-10805756_T128", "type": "TranscriptionFactor", "text": [ "Sox9" ], "offsets": [ [ 2644, 2648 ] ], "normalized": [] }, { "id": "PMID-10805756_T130", "type": "Peptide", "text": [ "PTHrP" ], "offsets": [ [ 2677, 2682 ] ], "normalized": [] }, { "id": "PMID-10805756_T132", "type": "Cell", "text": [ "cells" ], "offsets": [ [ 2702, 2707 ] ], "normalized": [] }, { "id": "PMID-10805756_T133", "type": "Cell", "text": [ "nonhypertrophic chondrocytes" ], "offsets": [ [ 2711, 2739 ] ], "normalized": [] }, { "id": "PMID-10805756_T7", "type": "TranscriptionActivatorActivity", "text": [ "ability to transactivate" ], "offsets": [ [ 81, 105 ] ], "normalized": [] }, { "id": "PMID-10805756_T12", "type": "HMGTF", "text": [ "high-mobility-group domain-containing transcription factor" ], "offsets": [ [ 156, 214 ] ], "normalized": [] }, { "id": "PMID-10805756_T13", "type": "Protein", "text": [ "SOS" ], "offsets": [ [ 342, 345 ] ], "normalized": [] }, { "id": "PMID-10805756_T134", "type": "CatalyticActivity", "text": [ "catalytic" ], "offsets": [ [ 415, 424 ] ], "normalized": [] }, { "id": "PMID-10805756_T21", "type": "SecondMessenger", "text": [ "cyclic AMP" ], "offsets": [ [ 436, 446 ] ], "normalized": [] }, { "id": "PMID-10805756_T136", "type": "TranscriptionFactor", "text": [ "SOX9 protein" ], "offsets": [ [ 867, 879 ] ], "normalized": [] }, { "id": "PMID-10805756_T137", "type": "AminoAcid", "text": [ "PKA phosphorylation sites" ], "offsets": [ [ 897, 922 ] ], "normalized": [] }, { "id": "PMID-10805756_T138", "type": "AminoAcid", "text": [ "S(64)" ], "offsets": [ [ 924, 929 ] ], "normalized": [] }, { "id": "PMID-10805756_T139", "type": "AminoAcid", "text": [ "S(211)" ], "offsets": [ [ 934, 940 ] ], "normalized": [] }, { "id": "PMID-10805756_T64", "type": "Peptide", "text": [ "parathyroid hormone-related peptide" ], "offsets": [ [ 1442, 1477 ] ], "normalized": [] }, { "id": "PMID-10805756_T65", "type": "Peptide", "text": [ "PTHrP" ], "offsets": [ [ 1479, 1484 ] ], "normalized": [] }, { "id": "PMID-10805756_T66", "type": "Protein", "text": [ "receptor" ], "offsets": [ [ 1486, 1494 ] ], "normalized": [] }, { "id": "PMID-10805756_T141", "type": "TranscriptionFactorActivity", "text": [ "activity" ], "offsets": [ [ 1714, 1722 ] ], "normalized": [] }, { "id": "PMID-10805756_T145", "type": "Enzyme", "text": [ "PKA" ], "offsets": [ [ 2167, 2170 ] ], "normalized": [] }, { "id": "PMID-10805756_T147", "type": "AminoAcid", "text": [ "sites" ], "offsets": [ [ 2187, 2192 ] ], "normalized": [] }, { "id": "PMID-10805756_T115", "type": "TranscriptionFactorActivity", "text": [ "transcriptional" ], "offsets": [ [ 2426, 2441 ] ], "normalized": [] } ]

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"PMID-10805756_T16" } ] }, { "id": "PMID-10805756_E7", "type": "BindingToProtein", "trigger": { "text": [ "interacted" ], "offsets": [ [ 494, 504 ] ] }, "arguments": [ { "role": "hasPatient", "ref_id": "PMID-10805756_T26" }, { "role": "hasPatient2", "ref_id": "PMID-10805756_T20" } ] }, { "id": "PMID-10805756_E8", "type": "Phosphorylation", "trigger": { "text": [ "phosphorylation" ], "offsets": [ [ 566, 581 ] ] }, "arguments": [ { "role": "hasAgent", "ref_id": "PMID-10805756_T27" }, { "role": "hasPatient", "ref_id": "PMID-10805756_T29" } ] }, { "id": "PMID-10805756_E9", "type": "Phosphorylation", "trigger": { "text": [ "phosphorylated" ], "offsets": [ [ 609, 623 ] ] }, "arguments": [ { "role": "hasAgent", "ref_id": "PMID-10805756_T32" }, { "role": "hasPatient", "ref_id": "PMID-10805756_T29" } ] }, { "id": "PMID-10805756_E10", "type": "Phosphorylation", "trigger": { "text": [ "phosphorylated" ], "offsets": [ [ 663, 677 ] ] }, "arguments": [ { "role": "hasAgent", "ref_id": 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"PMID-10805756_E27" }, { "role": "hasPatient", "ref_id": "PMID-10805756_E51" } ] } ]

[]

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[ { "id": "PMID-10807548__text", "type": "abstract", "text": [ "cDNA cloning, tissue expression, and chromosome mapping of human homolog of SOX18. The SRY (sex-determining region Y) gene encodes a transcription factor characterized by a DNA-binding motif termed the HMG (high mobility group) domain. The SOX (Sry-box) genes comprise a large family related by homology to the HMG-box region. We isolated a cDNA clone with an open reading frame encoding a putative protein of 384 amino acids, which shared 83% identity to the mouse Sox18 protein. Northern blot analysis revealed that a 1.9-kb band of human SOX18 messenger RNAs was predominantly expressed in heart, although weak signals were seen in brain, liver, testis, and leukocyte. By polymerase chain reaction (PCR)-based analyses with both a human/rodent monochromosomal hybrid cell panel and a radiation hybrid panel, the gene was mapped to the chromosome 20q13.33 region.\n" ], "offsets": [ [ 0, 866 ] ] } ]

[ { "id": "PMID-10807548_T1", "type": "DNA", "text": [ "cDNA" ], "offsets": [ [ 0, 4 ] ], "normalized": [] }, { "id": "PMID-10807548_T2", "type": "Tissue", "text": [ "tissue" ], "offsets": [ [ 14, 20 ] ], "normalized": [] }, { "id": "PMID-10807548_T4", "type": "Chromosome", "text": [ "chromosome" ], "offsets": [ [ 37, 47 ] ], "normalized": [] }, { "id": "PMID-10807548_T6", "type": "Eukaryote", "text": [ "human" ], "offsets": [ [ 59, 64 ] ], "normalized": [] }, { "id": "PMID-10807548_T7", "type": "Gene", "text": [ "SOX18" ], "offsets": [ [ 76, 81 ] ], "normalized": [] }, { "id": "PMID-10807548_T10", "type": "TranscriptionFactor", "text": [ "transcription factor" ], "offsets": [ [ 133, 153 ] ], "normalized": [] }, { "id": "PMID-10807548_T11", "type": "DNA", "text": [ "DNA" ], "offsets": [ [ 173, 176 ] ], "normalized": [] }, { "id": "PMID-10807548_T13", "type": "ProteinDomain", "text": [ "motif" ], "offsets": [ [ 185, 190 ] ], "normalized": [] }, { "id": "PMID-10807548_T14", "type": "HMG", "text": [ "HMG" ], "offsets": [ [ 202, 205 ] ], "normalized": [] }, { "id": "PMID-10807548_T17", "type": "HMG", "text": [ "HMG-box region" ], "offsets": [ [ 311, 325 ] ], "normalized": [] }, { "id": "PMID-10807548_T19", "type": "OpenReadingFrame", "text": [ "open reading frame" ], "offsets": [ [ 360, 378 ] ], "normalized": [] }, { "id": "PMID-10807548_T20", "type": "Protein", "text": [ "protein" ], "offsets": [ [ 399, 406 ] ], "normalized": [] }, { "id": "PMID-10807548_T21", "type": "AminoAcid", "text": [ "amino acids" ], "offsets": [ [ 414, 425 ] ], "normalized": [] }, { "id": "PMID-10807548_T22", "type": "Eukaryote", "text": [ "mouse" ], "offsets": [ [ 460, 465 ] ], "normalized": [] }, { "id": "PMID-10807548_T23", "type": "Protein", "text": [ "Sox18 protein" ], "offsets": [ [ 466, 479 ] ], "normalized": [] }, { "id": "PMID-10807548_T24", "type": "Eukaryote", "text": [ "human" ], "offsets": [ [ 535, 540 ] ], "normalized": [] }, { "id": "PMID-10807548_T25", "type": "Protein", "text": [ "SOX18" ], "offsets": [ [ 541, 546 ] ], "normalized": [] }, { "id": "PMID-10807548_T26", "type": "MessengerRNA", "text": [ "messenger RNAs" ], "offsets": [ [ 547, 561 ] ], "normalized": [] }, { "id": "PMID-10807548_T28", "type": "Tissue", "text": [ "heart" ], "offsets": [ [ 593, 598 ] ], "normalized": [] }, { "id": "PMID-10807548_T29", "type": "Tissue", "text": [ "brain" ], "offsets": [ [ 635, 640 ] ], "normalized": [] }, { "id": "PMID-10807548_T30", "type": "Tissue", "text": [ "liver" ], "offsets": [ [ 642, 647 ] ], "normalized": [] }, { "id": "PMID-10807548_T31", "type": "Tissue", "text": [ "testis" ], "offsets": [ [ 649, 655 ] ], "normalized": [] }, { "id": "PMID-10807548_T32", "type": "Cell", "text": [ "leukocyte" ], "offsets": [ [ 661, 670 ] ], "normalized": [] }, { "id": "PMID-10807548_T33", "type": "Eukaryote", "text": [ "human/rodent" ], "offsets": [ [ 734, 746 ] ], "normalized": [] }, { "id": "PMID-10807548_T34", "type": "Gene", "text": [ "gene" ], "offsets": [ [ 815, 819 ] ], "normalized": [] }, { "id": "PMID-10807548_T36", "type": "Chromosome", "text": [ "chromosome 20q13.33 region" ], "offsets": [ [ 838, 864 ] ], "normalized": [] }, { "id": "PMID-10807548_T5", "type": "Gene", "text": [ "SRY" ], "offsets": [ [ 87, 90 ] ], "normalized": [] }, { "id": "PMID-10807548_T8", "type": "Gene", "text": [ "SOX" ], "offsets": [ [ 240, 243 ] ], "normalized": [] }, { "id": "PMID-10807548_T15", "type": "DNA", "text": [ "cDNA" ], "offsets": [ [ 341, 345 ] ], "normalized": [] } ]

[ { "id": "PMID-10807548_E1", "type": "GeneExpression", "trigger": { "text": [ "expression" ], "offsets": [ [ 21, 31 ] ] }, "arguments": [] }, { "id": "PMID-10807548_E3", "type": "BindingOfTranscriptionFactorToDNA", "trigger": { "text": [ "binding" ], "offsets": [ [ 177, 184 ] ] }, "arguments": [ { "role": "hasPatient", "ref_id": "PMID-10807548_T11" }, { "role": "hasAgent", "ref_id": "PMID-10807548_T13" } ] }, { "id": "PMID-10807548_E4", "type": "TranscriptionOfGene", "trigger": { "text": [ "expressed" ], "offsets": [ [ 580, 589 ] ] }, "arguments": [ { "role": "hasPatient", "ref_id": "PMID-10807548_T26" } ] } ]

[]

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[ { "id": "PMID-10816420__text", "type": "abstract", "text": [ "Human Sug1/p45 is involved in the proteasome-dependent degradation of Sp1. The transcription factor Sp1 was previously shown to undergo proteasome-dependent degradation when cells were glucose-starved and stimulated with the adenylate cyclase inducer, forskolin. However, the control of the Sp1 degradation process is largely unknown. Using in vitro and in vivo interaction studies, we show in the present study that Sp1 interacts with human Sug1 [hSug1, also known as p45 or thyroid-hormone-receptor interacting protein ('TRIP1')], an ATPase subunit of the 26 S proteasome and a putative transcriptional modulator. This interaction with Sp1 occurs through the C-terminus of hSug1, the region that contains the conserved ATPase domain in this protein. Both in vitro studies, in reconstituted degradation assays, and in vivo experiments, in which hSug1 is overexpressed in normal rat kidney cells, show that full-length hSug1 is able to stimulate the proteasome-dependent degradation of Sp1. However, hSug1 truncations that lack either the N- or C-terminal domain of hSug1 act as dominant negatives, inhibiting Sp1 degradation in vitro. Also, an ATPase mutant of hSug1, while still able to bind Sp1, acts as a dominant negative, blocking Sp1 degradation both in vitro and in vivo. These results demonstrate that hSug1 is involved in the degradation of Sp1 and that ATP hydrolysis by hSug1 is necessary for this process. Our findings indicate that hSug1 is an exchangeable proteasomal component that plays a critical regulatory role in the proteasome-dependent degradation of Sp1. However, hSug1 is not the factor limiting Sp1 degradation in the cells treated with glucosamine. This and other considerations suggest that hSug1 co-operation with other molecules is necessary to target Sp1 for proteasome degradation.\n" ], "offsets": [ [ 0, 1814 ] ] } ]

[ { "id": "PMID-10816420_T1", "type": "Eukaryote", "text": [ "Human" ], "offsets": [ [ 0, 5 ] ], "normalized": [] }, { "id": "PMID-10816420_T2", "type": "Protein", "text": [ "Sug1/p45" ], "offsets": [ [ 6, 14 ] ], "normalized": [] }, { "id": "PMID-10816420_T3", "type": "ProteinComplex", "text": [ "proteasome" ], "offsets": [ [ 34, 44 ] ], "normalized": [] }, { "id": "PMID-10816420_T5", "type": "TranscriptionFactor", "text": [ "Sp1" ], "offsets": [ [ 70, 73 ] ], "normalized": [] }, { "id": "PMID-10816420_T6", "type": "TranscriptionFactor", "text": [ "transcription factor Sp1" ], "offsets": [ [ 79, 103 ] ], "normalized": [] }, { "id": "PMID-10816420_T7", "type": "ProteinComplex", "text": [ "proteasome" ], "offsets": [ [ 136, 146 ] ], "normalized": [] }, { "id": "PMID-10816420_T9", "type": "Cell", "text": [ "cells" ], "offsets": [ [ 174, 179 ] ], "normalized": [] }, { "id": "PMID-10816420_T12", "type": "OrganicChemical", "text": [ "forskolin" ], "offsets": [ [ 252, 261 ] ], "normalized": [] }, { "id": "PMID-10816420_T13", "type": "TranscriptionFactor", "text": [ "Sp1" ], "offsets": [ [ 417, 420 ] ], "normalized": [] }, { "id": "PMID-10816420_T15", "type": "Eukaryote", "text": [ "human" ], "offsets": [ [ 436, 441 ] ], "normalized": [] }, { "id": "PMID-10816420_T16", "type": "Protein", "text": [ "Sug1" ], "offsets": [ [ 442, 446 ] ], "normalized": [] }, { "id": "PMID-10816420_T17", "type": "Protein", "text": [ "[hSug1" ], "offsets": [ [ 447, 453 ] ], "normalized": [] }, { "id": "PMID-10816420_T18", "type": "Protein", "text": [ "p45" ], "offsets": [ [ 469, 472 ] ], "normalized": [] }, { "id": "PMID-10816420_T19", "type": "Protein", "text": [ "thyroid-hormone-receptor interacting protein" ], "offsets": [ [ 476, 520 ] ], "normalized": [] }, { "id": "PMID-10816420_T20", "type": "ProteinSubunit", "text": [ "ATPase subunit" ], "offsets": [ [ 536, 550 ] ], "normalized": [] }, { "id": "PMID-10816420_T21", "type": "ProteinComplex", "text": [ "proteasome" ], "offsets": [ [ 563, 573 ] ], "normalized": [] }, { "id": "PMID-10816420_T25", "type": "TranscriptionFactor", "text": [ "Sp1" ], "offsets": [ [ 638, 641 ] ], "normalized": [] }, { "id": "PMID-10816420_T26", "type": "ProteinDomain", "text": [ "C-terminus" ], "offsets": [ [ 661, 671 ] ], "normalized": [] }, { "id": "PMID-10816420_T27", "type": "Protein", "text": [ "hSug1" ], "offsets": [ [ 675, 680 ] ], "normalized": [] }, { "id": "PMID-10816420_T28", "type": "ProteinDomain", "text": [ "the region" ], "offsets": [ [ 682, 692 ] ], "normalized": [] }, { "id": "PMID-10816420_T29", "type": "ProteinDomain", "text": [ "ATPase domain" ], "offsets": [ [ 721, 734 ] ], "normalized": [] }, { "id": "PMID-10816420_T30", "type": "Protein", "text": [ "this protein" ], "offsets": [ [ 738, 750 ] ], "normalized": [] }, { "id": "PMID-10816420_T31", "type": "Protein", "text": [ "hSug1" ], "offsets": [ [ 846, 851 ] ], "normalized": [] }, { "id": "PMID-10816420_T33", "type": "Eukaryote", "text": [ "rat" ], "offsets": [ [ 879, 882 ] ], "normalized": [] }, { "id": "PMID-10816420_T34", "type": "Tissue", "text": [ "kidney" ], "offsets": [ [ 883, 889 ] ], "normalized": [] }, { "id": "PMID-10816420_T35", "type": "Cell", "text": [ "cells" ], "offsets": [ [ 890, 895 ] ], "normalized": [] }, { "id": "PMID-10816420_T36", "type": "Protein", "text": [ "full-length hSug1" ], "offsets": [ [ 907, 924 ] ], "normalized": [] }, { "id": "PMID-10816420_T38", "type": "ProteinComplex", "text": [ "proteasome" ], "offsets": [ [ 950, 960 ] ], "normalized": [] }, { "id": "PMID-10816420_T40", "type": "TranscriptionFactor", "text": [ "Sp1" ], "offsets": [ [ 986, 989 ] ], "normalized": [] }, { "id": "PMID-10816420_T41", "type": "MutatedProtein", "text": [ "hSug1 truncations" ], "offsets": [ [ 1000, 1017 ] ], "normalized": [] }, { "id": "PMID-10816420_T42", "type": "Protein", "text": [ "hSug1" ], "offsets": [ [ 1066, 1071 ] ], "normalized": [] }, { "id": "PMID-10816420_T44", "type": "TranscriptionFactor", "text": [ "Sp1" ], "offsets": [ [ 1110, 1113 ] ], "normalized": [] }, { "id": "PMID-10816420_T46", "type": "MutantProtein", "text": [ "ATPase mutant" ], "offsets": [ [ 1145, 1158 ] ], "normalized": [] }, { "id": "PMID-10816420_T47", "type": "Protein", "text": [ "hSug1" ], "offsets": [ [ 1162, 1167 ] ], "normalized": [] }, { "id": "PMID-10816420_T49", "type": "TranscriptionFactor", "text": [ "Sp1" ], "offsets": [ [ 1194, 1197 ] ], "normalized": [] }, { "id": "PMID-10816420_T51", "type": "TranscriptionFactor", "text": [ "Sp1" ], "offsets": [ [ 1237, 1240 ] ], "normalized": [] }, { "id": "PMID-10816420_T53", "type": "Protein", "text": [ "hSug1" ], "offsets": [ [ 1311, 1316 ] ], "normalized": [] }, { "id": "PMID-10816420_T55", "type": "TranscriptionFactor", "text": [ "Sp1" ], "offsets": [ [ 1351, 1354 ] ], "normalized": [] }, { "id": "PMID-10816420_T58", "type": "Protein", "text": [ "hSug1" ], "offsets": [ [ 1382, 1387 ] ], "normalized": [] }, { "id": "PMID-10816420_T60", "type": "Protein", "text": [ "hSug1" ], "offsets": [ [ 1446, 1451 ] ], "normalized": [] }, { "id": "PMID-10816420_T61", "type": "ProteinComplex", "text": [ "proteasomal" ], "offsets": [ [ 1471, 1482 ] ], "normalized": [] }, { "id": "PMID-10816420_T62", "type": "ProteinComplex", "text": [ "proteasome" ], "offsets": [ [ 1538, 1548 ] ], "normalized": [] }, { "id": "PMID-10816420_T64", "type": "TranscriptionFactor", "text": [ "Sp1" ], "offsets": [ [ 1574, 1577 ] ], "normalized": [] }, { "id": "PMID-10816420_T65", "type": "Protein", "text": [ "hSug1" ], "offsets": [ [ 1719, 1724 ] ], "normalized": [] }, { "id": "PMID-10816420_T67", "type": "TranscriptionFactor", "text": [ "Sp1" ], "offsets": [ [ 1782, 1785 ] ], "normalized": [] }, { "id": "PMID-10816420_T68", "type": "ProteinComplex", "text": [ "proteasome" ], "offsets": [ [ 1790, 1800 ] ], "normalized": [] }, { "id": "PMID-10816420_T11", "type": "OrganicChemical", "text": [ "adenylate cyclase inducer" ], "offsets": [ [ 225, 250 ] ], "normalized": [] }, { "id": "PMID-10816420_T71", "type": "TranscriptionFactor", "text": [ "Sp1" ], "offsets": [ [ 291, 294 ] ], "normalized": [] }, { "id": "PMID-10816420_T72", "type": "Protein", "text": [ "TRIP1" ], "offsets": [ [ 523, 528 ] ], "normalized": [] }, { "id": "PMID-10816420_T22", "type": "TranscriptionRegulator", "text": [ "transcriptional modulator" ], "offsets": [ [ 589, 614 ] ], "normalized": [] }, { "id": "PMID-10816420_T56", "type": "TranscriptionFactor", "text": [ "Sp1" ], "offsets": [ [ 1621, 1624 ] ], "normalized": [] }, { "id": "PMID-10816420_T57", "type": "Protein", "text": [ "hSug1" ], "offsets": [ [ 1588, 1593 ] ], "normalized": [] }, { "id": "PMID-10816420_T74", "type": "Cell", "text": [ "cells" ], "offsets": [ [ 1644, 1649 ] ], "normalized": [] } ]

[ { "id": "PMID-10816420_E1", "type": "ProteinCatabolism", "trigger": { "text": [ "degradation" ], "offsets": [ [ 55, 66 ] ] }, "arguments": [ { "role": "hasPatient", "ref_id": "PMID-10816420_T5" } ] }, { "id": "PMID-10816420_E2", "type": "ProteinCatabolism", "trigger": { "text": [ "degradation" ], "offsets": [ [ 157, 168 ] ] }, "arguments": [ { "role": "hasPatient", "ref_id": "PMID-10816420_T6" } ] }, { "id": "PMID-10816420_E3", "type": "PositiveRegulation", "trigger": { "text": [ "stimulated" ], "offsets": [ [ 205, 215 ] ] }, "arguments": [ { "role": "hasAgent", "ref_id": "PMID-10816420_T12" }, { "role": "hasPatient", "ref_id": "PMID-10816420_T9" } ] }, { "id": "PMID-10816420_E5", "type": "BindingToProtein", "trigger": { "text": [ "interacts" ], "offsets": [ [ 421, 430 ] ] }, "arguments": [ { "role": "hasPatient", "ref_id": "PMID-10816420_T16" }, { "role": "hasPatient2", "ref_id": "PMID-10816420_T13" } ] }, { "id": "PMID-10816420_E8", "type": "BindingOfTFToTFBindingSiteOfProtein", "trigger": { "text": [ "This interaction" ], "offsets": [ [ 616, 632 ] ] }, "arguments": [ { "role": "hasAgent", "ref_id": "PMID-10816420_T25" }, { "role": "hasPatient", "ref_id": "PMID-10816420_T26" } ] }, { "id": "PMID-10816420_E9", "type": "PositiveRegulationOfGeneExpression", "trigger": { "text": [ "overexpressed" ], "offsets": [ [ 855, 868 ] ] }, "arguments": [ { "role": "hasPatient", "ref_id": "PMID-10816420_T31" } ] }, { "id": "PMID-10816420_E10", "type": "PositiveRegulation", "trigger": { "text": [ "stimulate" ], "offsets": [ [ 936, 945 ] ] }, "arguments": [ { "role": "hasAgent", "ref_id": "PMID-10816420_T36" }, { "role": "hasPatient", "ref_id": "PMID-10816420_E11" } ] }, { "id": "PMID-10816420_E11", "type": "ProteinCatabolism", "trigger": { "text": [ "degradation" ], "offsets": [ [ 971, 982 ] ] }, "arguments": [ { "role": "hasPatient", "ref_id": "PMID-10816420_T40" } ] }, { "id": "PMID-10816420_E12", "type": "NegativeRegulation", "trigger": { "text": [ "inhibiting" ], "offsets": [ [ 1099, 1109 ] ] }, "arguments": [ { "role": "hasAgent", "ref_id": "PMID-10816420_T41" }, { "role": "hasPatient", "ref_id": "PMID-10816420_E13" } ] }, { "id": "PMID-10816420_E13", "type": "ProteinCatabolism", "trigger": { "text": [ "degradation" ], "offsets": [ [ 1114, 1125 ] ] }, "arguments": [ { "role": "hasPatient", "ref_id": "PMID-10816420_T44" } ] }, { "id": "PMID-10816420_E14", "type": "BindingToProtein", "trigger": { "text": [ "bind" ], "offsets": [ [ 1189, 1193 ] ] }, "arguments": [ { "role": "hasPatient", "ref_id": "PMID-10816420_T49" }, { "role": "hasPatient2", "ref_id": "PMID-10816420_T46" } ] }, { "id": "PMID-10816420_E15", "type": "NegativeRegulation", "trigger": { "text": [ "blocking" ], "offsets": [ [ 1228, 1236 ] ] }, "arguments": [ { "role": "hasAgent", "ref_id": "PMID-10816420_T46" }, { "role": "hasPatient", "ref_id": "PMID-10816420_E16" } ] }, { "id": "PMID-10816420_E16", "type": "ProteinCatabolism", "trigger": { "text": [ "degradation" ], "offsets": [ [ 1241, 1252 ] ] }, "arguments": [ { "role": "hasPatient", "ref_id": "PMID-10816420_T51" } ] }, { "id": "PMID-10816420_E17", "type": "ProteinCatabolism", "trigger": { "text": [ "degradation" ], "offsets": [ [ 1336, 1347 ] ] }, "arguments": [ { "role": "hasPatient", "ref_id": "PMID-10816420_T55" } ] }, { "id": "PMID-10816420_E18", "type": "ProteinCatabolism", "trigger": { "text": [ "this process" ], "offsets": [ [ 1405, 1417 ] ] }, "arguments": [] }, { "id": "PMID-10816420_E19", "type": "ProteinCatabolism", "trigger": { "text": [ "degradation" ], "offsets": [ [ 1559, 1570 ] ] }, "arguments": [ { "role": "hasPatient", "ref_id": "PMID-10816420_T64" } ] }, { "id": "PMID-10816420_E20", "type": "ProteinTargeting", "trigger": { "text": [ "target" ], "offsets": [ [ 1775, 1781 ] ] }, "arguments": [ { "role": "hasAgent", "ref_id": "PMID-10816420_T65" }, { "role": "hasPatient", "ref_id": "PMID-10816420_T67" } ] }, { "id": "PMID-10816420_E21", "type": "ProteinCatabolism", "trigger": { "text": [ "degradation" ], "offsets": [ [ 1801, 1812 ] ] }, "arguments": [ { "role": "hasPatient", "ref_id": "PMID-10816420_T67" } ] }, { "id": "PMID-10816420_E4", "type": "ProteinCatabolism", "trigger": { "text": [ "degradation process" ], "offsets": [ [ 295, 314 ] ] }, "arguments": [ { "role": "hasPatient", "ref_id": "PMID-10816420_T71" } ] }, { "id": "PMID-10816420_E6", "type": "CatabolicPathway", "trigger": { "text": [ "ATP hydrolysis" ], "offsets": [ [ 1364, 1378 ] ] }, "arguments": [ { "role": "hasAgent", "ref_id": "PMID-10816420_T58" } ] }, { "id": "PMID-10816420_E7", "type": "ProteinCatabolism", "trigger": { "text": [ "degradation" ], "offsets": [ [ 1625, 1636 ] ] }, "arguments": [ { "role": "hasPatient", "ref_id": "PMID-10816420_T56" } ] } ]

[]

[ { "id": "PMID-10816420_R1", "type": "fromSpecies", "arg1_id": "PMID-10816420_T2", "arg2_id": "PMID-10816420_T1", "normalized": [] }, { "id": "PMID-10816420_R2", "type": "fromSpecies", "arg1_id": "PMID-10816420_T16", "arg2_id": "PMID-10816420_T15", "normalized": [] }, { "id": "PMID-10816420_R4", "type": "hasPart", "arg1_id": "PMID-10816420_T27", "arg2_id": "PMID-10816420_T26", "normalized": [] }, { "id": "PMID-10816420_R5", "type": "hasPart", "arg1_id": "PMID-10816420_T28", "arg2_id": "PMID-10816420_T29", "normalized": [] }, { "id": "PMID-10816420_R8", "type": "fromSpecies", "arg1_id": "PMID-10816420_T34", "arg2_id": "PMID-10816420_T33", "normalized": [] }, { "id": "PMID-10816420_R9", "type": "locatedIn", "arg1_id": "PMID-10816420_T35", "arg2_id": "PMID-10816420_T34", "normalized": [] }, { "id": "PMID-10816420_R3", "type": "hasPart", "arg1_id": "PMID-10816420_T21", "arg2_id": "PMID-10816420_T20", "normalized": [] }, { "id": "PMID-10816420_R6", "type": "hasPart", "arg1_id": "PMID-10816420_T30", "arg2_id": "PMID-10816420_T28", "normalized": [] } ]

[ { "id": "PMID-10854063__text", "type": "abstract", "text": [ "Nuclear distribution of prothymosin alpha and parathymosin: evidence that prothymosin alpha is associated with RNA synthesis processing and parathymosin with early DNA replication. Prothymosin alpha and parathymosin are two ubiquitous small acidic nuclear proteins that are thought to be involved in cell cycle progression, proliferation, and cell differentiation. In an effort to investigate the molecular function of the two proteins, we studied their spatial distribution by indirect immunofluorescence labeling and confocal scanning laser microscopy in relation to nuclear components involved in transcription, translation, and splicing. Results indicate that both proteins exhibit a punctuated nuclear distribution and are excluded by nucleoli. The distribution of prothymosin alpha in the nucleus is related to that of transcription sites, whereas the distribution of parathymosin correlates with early replication sites. This implies that prothymosin alpha and parathymosin are involved in transcription and replication, respectively. In addition to the punctate distribution, prothymosin alpha also is found concentrated in 1-6 nuclear domains per cell. These domains are found in more than 80% of randomly growing T24 human bladder carcinoma cells. They have a diameter of 0.2-2.5 microm, their size being inversely related to the number of domains per cell. The domains disappear during mitosis and the protein is excluded from the metaphase chromosomes. Double-labeling experiments associate these prothymosin alpha domains with PML and CstF64 containing nuclear bodies, but not with hnRNP-I containing domains or coiled bodies.\n" ], "offsets": [ [ 0, 1640 ] ] } ]

[ { "id": "PMID-10854063_T1", "type": "Nucleus", "text": [ "Nuclear" ], "offsets": [ [ 0, 7 ] ], "normalized": [] }, { "id": "PMID-10854063_T2", "type": "Protein", "text": [ "prothymosin alpha" ], "offsets": [ [ 24, 41 ] ], "normalized": [] }, { "id": "PMID-10854063_T3", "type": "Protein", "text": [ "parathymosin" ], "offsets": [ [ 46, 58 ] ], "normalized": [] }, { "id": "PMID-10854063_T4", "type": "Protein", "text": [ "prothymosin alpha" ], "offsets": [ [ 74, 91 ] ], "normalized": [] }, { "id": "PMID-10854063_T6", "type": "Protein", "text": [ "parathymosin" ], "offsets": [ [ 140, 152 ] ], "normalized": [] }, { "id": "PMID-10854063_T7", "type": "DNA", "text": [ "DNA" ], "offsets": [ [ 164, 167 ] ], "normalized": [] }, { "id": "PMID-10854063_T8", "type": "Protein", "text": [ "Prothymosin alpha" ], "offsets": [ [ 181, 198 ] ], "normalized": [] }, { "id": "PMID-10854063_T9", "type": "Protein", "text": [ "parathymosin" ], "offsets": [ [ 203, 215 ] ], "normalized": [] }, { "id": "PMID-10854063_T10", "type": "Nucleus", "text": [ "nuclear" ], "offsets": [ [ 248, 255 ] ], "normalized": [] }, { "id": "PMID-10854063_T11", "type": "Protein", "text": [ "proteins" ], "offsets": [ [ 256, 264 ] ], "normalized": [] }, { "id": "PMID-10854063_T15", "type": "Protein", "text": [ "two proteins" ], "offsets": [ [ 423, 435 ] ], "normalized": [] }, { "id": "PMID-10854063_T20", "type": "Protein", "text": [ "both proteins" ], "offsets": [ [ 664, 677 ] ], "normalized": [] }, { "id": "PMID-10854063_T21", "type": "Nucleus", "text": [ "nuclear" ], "offsets": [ [ 699, 706 ] ], "normalized": [] }, { "id": "PMID-10854063_T22", "type": "Protein", "text": [ "prothymosin alpha" ], "offsets": [ [ 770, 787 ] ], "normalized": [] }, { "id": "PMID-10854063_T23", "type": "Nucleus", "text": [ "nucleus" ], "offsets": [ [ 795, 802 ] ], "normalized": [] }, { "id": "PMID-10854063_T26", "type": "Protein", "text": [ "parathymosin" ], "offsets": [ [ 874, 886 ] ], "normalized": [] }, { "id": "PMID-10854063_T28", "type": "Protein", "text": [ "prothymosin alpha" ], "offsets": [ [ 946, 963 ] ], "normalized": [] }, { "id": "PMID-10854063_T29", "type": "Protein", "text": [ "parathymosin" ], "offsets": [ [ 968, 980 ] ], "normalized": [] }, { "id": "PMID-10854063_T31", "type": "Protein", "text": [ "prothymosin alpha" ], "offsets": [ [ 1084, 1101 ] ], "normalized": [] }, { "id": "PMID-10854063_T32", "type": "Cell", "text": [ "cell" ], "offsets": [ [ 1156, 1160 ] ], "normalized": [] }, { "id": "PMID-10854063_T33", "type": "Eukaryote", "text": [ "human" ], "offsets": [ [ 1227, 1232 ] ], "normalized": [] }, { "id": "PMID-10854063_T34", "type": "Cell", "text": [ "bladder carcinoma cells" ], "offsets": [ [ 1233, 1256 ] ], "normalized": [] }, { "id": "PMID-10854063_T35", "type": "Cell", "text": [ "cell" ], "offsets": [ [ 1362, 1366 ] ], "normalized": [] }, { "id": "PMID-10854063_T37", "type": "Protein", "text": [ "protein" ], "offsets": [ [ 1413, 1420 ] ], "normalized": [] }, { "id": "PMID-10854063_T39", "type": "Chromosome", "text": [ "chromosomes" ], "offsets": [ [ 1452, 1463 ] ], "normalized": [] }, { "id": "PMID-10854063_T41", "type": "ProteinDomain", "text": [ "prothymosin alpha domains" ], "offsets": [ [ 1509, 1534 ] ], "normalized": [] }, { "id": "PMID-10854063_T42", "type": "Protein", "text": [ "PML" ], "offsets": [ [ 1540, 1543 ] ], "normalized": [] }, { "id": "PMID-10854063_T43", "type": "Protein", "text": [ "CstF64" ], "offsets": [ [ 1548, 1554 ] ], "normalized": [] }, { "id": "PMID-10854063_T46", "type": "MolecularFunction", "text": [ "molecular function" ], "offsets": [ [ 397, 415 ] ], "normalized": [] }, { "id": "PMID-10854063_T16", "type": "CellComponent", "text": [ "components" ], "offsets": [ [ 577, 587 ] ], "normalized": [] }, { "id": "PMID-10854063_T47", "type": "Nucleus", "text": [ "nuclear" ], "offsets": [ [ 569, 576 ] ], "normalized": [] }, { "id": "PMID-10854063_T50", "type": "Nucleus", "text": [ "nuclear" ], "offsets": [ [ 1136, 1143 ] ], "normalized": [] }, { "id": "PMID-10854063_T51", "type": "CellComponent", "text": [ "domains" ], "offsets": [ [ 1144, 1151 ] ], "normalized": [] }, { "id": "PMID-10854063_T40", "type": "CellComponent", "text": [ "bodies" ], "offsets": [ [ 1574, 1580 ] ], "normalized": [] }, { "id": "PMID-10854063_T44", "type": "Nucleus", "text": [ "nuclear" ], "offsets": [ [ 1566, 1573 ] ], "normalized": [] } ]

[ { "id": "PMID-10854063_E1", "type": "RNABiosynthesis", "trigger": { "text": [ "RNA synthesis processing" ], "offsets": [ [ 111, 135 ] ] }, "arguments": [] }, { "id": "PMID-10854063_E2", "type": "CellCyclePhaseTransition", "trigger": { "text": [ "cell cycle progression" ], "offsets": [ [ 300, 322 ] ] }, "arguments": [] }, { "id": "PMID-10854063_E3", "type": "CellGrowth", "trigger": { "text": [ "proliferation" ], "offsets": [ [ 324, 337 ] ] }, "arguments": [] }, { "id": "PMID-10854063_E4", "type": "CellDifferentiation", "trigger": { "text": [ "cell differentiation" ], "offsets": [ [ 343, 363 ] ] }, "arguments": [] }, { "id": "PMID-10854063_E5", "type": "Transcription", "trigger": { "text": [ "transcription" ], "offsets": [ [ 600, 613 ] ] }, "arguments": [] }, { "id": "PMID-10854063_E6", "type": "Translation", "trigger": { "text": [ "translation" ], "offsets": [ [ 615, 626 ] ] }, "arguments": [] }, { "id": "PMID-10854063_E7", "type": "RNASplicing", "trigger": { "text": [ "splicing" ], "offsets": [ [ 632, 640 ] ] }, "arguments": [] }, { "id": "PMID-10854063_E8", "type": "Transcription", "trigger": { "text": [ "transcription" ], "offsets": [ [ 825, 838 ] ] }, "arguments": [] }, { "id": "PMID-10854063_E9", "type": "Transcription", "trigger": { "text": [ "transcription" ], "offsets": [ [ 997, 1010 ] ] }, "arguments": [] }, { "id": "PMID-10854063_E10", "type": "Mitosis", "trigger": { "text": [ "mitosis" ], "offsets": [ [ 1397, 1404 ] ] }, "arguments": [] }, { "id": "PMID-10854063_E11", "type": "CellCyclePhase", "trigger": { "text": [ "metaphase" ], "offsets": [ [ 1442, 1451 ] ] }, "arguments": [] }, { "id": "PMID-10854063_E13", "type": "CellularMetabolicProcess", "trigger": { "text": [ "replication" ], "offsets": [ [ 168, 179 ] ] }, "arguments": [ { "role": "hasPatient", "ref_id": "PMID-10854063_T7" } ] }, { "id": "PMID-10854063_E14", "type": "Localization", "trigger": { "text": [ "sites" ], "offsets": [ [ 839, 844 ] ] }, "arguments": [ { "role": "hasPatient", "ref_id": "PMID-10854063_T22" } ] }, { "id": "PMID-10854063_E15", "type": "CellularMetabolicProcess", "trigger": { "text": [ "early replicatio" ], "offsets": [ [ 903, 919 ] ] }, "arguments": [] }, { "id": "PMID-10854063_E16", "type": "Localization", "trigger": { "text": [ "sites" ], "offsets": [ [ 921, 926 ] ] }, "arguments": [ { "role": "hasPatient", "ref_id": "PMID-10854063_T26" } ] }, { "id": "PMID-10854063_E17", "type": "CellularMetabolicProcess", "trigger": { "text": [ "replication" ], "offsets": [ [ 1015, 1026 ] ] }, "arguments": [] } ]

[]

[ { "id": "PMID-10854063_R1", "type": "locatedIn", "arg1_id": "PMID-10854063_T2", "arg2_id": "PMID-10854063_T1", "normalized": [] }, { "id": "PMID-10854063_R2", "type": "locatedIn", "arg1_id": "PMID-10854063_T3", "arg2_id": "PMID-10854063_T1", "normalized": [] }, { "id": "PMID-10854063_R5", "type": "locatedIn", "arg1_id": "PMID-10854063_T20", "arg2_id": "PMID-10854063_T21", "normalized": [] }, { "id": "PMID-10854063_R6", "type": "locatedIn", "arg1_id": "PMID-10854063_T22", "arg2_id": "PMID-10854063_T23", "normalized": [] }, { "id": "PMID-10854063_R7", "type": "fromSpecies", "arg1_id": "PMID-10854063_T34", "arg2_id": "PMID-10854063_T33", "normalized": [] }, { "id": "PMID-10854063_R3", "type": "locatedIn", "arg1_id": "PMID-10854063_T11", "arg2_id": "PMID-10854063_T10", "normalized": [] }, { "id": "PMID-10854063_R4", "type": "locatedIn", "arg1_id": "PMID-10854063_T16", "arg2_id": "PMID-10854063_T47", "normalized": [] }, { "id": "PMID-10854063_R10", "type": "locatedIn", "arg1_id": "PMID-10854063_T51", "arg2_id": "PMID-10854063_T50", "normalized": [] }, { "id": "PMID-10854063_R11", "type": "locatedIn", "arg1_id": "PMID-10854063_T50", "arg2_id": "PMID-10854063_T32", "normalized": [] }, { "id": "PMID-10854063_R12", "type": "locatedIn", "arg1_id": "PMID-10854063_T31", "arg2_id": "PMID-10854063_T51", "normalized": [] }, { "id": "PMID-10854063_R8", "type": "locatedIn", "arg1_id": "PMID-10854063_T40", "arg2_id": "PMID-10854063_T44", "normalized": [] }, { "id": "PMID-10854063_R9", "type": "locatedIn", "arg1_id": "PMID-10854063_T41", "arg2_id": "PMID-10854063_T40", "normalized": [] }, { "id": "PMID-10854063_R13", "type": "locatedIn", "arg1_id": "PMID-10854063_T42", "arg2_id": "PMID-10854063_T40", "normalized": [] }, { "id": "PMID-10854063_R14", "type": "locatedIn", "arg1_id": "PMID-10854063_T43", "arg2_id": "PMID-10854063_T40", "normalized": [] } ]

[ { "id": "PMID-10888599__text", "type": "abstract", "text": [ "The fragile X-related proteins FXR1P and FXR2P contain a functional nucleolar-targeting signal equivalent to the HIV-1 regulatory proteins. Fragile X syndrome is caused by the absence of the fragile X mental-retardation protein (FMRP). FMRP and the fragile X-related proteins 1 and 2 (FXR1P and FXR2P) form a gene family with functional similarities, such as RNA binding, polyribosomal association and nucleocytoplasmic shuttling. In a previous study, we found that FMRP and FXR1P shuttle between cytoplasm and nucleoplasm, while FXR2P shuttles between cytoplasm and nucleolus. The nuclear and nucleolar-targeting properties of these proteins were investigated further. Here, we show that FXR2P contains in its C-terminal part, a stretch of basic amino acids 'RPQRRNRSRRRRFR' that resemble the nucleolar-targeting signal (NoS) of the viral protein Rev. This particular sequence is also present within exon 15 of the FXR1 gene. This exon undergoes alternative splicing and is therefore only present in some of the FXR1P isoforms. We investigated the intracellular distribution of various FXR1P isoforms with (iso-e and iso-f) and without (iso-d) the potential NoS in transfected COS cells treated with the nuclear export inhibitor leptomycin-B. Both iso-e and iso-f showed a nucleolar localization, as observed for FXR2P; iso-d was detected in the nucleo-plasm outside the nucleoli. Further, when a labelled 16-residue synthetic peptide corresponding to the NoS of FXR1P was added to human fibroblast cultures a clear nucleolar signal was observed. Based on these data we argue that the intranuclear distribution of FXR2P and FXR1P isoforms is very likely to be mediated by a similar NoS localized in their C-terminal region. This domain is absent in some FXR1P isoforms as well as in all FMRP isoforms, suggesting functional differences for this family of proteins, possibly related to RNA metabolism in different tissues.\n" ], "offsets": [ [ 0, 1923 ] ] } ]

[ { "id": "PMID-10888599_T1", "type": "Protein", "text": [ "fragile X-related proteins FXR1P" ], "offsets": [ [ 4, 36 ] ], "normalized": [] }, { "id": "PMID-10888599_T2", "type": "Protein", "text": [ "FXR2P" ], "offsets": [ [ 41, 46 ] ], "normalized": [] }, { "id": "PMID-10888599_T3", "type": "Nucleus", "text": [ "nucleolar" ], "offsets": [ [ 68, 77 ] ], "normalized": [] }, { "id": "PMID-10888599_T5", "type": "Virus", "text": [ "HIV-1" ], "offsets": [ [ 113, 118 ] ], "normalized": [] }, { "id": "PMID-10888599_T8", "type": "Protein", "text": [ "fragile X mental-retardation protein" ], "offsets": [ [ 191, 227 ] ], "normalized": [] }, { "id": "PMID-10888599_T9", "type": "Protein", "text": [ "FMRP" ], "offsets": [ [ 229, 233 ] ], "normalized": [] }, { "id": "PMID-10888599_T10", "type": "Protein", "text": [ "FMRP" ], "offsets": [ [ 236, 240 ] ], "normalized": [] }, { "id": "PMID-10888599_T11", "type": "Protein", "text": [ "fragile X-related proteins 1 and 2" ], "offsets": [ [ 249, 283 ] ], "normalized": [] }, { "id": "PMID-10888599_T13", "type": "Protein", "text": [ "FXR1P" ], "offsets": [ [ 285, 290 ] ], "normalized": [] }, { "id": "PMID-10888599_T14", "type": "Protein", "text": [ "FXR2P" ], "offsets": [ [ 295, 300 ] ], "normalized": [] }, { "id": "PMID-10888599_T15", "type": "Gene", "text": [ "gene family" ], "offsets": [ [ 309, 320 ] ], "normalized": [] }, { "id": "PMID-10888599_T16", "type": "RNA", "text": [ "RNA" ], "offsets": [ [ 359, 362 ] ], "normalized": [] }, { "id": "PMID-10888599_T18", "type": "Ribosome", "text": [ "polyribosomal" ], "offsets": [ [ 372, 385 ] ], "normalized": [] }, { "id": "PMID-10888599_T20", "type": "CellComponent", "text": [ "nucleocytoplasmic" ], "offsets": [ [ 402, 419 ] ], "normalized": [] }, { "id": "PMID-10888599_T22", "type": "Protein", "text": [ "FMRP" ], "offsets": [ [ 466, 470 ] ], "normalized": [] }, { "id": "PMID-10888599_T23", "type": "Protein", "text": [ "FXR1P" ], "offsets": [ [ 475, 480 ] ], "normalized": [] }, { "id": "PMID-10888599_T25", "type": "CellComponent", "text": [ "cytoplasm" ], "offsets": [ [ 497, 506 ] ], "normalized": [] }, { "id": "PMID-10888599_T26", "type": "CellComponent", "text": [ "nucleoplasm" ], "offsets": [ [ 511, 522 ] ], "normalized": [] }, { "id": "PMID-10888599_T27", "type": "Protein", "text": [ "FXR2P" ], "offsets": [ [ 530, 535 ] ], "normalized": [] }, { "id": "PMID-10888599_T29", "type": "CellComponent", "text": [ "cytoplasm" ], "offsets": [ [ 553, 562 ] ], "normalized": [] }, { "id": "PMID-10888599_T30", "type": "CellComponent", "text": [ "nucleolus" ], "offsets": [ [ 567, 576 ] ], "normalized": [] }, { "id": "PMID-10888599_T31", "type": "Nucleus", "text": [ "nuclear" ], "offsets": [ [ 582, 589 ] ], "normalized": [] }, { "id": "PMID-10888599_T32", "type": "CellComponent", "text": [ "nucleolar" ], "offsets": [ [ 594, 603 ] ], "normalized": [] }, { "id": "PMID-10888599_T34", "type": "Protein", "text": [ "proteins" ], "offsets": [ [ 634, 642 ] ], "normalized": [] }, { "id": "PMID-10888599_T35", "type": "Protein", "text": [ "FXR2P" ], "offsets": [ [ 689, 694 ] ], "normalized": [] }, { "id": "PMID-10888599_T36", "type": "AminoAcid", "text": [ "amino acids" ], "offsets": [ [ 747, 758 ] ], "normalized": [] }, { "id": "PMID-10888599_T37", "type": "CellComponent", "text": [ "nucleolar" ], "offsets": [ [ 794, 803 ] ], "normalized": [] }, { "id": "PMID-10888599_T38", "type": "Virus", "text": [ "viral" ], "offsets": [ [ 834, 839 ] ], "normalized": [] }, { "id": "PMID-10888599_T39", "type": "Protein", "text": [ "protein Rev" ], "offsets": [ [ 840, 851 ] ], "normalized": [] }, { "id": "PMID-10888599_T40", "type": "Exon", "text": [ "exon" ], "offsets": [ [ 901, 905 ] ], "normalized": [] }, { "id": "PMID-10888599_T41", "type": "Gene", "text": [ "FXR1 gene" ], "offsets": [ [ 916, 925 ] ], "normalized": [] }, { "id": "PMID-10888599_T42", "type": "Exon", "text": [ "exon" ], "offsets": [ [ 932, 936 ] ], "normalized": [] }, { "id": "PMID-10888599_T44", "type": "Protein", "text": [ "FXR1P isoforms" ], "offsets": [ [ 1013, 1027 ] ], "normalized": [] }, { "id": "PMID-10888599_T45", "type": "Protein", "text": [ "FXR1P isoforms" ], "offsets": [ [ 1087, 1101 ] ], "normalized": [] }, { "id": "PMID-10888599_T46", "type": "Nucleus", "text": [ "nuclear" ], "offsets": [ [ 1205, 1212 ] ], "normalized": [] }, { "id": "PMID-10888599_T49", "type": "Lipid", "text": [ "leptomycin-B" ], "offsets": [ [ 1230, 1242 ] ], "normalized": [] }, { "id": "PMID-10888599_T50", "type": "Protein", "text": [ "iso-e" ], "offsets": [ [ 1249, 1254 ] ], "normalized": [] }, { "id": "PMID-10888599_T51", "type": "Protein", "text": [ "iso-f" ], "offsets": [ [ 1259, 1264 ] ], "normalized": [] }, { "id": "PMID-10888599_T52", "type": "CellComponent", "text": [ "nucleolar" ], "offsets": [ [ 1274, 1283 ] ], "normalized": [] }, { "id": "PMID-10888599_T54", "type": "Protein", "text": [ "FXR2P" ], "offsets": [ [ 1314, 1319 ] ], "normalized": [] }, { "id": "PMID-10888599_T55", "type": "Protein", "text": [ "iso-d" ], "offsets": [ [ 1321, 1326 ] ], "normalized": [] }, { "id": "PMID-10888599_T56", "type": "CellComponent", "text": [ "nucleo-plasm" ], "offsets": [ [ 1347, 1359 ] ], "normalized": [] }, { "id": "PMID-10888599_T57", "type": "CellComponent", "text": [ "nucleoli" ], "offsets": [ [ 1372, 1380 ] ], "normalized": [] }, { "id": "PMID-10888599_T58", "type": "Protein", "text": [ "FXR1P" ], "offsets": [ [ 1464, 1469 ] ], "normalized": [] }, { "id": "PMID-10888599_T59", "type": "Eukaryote", "text": [ "human" ], "offsets": [ [ 1483, 1488 ] ], "normalized": [] }, { "id": "PMID-10888599_T60", "type": "Cell", "text": [ "fibroblast cultures" ], "offsets": [ [ 1489, 1508 ] ], "normalized": [] }, { "id": "PMID-10888599_T62", "type": "Protein", "text": [ "FXR2P" ], "offsets": [ [ 1615, 1620 ] ], "normalized": [] }, { "id": "PMID-10888599_T63", "type": "Protein", "text": [ "FXR1P" ], "offsets": [ [ 1625, 1630 ] ], "normalized": [] }, { "id": "PMID-10888599_T65", "type": "Protein", "text": [ "FXR1P isoforms" ], "offsets": [ [ 1755, 1769 ] ], "normalized": [] }, { "id": "PMID-10888599_T66", "type": "Protein", "text": [ "FMRP isoforms" ], "offsets": [ [ 1788, 1801 ] ], "normalized": [] }, { "id": "PMID-10888599_T67", "type": "Protein", "text": [ "family of proteins" ], "offsets": [ [ 1846, 1864 ] ], "normalized": [] }, { "id": "PMID-10888599_T69", "type": "Tissue", "text": [ "tissues" ], "offsets": [ [ 1914, 1921 ] ], "normalized": [] }, { "id": "PMID-10888599_T70", "type": "Peptide", "text": [ "signal" ], "offsets": [ [ 88, 94 ] ], "normalized": [] }, { "id": "PMID-10888599_T71", "type": "Peptide", "text": [ "signal" ], "offsets": [ [ 814, 820 ] ], "normalized": [] }, { "id": "PMID-10888599_T72", "type": "Peptide", "text": [ "NoS" ], "offsets": [ [ 822, 825 ] ], "normalized": [] }, { "id": "PMID-10888599_T6", "type": "Protein", "text": [ "regulatory proteins" ], "offsets": [ [ 119, 138 ] ], "normalized": [] }, { "id": "PMID-10888599_T73", "type": "Peptide", "text": [ "NoS" ], "offsets": [ [ 1159, 1162 ] ], "normalized": [] }, { "id": "PMID-10888599_T74", "type": "Cell", "text": [ "COS cells" ], "offsets": [ [ 1178, 1187 ] ], "normalized": [] }, { "id": "PMID-10888599_T75", "type": "Peptide", "text": [ "peptide" ], "offsets": [ [ 1428, 1435 ] ], "normalized": [] }, { "id": "PMID-10888599_T76", "type": "Peptide", "text": [ "NoS" ], "offsets": [ [ 1457, 1460 ] ], "normalized": [] }, { "id": "PMID-10888599_T77", "type": "Peptide", "text": [ "NoS" ], "offsets": [ [ 1683, 1686 ] ], "normalized": [] }, { "id": "PMID-10888599_T78", "type": "ProteinDomain", "text": [ "C-terminal region" ], "offsets": [ [ 1706, 1723 ] ], "normalized": [] }, { "id": "PMID-10888599_T79", "type": "CellComponent", "text": [ "nucleolar" ], "offsets": [ [ 1517, 1526 ] ], "normalized": [] } ]

[ { "id": "PMID-10888599_E1", "type": "ProteinTargeting", "trigger": { "text": [ "targeting" ], "offsets": [ [ 78, 87 ] ] }, "arguments": [] }, { "id": "PMID-10888599_E2", "type": "Disease", "trigger": { "text": [ "Fragile X syndrome" ], "offsets": [ [ 140, 158 ] ] }, "arguments": [] }, { "id": "PMID-10888599_E3", "type": "BindingToRNA", "trigger": { "text": [ "binding" ], "offsets": [ [ 363, 370 ] ] }, "arguments": [ { "role": "hasPatient", "ref_id": "PMID-10888599_T16" } ] }, { "id": "PMID-10888599_E4", "type": "Binding", "trigger": { "text": [ "association" ], "offsets": [ [ 386, 397 ] ] }, "arguments": [ { "role": "hasPatient", "ref_id": "PMID-10888599_T18" } ] }, { "id": "PMID-10888599_E5", "type": "Transport", "trigger": { "text": [ "shuttling" ], "offsets": [ [ 420, 429 ] ] }, "arguments": [] }, { "id": "PMID-10888599_E6", "type": "Transport", "trigger": { "text": [ "shuttle" ], "offsets": [ [ 481, 488 ] ] }, "arguments": [ { "role": "hasPatient", "ref_id": "PMID-10888599_T22" } ] }, { "id": "PMID-10888599_E7", "type": "Transport", "trigger": { "text": [ "shuttles" ], "offsets": [ [ 536, 544 ] ] }, "arguments": [ { "role": "hasPatient", "ref_id": "PMID-10888599_T27" } ] }, { "id": "PMID-10888599_E8", "type": "ProteinTargeting", "trigger": { "text": [ "targeting" ], "offsets": [ [ 604, 613 ] ] }, "arguments": [ { "role": "hasPatient", "ref_id": "PMID-10888599_T34" } ] }, { "id": "PMID-10888599_E9", "type": "RNASplicing", "trigger": { "text": [ "alternative splicing" ], "offsets": [ [ 947, 967 ] ] }, "arguments": [ { "role": "hasPatient", "ref_id": "PMID-10888599_T42" } ] }, { "id": "PMID-10888599_E10", "type": "Transport", "trigger": { "text": [ "export" ], "offsets": [ [ 1213, 1219 ] ] }, "arguments": [] }, { "id": "PMID-10888599_E11", "type": "NegativeRegulation", "trigger": { "text": [ "inhibitor" ], "offsets": [ [ 1220, 1229 ] ] }, "arguments": [ { "role": "hasAgent", "ref_id": "PMID-10888599_T49" }, { "role": "hasPatient", "ref_id": "PMID-10888599_E10" } ] }, { "id": "PMID-10888599_E12", "type": "Localization", "trigger": { "text": [ "localization" ], "offsets": [ [ 1284, 1296 ] ] }, "arguments": [ { "role": "hasPatient", "ref_id": "PMID-10888599_T50" } ] }, { "id": "PMID-10888599_E13", "type": "Localization", "trigger": { "text": [ "intranuclear distribution" ], "offsets": [ [ 1586, 1611 ] ] }, "arguments": [ { "role": "hasPatient", "ref_id": "PMID-10888599_T62" } ] }, { "id": "PMID-10888599_E14", "type": "RegulatoryProcess", "trigger": { "text": [ "mediated" ], "offsets": [ [ 1661, 1669 ] ] }, "arguments": [ { "role": "hasAgent", "ref_id": "PMID-10888599_T77" }, { "role": "hasPatient", "ref_id": "PMID-10888599_E13" } ] }, { "id": "PMID-10888599_E15", "type": "RNAMetabolism", "trigger": { "text": [ "RNA metabolism" ], "offsets": [ [ 1886, 1900 ] ] }, "arguments": [] }, { "id": "PMID-10888599_E16", "type": "ProteinTargeting", "trigger": { "text": [ "targeting" ], "offsets": [ [ 804, 813 ] ] }, "arguments": [ { "role": "hasAgent", "ref_id": "PMID-10888599_T71" } ] }, { "id": "PMID-10888599_E17", "type": "Localization", "trigger": { "text": [ "signal" ], "offsets": [ [ 1527, 1533 ] ] }, "arguments": [] }, { "id": "PMID-10888599_E18", "type": "Localization", "trigger": { "text": [ "localization" ], "offsets": [ [ 1284, 1296 ] ] }, "arguments": [ { "role": "hasPatient", "ref_id": "PMID-10888599_T51" } ] }, { "id": "PMID-10888599_E19", "type": "Localization", "trigger": { "text": [ "intranuclear distribution" ], "offsets": [ [ 1586, 1611 ] ] }, "arguments": [ { "role": "hasPatient", "ref_id": "PMID-10888599_T63" } ] }, { "id": "PMID-10888599_E20", "type": "RegulatoryProcess", "trigger": { "text": [ "mediated" ], "offsets": [ [ 1661, 1669 ] ] }, "arguments": [ { "role": "hasAgent", "ref_id": "PMID-10888599_T77" }, { "role": "hasPatient", "ref_id": "PMID-10888599_E19" } ] }, { "id": "PMID-10888599_E21", "type": "Transport", "trigger": { "text": [ "shuttle" ], "offsets": [ [ 481, 488 ] ] }, "arguments": [ { "role": "hasPatient", "ref_id": "PMID-10888599_T23" } ] } ]

[]

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[ { "id": "PMID-10893263__text", "type": "abstract", "text": [ "Evidence that dynamin-2 functions as a signal-transducing GTPase. The role of dynamin GTPases in the regulation of receptor-mediated endocytosis is well established. Here, we present new evidence that the ubiquitously expressed isoform dynamin-2 (dyn2) can also function in a signal transduction pathway(s). A </=5-fold increase of dyn2 relative to endogenous levels activates the transcription factor p53 and induces apoptosis, as demonstrated by reduced cell proliferation, DNA fragmentation, and caspase-3 activation. Dyn2-triggered apoptosis occurs only in dividing cells and is p53 dependent. A mutant defective in GTP binding does not trigger apoptosis, indicating that increased levels of dyn2.GTP, rather than protein levels per se, are required to transduce signals that activate p53. A truncated dyn2 lacking the COOH-terminal proline/arginine-rich domain (PRD), which interacts with many SH3 domain-containing partners implicated in both endocytosis and signal transduction, triggers apoptosis even more potently than the wild-type. This observation provides additional support for the importance of the NH(2)-terminal GTPase domain for the apoptotic phenotype. All described effects are dyn2-specific because >200-fold overexpression of dyn1, the 70% identical neuronal isoform, has no effect. Our data suggest that dyn2 can act as a signal transducing GTPase affecting transcriptional regulation.\n" ], "offsets": [ [ 0, 1410 ] ] } ]

[ { "id": "PMID-10893263_T1", "type": "Enzyme", "text": [ "dynamin-2" ], "offsets": [ [ 14, 23 ] ], "normalized": [] }, { "id": "PMID-10893263_T2", "type": "Enzyme", "text": [ "GTPase" ], "offsets": [ [ 58, 64 ] ], "normalized": [] }, { "id": "PMID-10893263_T3", "type": "Enzyme", "text": [ "dynamin GTPases" ], "offsets": [ [ 78, 93 ] ], "normalized": [] }, { "id": "PMID-10893263_T5", "type": "Protein", "text": [ "receptor" ], "offsets": [ [ 115, 123 ] ], "normalized": [] }, { "id": "PMID-10893263_T9", "type": "Enzyme", "text": [ "isoform dynamin-2" ], "offsets": [ [ 228, 245 ] ], "normalized": [] }, { "id": "PMID-10893263_T10", "type": "Enzyme", "text": [ "dyn2" ], "offsets": [ [ 247, 251 ] ], "normalized": [] }, { "id": "PMID-10893263_T12", "type": "Enzyme", "text": [ "dyn2" ], "offsets": [ [ 332, 336 ] ], "normalized": [] }, { "id": "PMID-10893263_T14", "type": "TranscriptionFactor", "text": [ "transcription factor p53" ], "offsets": [ [ 381, 405 ] ], "normalized": [] }, { "id": "PMID-10893263_T19", "type": "Enzyme", "text": [ "caspase-3" ], "offsets": [ [ 499, 508 ] ], "normalized": [] }, { "id": "PMID-10893263_T21", "type": "Enzyme", "text": [ "Dyn2" ], "offsets": [ [ 521, 525 ] ], "normalized": [] }, { "id": "PMID-10893263_T23", "type": "Cell", "text": [ "dividing cells" ], "offsets": [ [ 561, 575 ] ], "normalized": [] }, { "id": "PMID-10893263_T24", "type": "TranscriptionFactor", "text": [ "p53" ], "offsets": [ [ 583, 586 ] ], "normalized": [] }, { "id": "PMID-10893263_T25", "type": "Enzyme", "text": [ "dyn2" ], "offsets": [ [ 696, 700 ] ], "normalized": [] }, { "id": "PMID-10893263_T26", "type": "Nucleotide", "text": [ "GTP" ], "offsets": [ [ 701, 704 ] ], "normalized": [] }, { "id": "PMID-10893263_T27", "type": "Protein", "text": [ "protein" ], "offsets": [ [ 718, 725 ] ], "normalized": [] }, { "id": "PMID-10893263_T29", "type": "TranscriptionFactor", "text": [ "p53" ], "offsets": [ [ 789, 792 ] ], "normalized": [] }, { "id": "PMID-10893263_T30", "type": "MutatedProtein", "text": [ "truncated dyn2" ], "offsets": [ [ 796, 810 ] ], "normalized": [] }, { "id": "PMID-10893263_T31", "type": "ProteinDomain", "text": [ "domain" ], "offsets": [ [ 859, 865 ] ], "normalized": [] }, { "id": "PMID-10893263_T32", "type": "ProteinDomain", "text": [ "PRD" ], "offsets": [ [ 867, 870 ] ], "normalized": [] }, { "id": "PMID-10893263_T34", "type": "ProteinDomain", "text": [ "SH3 domain" ], "offsets": [ [ 899, 909 ] ], "normalized": [] }, { "id": "PMID-10893263_T35", "type": "Protein", "text": [ "partners" ], "offsets": [ [ 921, 929 ] ], "normalized": [] }, { "id": "PMID-10893263_T40", "type": "Enzyme", "text": [ "wild-type" ], "offsets": [ [ 1033, 1042 ] ], "normalized": [] }, { "id": "PMID-10893263_T41", "type": "ProteinDomain", "text": [ "GTPase domain" ], "offsets": [ [ 1130, 1143 ] ], "normalized": [] }, { "id": "PMID-10893263_T42", "type": "Phenotype", "text": [ "phenotype" ], "offsets": [ [ 1162, 1171 ] ], "normalized": [] }, { "id": "PMID-10893263_T43", "type": "Enzyme", "text": [ "dyn2" ], "offsets": [ [ 1199, 1203 ] ], "normalized": [] }, { "id": "PMID-10893263_T45", "type": "Enzyme", "text": [ "dyn1" ], "offsets": [ [ 1249, 1253 ] ], "normalized": [] }, { "id": "PMID-10893263_T46", "type": "Enzyme", "text": [ "dyn2" ], "offsets": [ [ 1328, 1332 ] ], "normalized": [] }, { "id": "PMID-10893263_T47", "type": "Enzyme", "text": [ "GTPase" ], "offsets": [ [ 1365, 1371 ] ], "normalized": [] }, { "id": "PMID-10893263_T51", "type": "DNA", "text": [ "DNA" ], "offsets": [ [ 476, 479 ] ], "normalized": [] } ]

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"PositiveRegulation", "trigger": { "text": [ "activates" ], "offsets": [ [ 367, 376 ] ] }, "arguments": [ { "role": "hasAgent", "ref_id": "PMID-10893263_T12" }, { "role": "hasPatient", "ref_id": "PMID-10893263_T14" } ] }, { "id": "PMID-10893263_E7", "type": "PositiveRegulation", "trigger": { "text": [ "induces" ], "offsets": [ [ 410, 417 ] ] }, "arguments": [ { "role": "hasAgent", "ref_id": "PMID-10893263_T12" }, { "role": "hasPatient", "ref_id": "PMID-10893263_E8" } ] }, { "id": "PMID-10893263_E8", "type": "CellDeath", "trigger": { "text": [ "apoptosis" ], "offsets": [ [ 418, 427 ] ] }, "arguments": [] }, { "id": "PMID-10893263_E9", "type": "NegativeRegulation", "trigger": { "text": [ "reduced" ], "offsets": [ [ 448, 455 ] ] }, "arguments": [ { "role": "hasPatient", "ref_id": "PMID-10893263_E10" } ] }, { "id": "PMID-10893263_E10", "type": "CellGrowth", "trigger": { "text": [ "cell proliferation" ], "offsets": [ [ 456, 474 ] ] }, "arguments": [] }, { "id": "PMID-10893263_E11", "type": "PositiveRegulation", "trigger": { "text": [ "activation" ], "offsets": [ [ 509, 519 ] ] }, "arguments": [ { "role": "hasPatient", "ref_id": "PMID-10893263_T19" } ] }, { "id": "PMID-10893263_E12", "type": "CellDeath", "trigger": { "text": [ "apoptosis" ], "offsets": [ [ 536, 545 ] ] }, "arguments": [ { "role": "hasAgent", "ref_id": "PMID-10893263_T21" } ] }, { "id": "PMID-10893263_E13", "type": "PositiveRegulation", "trigger": { "text": [ "activate" ], "offsets": [ [ 780, 788 ] ] }, "arguments": [ { "role": "hasPatient", "ref_id": "PMID-10893263_T29" } ] }, { "id": "PMID-10893263_E14", "type": "CellularProcess", "trigger": { "text": [ "endocytosis" ], "offsets": [ [ 949, 960 ] ] }, "arguments": [] }, { "id": "PMID-10893263_E15", "type": "SignalingPathway", "trigger": { "text": [ "signal transduction" ], "offsets": [ [ 965, 984 ] ] }, "arguments": [] }, { "id": "PMID-10893263_E16", "type": "PositiveRegulation", "trigger": { "text": [ "triggers" ], "offsets": [ [ 986, 994 ] ] }, "arguments": [ { "role": "hasPatient", "ref_id": "PMID-10893263_E17" } ] }, { "id": "PMID-10893263_E17", "type": "CellDeath", "trigger": { "text": [ "apoptosis" ], "offsets": [ [ 995, 1004 ] ] }, "arguments": [] }, { "id": "PMID-10893263_E18", "type": "PositiveRegulationOfGeneExpression", "trigger": { "text": [ "overexpression" ], "offsets": [ [ 1231, 1245 ] ] }, "arguments": [ { "role": "hasPatient", "ref_id": "PMID-10893263_T45" } ] }, { "id": "PMID-10893263_E21", "type": "SignalingPathway", "trigger": { "text": [ "signal-transducing" ], "offsets": [ [ 39, 57 ] ] }, "arguments": [] }, { "id": "PMID-10893263_E22", "type": "CatabolicPathway", "trigger": { "text": [ "fragmentation" ], "offsets": [ [ 480, 493 ] ] }, "arguments": [ { "role": "hasPatient", "ref_id": "PMID-10893263_T51" } ] }, { "id": "PMID-10893263_E23", "type": "Increase", "trigger": { "text": [ "increased" ], "offsets": [ [ 676, 685 ] ] }, "arguments": [ { "role": "hasPatient", "ref_id": "PMID-10893263_T25" } ] }, { "id": "PMID-10893263_E24", "type": "SignalingPathway", "trigger": { "text": [ "transduce signals" ], "offsets": [ [ 757, 774 ] ] }, "arguments": [ { "role": "hasPatient", "ref_id": "PMID-10893263_E13" } ] }, { "id": "PMID-10893263_E25", "type": "BindingOfProteinToProteinBindingSiteOfProtein", "trigger": { "text": [ "interacts" ], "offsets": [ [ 879, 888 ] ] }, "arguments": [ { "role": "hasPatient", "ref_id": "PMID-10893263_T35" } ] }, { "id": "PMID-10893263_E26", "type": "CellDeath", "trigger": { "text": [ "apoptotic" ], "offsets": [ [ 1152, 1161 ] ] }, "arguments": [] }, { "id": "PMID-10893263_E27", "type": "SignalingPathway", "trigger": { "text": [ "signal transducing" ], "offsets": [ [ 1346, 1364 ] ] }, "arguments": [ { "role": "hasAgent", "ref_id": "PMID-10893263_T47" } ] }, { "id": "PMID-10893263_E28", "type": "Affecting", "trigger": { "text": [ "affecting" ], "offsets": [ [ 1372, 1381 ] ] }, "arguments": [ { "role": "hasAgent", "ref_id": "PMID-10893263_T47" } ] }, { "id": "PMID-10893263_E19", "type": "RegulationOfTranscription", "trigger": { "text": [ "transcriptional regulation" ], "offsets": [ [ 1382, 1408 ] ] }, "arguments": [] } ]

[]

[ { "id": "PMID-10893263_R2", "type": "hasPart", "arg1_id": "PMID-10893263_T35", "arg2_id": "PMID-10893263_T34", "normalized": [] } ]

[ { "id": "PMID-10976108__text", "type": "abstract", "text": [ "RET finger protein is a transcriptional repressor and interacts with enhancer of polycomb that has dual transcriptional functions. RET finger protein (RFP) belongs to the large B-box RING finger protein family and is known to become oncogenic by fusion with RET tyrosine kinase. Although RFP is reported to be a nuclear protein that is present in the nuclear matrix, its function is largely unknown. Here we show that RFP interacts with Enhancer of Polycomb (EPC) and strongly represses the gene transcription. Yeast two-hybrid assays revealed that the coiled-coil domain of RFP was associated with the EPcA domain and the carboxyl-terminal region of EPC. In addition, both proteins were co-precipitated from the lysates of human cells and mostly colocalized in the nucleus. Using the luciferase reporter-gene assay, we found that they repress the gene transcription activity independent of the differences of enhancers and promoters used, although the repressive activity of RFP was much stronger than that of EPC. The coiled-coil domain of RFP and the carboxyl-terminal region of EPC were most important for the repressive activity of each protein, whereas the EPcA domain had the transcription activating ability that is unique as the Polycomb group protein function. These results suggested that RFP may be involved in the epigenetic gene silencing mechanism cooperating with Polycomb group proteins and that EPC is a unique molecule with both repressive and transactivating activities.\n" ], "offsets": [ [ 0, 1491 ] ] } ]

[ { "id": "PMID-10976108_T1", "type": "TranscriptionRepressor", "text": [ "RET finger protein" ], "offsets": [ [ 0, 18 ] ], "normalized": [] }, { "id": "PMID-10976108_T2", "type": "TranscriptionRepressor", "text": [ "transcriptional repressor" ], "offsets": [ [ 24, 49 ] ], "normalized": [] }, { "id": "PMID-10976108_T6", "type": "TranscriptionRepressor", "text": [ "RET finger protein" ], "offsets": [ [ 131, 149 ] ], "normalized": [] }, { "id": "PMID-10976108_T7", "type": "TranscriptionRepressor", "text": [ "RFP" ], "offsets": [ [ 151, 154 ] ], "normalized": [] }, { "id": "PMID-10976108_T8", "type": "ZincCoordinatingDomainTF", "text": [ "B-box RING finger protein family" ], "offsets": [ [ 177, 209 ] ], "normalized": [] }, { "id": "PMID-10976108_T9", "type": "Enzyme", "text": [ "RET tyrosine kinase" ], "offsets": [ [ 258, 277 ] ], "normalized": [] }, { "id": "PMID-10976108_T10", "type": "TranscriptionRepressor", "text": [ "RFP" ], "offsets": [ [ 288, 291 ] ], "normalized": [] }, { "id": "PMID-10976108_T11", "type": "Nucleus", "text": [ "nuclear" ], "offsets": [ [ 312, 319 ] ], "normalized": [] }, { "id": "PMID-10976108_T12", "type": "Protein", "text": [ "protein" ], "offsets": [ [ 320, 327 ] ], "normalized": [] }, { "id": "PMID-10976108_T14", "type": "TranscriptionRepressor", "text": [ "RFP" ], "offsets": [ [ 418, 421 ] ], "normalized": [] }, { "id": "PMID-10976108_T16", "type": "Protein", "text": [ "Enhancer of Polycomb" ], "offsets": [ [ 437, 457 ] ], "normalized": [] }, { "id": "PMID-10976108_T17", "type": "Protein", "text": [ "EPC" ], "offsets": [ [ 459, 462 ] ], "normalized": [] }, { "id": "PMID-10976108_T21", "type": "ProteinDomain", "text": [ "coiled-coil domain" ], "offsets": [ [ 553, 571 ] ], "normalized": [] }, { "id": "PMID-10976108_T22", "type": "Protein", "text": [ "RFP" ], "offsets": [ [ 575, 578 ] ], "normalized": [] }, { "id": "PMID-10976108_T24", "type": "ProteinDomain", "text": [ "EPcA domain" ], "offsets": [ [ 603, 614 ] ], "normalized": [] }, { "id": "PMID-10976108_T25", "type": "ProteinDomain", "text": [ "carboxyl-terminal region" ], "offsets": [ [ 623, 647 ] ], "normalized": [] }, { "id": "PMID-10976108_T26", "type": "Protein", "text": [ "EPC" ], "offsets": [ [ 651, 654 ] ], "normalized": [] }, { "id": "PMID-10976108_T27", "type": "Protein", "text": [ "both proteins" ], "offsets": [ [ 669, 682 ] ], "normalized": [] }, { "id": "PMID-10976108_T28", "type": "Eukaryote", "text": [ "human" ], "offsets": [ [ 724, 729 ] ], "normalized": [] }, { "id": "PMID-10976108_T29", "type": "Cell", "text": [ "cells" ], "offsets": [ [ 730, 735 ] ], "normalized": [] }, { "id": "PMID-10976108_T31", "type": "Nucleus", "text": [ "nucleus" ], "offsets": [ [ 766, 773 ] ], "normalized": [] }, { "id": "PMID-10976108_T32", "type": "ReporterGene", "text": [ "reporter-gene" ], "offsets": [ [ 796, 809 ] ], "normalized": [] }, { "id": "PMID-10976108_T33", "type": "Protein", "text": [ "they" ], "offsets": [ [ 831, 835 ] ], "normalized": [] }, { "id": "PMID-10976108_T37", "type": "Enhancer", "text": [ "enhancers" ], "offsets": [ [ 910, 919 ] ], "normalized": [] }, { "id": "PMID-10976108_T38", "type": "Promoter", "text": [ "promoters" ], "offsets": [ [ 924, 933 ] ], "normalized": [] }, { "id": "PMID-10976108_T39", "type": "TranscriptionRepressorActivity", "text": [ "repressive activity" ], "offsets": [ [ 953, 972 ] ], "normalized": [] }, { "id": "PMID-10976108_T40", "type": "Protein", "text": [ "RFP" ], "offsets": [ [ 976, 979 ] ], "normalized": [] }, { "id": "PMID-10976108_T41", "type": "Protein", "text": [ "EPC" ], "offsets": [ [ 1011, 1014 ] ], "normalized": [] }, { "id": "PMID-10976108_T42", "type": "ProteinDomain", "text": [ "coiled-coil domain" ], "offsets": [ [ 1020, 1038 ] ], "normalized": [] }, { "id": "PMID-10976108_T43", "type": "Protein", "text": [ "RFP" ], "offsets": [ [ 1042, 1045 ] ], "normalized": [] }, { "id": "PMID-10976108_T44", "type": "ProteinDomain", "text": [ "carboxyl-terminal region" ], "offsets": [ [ 1054, 1078 ] ], "normalized": [] }, { "id": "PMID-10976108_T45", "type": "Protein", "text": [ "EPC" ], "offsets": [ [ 1082, 1085 ] ], "normalized": [] }, { "id": "PMID-10976108_T46", "type": "TranscriptionRepressorActivity", "text": [ "repressive activity" ], "offsets": [ [ 1114, 1133 ] ], "normalized": [] }, { "id": "PMID-10976108_T47", "type": "Protein", "text": [ "protein" ], "offsets": [ [ 1142, 1149 ] ], "normalized": [] }, { "id": "PMID-10976108_T48", "type": "ProteinDomain", "text": [ "EPcA domain" ], "offsets": [ [ 1163, 1174 ] ], "normalized": [] }, { "id": "PMID-10976108_T51", "type": "Protein", "text": [ "Polycomb group protein" ], "offsets": [ [ 1238, 1260 ] ], "normalized": [] }, { "id": "PMID-10976108_T52", "type": "Protein", "text": [ "RFP" ], "offsets": [ [ 1300, 1303 ] ], "normalized": [] }, { "id": "PMID-10976108_T54", "type": "Protein", "text": [ "Polycomb group proteins" ], "offsets": [ [ 1380, 1403 ] ], "normalized": [] }, { "id": "PMID-10976108_T55", "type": "Protein", "text": [ "EPC" ], "offsets": [ [ 1413, 1416 ] ], "normalized": [] }, { "id": "PMID-10976108_T56", "type": "TranscriptionRepressorActivity", "text": [ "repressive" ], "offsets": [ [ 1448, 1458 ] ], "normalized": [] }, { "id": "PMID-10976108_T57", "type": "TranscriptionActivatorActivity", "text": [ "transactivating activities" ], "offsets": [ [ 1463, 1489 ] ], "normalized": [] }, { "id": "PMID-10976108_T59", "type": "Function", "text": [ "functions" ], "offsets": [ [ 120, 129 ] ], "normalized": [] }, { "id": "PMID-10976108_T13", "type": "CellComponent", "text": [ "matrix" ], "offsets": [ [ 359, 365 ] ], "normalized": [] }, { "id": "PMID-10976108_T60", "type": "Nucleus", "text": [ "nuclear" ], "offsets": [ [ 351, 358 ] ], "normalized": [] }, { "id": "PMID-10976108_T4", "type": "Protein", "text": [ "enhancer of polycomb" ], "offsets": [ [ 69, 89 ] ], "normalized": [] }, { "id": "PMID-10976108_T35", "type": "TranscriptionActivatorActivity", "text": [ "transcription activating ability" ], "offsets": [ [ 1183, 1215 ] ], "normalized": [] } ]

[ { "id": "PMID-10976108_E1", "type": "BindingToProtein", "trigger": { "text": [ "interacts" ], "offsets": [ [ 54, 63 ] ] }, "arguments": [ { "role": "hasPatient", "ref_id": "PMID-10976108_T4" }, { "role": "hasPatient2", "ref_id": "PMID-10976108_T1" } ] }, { "id": "PMID-10976108_E2", "type": "BindingToProtein", "trigger": { "text": [ "interacts" ], "offsets": [ [ 422, 431 ] ] }, "arguments": [ { "role": "hasPatient", "ref_id": "PMID-10976108_T16" }, { "role": "hasPatient2", "ref_id": "PMID-10976108_T14" } ] }, { "id": "PMID-10976108_E3", "type": "NegativeRegulation", "trigger": { "text": [ "represses" ], "offsets": [ [ 477, 486 ] ] }, "arguments": [ { "role": "hasAgent", "ref_id": "PMID-10976108_E2" }, { "role": "hasPatient", "ref_id": "PMID-10976108_E4" } ] }, { "id": "PMID-10976108_E5", "type": "BindingToProtein", "trigger": { "text": [ "associated" ], "offsets": [ [ 583, 593 ] ] }, "arguments": [ { "role": "hasPatient", "ref_id": "PMID-10976108_T24" }, { "role": "hasPatient2", "ref_id": "PMID-10976108_T25" }, { "role": "hasPatient3", "ref_id": "PMID-10976108_T21" } ] }, { "id": "PMID-10976108_E6", "type": "Localization", "trigger": { "text": [ "colocalized" ], "offsets": [ [ 747, 758 ] ] }, "arguments": [ { "role": "hasPatient", "ref_id": "PMID-10976108_T27" } ] }, { "id": "PMID-10976108_E7", "type": "NegativeRegulation", "trigger": { "text": [ "repress" ], "offsets": [ [ 836, 843 ] ] }, "arguments": [ { "role": "hasAgent", "ref_id": "PMID-10976108_T33" }, { "role": "hasPatient", "ref_id": "PMID-10976108_E8" } ] }, { "id": "PMID-10976108_E10", "type": "GeneSilencing", "trigger": { "text": [ "gene silencing" ], "offsets": [ [ 1338, 1352 ] ] }, "arguments": [] }, { "id": "PMID-10976108_E11", "type": "Transcription", "trigger": { "text": [ "transcriptional" ], "offsets": [ [ 104, 119 ] ] }, "arguments": [] }, { "id": "PMID-10976108_E4", "type": "TranscriptionOfGene", "trigger": { "text": [ "gene transcription" ], "offsets": [ [ 491, 509 ] ] }, "arguments": [] }, { "id": "PMID-10976108_E8", "type": "TranscriptionOfGene", "trigger": { "text": [ "gene transcription" ], "offsets": [ [ 848, 866 ] ] }, "arguments": [] } ]

[]

[ { "id": "PMID-10976108_R3", "type": "hasPart", "arg1_id": "PMID-10976108_T22", "arg2_id": "PMID-10976108_T21", "normalized": [] }, { "id": "PMID-10976108_R4", "type": "hasPart", "arg1_id": "PMID-10976108_T26", "arg2_id": "PMID-10976108_T24", "normalized": [] }, { "id": "PMID-10976108_R5", "type": "hasPart", "arg1_id": "PMID-10976108_T26", "arg2_id": "PMID-10976108_T25", "normalized": [] }, { "id": "PMID-10976108_R6", "type": "fromSpecies", "arg1_id": "PMID-10976108_T29", "arg2_id": "PMID-10976108_T28", "normalized": [] }, { "id": "PMID-10976108_R8", "type": "hasFunction", "arg1_id": "PMID-10976108_T40", "arg2_id": "PMID-10976108_T39", "normalized": [] }, { "id": "PMID-10976108_R9", "type": "hasPart", "arg1_id": "PMID-10976108_T43", "arg2_id": "PMID-10976108_T42", "normalized": [] }, { "id": "PMID-10976108_R10", "type": "hasPart", "arg1_id": "PMID-10976108_T45", "arg2_id": "PMID-10976108_T44", "normalized": [] }, { "id": "PMID-10976108_R11", "type": "hasFunction", "arg1_id": "PMID-10976108_T47", "arg2_id": "PMID-10976108_T46", "normalized": [] }, { "id": "PMID-10976108_R13", "type": "hasFunction", "arg1_id": "PMID-10976108_T55", "arg2_id": "PMID-10976108_T56", "normalized": [] }, { "id": "PMID-10976108_R14", "type": "hasFunction", "arg1_id": "PMID-10976108_T55", "arg2_id": "PMID-10976108_T57", "normalized": [] }, { "id": "PMID-10976108_R2", "type": "locatedIn", "arg1_id": "PMID-10976108_T13", "arg2_id": "PMID-10976108_T60", "normalized": [] }, { "id": "PMID-10976108_R16", "type": "locatedIn", "arg1_id": "PMID-10976108_T12", "arg2_id": "PMID-10976108_T11", "normalized": [] }, { "id": "PMID-10976108_R17", "type": "locatedIn", "arg1_id": "PMID-10976108_T10", "arg2_id": "PMID-10976108_T13", "normalized": [] }, { "id": "PMID-10976108_R1", "type": "hasFunction", "arg1_id": "PMID-10976108_T4", "arg2_id": "PMID-10976108_T59", "normalized": [] }, { "id": "PMID-10976108_R12", "type": "hasFunction", "arg1_id": "PMID-10976108_T48", "arg2_id": "PMID-10976108_T35", "normalized": [] } ]

[ { "id": "PMID-11315969__text", "type": "abstract", "text": [ "Electron microscopic in situ hybridization study of simultaneous expression of TNP1 and PRM1 genes in human spermatids. Nuclear changes in the basic nucleoprotein complement occur during human spermiogenesis. Somatic type histones are displaced by transition proteins which are replaced themselves by protamines, the major nuclear proteins found in late spermatids and spermatozoa nuclei. Digoxigenin or Biotin labeled probes, coding respectively for human transition protein 1 (TP1) and protamine 1 (HP1), were used for double EM in situ hybridization. Immunodetection of hybrids with specific antibodies coupled to colloidal gold particles of different size (10 nm and 15 nm) was performed on the same preparations. Quantitative analysis of the nuclear and cytoplasmic labeling densities for the mRNAs coding for TP1 and HP1 showed the presence of transcripts in both the nucleus and cytoplasm of round spermatids until the elongation phase. Transcripts accumulated in the spermatid cytoplasm without any particular cellular compartmentalization. At the end of the spermatid elongation phase, the disappearing of TP1 and HP1 transcripts may be related to the arrest of transcriptional activity while the deposition of transition proteins and protamines successively occurs within spermatid nuclei.\n" ], "offsets": [ [ 0, 1300 ] ] } ]

[ { "id": "PMID-11315969_T2", "type": "Gene", "text": [ "TNP1" ], "offsets": [ [ 79, 83 ] ], "normalized": [] }, { "id": "PMID-11315969_T3", "type": "Gene", "text": [ "PRM1 genes" ], "offsets": [ [ 88, 98 ] ], "normalized": [] }, { "id": "PMID-11315969_T4", "type": "Eukaryote", "text": [ "human" ], "offsets": [ [ 102, 107 ] ], "normalized": [] }, { "id": "PMID-11315969_T5", "type": "Cell", "text": [ "spermatids" ], "offsets": [ [ 108, 118 ] ], "normalized": [] }, { "id": "PMID-11315969_T6", "type": "Nucleus", "text": [ "Nuclear" ], "offsets": [ [ 120, 127 ] ], "normalized": [] }, { "id": "PMID-11315969_T7", "type": "Protein", "text": [ "nucleoprotein" ], "offsets": [ [ 149, 162 ] ], "normalized": [] }, { "id": "PMID-11315969_T8", "type": "Eukaryote", "text": [ "human" ], "offsets": [ [ 187, 192 ] ], "normalized": [] }, { "id": "PMID-11315969_T9", "type": "Histone", "text": [ "Somatic type histones" ], "offsets": [ [ 209, 230 ] ], "normalized": [] }, { "id": "PMID-11315969_T10", "type": "Protein", "text": [ "transition proteins" ], "offsets": [ [ 248, 267 ] ], "normalized": [] }, { "id": "PMID-11315969_T11", "type": "Protein", "text": [ "protamines" ], "offsets": [ [ 301, 311 ] ], "normalized": [] }, { "id": "PMID-11315969_T12", "type": "Protein", "text": [ "nuclear proteins" ], "offsets": [ [ 323, 339 ] ], "normalized": [] }, { "id": "PMID-11315969_T13", "type": "Cell", "text": [ "spermatids" ], "offsets": [ [ 354, 364 ] ], "normalized": [] }, { "id": "PMID-11315969_T14", "type": "Cell", "text": [ "spermatozoa" ], "offsets": [ [ 369, 380 ] ], "normalized": [] }, { "id": "PMID-11315969_T15", "type": "Nucleus", "text": [ "nuclei" ], "offsets": [ [ 381, 387 ] ], "normalized": [] }, { "id": "PMID-11315969_T16", "type": "Eukaryote", "text": [ "human" ], "offsets": [ [ 451, 456 ] ], "normalized": [] }, { "id": "PMID-11315969_T17", "type": "Protein", "text": [ "transition protein 1" ], "offsets": [ [ 457, 477 ] ], "normalized": [] }, { "id": "PMID-11315969_T18", "type": "Protein", "text": [ "TP1" ], "offsets": [ [ 479, 482 ] ], "normalized": [] }, { "id": "PMID-11315969_T19", "type": "Protein", "text": [ "protamine 1" ], "offsets": [ [ 488, 499 ] ], "normalized": [] }, { "id": "PMID-11315969_T20", "type": "Protein", "text": [ "HP1" ], "offsets": [ [ 501, 504 ] ], "normalized": [] }, { "id": "PMID-11315969_T21", "type": "Nucleus", "text": [ "nuclear" ], "offsets": [ [ 747, 754 ] ], "normalized": [] }, { "id": "PMID-11315969_T22", "type": "CellComponent", "text": [ "cytoplasmic" ], "offsets": [ [ 759, 770 ] ], "normalized": [] }, { "id": "PMID-11315969_T23", "type": "MessengerRNA", "text": [ "mRNAs" ], "offsets": [ [ 798, 803 ] ], "normalized": [] }, { "id": "PMID-11315969_T24", "type": "Protein", "text": [ "TP1" ], "offsets": [ [ 815, 818 ] ], "normalized": [] }, { "id": "PMID-11315969_T25", "type": "Protein", "text": [ "HP1" ], "offsets": [ [ 823, 826 ] ], "normalized": [] }, { "id": "PMID-11315969_T26", "type": "Transcript", "text": [ "transcripts" ], "offsets": [ [ 850, 861 ] ], "normalized": [] }, { "id": "PMID-11315969_T27", "type": "Nucleus", "text": [ "nucleus" ], "offsets": [ [ 874, 881 ] ], "normalized": [] }, { "id": "PMID-11315969_T28", "type": "CellComponent", "text": [ "cytoplasm" ], "offsets": [ [ 886, 895 ] ], "normalized": [] }, { "id": "PMID-11315969_T29", "type": "Cell", "text": [ "round spermatids" ], "offsets": [ [ 899, 915 ] ], "normalized": [] }, { "id": "PMID-11315969_T31", "type": "Transcript", "text": [ "Transcripts" ], "offsets": [ [ 944, 955 ] ], "normalized": [] }, { "id": "PMID-11315969_T33", "type": "Cell", "text": [ "spermatid" ], "offsets": [ [ 975, 984 ] ], "normalized": [] }, { "id": "PMID-11315969_T34", "type": "CellComponent", "text": [ "cytoplasm" ], "offsets": [ [ 985, 994 ] ], "normalized": [] }, { "id": "PMID-11315969_T35", "type": "Cell", "text": [ "spermatid" ], "offsets": [ [ 1067, 1076 ] ], "normalized": [] }, { "id": "PMID-11315969_T37", "type": "Protein", "text": [ "TP1" ], "offsets": [ [ 1115, 1118 ] ], "normalized": [] }, { "id": "PMID-11315969_T38", "type": "Protein", "text": [ "HP1" ], "offsets": [ [ 1123, 1126 ] ], "normalized": [] }, { "id": "PMID-11315969_T39", "type": "Transcript", "text": [ "transcripts" ], "offsets": [ [ 1127, 1138 ] ], "normalized": [] }, { "id": "PMID-11315969_T41", "type": "Protein", "text": [ "transition proteins" ], "offsets": [ [ 1220, 1239 ] ], "normalized": [] }, { "id": "PMID-11315969_T42", "type": "Protein", "text": [ "protamines" ], "offsets": [ [ 1244, 1254 ] ], "normalized": [] }, { "id": "PMID-11315969_T43", "type": "Cell", "text": [ "spermatid" ], "offsets": [ [ 1282, 1291 ] ], "normalized": [] }, { "id": "PMID-11315969_T44", "type": "Nucleus", "text": [ "nuclei" ], "offsets": [ [ 1292, 1298 ] ], "normalized": [] } ]

[ { "id": "PMID-11315969_E1", "type": "GeneExpression", "trigger": { "text": [ "expression" ], "offsets": [ [ 65, 75 ] ] }, "arguments": [ { "role": "hasPatient", "ref_id": "PMID-11315969_T2" } ] }, { "id": "PMID-11315969_E2", "type": "Elongation", "trigger": { "text": [ "elongation phase" ], "offsets": [ [ 926, 942 ] ] }, "arguments": [] }, { "id": "PMID-11315969_E3", "type": "Localization", "trigger": { "text": [ "accumulated" ], "offsets": [ [ 956, 967 ] ] }, "arguments": [ { "role": "hasPatient", "ref_id": "PMID-11315969_T31" } ] }, { "id": "PMID-11315969_E4", "type": "Elongation", "trigger": { "text": [ "elongation phase" ], "offsets": [ [ 1077, 1093 ] ] }, "arguments": [] }, { "id": "PMID-11315969_E5", "type": "Transcription", "trigger": { "text": [ "transcriptional activity" ], "offsets": [ [ 1171, 1195 ] ] }, "arguments": [] }, { "id": "PMID-11315969_E6", "type": "CellularDevelopmentalProcess", "trigger": { "text": [ "spermiogenesis" ], "offsets": [ [ 193, 207 ] ] }, "arguments": [] }, { "id": "PMID-11315969_E7", "type": "Decrease", "trigger": { "text": [ "arrest" ], "offsets": [ [ 1161, 1167 ] ] }, "arguments": [ { "role": "hasPatient", "ref_id": "PMID-11315969_E5" } ] }, { "id": "PMID-11315969_E8", "type": "Localization", "trigger": { "text": [ "deposition" ], "offsets": [ [ 1206, 1216 ] ] }, "arguments": [ { "role": "hasPatient", "ref_id": "PMID-11315969_T41" } ] }, { "id": "PMID-11315969_E9", "type": "GeneExpression", "trigger": { "text": [ "expression" ], "offsets": [ [ 65, 75 ] ] }, "arguments": [ { "role": "hasPatient", "ref_id": "PMID-11315969_T3" } ] }, { "id": "PMID-11315969_E10", "type": "Localization", "trigger": { "text": [ "deposition" ], "offsets": [ [ 1206, 1216 ] ] }, "arguments": [ { "role": "hasPatient", "ref_id": "PMID-11315969_T42" } ] } ]

[]

[ { "id": "PMID-11315969_R2", "type": "fromSpecies", "arg1_id": "PMID-11315969_T5", "arg2_id": "PMID-11315969_T4", "normalized": [] }, { "id": "PMID-11315969_R3", "type": "locatedIn", "arg1_id": "PMID-11315969_T12", "arg2_id": "PMID-11315969_T13", "normalized": [] }, { "id": "PMID-11315969_R4", "type": "locatedIn", "arg1_id": "PMID-11315969_T12", "arg2_id": "PMID-11315969_T15", "normalized": [] }, { "id": "PMID-11315969_R5", "type": "locatedIn", "arg1_id": "PMID-11315969_T15", "arg2_id": "PMID-11315969_T14", "normalized": [] }, { "id": "PMID-11315969_R6", "type": "fromSpecies", "arg1_id": "PMID-11315969_T17", "arg2_id": "PMID-11315969_T16", "normalized": [] }, { "id": "PMID-11315969_R7", "type": "fromSpecies", "arg1_id": "PMID-11315969_T19", "arg2_id": "PMID-11315969_T16", "normalized": [] }, { "id": "PMID-11315969_R8", "type": "encodes", "arg1_id": "PMID-11315969_T23", "arg2_id": "PMID-11315969_T24", "normalized": [] }, { "id": "PMID-11315969_R9", "type": "encodes", "arg1_id": "PMID-11315969_T23", "arg2_id": "PMID-11315969_T25", "normalized": [] }, { "id": "PMID-11315969_R10", "type": "locatedIn", "arg1_id": "PMID-11315969_T23", "arg2_id": "PMID-11315969_T21", "normalized": [] }, { "id": "PMID-11315969_R11", "type": "locatedIn", "arg1_id": "PMID-11315969_T23", "arg2_id": "PMID-11315969_T22", "normalized": [] }, { "id": "PMID-11315969_R12", "type": "locatedIn", "arg1_id": "PMID-11315969_T26", "arg2_id": "PMID-11315969_T27", "normalized": [] }, { "id": "PMID-11315969_R13", "type": "locatedIn", "arg1_id": "PMID-11315969_T26", "arg2_id": "PMID-11315969_T28", "normalized": [] }, { "id": "PMID-11315969_R14", "type": "locatedIn", "arg1_id": "PMID-11315969_T27", "arg2_id": "PMID-11315969_T29", "normalized": [] }, { "id": "PMID-11315969_R15", "type": "locatedIn", "arg1_id": "PMID-11315969_T28", "arg2_id": "PMID-11315969_T29", "normalized": [] }, { "id": "PMID-11315969_R17", "type": "locatedIn", "arg1_id": "PMID-11315969_T34", "arg2_id": "PMID-11315969_T33", "normalized": [] }, { "id": "PMID-11315969_R18", "type": "encodes", "arg1_id": "PMID-11315969_T39", "arg2_id": "PMID-11315969_T37", "normalized": [] }, { "id": "PMID-11315969_R19", "type": "encodes", "arg1_id": "PMID-11315969_T39", "arg2_id": "PMID-11315969_T38", "normalized": [] }, { "id": "PMID-11315969_R22", "type": "locatedIn", "arg1_id": "PMID-11315969_T44", "arg2_id": "PMID-11315969_T43", "normalized": [] }, { "id": "PMID-11315969_R24", "type": "locatedIn", "arg1_id": "PMID-11315969_T7", "arg2_id": "PMID-11315969_T6", "normalized": [] } ]

[ { "id": "PMID-11420681__text", "type": "abstract", "text": [ "Identification of functional domains involved in BTG1 cell localization. We have previously shown that BTG1 stimulates myoblast differentiation. In addition, this protein displays a major nuclear localization in confluent myoblasts, decreasing during the early steps of differentiation, and is essentially detected in the cytoplasm of mature myotubes. To identify the domains involved in the cellular trafficking of BTG1, we observed the localization of several BTG1 sequences fused to betaGalactosidase. The highly conserved B box among all members of the BTG family induces a significant nuclear localization of the betaGal moiety, enhanced by presence of the BTG1 carboxy-terminal sequence. In addition, a functional Nuclear Export Signal (NES) overlaps the B box. Moreover, presence of the first 43 NH(2)-terminal amino acids reduced the nuclear localization of each chimeric protein tested. Last, the BTG1 amino-terminal domain bears an LxxLL motif favouring nuclear accumulation, and another region encompassing the A box inhibiting nuclear localization. In contrast to a BTG1 mutant exclusively localized in the cytoplasm, transient expression of a mutant displaying a nuclear localization enhanced myoblasts withdrawal from the cell cycle and terminal differentiation, thus mimicking the myogenic influence of BTG1. In conclusion, several regions of BTG1 are implicated in its cellular localization, and BTG1 myogenic activity is induced at the nuclear level.\n" ], "offsets": [ [ 0, 1468 ] ] } ]

[ { "id": "PMID-11420681_T1", "type": "ProteinDomain", "text": [ "functional domains" ], "offsets": [ [ 18, 36 ] ], "normalized": [] }, { "id": "PMID-11420681_T2", "type": "Protein", "text": [ "BTG1" ], "offsets": [ [ 49, 53 ] ], "normalized": [] }, { "id": "PMID-11420681_T3", "type": "Cell", "text": [ "cell" ], "offsets": [ [ 54, 58 ] ], "normalized": [] }, { "id": "PMID-11420681_T5", "type": "Protein", "text": [ "BTG1" ], "offsets": [ [ 103, 107 ] ], "normalized": [] }, { "id": "PMID-11420681_T8", "type": "Protein", "text": [ "protein" ], "offsets": [ [ 163, 170 ] ], "normalized": [] }, { "id": "PMID-11420681_T9", "type": "Nucleus", "text": [ "nuclear" ], "offsets": [ [ 188, 195 ] ], "normalized": [] }, { "id": "PMID-11420681_T11", "type": "Cell", "text": [ "confluent myoblasts" ], "offsets": [ [ 212, 231 ] ], "normalized": [] }, { "id": "PMID-11420681_T14", "type": "CellComponent", "text": [ "cytoplasm" ], "offsets": [ [ 322, 331 ] ], "normalized": [] }, { "id": "PMID-11420681_T15", "type": "Tissue", "text": [ "mature myotubes" ], "offsets": [ [ 335, 350 ] ], "normalized": [] }, { "id": "PMID-11420681_T16", "type": "ProteinDomain", "text": [ "domains" ], "offsets": [ [ 368, 375 ] ], "normalized": [] }, { "id": "PMID-11420681_T18", "type": "Protein", "text": [ "BTG1" ], "offsets": [ [ 416, 420 ] ], "normalized": [] }, { "id": "PMID-11420681_T20", "type": "Protein", "text": [ "BTG1" ], "offsets": [ [ 462, 466 ] ], "normalized": [] }, { "id": "PMID-11420681_T21", "type": "Enzyme", "text": [ "betaGalactosidase" ], "offsets": [ [ 486, 503 ] ], "normalized": [] }, { "id": "PMID-11420681_T22", "type": "ProteinDomain", "text": [ "B box" ], "offsets": [ [ 526, 531 ] ], "normalized": [] }, { "id": "PMID-11420681_T23", "type": "Protein", "text": [ "BTG family" ], "offsets": [ [ 557, 567 ] ], "normalized": [] }, { "id": "PMID-11420681_T25", "type": "Nucleus", "text": [ "nuclear" ], "offsets": [ [ 590, 597 ] ], "normalized": [] }, { "id": "PMID-11420681_T28", "type": "Protein", "text": [ "BTG1" ], "offsets": [ [ 662, 666 ] ], "normalized": [] }, { "id": "PMID-11420681_T29", "type": "Sequence", "text": [ "Nuclear Export Signal" ], "offsets": [ [ 720, 741 ] ], "normalized": [] }, { "id": "PMID-11420681_T30", "type": "Sequence", "text": [ "NES" ], "offsets": [ [ 743, 746 ] ], "normalized": [] }, { "id": "PMID-11420681_T31", "type": "ProteinDomain", "text": [ "B box" ], "offsets": [ [ 761, 766 ] ], "normalized": [] }, { "id": "PMID-11420681_T32", "type": "AminoAcid", "text": [ "amino acids" ], "offsets": [ [ 818, 829 ] ], "normalized": [] }, { "id": "PMID-11420681_T34", "type": "Nucleus", "text": [ "nuclear" ], "offsets": [ [ 842, 849 ] ], "normalized": [] }, { "id": "PMID-11420681_T36", "type": "Protein", "text": [ "protein" ], "offsets": [ [ 880, 887 ] ], "normalized": [] }, { "id": "PMID-11420681_T37", "type": "Protein", "text": [ "BTG1" ], "offsets": [ [ 906, 910 ] ], "normalized": [] }, { "id": "PMID-11420681_T38", "type": "ProteinDomain", "text": [ "amino-terminal domain" ], "offsets": [ [ 911, 932 ] ], "normalized": [] }, { "id": "PMID-11420681_T39", "type": "ProteinDomain", "text": [ "LxxLL motif" ], "offsets": [ [ 942, 953 ] ], "normalized": [] }, { "id": "PMID-11420681_T40", "type": "Nucleus", "text": [ "nuclear" ], "offsets": [ [ 964, 971 ] ], "normalized": [] }, { "id": "PMID-11420681_T42", "type": "ProteinDomain", "text": [ "A box" ], "offsets": [ [ 1022, 1027 ] ], "normalized": [] }, { "id": "PMID-11420681_T44", "type": "Nucleus", "text": [ "nuclear" ], "offsets": [ [ 1039, 1046 ] ], "normalized": [] }, { "id": "PMID-11420681_T46", "type": "MutantProtein", "text": [ "BTG1 mutant" ], "offsets": [ [ 1078, 1089 ] ], "normalized": [] }, { "id": "PMID-11420681_T48", "type": "CellComponent", "text": [ "cytoplasm" ], "offsets": [ [ 1119, 1128 ] ], "normalized": [] }, { "id": "PMID-11420681_T50", "type": "MutantProtein", "text": [ "mutant" ], "offsets": [ [ 1156, 1162 ] ], "normalized": [] }, { "id": "PMID-11420681_T54", "type": "Protein", "text": [ "BTG1" ], "offsets": [ [ 1318, 1322 ] ], "normalized": [] }, { "id": "PMID-11420681_T55", "type": "Protein", "text": [ "BTG1" ], "offsets": [ [ 1358, 1362 ] ], "normalized": [] }, { "id": "PMID-11420681_T56", "type": "Cell", "text": [ "cellular" ], "offsets": [ [ 1385, 1393 ] ], "normalized": [] }, { "id": "PMID-11420681_T58", "type": "Protein", "text": [ "BTG1" ], "offsets": [ [ 1412, 1416 ] ], "normalized": [] }, { "id": "PMID-11420681_T60", "type": "Nucleus", "text": [ "nuclear" ], "offsets": [ [ 1453, 1460 ] ], "normalized": [] }, { "id": "PMID-11420681_T61", "type": "FusionOfGeneWithReporterGene", "text": [ "fused" ], "offsets": [ [ 477, 482 ] ], "normalized": [] }, { "id": "PMID-11420681_T62", "type": "Nucleus", "text": [ "nuclear" ], "offsets": [ [ 1176, 1183 ] ], "normalized": [] }, { "id": "PMID-11420681_T65", "type": "Cell", "text": [ "myoblasts" ], "offsets": [ [ 1206, 1215 ] ], "normalized": [] } ]

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[]

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[ { "id": "PMID-12402362__text", "type": "abstract", "text": [ "Solution structure of the DNA-binding domain of interleukin enhancer binding factor 1 (FOXK1a). Interleukin enhancer binding factor (ILF) binds to the interleukin-2 (IL-2) promoter and regulates IL-2 gene expression. In this study, the 3D structure of the DNA-binding domain of ILF was determined by multidimensional NMR spectroscopy. NMR structure analysis revealed that the DNA-binding domain of ILF is a new member of the winged helix/forkhead family, and that its wing 2 contains an extra alpha-helix. This is the first study to report the presence of a C-terminal alpha-helix in place of a typical wing 2 in a member of this family. This structural difference may be responsible for the different DNA-binding specificity of ILF compared to other winged helix/forkhead proteins. Our deletion studies of the fragments of ILF also suggest that the C-terminal region plays a regulatory role in DNA binding.\n" ], "offsets": [ [ 0, 908 ] ] } ]

[ { "id": "PMID-12402362_T1", "type": "MolecularStructure", "text": [ "structure" ], "offsets": [ [ 9, 18 ] ], "normalized": [] }, { "id": "PMID-12402362_T2", "type": "DNABindingDomainOfProtein", "text": [ "DNA-binding domain" ], "offsets": [ [ 26, 44 ] ], "normalized": [] }, { "id": "PMID-12402362_T3", "type": "Protein", "text": [ "interleukin enhancer binding factor 1" ], "offsets": [ [ 48, 85 ] ], "normalized": [] }, { "id": "PMID-12402362_T4", "type": "Protein", "text": [ "FOXK1a" ], "offsets": [ [ 87, 93 ] ], "normalized": [] }, { "id": "PMID-12402362_T5", "type": "Protein", "text": [ "Interleukin enhancer binding factor" ], "offsets": [ [ 96, 131 ] ], "normalized": [] }, { "id": "PMID-12402362_T6", "type": "Protein", "text": [ "ILF" ], "offsets": [ [ 133, 136 ] ], "normalized": [] }, { "id": "PMID-12402362_T8", "type": "Gene", "text": [ "interleukin-2" ], "offsets": [ [ 151, 164 ] ], "normalized": [] }, { "id": "PMID-12402362_T9", "type": "Gene", "text": [ "IL-2" ], "offsets": [ [ 166, 170 ] ], "normalized": [] }, { "id": "PMID-12402362_T10", "type": "Promoter", "text": [ "promoter" ], "offsets": [ [ 172, 180 ] ], "normalized": [] }, { "id": "PMID-12402362_T12", "type": "Gene", "text": [ "IL-2" ], "offsets": [ [ 195, 199 ] ], "normalized": [] }, { "id": "PMID-12402362_T14", "type": "ThreeDimensionalMolecularStructure", "text": [ "3D structure" ], "offsets": [ [ 236, 248 ] ], "normalized": [] }, { "id": "PMID-12402362_T15", "type": "DNABindingDomainOfProtein", "text": [ "DNA-binding domain" ], "offsets": [ [ 256, 274 ] ], "normalized": [] }, { "id": "PMID-12402362_T16", "type": "Protein", "text": [ "ILF" ], "offsets": [ [ 278, 281 ] ], "normalized": [] }, { "id": "PMID-12402362_T17", "type": "DNABindingDomainOfProtein", "text": [ "DNA-binding domain" ], "offsets": [ [ 376, 394 ] ], "normalized": [] }, { "id": "PMID-12402362_T18", "type": "Protein", "text": [ "ILF" ], "offsets": [ [ 398, 401 ] ], "normalized": [] }, { "id": "PMID-12402362_T19", "type": "ForkheadWingedHelixTF", "text": [ "winged helix/forkhead family" ], "offsets": [ [ 425, 453 ] ], "normalized": [] }, { "id": "PMID-12402362_T20", "type": "ProteinDomain", "text": [ "wing 2" ], "offsets": [ [ 468, 474 ] ], "normalized": [] }, { "id": "PMID-12402362_T21", "type": "MolecularStructure", "text": [ "alpha-helix" ], "offsets": [ [ 493, 504 ] ], "normalized": [] }, { "id": "PMID-12402362_T22", "type": "MolecularStructure", "text": [ "alpha-helix" ], "offsets": [ [ 569, 580 ] ], "normalized": [] }, { "id": "PMID-12402362_T23", "type": "ProteinDomain", "text": [ "wing 2" ], "offsets": [ [ 603, 609 ] ], "normalized": [] }, { "id": "PMID-12402362_T24", "type": "Protein", "text": [ "this family" ], "offsets": [ [ 625, 636 ] ], "normalized": [] }, { "id": "PMID-12402362_T25", "type": "DNA", "text": [ "DNA" ], "offsets": [ [ 702, 705 ] ], "normalized": [] }, { "id": "PMID-12402362_T27", "type": "Protein", "text": [ "ILF" ], "offsets": [ [ 729, 732 ] ], "normalized": [] }, { "id": "PMID-12402362_T30", "type": "Protein", "text": [ "ILF" ], "offsets": [ [ 824, 827 ] ], "normalized": [] }, { "id": "PMID-12402362_T32", "type": "DNA", "text": [ "DNA" ], "offsets": [ [ 895, 898 ] ], "normalized": [] }, { "id": "PMID-12402362_T28", "type": "ForkheadWingedHelixTF", "text": [ "winged helix/forkhead proteins" ], "offsets": [ [ 751, 781 ] ], "normalized": [] } ]

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[]

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[ { "id": "PMID-12411430__text", "type": "abstract", "text": [ "Role for RFX transcription factors in non-neuronal cell-specific inactivation of the microtubule-associated protein MAP1A promoter. Microtubule-associated protein MAP1A is expressed abundantly in mature neurons and is necessary for maintenance of neuronal morphology and localization of some molecules in association with the microtubule-based cytoskeleton. Previous studies indicated that its complementary expression together with MAP1B during nervous system development is regulated at the transcriptional level and that the mouse Map1A gene is transcribed under the control of 5' and intronic promoters. In this study, we investigated the regulatory mechanisms that govern the neuronal cell-specific activation of the MAP1A 5' promoter. We found that two regulatory factor for X box (RFX) binding sites in exon1 of both the mouse and human genes are important for effective transcriptional repression observed only in non-neuronal cells by reporter assays. Among RFX transcription factor family members, RFX1 and 3 mainly interact with repressive elements in vitro. Cotransfection studies indicated that RFX1, which is expressed ubiquitously, down-regulated the MAP1A 5' promoter activity in non-neuronal cells. Unexpectedly, RFX3, which is abundantly expressed in neuronal cells, down-regulated the transactivity as well, when it was expressed in non-neuronal cells. Both RFX1 and 3 did not down-regulate the transactivity in neuronal cells. These results suggest that RFX1 and 3 are pivotal factors in down-regulation of the MAP1A 5' promoter in non-neuronal cells. The cell type-specific down-regulation, however, does not depend simply on which RFX interacts with the elements, but seems to depend on underlying profound mechanisms.\n" ], "offsets": [ [ 0, 1741 ] ] } ]

[ { "id": "PMID-12411430_T1", "type": "TranscriptionFactor", "text": [ "RFX transcription factors" ], "offsets": [ [ 9, 34 ] ], "normalized": [] }, { "id": "PMID-12411430_T2", "type": "Cell", "text": [ "non-neuronal cell" ], "offsets": [ [ 38, 55 ] ], "normalized": [] }, { "id": "PMID-12411430_T5", "type": "Gene", "text": [ "MAP1A" ], "offsets": [ [ 116, 121 ] ], "normalized": [] }, { "id": "PMID-12411430_T6", "type": "Promoter", "text": [ "promoter" ], "offsets": [ [ 122, 130 ] ], "normalized": [] }, { "id": "PMID-12411430_T10", "type": "Cell", "text": [ "mature neurons" ], "offsets": [ [ 196, 210 ] ], "normalized": [] }, { "id": "PMID-12411430_T12", "type": "Phenotype", "text": [ "neuronal morphology" ], "offsets": [ [ 247, 266 ] ], "normalized": [] }, { "id": "PMID-12411430_T14", "type": "MolecularEntity", "text": [ "molecules" ], "offsets": [ [ 292, 301 ] ], "normalized": [] }, { "id": "PMID-12411430_T15", "type": "CellComponent", "text": [ "microtubule" ], "offsets": [ [ 326, 337 ] ], "normalized": [] }, { "id": "PMID-12411430_T16", "type": "CellComponent", "text": [ "cytoskeleton" ], "offsets": [ [ 344, 356 ] ], "normalized": [] }, { "id": "PMID-12411430_T17", "type": "Protein", "text": [ "its" ], "offsets": [ [ 390, 393 ] ], "normalized": [] }, { "id": "PMID-12411430_T19", "type": "Protein", "text": [ "MAP1B" ], "offsets": [ [ 433, 438 ] ], "normalized": [] }, { "id": "PMID-12411430_T23", "type": "Eukaryote", "text": [ "mouse" ], "offsets": [ [ 528, 533 ] ], "normalized": [] }, { "id": "PMID-12411430_T24", "type": "Gene", "text": [ "Map1A gene" ], "offsets": [ [ 534, 544 ] ], "normalized": [] }, { "id": "PMID-12411430_T29", "type": "Cell", "text": [ "neuronal cell" ], "offsets": [ [ 681, 694 ] ], "normalized": [] }, { "id": "PMID-12411430_T31", "type": "Gene", "text": [ "MAP1A" ], "offsets": [ [ 722, 727 ] ], "normalized": [] }, { "id": "PMID-12411430_T32", "type": "Promoter", "text": [ "5' promoter" ], "offsets": [ [ 728, 739 ] ], "normalized": [] }, { "id": "PMID-12411430_T33", "type": "TranscriptionRegulator", "text": [ "regulatory factor" ], "offsets": [ [ 759, 776 ] ], "normalized": [] }, { "id": "PMID-12411430_T34", "type": "TranscriptionFactorBindingSiteOfDNA", "text": [ "X box (RFX) binding sites" ], "offsets": [ [ 781, 806 ] ], "normalized": [] }, { "id": "PMID-12411430_T36", "type": "Exon", "text": [ "exon1" ], "offsets": [ [ 810, 815 ] ], "normalized": [] }, { "id": "PMID-12411430_T37", "type": "Eukaryote", "text": [ "mouse" ], "offsets": [ [ 828, 833 ] ], "normalized": [] }, { "id": "PMID-12411430_T38", "type": "Eukaryote", "text": [ "human" ], "offsets": [ [ 838, 843 ] ], "normalized": [] }, { "id": "PMID-12411430_T39", "type": "Gene", "text": [ "genes" ], "offsets": [ [ 844, 849 ] ], "normalized": [] }, { "id": "PMID-12411430_T42", "type": "Cell", "text": [ "non-neuronal cells" ], "offsets": [ [ 922, 940 ] ], "normalized": [] }, { "id": "PMID-12411430_T43", "type": "TranscriptionFactor", "text": [ "RFX transcription factor family" ], "offsets": [ [ 967, 998 ] ], "normalized": [] }, { "id": "PMID-12411430_T44", "type": "TranscriptionFactor", "text": [ "RFX1" ], "offsets": [ [ 1008, 1012 ] ], "normalized": [] }, { "id": "PMID-12411430_T45", "type": "TranscriptionFactor", "text": [ "RFX", "3" ], "offsets": [ [ 1008, 1011 ], [ 1017, 1018 ] ], "normalized": [] }, { "id": "PMID-12411430_T47", "type": "RegulatoryDNARegion", "text": [ "repressive elements" ], "offsets": [ [ 1040, 1059 ] ], "normalized": [] }, { "id": "PMID-12411430_T48", "type": "TranscriptionFactor", "text": [ "RFX1" ], "offsets": [ [ 1108, 1112 ] ], "normalized": [] }, { "id": "PMID-12411430_T52", "type": "Gene", "text": [ "MAP1A" ], "offsets": [ [ 1166, 1171 ] ], "normalized": [] }, { "id": "PMID-12411430_T53", "type": "Promoter", "text": [ "5' promoter" ], "offsets": [ [ 1172, 1183 ] ], "normalized": [] }, { "id": "PMID-12411430_T54", "type": "Cell", "text": [ "non-neuronal cells" ], "offsets": [ [ 1196, 1214 ] ], "normalized": [] }, { "id": "PMID-12411430_T55", "type": "TranscriptionFactor", "text": [ "RFX3" ], "offsets": [ [ 1230, 1234 ] ], "normalized": [] }, { "id": "PMID-12411430_T57", "type": "Cell", "text": [ "neuronal cells" ], "offsets": [ [ 1269, 1283 ] ], "normalized": [] }, { "id": "PMID-12411430_T62", "type": "Cell", "text": [ "non-neuronal cells" ], "offsets": [ [ 1352, 1370 ] ], "normalized": [] }, { "id": "PMID-12411430_T63", "type": "TranscriptionFactor", "text": [ "RFX1" ], "offsets": [ [ 1474, 1478 ] ], "normalized": [] }, { "id": "PMID-12411430_T64", "type": "TranscriptionFactor", "text": [ "RFX", "3" ], "offsets": [ [ 1474, 1477 ], [ 1483, 1484 ] ], "normalized": [] }, { "id": "PMID-12411430_T67", "type": "Gene", "text": [ "MAP1A" ], "offsets": [ [ 1531, 1536 ] ], "normalized": [] }, { "id": "PMID-12411430_T68", "type": "Promoter", "text": [ "5' promoter" ], "offsets": [ [ 1537, 1548 ] ], "normalized": [] }, { "id": "PMID-12411430_T69", "type": "Cell", "text": [ "non-neuronal cells" ], "offsets": [ [ 1552, 1570 ] ], "normalized": [] }, { "id": "PMID-12411430_T70", "type": "Cell", "text": [ "cell type" ], "offsets": [ [ 1576, 1585 ] ], "normalized": [] }, { "id": "PMID-12411430_T3", "type": "Gene", "text": [ "microtubule-associated protein" ], "offsets": [ [ 85, 115 ] ], "normalized": [] }, { "id": "PMID-12411430_T4", "type": "Protein", "text": [ "Microtubule-associated protein" ], "offsets": [ [ 132, 162 ] ], "normalized": [] }, { "id": "PMID-12411430_T7", "type": "Protein", "text": [ "MAP1A" ], "offsets": [ [ 163, 168 ] ], "normalized": [] }, { "id": "PMID-12411430_T8", "type": "Promoter", "text": [ "5' and intronic promoters" ], "offsets": [ [ 581, 606 ] ], "normalized": [] }, { "id": "PMID-12411430_T51", "type": "TranscriptionFactor", "text": [ "RFX" ], "offsets": [ [ 1653, 1656 ] ], "normalized": [] }, { "id": "PMID-12411430_T59", "type": "RegulatoryDNARegion", "text": [ "elements" ], "offsets": [ [ 1676, 1684 ] ], "normalized": [] } ]

[ { "id": "PMID-12411430_E1", "type": "GeneExpression", "trigger": { "text": [ "expressed" ], "offsets": [ [ 172, 181 ] ] }, "arguments": [ { "role": "hasPatient", "ref_id": "PMID-12411430_T4" } ] }, { "id": "PMID-12411430_E2", "type": "Maintenance", "trigger": { "text": [ "maintenance" ], "offsets": [ [ 232, 243 ] ] }, "arguments": [ { "role": "hasPatient", "ref_id": "PMID-12411430_T12" } ] }, { "id": "PMID-12411430_E3", "type": "Localization", "trigger": { "text": [ "localization" ], "offsets": [ [ 271, 283 ] ] }, "arguments": [ { "role": "hasPatient", "ref_id": "PMID-12411430_T14" } ] }, { "id": "PMID-12411430_E4", "type": "GeneExpression", "trigger": { "text": [ "expression" ], "offsets": [ [ 408, 418 ] ] }, "arguments": [ { "role": "hasPatient", "ref_id": "PMID-12411430_T17" } ] }, { "id": "PMID-12411430_E5", "type": "DevelopmentalProcess", "trigger": { "text": [ "nervous system development" ], "offsets": [ [ 446, 472 ] ] }, "arguments": [] }, { "id": "PMID-12411430_E6", "type": "RegulatoryProcess", "trigger": { "text": [ "regulated" ], "offsets": [ [ 476, 485 ] ] }, "arguments": [ { "role": "hasPatient", "ref_id": "PMID-12411430_E4" } ] }, { "id": "PMID-12411430_E7", "type": "Transcription", "trigger": { "text": [ "transcriptional" ], "offsets": [ [ 493, 508 ] ] }, "arguments": [] }, { "id": "PMID-12411430_E8", "type": "Transcription", "trigger": { "text": [ "transcribed" ], "offsets": [ [ 548, 559 ] ] }, "arguments": [ { "role": "hasPatient", "ref_id": "PMID-12411430_T24" } ] }, { "id": "PMID-12411430_E9", "type": "RegulatoryProcess", "trigger": { "text": [ "control" ], "offsets": [ [ 570, 577 ] ] }, "arguments": [ { "role": "hasPatient", "ref_id": "PMID-12411430_E8" }, { "role": "hasAgent", "ref_id": "PMID-12411430_T8" } ] }, { "id": "PMID-12411430_E10", "type": "RegulatoryProcess", "trigger": { "text": [ "regulatory mechanisms" ], "offsets": [ [ 643, 664 ] ] }, "arguments": [ { "role": "hasPatient", "ref_id": "PMID-12411430_E11" } ] }, { "id": "PMID-12411430_E11", "type": "PositiveRegulation", "trigger": { "text": [ "activation" ], "offsets": [ [ 704, 714 ] ] }, "arguments": [ { "role": "hasPatient", "ref_id": "PMID-12411430_T32" } ] }, { "id": "PMID-12411430_E14", "type": "BindingToProtein", "trigger": { "text": [ "interact" ], "offsets": [ [ 1026, 1034 ] ] }, "arguments": [ { "role": "hasPatient", "ref_id": "PMID-12411430_T47" }, { "role": "hasPatient2", "ref_id": "PMID-12411430_T45" }, { "role": "hasPatient3", "ref_id": "PMID-12411430_T44" } ] }, { "id": "PMID-12411430_E15", "type": "GeneExpression", "trigger": { "text": [ "expressed" ], "offsets": [ [ 1123, 1132 ] ] }, "arguments": [ { "role": "hasPatient", "ref_id": "PMID-12411430_T48" } ] }, { "id": "PMID-12411430_E17", "type": "GeneExpression", "trigger": { "text": [ "expressed" ], "offsets": [ [ 1256, 1265 ] ] }, "arguments": [ { "role": "hasPatient", "ref_id": "PMID-12411430_T55" } ] }, { "id": "PMID-12411430_E19", "type": "GeneExpression", "trigger": { "text": [ "expressed" ], "offsets": [ [ 1339, 1348 ] ] }, "arguments": [ { "role": "hasPatient", "ref_id": "PMID-12411430_T55" } ] }, { "id": "PMID-12411430_E22", "type": "NegativeRegulation", "trigger": { "text": [ "inactivation" ], "offsets": [ [ 65, 77 ] ] }, "arguments": [ { "role": "hasPatient", "ref_id": "PMID-12411430_T6" } ] }, { "id": "PMID-12411430_E12", "type": "NegativeRegulationOfTranscription", "trigger": { "text": [ "transcriptional repression" ], "offsets": [ [ 878, 904 ] ] }, "arguments": [ { "role": "hasAgent", "ref_id": "PMID-12411430_T33" } ] }, { "id": "PMID-12411430_E13", "type": "NegativeRegulation", "trigger": { "text": [ "down-regulated" ], "offsets": [ [ 1147, 1161 ] ] }, "arguments": [ { "role": "hasAgent", "ref_id": "PMID-12411430_T48" }, { "role": "hasPatient", "ref_id": "PMID-12411430_T53" } ] }, { "id": "PMID-12411430_E16", "type": "NegativeRegulationOfTranscription", "trigger": { "text": [ "down-regulated the transactivity" ], "offsets": [ [ 1285, 1317 ] ] }, "arguments": [ { "role": "hasAgent", "ref_id": "PMID-12411430_T55" } ] }, { "id": "PMID-12411430_E18", "type": "NegativeRegulation", "trigger": { "text": [ "down-regulation" ], "offsets": [ [ 1508, 1523 ] ] }, "arguments": [ { "role": "hasPatient", "ref_id": "PMID-12411430_T68" }, { "role": "hasAgent", "ref_id": "PMID-12411430_T63" } ] }, { "id": "PMID-12411430_E20", "type": "NegativeRegulation", "trigger": { "text": [ "down-regulation" ], "offsets": [ [ 1595, 1610 ] ] }, "arguments": [] }, { "id": "PMID-12411430_E21", "type": "BindingOfTFToTFBindingSiteOfDNA", "trigger": { "text": [ "interacts" ], "offsets": [ [ 1657, 1666 ] ] }, "arguments": [ { "role": "hasPatient", "ref_id": "PMID-12411430_T59" }, { "role": "hasAgent", "ref_id": "PMID-12411430_T51" } ] }, { "id": "PMID-12411430_E23", "type": "GeneExpression", "trigger": { "text": [ "expression" ], "offsets": [ [ 408, 418 ] ] }, "arguments": [ { "role": "hasPatient", "ref_id": "PMID-12411430_T19" } ] }, { "id": "PMID-12411430_E24", "type": "RegulatoryProcess", "trigger": { "text": [ "regulated" ], "offsets": [ [ 476, 485 ] ] }, "arguments": [ { "role": "hasPatient", "ref_id": "PMID-12411430_E23" } ] }, { "id": "PMID-12411430_E25", "type": "NegativeRegulation", "trigger": { "text": [ "down-regulation" ], "offsets": [ [ 1508, 1523 ] ] }, "arguments": [ { "role": "hasPatient", "ref_id": "PMID-12411430_T68" }, { "role": "hasAgent", "ref_id": "PMID-12411430_T64" } ] } ]

[]

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[ { "id": "PMID-12665502__text", "type": "abstract", "text": [ "Identification of a functional binding site for activin on the type I receptor ALK4. Activins, like other members of the transforming growth factor-beta (TGF-beta) superfamily, initiate signaling by assembling a complex of two types of transmembrane serine/threonine receptor kinases classified as type II (ActRII or ActRIIB) and type I (ALK4). A kinase-deleted version of ALK4 can form an inactive complex with activin and ActRII/IIB and thereby acts in a dominant negative manner to block activin signaling. Using the complex structure of bone morphogenetic protein-2 bound to its type I receptor (ALK3) as a guide, we introduced extracellular domain mutations in the context of the truncated ALK4 (ALK4-trunc) construct and assessed the ability of the mutants to inhibit activin function. We have identified five hydrophobic amino acid residues on the ALK4 extracellular domain (Leu40, Ile70, Val73, Leu75, and Pro77) that, when mutated to alanine, have substantial effects on ALK4-trunc dominant negative activity. In addition, eleven mutants partially affected activin binding to ALK4. Together, these residues likely constitute the binding surface for activin on ALK4. Cross-linking studies measuring binding of 125I-activin-A to the ALK4-trunc mutants in the presence of ActRII implicated the same residues. Our results indicate that there is only a partial overlap of the binding sites on ALK4 and ALK3 for activin-A and bone morphogenetic protein-2, respectively. In addition three of the residues required for activin binding to ALK4 are conserved on the type I TGF-beta receptor ALK5, suggesting the corresponding region on ALK5 may be important for TGF-beta binding.\n" ], "offsets": [ [ 0, 1679 ] ] } ]

[ { "id": "PMID-12665502_T1", "type": "ProteinBindingSiteOfProtein", "text": [ "binding site" ], "offsets": [ [ 31, 43 ] ], "normalized": [] }, { "id": "PMID-12665502_T2", "type": "Protein", "text": [ "activin" ], "offsets": [ [ 48, 55 ] ], "normalized": [] }, { "id": "PMID-12665502_T3", "type": "Protein", "text": [ "type I receptor ALK4" ], "offsets": [ [ 63, 83 ] ], "normalized": [] }, { "id": "PMID-12665502_T4", "type": "Protein", "text": [ "Activins" ], "offsets": [ [ 85, 93 ] ], "normalized": [] }, { "id": "PMID-12665502_T5", "type": "Protein", "text": [ "transforming growth factor-beta" ], "offsets": [ [ 121, 152 ] ], "normalized": [] }, { "id": "PMID-12665502_T6", "type": "Protein", "text": [ "TGF-beta" ], "offsets": [ [ 154, 162 ] ], "normalized": [] }, { "id": "PMID-12665502_T10", "type": "ProteinComplex", "text": [ "complex" ], "offsets": [ [ 212, 219 ] ], "normalized": [] }, { "id": "PMID-12665502_T11", "type": "CellComponent", "text": [ "transmembrane" ], "offsets": [ [ 236, 249 ] ], "normalized": [] }, { "id": "PMID-12665502_T12", "type": "Enzyme", "text": [ "serine/threonine receptor kinases" ], "offsets": [ [ 250, 283 ] ], "normalized": [] }, { "id": "PMID-12665502_T13", "type": "Protein", "text": [ "ActRII" ], "offsets": [ [ 307, 313 ] ], "normalized": [] }, { "id": "PMID-12665502_T14", "type": "Protein", "text": [ "ActRIIB" ], "offsets": [ [ 317, 324 ] ], "normalized": [] }, { "id": "PMID-12665502_T15", "type": "Protein", "text": [ "ALK4" ], "offsets": [ [ 338, 342 ] ], "normalized": [] }, { "id": "PMID-12665502_T16", "type": "MutatedProtein", "text": [ "kinase-deleted version of ALK4" ], "offsets": [ [ 347, 377 ] ], "normalized": [] }, { "id": "PMID-12665502_T17", "type": "ProteinComplex", "text": [ "complex" ], "offsets": [ [ 399, 406 ] ], "normalized": [] }, { "id": "PMID-12665502_T18", "type": "Protein", "text": [ "activin" ], "offsets": [ [ 412, 419 ] ], "normalized": [] }, { "id": "PMID-12665502_T19", "type": "Protein", "text": [ "ActRII/IIB" ], "offsets": [ [ 424, 434 ] ], "normalized": [] }, { "id": "PMID-12665502_T21", "type": "Protein", "text": [ "activin" ], "offsets": [ [ 491, 498 ] ], "normalized": [] }, { "id": "PMID-12665502_T23", "type": "Protein", "text": [ "bone morphogenetic protein-2" ], "offsets": [ [ 541, 569 ] ], "normalized": [] }, { "id": "PMID-12665502_T25", "type": "Protein", "text": [ "type I receptor" ], "offsets": [ [ 583, 598 ] ], "normalized": [] }, { "id": "PMID-12665502_T26", "type": "Protein", "text": [ "ALK3" ], "offsets": [ [ 600, 604 ] ], "normalized": [] }, { "id": "PMID-12665502_T27", "type": "ProteinDomain", "text": [ "extracellular domain" ], "offsets": [ [ 632, 652 ] ], "normalized": [] }, { "id": "PMID-12665502_T29", "type": "MutatedProtein", "text": [ "truncated ALK4" ], "offsets": [ [ 685, 699 ] ], "normalized": [] }, { "id": "PMID-12665502_T30", "type": "MutatedProtein", "text": [ "ALK4-trunc" ], "offsets": [ [ 701, 711 ] ], "normalized": [] }, { "id": "PMID-12665502_T32", "type": "Protein", "text": [ "activin" ], "offsets": [ [ 774, 781 ] ], "normalized": [] }, { "id": "PMID-12665502_T33", "type": "AminoAcid", "text": [ "amino acid residues" ], "offsets": [ [ 828, 847 ] ], "normalized": [] }, { "id": "PMID-12665502_T34", "type": "Protein", "text": [ "ALK4" ], "offsets": [ [ 855, 859 ] ], "normalized": [] }, { "id": "PMID-12665502_T36", "type": "AminoAcid", "text": [ "Leu40" ], "offsets": [ [ 882, 887 ] ], "normalized": [] }, { "id": "PMID-12665502_T37", "type": "AminoAcid", "text": [ "Ile70" ], "offsets": [ [ 889, 894 ] ], "normalized": [] }, { "id": "PMID-12665502_T38", "type": "AminoAcid", "text": [ "Val73" ], "offsets": [ [ 896, 901 ] ], "normalized": [] }, { "id": "PMID-12665502_T39", "type": "AminoAcid", "text": [ "Leu75" ], "offsets": [ [ 903, 908 ] ], "normalized": [] }, { "id": "PMID-12665502_T40", "type": "AminoAcid", "text": [ "Pro77" ], "offsets": [ [ 914, 919 ] ], "normalized": [] }, { "id": "PMID-12665502_T42", "type": "AminoAcid", "text": [ "alanine" ], "offsets": [ [ 943, 950 ] ], "normalized": [] }, { "id": "PMID-12665502_T43", "type": "MutatedProtein", "text": [ "ALK4-trunc" ], "offsets": [ [ 980, 990 ] ], "normalized": [] }, { "id": "PMID-12665502_T44", "type": "MutatedProtein", "text": [ "mutants" ], "offsets": [ [ 1039, 1046 ] ], "normalized": [] }, { "id": "PMID-12665502_T46", "type": "Protein", "text": [ "activin" ], "offsets": [ [ 1066, 1073 ] ], "normalized": [] }, { "id": "PMID-12665502_T48", "type": "Protein", "text": [ "ALK4" ], "offsets": [ [ 1085, 1089 ] ], "normalized": [] }, { "id": "PMID-12665502_T49", "type": "Protein", "text": [ "activin" ], "offsets": [ [ 1158, 1165 ] ], "normalized": [] }, { "id": "PMID-12665502_T50", "type": "Protein", "text": [ "ALK4" ], "offsets": [ [ 1169, 1173 ] ], "normalized": [] }, { "id": "PMID-12665502_T51", "type": "Protein", "text": [ "ActRII" ], "offsets": [ [ 1278, 1284 ] ], "normalized": [] }, { "id": "PMID-12665502_T52", "type": "ProteinBindingSiteOfProtein", "text": [ "binding sites" ], "offsets": [ [ 1380, 1393 ] ], "normalized": [] }, { "id": "PMID-12665502_T53", "type": "Protein", "text": [ "ALK4" ], "offsets": [ [ 1397, 1401 ] ], "normalized": [] }, { "id": "PMID-12665502_T54", "type": "Protein", "text": [ "ALK3" ], "offsets": [ [ 1406, 1410 ] ], "normalized": [] }, { "id": "PMID-12665502_T55", "type": "Protein", "text": [ "activin-A" ], "offsets": [ [ 1415, 1424 ] ], "normalized": [] }, { "id": "PMID-12665502_T56", "type": "Protein", "text": [ "bone morphogenetic protein-2" ], "offsets": [ [ 1429, 1457 ] ], "normalized": [] }, { "id": "PMID-12665502_T57", "type": "AminoAcid", "text": [ "residues" ], "offsets": [ [ 1498, 1506 ] ], "normalized": [] }, { "id": "PMID-12665502_T58", "type": "Protein", "text": [ "activin" ], "offsets": [ [ 1520, 1527 ] ], "normalized": [] }, { "id": "PMID-12665502_T60", "type": "Protein", "text": [ "ALK4" ], "offsets": [ [ 1539, 1543 ] ], "normalized": [] }, { "id": "PMID-12665502_T61", "type": "Protein", "text": [ "type I TGF-beta receptor ALK5" ], "offsets": [ [ 1565, 1594 ] ], "normalized": [] }, { "id": "PMID-12665502_T62", "type": "ProteinDomain", "text": [ "corresponding region" ], "offsets": [ [ 1611, 1631 ] ], "normalized": [] }, { "id": "PMID-12665502_T63", "type": "Protein", "text": [ "ALK5" ], "offsets": [ [ 1635, 1639 ] ], "normalized": [] }, { "id": "PMID-12665502_T64", "type": "Protein", "text": [ "TGF-beta" ], "offsets": [ [ 1661, 1669 ] ], "normalized": [] }, { "id": "PMID-12665502_T66", "type": "MutatedProtein", "text": [ "mutants" ], "offsets": [ [ 755, 762 ] ], "normalized": [] }, { "id": "PMID-12665502_T35", "type": "ProteinDomain", "text": [ "extracellular domain" ], "offsets": [ [ 860, 880 ] ], "normalized": [] }, { "id": "PMID-12665502_T67", "type": "AminoAcid", "text": [ "residues" ], "offsets": [ [ 1107, 1115 ] ], "normalized": [] }, { "id": "PMID-12665502_T68", "type": "ProteinBindingSiteOfProtein", "text": [ "binding surface" ], "offsets": [ [ 1138, 1153 ] ], "normalized": [] }, { "id": "PMID-12665502_T69", "type": "Protein", "text": [ "activin-A" ], "offsets": [ [ 1223, 1232 ] ], "normalized": [] }, { "id": "PMID-12665502_T70", "type": "MutatedProtein", "text": [ "ALK4-trunc mutants" ], "offsets": [ [ 1240, 1258 ] ], "normalized": [] }, { "id": "PMID-12665502_T72", "type": "AminoAcid", "text": [ "residues" ], "offsets": [ [ 1305, 1313 ] ], "normalized": [] } ]

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[]

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[ { "id": "PMID-12724404__text", "type": "abstract", "text": [ "Identification and characterization of three new components of the mSin3A corepressor complex. The mSin3A corepressor complex contains 7 to 10 tightly associated polypeptides and is utilized by many transcriptional repressors. Much of the corepressor function of mSin3A derives from associations with the histone deacetylases HDAC1 and HDAC2; however, the contributions of the other mSin3A-associated polypeptides remain largely unknown. We have purified an mSin3A complex from K562 erythroleukemia cells and identified three new mSin3A-associated proteins (SAP): SAP180, SAP130, and SAP45. SAP180 is 40% identical to a previously identified mSin3A-associated protein, RBP1. SAP45 is identical to mSDS3, the human ortholog of the SDS3p component of the Saccharomyces cerevisiae Sin3p-Rpd3p corepressor complex. SAP130 does not have detectable homology to other proteins. Coimmunoprecipitation and gel filtration data suggest that the new SAPs are, at the very least, components of the same mSin3A complex. Each new SAP repressed transcription when tethered to DNA. Furthermore, repression correlated with mSin3A binding, suggesting that the new SAPs are components of functional mSin3A corepressor complexes. SAP180 has two repression domains: a C-terminal domain, which interacts with the mSin3A-HDAC complex, and an N-terminal domain, which functions independently of mSin3A-HDAC. SAP130 has a repression domain at its C terminus that interacts with the mSin3A-HDAC complex and an N-terminal domain that probably mediates an interaction with a transcriptional activator. Together, our data suggest that these novel SAPs function in the assembly and/or enzymatic activity of the mSin3A complex or in mediating interactions between the mSin3A complex and other regulatory complexes. Finally, all three SAPs bind to the HDAC-interaction domain (HID) of mSin3A, suggesting that the HID functions as the assembly interface for the mSin3A corepressor complex.\n" ], "offsets": [ [ 0, 1956 ] ] } ]

[ { "id": "PMID-12724404_T1", "type": "ProteinComplex", "text": [ "mSin3A corepressor complex" ], "offsets": [ [ 67, 93 ] ], "normalized": [] }, { "id": "PMID-12724404_T2", "type": "ProteinComplex", "text": [ "mSin3A corepressor complex" ], "offsets": [ [ 99, 125 ] ], "normalized": [] }, { "id": "PMID-12724404_T3", "type": "Peptide", "text": [ "polypeptides" ], "offsets": [ [ 162, 174 ] ], "normalized": [] }, { "id": "PMID-12724404_T4", "type": "TranscriptionRepressor", "text": [ "transcriptional repressors" ], "offsets": [ [ 199, 225 ] ], "normalized": [] }, { "id": "PMID-12724404_T6", "type": "ProteinComplex", "text": [ "mSin3A" ], "offsets": [ [ 263, 269 ] ], "normalized": [] }, { "id": "PMID-12724404_T8", "type": "Enzyme", "text": [ "histone deacetylases HDAC1" ], "offsets": [ [ 305, 331 ] ], "normalized": [] }, { "id": "PMID-12724404_T9", "type": "Enzyme", "text": [ "HDAC2" ], "offsets": [ [ 336, 341 ] ], "normalized": [] }, { "id": "PMID-12724404_T10", "type": "ProteinComplex", "text": [ "mSin3A" ], "offsets": [ [ 383, 389 ] ], "normalized": [] }, { "id": "PMID-12724404_T11", "type": "Peptide", "text": [ "polypeptides" ], "offsets": [ [ 401, 413 ] ], "normalized": [] }, { "id": "PMID-12724404_T12", "type": "ProteinComplex", "text": [ "mSin3A complex" ], "offsets": [ [ 458, 472 ] ], "normalized": [] }, { "id": "PMID-12724404_T13", "type": "Cell", "text": [ "K562 erythroleukemia cells" ], "offsets": [ [ 478, 504 ] ], "normalized": [] }, { "id": "PMID-12724404_T17", "type": "Protein", "text": [ "SAP" ], "offsets": [ [ 558, 561 ] ], "normalized": [] }, { "id": "PMID-12724404_T18", "type": "Protein", "text": [ "SAP180" ], "offsets": [ [ 564, 570 ] ], "normalized": [] }, { "id": "PMID-12724404_T19", "type": "Protein", "text": [ "SAP130" ], "offsets": [ [ 572, 578 ] ], "normalized": [] }, { "id": "PMID-12724404_T20", "type": "Protein", "text": [ "SAP45" ], "offsets": [ [ 584, 589 ] ], "normalized": [] }, { "id": "PMID-12724404_T21", "type": "Protein", "text": [ "SAP180" ], "offsets": [ [ 591, 597 ] ], "normalized": [] }, { "id": "PMID-12724404_T22", "type": "ProteinComplex", "text": [ "mSin3A" ], "offsets": [ [ 642, 648 ] ], "normalized": [] }, { "id": "PMID-12724404_T24", "type": "Protein", "text": [ "protein" ], "offsets": [ [ 660, 667 ] ], "normalized": [] }, { "id": "PMID-12724404_T25", "type": "Protein", "text": [ "RBP1" ], "offsets": [ [ 669, 673 ] ], "normalized": [] }, { "id": "PMID-12724404_T26", "type": "Protein", "text": [ "SAP45" ], "offsets": [ [ 675, 680 ] ], "normalized": [] }, { "id": "PMID-12724404_T27", "type": "Protein", "text": [ "mSDS3" ], "offsets": [ [ 697, 702 ] ], "normalized": [] }, { "id": "PMID-12724404_T28", "type": "Eukaryote", "text": [ "human" ], "offsets": [ [ 708, 713 ] ], "normalized": [] }, { "id": "PMID-12724404_T29", "type": "Protein", "text": [ "SDS3p" ], "offsets": [ [ 730, 735 ] ], "normalized": [] }, { "id": "PMID-12724404_T30", "type": "Eukaryote", "text": [ "Saccharomyces cerevisiae" ], "offsets": [ [ 753, 777 ] ], "normalized": [] }, { "id": "PMID-12724404_T31", "type": "ProteinComplex", "text": [ "Sin3p-Rpd3p corepressor complex" ], "offsets": [ [ 778, 809 ] ], "normalized": [] }, { "id": "PMID-12724404_T32", "type": "Protein", "text": [ "SAPs" ], "offsets": [ [ 938, 942 ] ], "normalized": [] }, { "id": "PMID-12724404_T33", "type": "ProteinComplex", "text": [ "mSin3A complex" ], "offsets": [ [ 990, 1004 ] ], "normalized": [] }, { "id": "PMID-12724404_T34", "type": "Protein", "text": [ "SAP" ], "offsets": [ [ 1015, 1018 ] ], "normalized": [] }, { "id": "PMID-12724404_T38", "type": "DNA", "text": [ "DNA" ], "offsets": [ [ 1060, 1063 ] ], "normalized": [] }, { "id": "PMID-12724404_T40", "type": "ProteinComplex", "text": [ "mSin3A" ], "offsets": [ [ 1105, 1111 ] ], "normalized": [] }, { "id": "PMID-12724404_T42", "type": "Protein", "text": [ "SAPs" ], "offsets": [ [ 1145, 1149 ] ], "normalized": [] }, { "id": "PMID-12724404_T43", "type": "ProteinComplex", "text": [ "mSin3A corepressor complexes" ], "offsets": [ [ 1179, 1207 ] ], "normalized": [] }, { "id": "PMID-12724404_T44", "type": "Protein", "text": [ "SAP180" ], "offsets": [ [ 1209, 1215 ] ], "normalized": [] }, { "id": "PMID-12724404_T46", "type": "ProteinDomain", "text": [ "domains" ], "offsets": [ [ 1235, 1242 ] ], "normalized": [] }, { "id": "PMID-12724404_T47", "type": "ProteinDomain", "text": [ "C-terminal domain" ], "offsets": [ [ 1246, 1263 ] ], "normalized": [] }, { "id": "PMID-12724404_T49", "type": "ProteinComplex", "text": [ "mSin3A-HDAC complex" ], "offsets": [ [ 1290, 1309 ] ], "normalized": [] }, { "id": "PMID-12724404_T50", "type": "ProteinDomain", "text": [ "N-terminal domain" ], "offsets": [ [ 1318, 1335 ] ], "normalized": [] }, { "id": "PMID-12724404_T51", "type": "ProteinComplex", "text": [ "mSin3A-HDAC" ], "offsets": [ [ 1370, 1381 ] ], "normalized": [] }, { "id": "PMID-12724404_T52", "type": "Protein", "text": [ "SAP130" ], "offsets": [ [ 1383, 1389 ] ], "normalized": [] }, { "id": "PMID-12724404_T54", "type": "ProteinDomain", "text": [ "domain" ], "offsets": [ [ 1407, 1413 ] ], "normalized": [] }, { "id": "PMID-12724404_T56", "type": "ProteinComplex", "text": [ "mSin3A-HDAC complex" ], "offsets": [ [ 1456, 1475 ] ], "normalized": [] }, { "id": "PMID-12724404_T57", "type": "ProteinDomain", "text": [ "N-terminal domain" ], "offsets": [ [ 1483, 1500 ] ], "normalized": [] }, { "id": "PMID-12724404_T60", "type": "TranscriptionActivator", "text": [ "transcriptional activator" ], "offsets": [ [ 1546, 1571 ] ], "normalized": [] }, { "id": "PMID-12724404_T61", "type": "Protein", "text": [ "SAPs" ], "offsets": [ [ 1617, 1621 ] ], "normalized": [] }, { "id": "PMID-12724404_T63", "type": "CatalyticActivity", "text": [ "enzymatic activity" ], "offsets": [ [ 1654, 1672 ] ], "normalized": [] }, { "id": "PMID-12724404_T64", "type": "ProteinComplex", "text": [ "mSin3A complex" ], "offsets": [ [ 1680, 1694 ] ], "normalized": [] }, { "id": "PMID-12724404_T67", "type": "ProteinComplex", "text": [ "mSin3A complex" ], "offsets": [ [ 1736, 1750 ] ], "normalized": [] }, { "id": "PMID-12724404_T68", "type": "ProteinComplex", "text": [ "regulatory complexes" ], "offsets": [ [ 1761, 1781 ] ], "normalized": [] }, { "id": "PMID-12724404_T69", "type": "Protein", "text": [ "SAPs" ], "offsets": [ [ 1802, 1806 ] ], "normalized": [] }, { "id": "PMID-12724404_T71", "type": "ProteinDomain", "text": [ "HDAC-interaction domain" ], "offsets": [ [ 1819, 1842 ] ], "normalized": [] }, { "id": "PMID-12724404_T72", "type": "ProteinDomain", "text": [ "HID" ], "offsets": [ [ 1844, 1847 ] ], "normalized": [] }, { "id": "PMID-12724404_T73", "type": "ProteinComplex", "text": [ "mSin3A" ], "offsets": [ [ 1852, 1858 ] ], "normalized": [] }, { "id": "PMID-12724404_T74", "type": "ProteinDomain", "text": [ "HID" ], "offsets": [ [ 1880, 1883 ] ], "normalized": [] }, { "id": "PMID-12724404_T75", "type": "ProteinComplex", "text": [ "mSin3A corepressor complex" ], "offsets": [ [ 1928, 1954 ] ], "normalized": [] }, { "id": "PMID-12724404_T14", "type": "Protein", "text": [ "mSin3A-associated proteins" ], "offsets": [ [ 530, 556 ] ], "normalized": [] }, { "id": "PMID-12724404_T16", "type": "TranscriptionRepressorActivity", "text": [ "repression" ], "offsets": [ [ 1224, 1234 ] ], "normalized": [] }, { "id": "PMID-12724404_T35", "type": "TranscriptionRepressorActivity", "text": [ "repression" ], "offsets": [ [ 1396, 1406 ] ], "normalized": [] }, { "id": "PMID-12724404_T5", "type": "TranscriptionCorepressor", "text": [ "corepressor" ], "offsets": [ [ 239, 250 ] ], "normalized": [] }, { "id": "PMID-12724404_T36", "type": "ProteinDomain", "text": [ "C terminus" ], "offsets": [ [ 1421, 1431 ] ], "normalized": [] } ]

[ { "id": "PMID-12724404_E1", "type": "BindingToProtein", "trigger": { "text": [ "associations" ], "offsets": [ [ 283, 295 ] ] }, "arguments": [ { "role": "hasPatient", "ref_id": "PMID-12724404_T9" }, { "role": "hasPatient2", "ref_id": "PMID-12724404_T8" }, { "role": "hasPatient3", "ref_id": "PMID-12724404_T6" } ] }, { "id": "PMID-12724404_E3", "type": "BindingToProtein", "trigger": { "text": [ "associated" ], "offsets": [ [ 649, 659 ] ] }, "arguments": [ { "role": "hasPatient", "ref_id": "PMID-12724404_T22" }, { "role": "hasPatient2", "ref_id": "PMID-12724404_T25" } ] }, { "id": "PMID-12724404_E6", "type": "BindingOfProteinToDNA", "trigger": { "text": [ "tethered" ], "offsets": [ [ 1048, 1056 ] ] }, "arguments": [ { "role": "hasAgent", "ref_id": "PMID-12724404_T34" }, { "role": "hasPatient", "ref_id": "PMID-12724404_T38" } ] }, { "id": "PMID-12724404_E7", "type": "NegativeRegulation", "trigger": { "text": [ "repression" ], "offsets": [ [ 1078, 1088 ] ] }, "arguments": [] }, { "id": "PMID-12724404_E8", "type": "BindingToProtein", "trigger": { "text": [ "binding" ], "offsets": [ [ 1112, 1119 ] ] }, "arguments": [ { "role": "hasPatient", "ref_id": "PMID-12724404_T40" } ] }, { "id": "PMID-12724404_E10", "type": "BindingToProtein", "trigger": { "text": [ "interacts" ], "offsets": [ [ 1271, 1280 ] ] }, "arguments": [ { "role": "hasPatient", "ref_id": "PMID-12724404_T49" }, { "role": "hasPatient2", "ref_id": "PMID-12724404_T47" } ] }, { "id": "PMID-12724404_E12", "type": "BindingToProtein", "trigger": { "text": [ "interacts" ], "offsets": [ [ 1437, 1446 ] ] }, "arguments": [ { "role": "hasPatient", "ref_id": "PMID-12724404_T56" }, { "role": "hasPatient2", "ref_id": "PMID-12724404_T36" } ] }, { "id": "PMID-12724404_E13", "type": "RegulatoryProcess", "trigger": { "text": [ "mediates" ], "offsets": [ [ 1515, 1523 ] ] }, "arguments": [ { "role": "hasAgent", "ref_id": "PMID-12724404_T57" }, { "role": "hasPatient", "ref_id": "PMID-12724404_E14" } ] }, { "id": "PMID-12724404_E14", "type": "BindingToProtein", "trigger": { "text": [ "interaction" ], "offsets": [ [ 1527, 1538 ] ] }, "arguments": [ { "role": "hasPatient", "ref_id": "PMID-12724404_T60" } ] }, { "id": "PMID-12724404_E15", "type": "BindingToProtein", "trigger": { "text": [ "assembly" ], "offsets": [ [ 1638, 1646 ] ] }, "arguments": [ { "role": "hasPatient", "ref_id": "PMID-12724404_T64" } ] }, { "id": "PMID-12724404_E16", "type": "RegulatoryProcess", "trigger": { "text": [ "mediating" ], "offsets": [ [ 1701, 1710 ] ] }, "arguments": [ { "role": "hasAgent", "ref_id": "PMID-12724404_T61" }, { "role": "hasPatient", "ref_id": "PMID-12724404_E17" } ] }, { "id": "PMID-12724404_E17", "type": "BindingToProtein", "trigger": { "text": [ "interactions" ], "offsets": [ [ 1711, 1723 ] ] }, "arguments": [ { "role": "hasPatient", "ref_id": "PMID-12724404_T68" }, { "role": "hasPatient2", "ref_id": "PMID-12724404_T67" } ] }, { "id": "PMID-12724404_E18", "type": "BindingToProtein", "trigger": { "text": [ "bind" ], "offsets": [ [ 1807, 1811 ] ] }, "arguments": [ { "role": "hasPatient", "ref_id": "PMID-12724404_T71" }, { "role": "hasPatient2", "ref_id": "PMID-12724404_T69" } ] }, { "id": "PMID-12724404_E2", "type": "NegativeRegulationOfTranscription", "trigger": { "text": [ "repressed transcription" ], "offsets": [ [ 1019, 1042 ] ] }, "arguments": [] }, { "id": "PMID-12724404_E4", "type": "BindingToProtein", "trigger": { "text": [ "assembly" ], "offsets": [ [ 1901, 1909 ] ] }, "arguments": [ { "role": "hasPatient", "ref_id": "PMID-12724404_T75" }, { "role": "hasPatient2", "ref_id": "PMID-12724404_T74" } ] } ]

[]

[ { "id": "PMID-12724404_R1", "type": "hasPart", "arg1_id": "PMID-12724404_T2", "arg2_id": "PMID-12724404_T3", "normalized": [] }, { "id": "PMID-12724404_R4", "type": "locatedIn", "arg1_id": "PMID-12724404_T12", "arg2_id": "PMID-12724404_T13", "normalized": [] }, { "id": "PMID-12724404_R6", "type": "fromSpecies", "arg1_id": "PMID-12724404_T31", "arg2_id": "PMID-12724404_T30", "normalized": [] }, { "id": "PMID-12724404_R7", "type": "hasPart", "arg1_id": "PMID-12724404_T43", "arg2_id": "PMID-12724404_T42", "normalized": [] }, { "id": "PMID-12724404_R8", "type": "hasPart", "arg1_id": "PMID-12724404_T44", "arg2_id": "PMID-12724404_T46", "normalized": [] }, { "id": "PMID-12724404_R10", "type": "hasPart", "arg1_id": "PMID-12724404_T52", "arg2_id": "PMID-12724404_T57", "normalized": [] }, { "id": "PMID-12724404_R11", "type": "hasFunction", "arg1_id": "PMID-12724404_T64", "arg2_id": "PMID-12724404_T63", "normalized": [] }, { "id": "PMID-12724404_R12", "type": "hasPart", "arg1_id": "PMID-12724404_T73", "arg2_id": "PMID-12724404_T71", "normalized": [] }, { "id": "PMID-12724404_R3", "type": "hasPart", "arg1_id": "PMID-12724404_T10", "arg2_id": "PMID-12724404_T11", "normalized": [] }, { "id": "PMID-12724404_R5", "type": "hasPart", "arg1_id": "PMID-12724404_T31", "arg2_id": "PMID-12724404_T29", "normalized": [] }, { "id": "PMID-12724404_R13", "type": "fromSpecies", "arg1_id": "PMID-12724404_T27", "arg2_id": "PMID-12724404_T28", "normalized": [] }, { "id": "PMID-12724404_R14", "type": "hasPart", "arg1_id": "PMID-12724404_T33", "arg2_id": "PMID-12724404_T32", "normalized": [] }, { "id": "PMID-12724404_R16", "type": "hasFunction", "arg1_id": "PMID-12724404_T46", "arg2_id": "PMID-12724404_T16", "normalized": [] }, { "id": "PMID-12724404_R9", "type": "hasFunction", "arg1_id": "PMID-12724404_T54", "arg2_id": "PMID-12724404_T35", "normalized": [] }, { "id": "PMID-12724404_R2", "type": "hasFunction", "arg1_id": "PMID-12724404_T6", "arg2_id": "PMID-12724404_T5", "normalized": [] }, { "id": "PMID-12724404_R17", "type": "hasPart", "arg1_id": "PMID-12724404_T36", "arg2_id": "PMID-12724404_T54", "normalized": [] }, { "id": "PMID-12724404_R18", "type": "hasPart", "arg1_id": "PMID-12724404_T52", "arg2_id": "PMID-12724404_T36", "normalized": [] } ]

[ { "id": "PMID-12761501__text", "type": "abstract", "text": [ "Large-scale identification and characterization of human genes that activate NF-kappaB and MAPK signaling pathways. We have carried out a large-scale identification and characterization of human genes that activate the NF-kappaB and MARK signaling pathways. We constructed full-length cDNA libraries using the oligo-capping method and prepared an arrayed cDNA pool consisting of 150 000 cDNAs randomly isolated from the libraries. For analysis of the NF-kappaB signaling pathway, we introduced each of the cDNAs into human embryonic kidney 293 cells and examined whether it activated the transcription of a luciferase reporter gene driven by a promoter containing the consensus NF-kappaB binding sites. In total, we identified 299 cDNAs that activate the NF-kappaB pathway, and we classified them into 83 genes, including 30 characterized activator genes of the NF-kappaB pathway, 28 genes whose involvement in the NF-kappaB pathways have not been characterized and 25 novel genes. We then carried out a similar analysis for the identification of genes that activate the MARK pathway, utilizing the same cDNA resource. We assayed 145 000 cDNAs and identified 57 genes that activate the MARK pathway. Interestingly, 27 genes were overlapping between the NF-kappaB and the MAPK pathways, which may indicate that these genes play cross-talking roles between these two pathways.\n" ], "offsets": [ [ 0, 1375 ] ] } ]

[ { "id": "PMID-12761501_T1", "type": "Eukaryote", "text": [ "human" ], "offsets": [ [ 51, 56 ] ], "normalized": [] }, { "id": "PMID-12761501_T2", "type": "Gene", "text": [ "genes" ], "offsets": [ [ 57, 62 ] ], "normalized": [] }, { "id": "PMID-12761501_T4", "type": "Protein", "text": [ "NF-kappaB" ], "offsets": [ [ 77, 86 ] ], "normalized": [] }, { "id": "PMID-12761501_T5", "type": "Protein", "text": [ "MAPK" ], "offsets": [ [ 91, 95 ] ], "normalized": [] }, { "id": "PMID-12761501_T7", "type": "Eukaryote", "text": [ "human" ], "offsets": [ [ 189, 194 ] ], "normalized": [] }, { "id": "PMID-12761501_T8", "type": "Gene", "text": [ "genes" ], "offsets": [ [ 195, 200 ] ], "normalized": [] }, { "id": "PMID-12761501_T10", "type": "Protein", "text": [ "NF-kappaB" ], "offsets": [ [ 219, 228 ] ], "normalized": [] }, { "id": "PMID-12761501_T11", "type": "Protein", "text": [ "MARK" ], "offsets": [ [ 233, 237 ] ], "normalized": [] }, { "id": "PMID-12761501_T13", "type": "DNA", "text": [ "cDNA libraries" ], "offsets": [ [ 285, 299 ] ], "normalized": [] }, { "id": "PMID-12761501_T14", "type": "DNA", "text": [ "cDNA pool" ], "offsets": [ [ 355, 364 ] ], "normalized": [] }, { "id": "PMID-12761501_T15", "type": "DNA", "text": [ "cDNAs" ], "offsets": [ [ 387, 392 ] ], "normalized": [] }, { "id": "PMID-12761501_T16", "type": "Protein", "text": [ "NF-kappaB" ], "offsets": [ [ 451, 460 ] ], "normalized": [] }, { "id": "PMID-12761501_T18", "type": "DNA", "text": [ "cDNAs" ], "offsets": [ [ 506, 511 ] ], "normalized": [] }, { "id": "PMID-12761501_T19", "type": "Eukaryote", "text": [ "human" ], "offsets": [ [ 517, 522 ] ], "normalized": [] }, { "id": "PMID-12761501_T24", "type": "ReporterGene", "text": [ "luciferase reporter gene" ], "offsets": [ [ 607, 631 ] ], "normalized": [] }, { "id": "PMID-12761501_T25", "type": "Promoter", "text": [ "promoter" ], "offsets": [ [ 644, 652 ] ], "normalized": [] }, { "id": "PMID-12761501_T26", "type": "ProteinBindingSiteOfDNA", "text": [ "NF-kappaB binding sites" ], "offsets": [ [ 678, 701 ] ], "normalized": [] }, { "id": "PMID-12761501_T27", "type": "DNA", "text": [ "cDNAs" ], "offsets": [ [ 731, 736 ] ], "normalized": [] }, { "id": "PMID-12761501_T29", "type": "Protein", "text": [ "NF-kappaB" ], "offsets": [ [ 755, 764 ] ], "normalized": [] }, { "id": "PMID-12761501_T31", "type": "Gene", "text": [ "genes" ], "offsets": [ [ 805, 810 ] ], "normalized": [] }, { "id": "PMID-12761501_T33", "type": "Gene", "text": [ "genes" ], "offsets": [ [ 849, 854 ] ], "normalized": [] }, { "id": "PMID-12761501_T34", "type": "Protein", "text": [ "NF-kappaB" ], "offsets": [ [ 862, 871 ] ], "normalized": [] }, { "id": "PMID-12761501_T36", "type": "Gene", "text": [ "genes" ], "offsets": [ [ 884, 889 ] ], "normalized": [] }, { "id": "PMID-12761501_T37", "type": "Protein", "text": [ "NF-kappaB" ], "offsets": [ [ 915, 924 ] ], "normalized": [] }, { "id": "PMID-12761501_T39", "type": "Gene", "text": [ "genes" ], "offsets": [ [ 975, 980 ] ], "normalized": [] }, { "id": "PMID-12761501_T40", "type": "Gene", "text": [ "genes" ], "offsets": [ [ 1047, 1052 ] ], "normalized": [] }, { "id": "PMID-12761501_T42", "type": "Protein", "text": [ "MARK" ], "offsets": [ [ 1071, 1075 ] ], "normalized": [] }, { "id": "PMID-12761501_T44", "type": "DNA", "text": [ "cDNA" ], "offsets": [ [ 1104, 1108 ] ], "normalized": [] }, { "id": "PMID-12761501_T45", "type": "DNA", "text": [ "cDNAs" ], "offsets": [ [ 1138, 1143 ] ], "normalized": [] }, { "id": "PMID-12761501_T46", "type": "Gene", "text": [ "genes" ], "offsets": [ [ 1162, 1167 ] ], "normalized": [] }, { "id": "PMID-12761501_T48", "type": "Protein", "text": [ "MARK" ], "offsets": [ [ 1186, 1190 ] ], "normalized": [] }, { "id": "PMID-12761501_T50", "type": "Gene", "text": [ "genes" ], "offsets": [ [ 1218, 1223 ] ], "normalized": [] }, { "id": "PMID-12761501_T51", "type": "Protein", "text": [ "NF-kappaB" ], "offsets": [ [ 1253, 1262 ] ], "normalized": [] }, { "id": "PMID-12761501_T52", "type": "Protein", "text": [ "MAPK" ], "offsets": [ [ 1271, 1275 ] ], "normalized": [] }, { "id": "PMID-12761501_T54", "type": "Gene", "text": [ "genes" ], "offsets": [ [ 1316, 1321 ] ], "normalized": [] }, { "id": "PMID-12761501_T20", "type": "Cell", "text": [ "embryonic kidney 293 cells" ], "offsets": [ [ 523, 549 ] ], "normalized": [] } ]

[ { "id": "PMID-12761501_E1", "type": "PositiveRegulation", "trigger": { "text": [ "activate" ], "offsets": [ [ 68, 76 ] ] }, "arguments": [ { "role": "hasAgent", "ref_id": "PMID-12761501_T2" }, { "role": "hasPatient", "ref_id": "PMID-12761501_E2" } ] }, { "id": "PMID-12761501_E2", "type": "SignalingPathway", "trigger": { "text": [ "signaling pathways" ], "offsets": [ [ 96, 114 ] ] }, "arguments": [] }, { "id": "PMID-12761501_E3", "type": "PositiveRegulation", "trigger": { "text": [ "activate" ], "offsets": [ [ 206, 214 ] ] }, "arguments": [ { "role": "hasAgent", "ref_id": "PMID-12761501_T8" }, { "role": "hasPatient", "ref_id": "PMID-12761501_E4" } ] }, { "id": "PMID-12761501_E4", "type": "SignalingPathway", "trigger": { "text": [ "signaling pathways" ], "offsets": [ [ 238, 256 ] ] }, "arguments": [] }, { "id": "PMID-12761501_E5", "type": "SignalingPathway", "trigger": { "text": [ "signaling pathway" ], "offsets": [ [ 461, 478 ] ] }, "arguments": [] }, { "id": "PMID-12761501_E6", "type": "PositiveRegulation", "trigger": { "text": [ "activated" ], "offsets": [ [ 574, 583 ] ] }, "arguments": [ { "role": "hasAgent", "ref_id": "PMID-12761501_T18" }, { "role": "hasPatient", "ref_id": "PMID-12761501_E7" } ] }, { "id": "PMID-12761501_E7", "type": "Transcription", "trigger": { "text": [ "transcription" ], "offsets": [ [ 588, 601 ] ] }, "arguments": [ { "role": "hasPatient", "ref_id": "PMID-12761501_T24" } ] }, { "id": "PMID-12761501_E8", "type": "PositiveRegulation", "trigger": { "text": [ "activate" ], "offsets": [ [ 742, 750 ] ] }, "arguments": [ { "role": "hasAgent", "ref_id": "PMID-12761501_T27" }, { "role": "hasPatient", "ref_id": "PMID-12761501_E9" } ] }, { "id": "PMID-12761501_E9", "type": "SignalingPathway", "trigger": { "text": [ "pathway" ], "offsets": [ [ 765, 772 ] ] }, "arguments": [] }, { "id": "PMID-12761501_E10", "type": "PositiveRegulation", "trigger": { "text": [ "activator" ], "offsets": [ [ 839, 848 ] ] }, "arguments": [ { "role": "hasAgent", "ref_id": "PMID-12761501_T33" }, { "role": "hasPatient", "ref_id": "PMID-12761501_E11" } ] }, { "id": "PMID-12761501_E11", "type": "SignalingPathway", "trigger": { "text": [ "pathway" ], "offsets": [ [ 872, 879 ] ] }, "arguments": [] }, { "id": "PMID-12761501_E12", "type": "SignalingPathway", "trigger": { "text": [ "pathways" ], "offsets": [ [ 925, 933 ] ] }, "arguments": [] }, { "id": "PMID-12761501_E13", "type": "PositiveRegulation", "trigger": { "text": [ "activate" ], "offsets": [ [ 1058, 1066 ] ] }, "arguments": [ { "role": "hasAgent", "ref_id": "PMID-12761501_T40" }, { "role": "hasPatient", "ref_id": "PMID-12761501_E14" } ] }, { "id": "PMID-12761501_E14", "type": "SignalingPathway", "trigger": { "text": [ "pathway" ], "offsets": [ [ 1076, 1083 ] ] }, "arguments": [] }, { "id": "PMID-12761501_E15", "type": "PositiveRegulation", "trigger": { "text": [ "activate" ], "offsets": [ [ 1173, 1181 ] ] }, "arguments": [ { "role": "hasAgent", "ref_id": "PMID-12761501_T46" }, { "role": "hasPatient", "ref_id": "PMID-12761501_E16" } ] }, { "id": "PMID-12761501_E16", "type": "SignalingPathway", "trigger": { "text": [ "pathway" ], "offsets": [ [ 1191, 1198 ] ] }, "arguments": [] }, { "id": "PMID-12761501_E17", "type": "SignalingPathway", "trigger": { "text": [ "pathways" ], "offsets": [ [ 1276, 1284 ] ] }, "arguments": [] }, { "id": "PMID-12761501_E18", "type": "SignalingPathway", "trigger": { "text": [ "pathways" ], "offsets": [ [ 1365, 1373 ] ] }, "arguments": [] } ]

[]

[ { "id": "PMID-12761501_R1", "type": "fromSpecies", "arg1_id": "PMID-12761501_T2", "arg2_id": "PMID-12761501_T1", "normalized": [] }, { "id": "PMID-12761501_R2", "type": "fromSpecies", "arg1_id": "PMID-12761501_T8", "arg2_id": "PMID-12761501_T7", "normalized": [] }, { "id": "PMID-12761501_R6", "type": "hasPart", "arg1_id": "PMID-12761501_T24", "arg2_id": "PMID-12761501_T25", "normalized": [] }, { "id": "PMID-12761501_R7", "type": "hasPart", "arg1_id": "PMID-12761501_T25", "arg2_id": "PMID-12761501_T26", "normalized": [] }, { "id": "PMID-12761501_R3", "type": "fromSpecies", "arg1_id": "PMID-12761501_T20", "arg2_id": "PMID-12761501_T19", "normalized": [] }, { "id": "PMID-12761501_R4", "type": "locatedIn", "arg1_id": "PMID-12761501_T18", "arg2_id": "PMID-12761501_T20", "normalized": [] } ]

[ { "id": "PMID-1346761__text", "type": "abstract", "text": [ "The upstream region of the human homeobox gene HOX3D is a target for regulation by retinoic acid and HOX homeoproteins. We studied the structure, regulation and expression of HOX3D, a human homeobox gene located in the HOX3 cluster on chromosome 12. HOX3D is developmentally regulated during embryogenesis and is activated by retinoic acid (RA) in cultured embryonal carcinoma (EC) cells. Transfection of HOX3D upstream genomic sequences linked to a reporter gene allowed the functional definition of its promoter, containing a canonical TATA element. This promoter directs the expression of the reporter gene in EC cells after induction with RA, and binds RA-induced nuclear factor(s) through a conserved palindromic sequence located approximately 100 bp upstream of the transcription start site. The HOX3D promoter is transactivated in both human and murine cells when cotransfected with vectors expressing the protein product of the upstream gene HOX3C and the paralogs of further upstream genes in the HOX4 cluster (i.e. HOX4D, HOX4C and the murine Hox 4.3). The HOX3D protein, and those encoded by the downstream gene HOX3E and its paralog HOX4B are instead inactive. HOX4C and HOX4D proteins synthesized in bacteria bind to the same conserved sequence located around position -120, as well as to the TATA box and immediately upstream and downstream nucleotides. These data provide evidence that cross-regulatory interactions between mammalian homeogenes take place in cultured cells, thus raising the possibility that a regulatory network may exist in vivo. The sequences on the HOX3D promoter involved in cross-regulation are different from those binding nuclear factors induced by RA.\n" ], "offsets": [ [ 0, 1693 ] ] } ]

[ { "id": "PMID-1346761_T1", "type": "UpstreamRegulatorySequence", "text": [ "upstream region" ], "offsets": [ [ 4, 19 ] ], "normalized": [] }, { "id": "PMID-1346761_T2", "type": "Eukaryote", "text": [ "human" ], "offsets": [ [ 27, 32 ] ], "normalized": [] }, { "id": "PMID-1346761_T3", "type": "Gene", "text": [ "homeobox gene HOX3D" ], "offsets": [ [ 33, 52 ] ], "normalized": [] }, { "id": "PMID-1346761_T5", "type": "OrganicChemical", "text": [ "retinoic acid" ], "offsets": [ [ 83, 96 ] ], "normalized": [] }, { "id": "PMID-1346761_T6", "type": "HomeoboxTF", "text": [ "HOX homeoproteins" ], "offsets": [ [ 101, 118 ] ], "normalized": [] }, { "id": "PMID-1346761_T9", "type": "Gene", "text": [ "HOX3D" ], "offsets": [ [ 175, 180 ] ], "normalized": [] }, { "id": "PMID-1346761_T10", "type": "Eukaryote", "text": [ "human" ], "offsets": [ [ 184, 189 ] ], "normalized": [] }, { "id": "PMID-1346761_T11", "type": "Gene", "text": [ "homeobox gene" ], "offsets": [ [ 190, 203 ] ], "normalized": [] }, { "id": "PMID-1346761_T12", "type": "DNARegion", "text": [ "HOX3 cluster" ], "offsets": [ [ 219, 231 ] ], "normalized": [] }, { "id": "PMID-1346761_T13", "type": "Chromosome", "text": [ "chromosome 12" ], "offsets": [ [ 235, 248 ] ], "normalized": [] }, { "id": "PMID-1346761_T14", "type": "Gene", "text": [ "HOX3D" ], "offsets": [ [ 250, 255 ] ], "normalized": [] }, { "id": "PMID-1346761_T18", "type": "OrganicChemical", "text": [ "RA" ], "offsets": [ [ 341, 343 ] ], "normalized": [] }, { "id": "PMID-1346761_T21", "type": "ExperimentalMethod", "text": [ "Transfection" ], "offsets": [ [ 389, 401 ] ], "normalized": [] }, { "id": "PMID-1346761_T22", "type": "Gene", "text": [ "HOX3D" ], "offsets": [ [ 405, 410 ] ], "normalized": [] }, { "id": "PMID-1346761_T23", "type": "UpstreamRegulatorySequence", "text": [ "upstream genomic sequences" ], "offsets": [ [ 411, 437 ] ], "normalized": [] }, { "id": "PMID-1346761_T24", "type": "ReporterGene", "text": [ "reporter gene" ], "offsets": [ [ 450, 463 ] ], "normalized": [] }, { "id": "PMID-1346761_T25", "type": "Promoter", "text": [ "promoter" ], "offsets": [ [ 505, 513 ] ], "normalized": [] }, { "id": "PMID-1346761_T26", "type": "TATAbox", "text": [ "TATA element" ], "offsets": [ [ 538, 550 ] ], "normalized": [] }, { "id": "PMID-1346761_T27", "type": "Promoter", "text": [ "promoter" ], "offsets": [ [ 557, 565 ] ], "normalized": [] }, { "id": "PMID-1346761_T30", "type": "ReporterGene", "text": [ "reporter gene" ], "offsets": [ [ 596, 609 ] ], "normalized": [] }, { "id": "PMID-1346761_T34", "type": "OrganicChemical", "text": [ "RA" ], "offsets": [ [ 643, 645 ] ], "normalized": [] }, { "id": "PMID-1346761_T36", "type": "OrganicChemical", "text": [ "RA" ], "offsets": [ [ 657, 659 ] ], "normalized": [] }, { "id": "PMID-1346761_T38", "type": "Protein", "text": [ "nuclear factor(s)" ], "offsets": [ [ 668, 685 ] ], "normalized": [] }, { "id": "PMID-1346761_T39", "type": "UpstreamRegulatorySequence", "text": [ "palindromic sequence" ], "offsets": [ [ 706, 726 ] ], "normalized": [] }, { "id": "PMID-1346761_T41", "type": "Gene", "text": [ "HOX3D" ], "offsets": [ [ 802, 807 ] ], "normalized": [] }, { "id": "PMID-1346761_T42", "type": "Promoter", "text": [ "promoter" ], "offsets": [ [ 808, 816 ] ], "normalized": [] }, { "id": "PMID-1346761_T44", "type": "Eukaryote", "text": [ "human" ], "offsets": [ [ 843, 848 ] ], "normalized": [] }, { "id": "PMID-1346761_T45", "type": "Eukaryote", "text": [ "murine" ], "offsets": [ [ 853, 859 ] ], "normalized": [] }, { "id": "PMID-1346761_T46", "type": "Cell", "text": [ "cells" ], "offsets": [ [ 860, 865 ] ], "normalized": [] }, { "id": "PMID-1346761_T47", "type": "ExperimentalMethod", "text": [ "cotransfected" ], "offsets": [ [ 871, 884 ] ], "normalized": [] }, { "id": "PMID-1346761_T48", "type": "DNA", "text": [ "vectors" ], "offsets": [ [ 890, 897 ] ], "normalized": [] }, { "id": "PMID-1346761_T50", "type": "Protein", "text": [ "protein" ], "offsets": [ [ 913, 920 ] ], "normalized": [] }, { "id": "PMID-1346761_T52", "type": "Gene", "text": [ "HOX3C" ], "offsets": [ [ 950, 955 ] ], "normalized": [] }, { "id": "PMID-1346761_T53", "type": "Gene", "text": [ "HOX4" ], "offsets": [ [ 1006, 1010 ] ], "normalized": [] }, { "id": "PMID-1346761_T54", "type": "Gene", "text": [ "HOX4D" ], "offsets": [ [ 1025, 1030 ] ], "normalized": [] }, { "id": "PMID-1346761_T55", "type": "Gene", "text": [ "HOX4C" ], "offsets": [ [ 1032, 1037 ] ], "normalized": [] }, { "id": "PMID-1346761_T56", "type": "Eukaryote", "text": [ "murine" ], "offsets": [ [ 1046, 1052 ] ], "normalized": [] }, { "id": "PMID-1346761_T57", "type": "Gene", "text": [ "Hox 4.3" ], "offsets": [ [ 1053, 1060 ] ], "normalized": [] }, { "id": "PMID-1346761_T58", "type": "Protein", "text": [ "HOX3D protein" ], "offsets": [ [ 1067, 1080 ] ], "normalized": [] }, { "id": "PMID-1346761_T59", "type": "Gene", "text": [ "HOX3E" ], "offsets": [ [ 1123, 1128 ] ], "normalized": [] }, { "id": "PMID-1346761_T60", "type": "Gene", "text": [ "HOX4B" ], "offsets": [ [ 1145, 1150 ] ], "normalized": [] }, { "id": "PMID-1346761_T63", "type": "Protein", "text": [ "HOX4D proteins" ], "offsets": [ [ 1183, 1197 ] ], "normalized": [] }, { "id": "PMID-1346761_T64", "type": "Prokaryote", "text": [ "bacteria" ], "offsets": [ [ 1213, 1221 ] ], "normalized": [] }, { "id": "PMID-1346761_T66", "type": "Sequence", "text": [ "sequence" ], "offsets": [ [ 1249, 1257 ] ], "normalized": [] }, { "id": "PMID-1346761_T67", "type": "TATAbox", "text": [ "TATA box" ], "offsets": [ [ 1306, 1314 ] ], "normalized": [] }, { "id": "PMID-1346761_T69", "type": "Eukaryote", "text": [ "mammalian" ], "offsets": [ [ 1439, 1448 ] ], "normalized": [] }, { "id": "PMID-1346761_T70", "type": "HomeoboxTF", "text": [ "homeogenes" ], "offsets": [ [ 1449, 1459 ] ], "normalized": [] }, { "id": "PMID-1346761_T71", "type": "Cell", "text": [ "cells" ], "offsets": [ [ 1483, 1488 ] ], "normalized": [] }, { "id": "PMID-1346761_T72", "type": "Gene", "text": [ "HOX3D" ], "offsets": [ [ 1585, 1590 ] ], "normalized": [] }, { "id": "PMID-1346761_T73", "type": "Promoter", "text": [ "promoter" ], "offsets": [ [ 1591, 1599 ] ], "normalized": [] }, { "id": "PMID-1346761_T76", "type": "Protein", "text": [ "nuclear factors" ], "offsets": [ [ 1662, 1677 ] ], "normalized": [] }, { "id": "PMID-1346761_T78", "type": "OrganicChemical", "text": [ "RA" ], "offsets": [ [ 1689, 1691 ] ], "normalized": [] }, { "id": "PMID-1346761_T19", "type": "Cell", "text": [ "EC" ], "offsets": [ [ 378, 380 ] ], "normalized": [] }, { "id": "PMID-1346761_T20", "type": "Cell", "text": [ "EC cells" ], "offsets": [ [ 613, 621 ] ], "normalized": [] }, { "id": "PMID-1346761_T31", "type": "Protein", "text": [ "paralogs" ], "offsets": [ [ 964, 972 ] ], "normalized": [] }, { "id": "PMID-1346761_T32", "type": "Protein", "text": [ "HOX4C" ], "offsets": [ [ 1173, 1178 ] ], "normalized": [] } ]

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[]

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[ { "id": "PMID-1354641__text", "type": "abstract", "text": [ "DLX2 (TES1), a homeobox gene of the Distal-less family, assigned to conserved regions on human and mouse chromosomes 2. Dlx-2 (also called Tes-1), a mammalian member of the Distal-less family of homeobox genes, is expressed during murine fetal development in spatially restricted domains of the forebrain. Searching for a candidate neurological mutation that might involve this gene, we have assigned the human and mouse loci to regions of conserved synteny on human chromosome 2, region cen--q33, and mouse chromosome 2 by Southern analysis of somatic cell hybrid lines. An EcoRI dimorphism, discovered in common inbred laboratory strains, was used for recombinant inbred strain mapping. The results place Dlx-2/Tes-1 near the Hox-4 cluster on mouse chromosome 2.\n" ], "offsets": [ [ 0, 765 ] ] } ]

[ { "id": "PMID-1354641_T1", "type": "HomeoboxTF", "text": [ "DLX2 (TES1)" ], "offsets": [ [ 0, 11 ] ], "normalized": [] }, { "id": "PMID-1354641_T2", "type": "HomeoboxTF", "text": [ "homeobox gene" ], "offsets": [ [ 15, 28 ] ], "normalized": [] }, { "id": "PMID-1354641_T3", "type": "Gene", "text": [ "Distal-less family" ], "offsets": [ [ 36, 54 ] ], "normalized": [] }, { "id": "PMID-1354641_T4", "type": "Eukaryote", "text": [ "human" ], "offsets": [ [ 89, 94 ] ], "normalized": [] }, { "id": "PMID-1354641_T5", "type": "Eukaryote", "text": [ "mouse" ], "offsets": [ [ 99, 104 ] ], "normalized": [] }, { "id": "PMID-1354641_T6", "type": "Chromosome", "text": [ "chromosomes 2" ], "offsets": [ [ 105, 118 ] ], "normalized": [] }, { "id": "PMID-1354641_T7", "type": "HomeoboxTF", "text": [ "Dlx-2" ], "offsets": [ [ 120, 125 ] ], "normalized": [] }, { "id": "PMID-1354641_T8", "type": "HomeoboxTF", "text": [ "Tes-1" ], "offsets": [ [ 139, 144 ] ], "normalized": [] }, { "id": "PMID-1354641_T9", "type": "Eukaryote", "text": [ "mammalian" ], "offsets": [ [ 149, 158 ] ], "normalized": [] }, { "id": "PMID-1354641_T10", "type": "Gene", "text": [ "Distal-less family" ], "offsets": [ [ 173, 191 ] ], "normalized": [] }, { "id": "PMID-1354641_T11", "type": "HomeoboxTF", "text": [ "homeobox genes" ], "offsets": [ [ 195, 209 ] ], "normalized": [] }, { "id": "PMID-1354641_T13", "type": "Eukaryote", "text": [ "murine" ], "offsets": [ [ 231, 237 ] ], "normalized": [] }, { "id": "PMID-1354641_T15", "type": "Tissue", "text": [ "forebrain" ], "offsets": [ [ 295, 304 ] ], "normalized": [] }, { "id": "PMID-1354641_T16", "type": "Eukaryote", "text": [ "human" ], "offsets": [ [ 405, 410 ] ], "normalized": [] }, { "id": "PMID-1354641_T17", "type": "Eukaryote", "text": [ "mouse" ], "offsets": [ [ 415, 420 ] ], "normalized": [] }, { "id": "PMID-1354641_T18", "type": "Locus", "text": [ "loci" ], "offsets": [ [ 421, 425 ] ], "normalized": [] }, { "id": "PMID-1354641_T19", "type": "Eukaryote", "text": [ "human" ], "offsets": [ [ 461, 466 ] ], "normalized": [] }, { "id": "PMID-1354641_T20", "type": "Chromosome", "text": [ "chromosome 2" ], "offsets": [ [ 467, 479 ] ], "normalized": [] }, { "id": "PMID-1354641_T21", "type": "ChromosomalDNA", "text": [ "region cen--q33" ], "offsets": [ [ 481, 496 ] ], "normalized": [] }, { "id": "PMID-1354641_T22", "type": "Eukaryote", "text": [ "mouse" ], "offsets": [ [ 502, 507 ] ], "normalized": [] }, { "id": "PMID-1354641_T23", "type": "Chromosome", "text": [ "chromosome 2" ], "offsets": [ [ 508, 520 ] ], "normalized": [] }, { "id": "PMID-1354641_T24", "type": "Cell", "text": [ "somatic cell" ], "offsets": [ [ 545, 557 ] ], "normalized": [] }, { "id": "PMID-1354641_T25", "type": "Enzyme", "text": [ "EcoRI" ], "offsets": [ [ 575, 580 ] ], "normalized": [] }, { "id": "PMID-1354641_T26", "type": "HomeoboxTF", "text": [ "Dlx-2/Tes-1" ], "offsets": [ [ 707, 718 ] ], "normalized": [] }, { "id": "PMID-1354641_T27", "type": "HomeoboxTF", "text": [ "Hox-4" ], "offsets": [ [ 728, 733 ] ], "normalized": [] }, { "id": "PMID-1354641_T28", "type": "Eukaryote", "text": [ "mouse" ], "offsets": [ [ 745, 750 ] ], "normalized": [] }, { "id": "PMID-1354641_T29", "type": "Chromosome", "text": [ "chromosome 2" ], "offsets": [ [ 751, 763 ] ], "normalized": [] }, { "id": "PMID-1354641_T31", "type": "Tissue", "text": [ "neurological" ], "offsets": [ [ 332, 344 ] ], "normalized": [] } ]

[ { "id": "PMID-1354641_E1", "type": "GeneExpression", "trigger": { "text": [ "expressed" ], "offsets": [ [ 214, 223 ] ] }, "arguments": [ { "role": "hasPatient", "ref_id": "PMID-1354641_T7" } ] }, { "id": "PMID-1354641_E2", "type": "DevelopmentalProcess", "trigger": { "text": [ "fetal development" ], "offsets": [ [ 238, 255 ] ] }, "arguments": [] }, { "id": "PMID-1354641_E3", "type": "Mutation", "trigger": { "text": [ "mutation" ], "offsets": [ [ 345, 353 ] ] }, "arguments": [ { "role": "hasPatient", "ref_id": "PMID-1354641_T31" } ] } ]

[]

[ { "id": "PMID-1354641_R1", "type": "fromSpecies", "arg1_id": "PMID-1354641_T6", "arg2_id": "PMID-1354641_T4", "normalized": [] }, { "id": "PMID-1354641_R2", "type": "fromSpecies", "arg1_id": "PMID-1354641_T6", "arg2_id": "PMID-1354641_T5", "normalized": [] }, { "id": "PMID-1354641_R3", "type": "fromSpecies", "arg1_id": "PMID-1354641_T7", "arg2_id": "PMID-1354641_T9", "normalized": [] }, { "id": "PMID-1354641_R5", "type": "locatedIn", "arg1_id": "PMID-1354641_T18", "arg2_id": "PMID-1354641_T21", "normalized": [] }, { "id": "PMID-1354641_R6", "type": "locatedIn", "arg1_id": "PMID-1354641_T18", "arg2_id": "PMID-1354641_T23", "normalized": [] }, { "id": "PMID-1354641_R7", "type": "fromSpecies", "arg1_id": "PMID-1354641_T18", "arg2_id": "PMID-1354641_T16", "normalized": [] }, { "id": "PMID-1354641_R8", "type": "fromSpecies", "arg1_id": "PMID-1354641_T18", "arg2_id": "PMID-1354641_T17", "normalized": [] }, { "id": "PMID-1354641_R9", "type": "fromSpecies", "arg1_id": "PMID-1354641_T20", "arg2_id": "PMID-1354641_T19", "normalized": [] }, { "id": "PMID-1354641_R10", "type": "hasPart", "arg1_id": "PMID-1354641_T20", "arg2_id": "PMID-1354641_T21", "normalized": [] }, { "id": "PMID-1354641_R11", "type": "fromSpecies", "arg1_id": "PMID-1354641_T23", "arg2_id": "PMID-1354641_T22", "normalized": [] }, { "id": "PMID-1354641_R12", "type": "locatedIn", "arg1_id": "PMID-1354641_T26", "arg2_id": "PMID-1354641_T29", "normalized": [] }, { "id": "PMID-1354641_R13", "type": "locatedIn", "arg1_id": "PMID-1354641_T27", "arg2_id": "PMID-1354641_T29", "normalized": [] }, { "id": "PMID-1354641_R14", "type": "fromSpecies", "arg1_id": "PMID-1354641_T29", "arg2_id": "PMID-1354641_T28", "normalized": [] }, { "id": "PMID-1354641_R15", "type": "locatedIn", "arg1_id": "PMID-1354641_T1", "arg2_id": "PMID-1354641_T6", "normalized": [] } ]

[ { "id": "PMID-1394192__text", "type": "abstract", "text": [ "A region of antisense RNA from human p120 cDNA with high homology to mouse p120 cDNA inhibits NIH 3T3 proliferation. The human nucleolar p120 protein is a proliferation-associated antigen which is expressed in G1 and peaks during the early S phase of the cell cycle. Overexpression of the human p120 protein caused the transformation of NIH 3T3 cells and expression of an antisense p120 construct inhibited the growth of NIH 3T3 cells (Perlaky et al., Cancer Res., 52:428-436, 1992). The middle region of the antisense p120 RNA was found to be almost as inhibitory as the full length antisense construct but the 5' and 3' antisense portions did not affect NIH 3T3 cell proliferation. After the mouse p120 complementary DNA was cloned and sequenced, comparison with the human p120 complementary DNA showed a striking conservation of 85% of the nucleotide sequence and 96% of the amino acid sequence. The two ends of the p120 molecule had less homology in their nucleotide and amino acid sequences. Based on this homology, the observed inhibitory effects of the middle portion of antisense human p120 RNA may be related to suppression of mouse p120 expression by RNA:RNA duplex formation. The high evolutionary conservation of the middle region suggests it has a critical role for the function of this protein.\n" ], "offsets": [ [ 0, 1309 ] ] } ]

[ { "id": "PMID-1394192_T1", "type": "AntisenseRNA", "text": [ "antisense RNA" ], "offsets": [ [ 12, 25 ] ], "normalized": [] }, { "id": "PMID-1394192_T2", "type": "Eukaryote", "text": [ "human" ], "offsets": [ [ 31, 36 ] ], "normalized": [] }, { "id": "PMID-1394192_T3", "type": "Protein", "text": [ "p120" ], "offsets": [ [ 37, 41 ] ], "normalized": [] }, { "id": "PMID-1394192_T4", "type": "DNA", "text": [ "cDNA" ], "offsets": [ [ 42, 46 ] ], "normalized": [] }, { "id": "PMID-1394192_T5", "type": "Eukaryote", "text": [ "mouse" ], "offsets": [ [ 69, 74 ] ], "normalized": [] }, { "id": "PMID-1394192_T6", "type": "Protein", "text": [ "p120" ], "offsets": [ [ 75, 79 ] ], "normalized": [] }, { "id": "PMID-1394192_T7", "type": "DNA", "text": [ "cDNA" ], "offsets": [ [ 80, 84 ] ], "normalized": [] }, { "id": "PMID-1394192_T9", "type": "Cell", "text": [ "NIH 3T3" ], "offsets": [ [ 94, 101 ] ], "normalized": [] }, { "id": "PMID-1394192_T11", "type": "Eukaryote", "text": [ "human" ], "offsets": [ [ 121, 126 ] ], "normalized": [] }, { "id": "PMID-1394192_T12", "type": "Nucleus", "text": [ "nucleolar" ], "offsets": [ [ 127, 136 ] ], "normalized": [] }, { "id": "PMID-1394192_T21", "type": "Eukaryote", "text": [ "human" ], "offsets": [ [ 289, 294 ] ], "normalized": [] }, { "id": "PMID-1394192_T24", "type": "Cell", "text": [ "NIH 3T3 cells" ], "offsets": [ [ 337, 350 ] ], "normalized": [] }, { "id": "PMID-1394192_T26", "type": "Gene", "text": [ "p120" ], "offsets": [ [ 382, 386 ] ], "normalized": [] }, { "id": "PMID-1394192_T29", "type": "Cell", "text": [ "NIH 3T3 cells" ], "offsets": [ [ 421, 434 ] ], "normalized": [] }, { "id": "PMID-1394192_T30", "type": "AntisenseRNA", "text": [ "antisense p120 RNA" ], "offsets": [ [ 509, 527 ] ], "normalized": [] }, { "id": "PMID-1394192_T32", "type": "Eukaryote", "text": [ "mouse" ], "offsets": [ [ 694, 699 ] ], "normalized": [] }, { "id": "PMID-1394192_T33", "type": "Gene", "text": [ "p120" ], "offsets": [ [ 700, 704 ] ], "normalized": [] }, { "id": "PMID-1394192_T34", "type": "DNA", "text": [ "complementary DNA" ], "offsets": [ [ 705, 722 ] ], "normalized": [] }, { "id": "PMID-1394192_T35", "type": "Eukaryote", "text": [ "human" ], "offsets": [ [ 769, 774 ] ], "normalized": [] }, { "id": "PMID-1394192_T36", "type": "Gene", "text": [ "p120" ], "offsets": [ [ 775, 779 ] ], "normalized": [] }, { "id": "PMID-1394192_T37", "type": "DNA", "text": [ "complementary DNA" ], "offsets": [ [ 780, 797 ] ], "normalized": [] }, { "id": "PMID-1394192_T38", "type": "Nucleotide", "text": [ "nucleotide sequence" ], "offsets": [ [ 843, 862 ] ], "normalized": [] }, { "id": "PMID-1394192_T39", "type": "AminoAcid", "text": [ "amino acid sequence" ], "offsets": [ [ 878, 897 ] ], "normalized": [] }, { "id": "PMID-1394192_T42", "type": "AminoAcid", "text": [ "amino acid sequences" ], "offsets": [ [ 975, 995 ] ], "normalized": [] }, { "id": "PMID-1394192_T43", "type": "AntisenseRNA", "text": [ "antisense human p120 RNA" ], "offsets": [ [ 1078, 1102 ] ], "normalized": [] }, { "id": "PMID-1394192_T47", "type": "Eukaryote", "text": [ "mouse" ], "offsets": [ [ 1136, 1141 ] ], "normalized": [] }, { "id": "PMID-1394192_T48", "type": "Gene", "text": [ "p120" ], "offsets": [ [ 1142, 1146 ] ], "normalized": [] }, { "id": "PMID-1394192_T50", "type": "Protein", "text": [ "this protein" ], "offsets": [ [ 1295, 1307 ] ], "normalized": [] }, { "id": "PMID-1394192_T13", "type": "Protein", "text": [ "p120 protein" ], "offsets": [ [ 137, 149 ] ], "normalized": [] }, { "id": "PMID-1394192_T14", "type": "Protein", "text": [ "p120 protein" ], "offsets": [ [ 295, 307 ] ], "normalized": [] }, { "id": "PMID-1394192_T22", "type": "AntisenseRNA", "text": [ "antisense" ], "offsets": [ [ 372, 381 ] ], "normalized": [] }, { "id": "PMID-1394192_T31", "type": "Cell", "text": [ "NIH 3T3 cell" ], "offsets": [ [ 656, 668 ] ], "normalized": [] }, { "id": "PMID-1394192_T40", "type": "DNAMolecule", "text": [ "p120 molecule" ], "offsets": [ [ 919, 932 ] ], "normalized": [] }, { "id": "PMID-1394192_T41", "type": "Nucleotide", "text": [ "nucleotide" ], "offsets": [ [ 960, 970 ] ], "normalized": [] } ]

[ { "id": "PMID-1394192_E1", "type": "NegativeRegulation", "trigger": { "text": [ "inhibits" ], "offsets": [ [ 85, 93 ] ] }, "arguments": [ { "role": "hasAgent", "ref_id": "PMID-1394192_T1" }, { "role": "hasPatient", "ref_id": "PMID-1394192_E2" } ] }, { "id": "PMID-1394192_E2", "type": "CellGrowth", "trigger": { "text": [ "proliferation" ], "offsets": [ [ 102, 115 ] ] }, "arguments": [ { "role": "hasPatient", "ref_id": "PMID-1394192_T9" } ] }, { "id": "PMID-1394192_E3", "type": "CellGrowth", "trigger": { "text": [ "proliferation" ], "offsets": [ [ 155, 168 ] ] }, "arguments": [] }, { "id": "PMID-1394192_E4", "type": "GeneExpression", "trigger": { "text": [ "expressed" ], "offsets": [ [ 197, 206 ] ] }, "arguments": [ { "role": "hasPatient", "ref_id": "PMID-1394192_T13" } ] }, { "id": "PMID-1394192_E5", "type": "G1Phase", "trigger": { "text": [ "G1" ], "offsets": [ [ 210, 212 ] ] }, "arguments": [] }, { "id": "PMID-1394192_E6", "type": "SPhase", "trigger": { "text": [ "early S phase" ], "offsets": [ [ 234, 247 ] ] }, "arguments": [] }, { "id": "PMID-1394192_E7", "type": "CellCycle", "trigger": { "text": [ "cell cycle" ], "offsets": [ [ 255, 265 ] ] }, "arguments": [] }, { "id": "PMID-1394192_E8", "type": "PositiveRegulationOfGeneExpression", "trigger": { "text": [ "Overexpression" ], "offsets": [ [ 267, 281 ] ] }, "arguments": [ { "role": "hasPatient", "ref_id": "PMID-1394192_T14" } ] }, { "id": "PMID-1394192_E9", "type": "GeneExpression", "trigger": { "text": [ "expression" ], "offsets": [ [ 355, 365 ] ] }, "arguments": [ { "role": "hasPatient", "ref_id": "PMID-1394192_T22" } ] }, { "id": "PMID-1394192_E10", "type": "NegativeRegulation", "trigger": { "text": [ "inhibited" ], "offsets": [ [ 397, 406 ] ] }, "arguments": [ { "role": "hasAgent", "ref_id": "PMID-1394192_E9" }, { "role": "hasPatient", "ref_id": "PMID-1394192_E11" } ] }, { "id": "PMID-1394192_E11", "type": "CellGrowth", "trigger": { "text": [ "growth" ], "offsets": [ [ 411, 417 ] ] }, "arguments": [ { "role": "hasPatient", "ref_id": "PMID-1394192_T29" } ] }, { "id": "PMID-1394192_E12", "type": "NegativeRegulation", "trigger": { "text": [ "suppression" ], "offsets": [ [ 1121, 1132 ] ] }, "arguments": [ { "role": "hasAgent", "ref_id": "PMID-1394192_T43" }, { "role": "hasPatient", "ref_id": "PMID-1394192_E13" } ] }, { "id": "PMID-1394192_E13", "type": "GeneExpression", "trigger": { "text": [ "expression" ], "offsets": [ [ 1147, 1157 ] ] }, "arguments": [ { "role": "hasPatient", "ref_id": "PMID-1394192_T48" } ] }, { "id": "PMID-1394192_E14", "type": "NegativeRegulation", "trigger": { "text": [ "inhibitory" ], "offsets": [ [ 554, 564 ] ] }, "arguments": [] }, { "id": "PMID-1394192_E15", "type": "CellGrowth", "trigger": { "text": [ "proliferation" ], "offsets": [ [ 669, 682 ] ] }, "arguments": [ { "role": "hasPatient", "ref_id": "PMID-1394192_T31" } ] }, { "id": "PMID-1394192_E16", "type": "NegativeRegulation", "trigger": { "text": [ "inhibitory" ], "offsets": [ [ 1034, 1044 ] ] }, "arguments": [] }, { "id": "PMID-1394192_E17", "type": "BindingToRNA", "trigger": { "text": [ "RNA:RNA duplex formation" ], "offsets": [ [ 1161, 1185 ] ] }, "arguments": [] } ]

[]

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[ { "id": "PMID-1406622__text", "type": "abstract", "text": [ "Characterization of Spi-B, a transcription factor related to the putative oncoprotein Spi-1/PU.1. We have cloned a human cDNA from a new gene, spi-B, on the basis of its homology with the DNA-binding domain of the Spi-1/PU.1 putative oncogene product. spi-B codes for a protein of 262 amino acids presenting 43% overall identity with Spi-1. Its highly basic carboxy-terminal region exhibits 34% sequence identity with the DNA-binding domain of the Ets-1 protein. We showed that the Spi-B protein is able to bind the purine-rich sequence (PU box) recognized by Spi-1/PU.1 and to activate transcription of a reporter plasmid containing PU boxes. Chromosome in situ hybridization allowed us to map spi-B to the 19q13.3-19q13.4 region of the human genome. spi-B, like spi-1, was found to be expressed in various murine and human hematopoietic cell lines except T lymphoid cell lines.\n" ], "offsets": [ [ 0, 880 ] ] } ]

[ { "id": "PMID-1406622_T1", "type": "TranscriptionFactor", "text": [ "Spi-B" ], "offsets": [ [ 20, 25 ] ], "normalized": [] }, { "id": "PMID-1406622_T2", "type": "TranscriptionFactor", "text": [ "transcription factor" ], "offsets": [ [ 29, 49 ] ], "normalized": [] }, { "id": "PMID-1406622_T3", "type": "Protein", "text": [ "oncoprotein Spi-1/PU.1" ], "offsets": [ [ 74, 96 ] ], "normalized": [] }, { "id": "PMID-1406622_T4", "type": "Eukaryote", "text": [ "human" ], "offsets": [ [ 115, 120 ] ], "normalized": [] }, { "id": "PMID-1406622_T5", "type": "DNA", "text": [ "cDNA" ], "offsets": [ [ 121, 125 ] ], "normalized": [] }, { "id": "PMID-1406622_T6", "type": "Gene", "text": [ "gene" ], "offsets": [ [ 137, 141 ] ], "normalized": [] }, { "id": "PMID-1406622_T7", "type": "Gene", "text": [ "spi-B" ], "offsets": [ [ 143, 148 ] ], "normalized": [] }, { "id": "PMID-1406622_T8", "type": "DNABindingDomainOfProtein", "text": [ "DNA-binding domain" ], "offsets": [ [ 188, 206 ] ], "normalized": [] }, { "id": "PMID-1406622_T9", "type": "Gene", "text": [ "Spi-1/PU.1" ], "offsets": [ [ 214, 224 ] ], "normalized": [] }, { "id": "PMID-1406622_T10", "type": "GeneProduct", "text": [ "oncogene product" ], "offsets": [ [ 234, 250 ] ], "normalized": [] }, { "id": "PMID-1406622_T11", "type": "Gene", "text": [ "spi-B" ], "offsets": [ [ 252, 257 ] ], "normalized": [] }, { "id": "PMID-1406622_T12", "type": "Protein", "text": [ "protein" ], "offsets": [ [ 270, 277 ] ], "normalized": [] }, { "id": "PMID-1406622_T13", "type": "AminoAcid", "text": [ "amino acids" ], "offsets": [ [ 285, 296 ] ], "normalized": [] }, { "id": "PMID-1406622_T14", "type": "Protein", "text": [ "Spi-1" ], "offsets": [ [ 334, 339 ] ], "normalized": [] }, { "id": "PMID-1406622_T15", "type": "DNABindingDomainOfProtein", "text": [ "DNA-binding domain" ], "offsets": [ [ 422, 440 ] ], "normalized": [] }, { "id": "PMID-1406622_T16", "type": "Protein", "text": [ "Ets-1 protein" ], "offsets": [ [ 448, 461 ] ], "normalized": [] }, { "id": "PMID-1406622_T17", "type": "TranscriptionFactor", "text": [ "Spi-B protein" ], "offsets": [ [ 482, 495 ] ], "normalized": [] }, { "id": "PMID-1406622_T19", "type": "DNARegion", "text": [ "PU box" ], "offsets": [ [ 538, 544 ] ], "normalized": [] }, { "id": "PMID-1406622_T20", "type": "Protein", "text": [ "Spi-1/PU.1" ], "offsets": [ [ 560, 570 ] ], "normalized": [] }, { "id": "PMID-1406622_T23", "type": "ReporterGene", "text": [ "reporter plasmid" ], "offsets": [ [ 606, 622 ] ], "normalized": [] }, { "id": "PMID-1406622_T24", "type": "DNARegion", "text": [ "PU boxes" ], "offsets": [ [ 634, 642 ] ], "normalized": [] }, { "id": "PMID-1406622_T25", "type": "Chromosome", "text": [ "Chromosome" ], "offsets": [ [ 644, 654 ] ], "normalized": [] }, { "id": "PMID-1406622_T26", "type": "Gene", "text": [ "spi-B" ], "offsets": [ [ 695, 700 ] ], "normalized": [] }, { "id": "PMID-1406622_T27", "type": "Chromosome", "text": [ "19q13.3-19q13.4" ], "offsets": [ [ 708, 723 ] ], "normalized": [] }, { "id": "PMID-1406622_T28", "type": "Eukaryote", "text": [ "human" ], "offsets": [ [ 738, 743 ] ], "normalized": [] }, { "id": "PMID-1406622_T29", "type": "DNA", "text": [ "genome" ], "offsets": [ [ 744, 750 ] ], "normalized": [] }, { "id": "PMID-1406622_T30", "type": "Gene", "text": [ "spi-B" ], "offsets": [ [ 752, 757 ] ], "normalized": [] }, { "id": "PMID-1406622_T31", "type": "Gene", "text": [ "spi-1" ], "offsets": [ [ 764, 769 ] ], "normalized": [] }, { "id": "PMID-1406622_T33", "type": "Eukaryote", "text": [ "murine" ], "offsets": [ [ 808, 814 ] ], "normalized": [] }, { "id": "PMID-1406622_T34", "type": "Eukaryote", "text": [ "human" ], "offsets": [ [ 819, 824 ] ], "normalized": [] }, { "id": "PMID-1406622_T35", "type": "Cell", "text": [ "hematopoietic cell lines" ], "offsets": [ [ 825, 849 ] ], "normalized": [] }, { "id": "PMID-1406622_T36", "type": "Cell", "text": [ "T lymphoid cell lines" ], "offsets": [ [ 857, 878 ] ], "normalized": [] } ]

[ { "id": "PMID-1406622_E1", "type": "BindingOfProteinToDNA", "trigger": { "text": [ "bind" ], "offsets": [ [ 507, 511 ] ] }, "arguments": [ { "role": "hasAgent", "ref_id": "PMID-1406622_T17" }, { "role": "hasPatient", "ref_id": "PMID-1406622_T19" } ] }, { "id": "PMID-1406622_E2", "type": "PositiveRegulation", "trigger": { "text": [ "activate" ], "offsets": [ [ 578, 586 ] ] }, "arguments": [ { "role": "hasAgent", "ref_id": "PMID-1406622_T17" }, { "role": "hasPatient", "ref_id": "PMID-1406622_E3" } ] }, { "id": "PMID-1406622_E3", "type": "Transcription", "trigger": { "text": [ "transcription" ], "offsets": [ [ 587, 600 ] ] }, "arguments": [ { "role": "hasPatient", "ref_id": "PMID-1406622_T23" } ] }, { "id": "PMID-1406622_E4", "type": "GeneExpression", "trigger": { "text": [ "expressed" ], "offsets": [ [ 787, 796 ] ] }, "arguments": [ { "role": "hasPatient", "ref_id": "PMID-1406622_T30" } ] } ]

[]

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[ { "id": "PMID-14654789__text", "type": "abstract", "text": [ "A member of the Pyrin family, IFI16, is a novel BRCA1-associated protein involved in the p53-mediated apoptosis pathway. We identified IFI16 as a BRCA1-associated protein involved in p53-mediated apoptosis. IFI16 contains the Pyrin/PAAD/DAPIN domain, commonly found in cell death-associated proteins. BRCA1 (aa 502-802) interacted with the IFI16 Pyrin domain (aa 1-130). We found that IFI16 was localized in the nucleoplasm and nucleoli. Clear nucleolar IFI16 localization was not observed in HCC1937 BRCA1 mutant cells, but reintroduction of wild-type BRCA1 restored IFI16 nuclear relocalization following IR (ionizing radiation). Coexpression of IFI16 and BRCA1 enhanced DNA damage-induced apoptosis in mouse embryonic fibroblasts from BRCA1 mutant mice expressing wild-type p53, although mutant IFI16 deficient in binding to BRCA1 did not induce apoptosis. Furthermore, tetracycline-induced IFI16 collaborated in inducing apoptosis when adenovirus p53 was expressed in DNA-damaged p53-deficient EJ cells. These results indicate a BRCA1-IFI16 role in p53-mediated transmission of DNA damage signals and apoptosis.\n" ], "offsets": [ [ 0, 1116 ] ] } ]

[ { "id": "PMID-14654789_T1", "type": "Protein", "text": [ "IFI16" ], "offsets": [ [ 30, 35 ] ], "normalized": [] }, { "id": "PMID-14654789_T2", "type": "Protein", "text": [ "BRCA1" ], "offsets": [ [ 48, 53 ] ], "normalized": [] }, { "id": "PMID-14654789_T3", "type": "Protein", "text": [ "protein" ], "offsets": [ [ 65, 72 ] ], "normalized": [] }, { "id": "PMID-14654789_T4", "type": "Protein", "text": [ "p53" ], "offsets": [ [ 89, 92 ] ], "normalized": [] }, { "id": "PMID-14654789_T7", "type": "Protein", "text": [ "IFI16" ], "offsets": [ [ 135, 140 ] ], "normalized": [] }, { "id": "PMID-14654789_T8", "type": "Protein", "text": [ "BRCA1" ], "offsets": [ [ 146, 151 ] ], "normalized": [] }, { "id": "PMID-14654789_T9", "type": "Protein", "text": [ "protein" ], "offsets": [ [ 163, 170 ] ], "normalized": [] }, { "id": "PMID-14654789_T10", "type": "Protein", "text": [ "p53" ], "offsets": [ [ 183, 186 ] ], "normalized": [] }, { "id": "PMID-14654789_T13", "type": "Protein", "text": [ "IFI16" ], "offsets": [ [ 207, 212 ] ], "normalized": [] }, { "id": "PMID-14654789_T14", "type": "ProteinDomain", "text": [ "Pyrin/PAAD/DAPIN domain" ], "offsets": [ [ 226, 249 ] ], "normalized": [] }, { "id": "PMID-14654789_T16", "type": "Protein", "text": [ "proteins" ], "offsets": [ [ 291, 299 ] ], "normalized": [] }, { "id": "PMID-14654789_T17", "type": "Protein", "text": [ "BRCA1" ], "offsets": [ [ 301, 306 ] ], "normalized": [] }, { "id": "PMID-14654789_T19", "type": "Protein", "text": [ "IFI16" ], "offsets": [ [ 340, 345 ] ], "normalized": [] }, { "id": "PMID-14654789_T20", "type": "ProteinDomain", "text": [ "Pyrin domain" ], "offsets": [ [ 346, 358 ] ], "normalized": [] }, { "id": "PMID-14654789_T21", "type": "Protein", "text": [ "IFI16" ], "offsets": [ [ 385, 390 ] ], "normalized": [] }, { "id": "PMID-14654789_T23", "type": "CellComponent", "text": [ "nucleoplasm" ], "offsets": [ [ 412, 423 ] ], "normalized": [] }, { "id": "PMID-14654789_T24", "type": "Nucleus", "text": [ "nucleoli" ], "offsets": [ [ 428, 436 ] ], "normalized": [] }, { "id": "PMID-14654789_T25", "type": "Protein", "text": [ "IFI16" ], "offsets": [ [ 454, 459 ] ], "normalized": [] }, { "id": "PMID-14654789_T26", "type": "Protein", "text": [ "wild-type BRCA1" ], "offsets": [ [ 543, 558 ] ], "normalized": [] }, { "id": "PMID-14654789_T27", "type": "Protein", "text": [ "IFI16" ], "offsets": [ [ 568, 573 ] ], "normalized": [] }, { "id": "PMID-14654789_T28", "type": "Nucleus", "text": [ "nuclear" ], "offsets": [ [ 574, 581 ] ], "normalized": [] }, { "id": "PMID-14654789_T31", "type": "Protein", "text": [ "IFI16" ], "offsets": [ [ 648, 653 ] ], "normalized": [] }, { "id": "PMID-14654789_T32", "type": "Protein", "text": [ "BRCA1" ], "offsets": [ [ 658, 663 ] ], "normalized": [] }, { "id": "PMID-14654789_T34", "type": "DNA", "text": [ "DNA" ], "offsets": [ [ 673, 676 ] ], "normalized": [] }, { "id": "PMID-14654789_T38", "type": "Eukaryote", "text": [ "mouse" ], "offsets": [ [ 705, 710 ] ], "normalized": [] }, { "id": "PMID-14654789_T39", "type": "Cell", "text": [ "embryonic fibroblasts" ], "offsets": [ [ 711, 732 ] ], "normalized": [] }, { "id": "PMID-14654789_T40", "type": "MutatedProtein", "text": [ "BRCA1 mutant" ], "offsets": [ [ 738, 750 ] ], "normalized": [] }, { "id": "PMID-14654789_T41", "type": "Eukaryote", "text": [ "mice" ], "offsets": [ [ 751, 755 ] ], "normalized": [] }, { "id": "PMID-14654789_T43", "type": "Protein", "text": [ "wild-type p53" ], "offsets": [ [ 767, 780 ] ], "normalized": [] }, { "id": "PMID-14654789_T44", "type": "OrganicChemical", "text": [ "tetracycline" ], "offsets": [ [ 873, 885 ] ], "normalized": [] }, { "id": "PMID-14654789_T46", "type": "Protein", "text": [ "IFI16" ], "offsets": [ [ 894, 899 ] ], "normalized": [] }, { "id": "PMID-14654789_T49", "type": "Virus", "text": [ "adenovirus" ], "offsets": [ [ 940, 950 ] ], "normalized": [] }, { "id": "PMID-14654789_T50", "type": "Protein", "text": [ "p53" ], "offsets": [ [ 951, 954 ] ], "normalized": [] }, { "id": "PMID-14654789_T52", "type": "DNA", "text": [ "DNA" ], "offsets": [ [ 972, 975 ] ], "normalized": [] }, { "id": "PMID-14654789_T54", "type": "Protein", "text": [ "p53" ], "offsets": [ [ 984, 987 ] ], "normalized": [] }, { "id": "PMID-14654789_T55", "type": "Cell", "text": [ "EJ cells" ], "offsets": [ [ 998, 1006 ] ], "normalized": [] }, { "id": "PMID-14654789_T56", "type": "Protein", "text": [ "BRCA1" ], "offsets": [ [ 1033, 1038 ] ], "normalized": [] }, { "id": "PMID-14654789_T57", "type": "Protein", "text": [ "IFI16" ], "offsets": [ [ 1039, 1044 ] ], "normalized": [] }, { "id": "PMID-14654789_T58", "type": "Protein", "text": [ "p53" ], "offsets": [ [ 1053, 1056 ] ], "normalized": [] }, { "id": "PMID-14654789_T60", "type": "DNA", "text": [ "DNA" ], "offsets": [ [ 1082, 1085 ] ], "normalized": [] }, { "id": "PMID-14654789_T63", "type": "Protein", "text": [ "Pyrin" ], "offsets": [ [ 16, 21 ] ], "normalized": [] }, { "id": "PMID-14654789_T66", "type": "Cell", "text": [ "HCC1937 BRCA1 mutant cell" ], "offsets": [ [ 493, 518 ] ], "normalized": [] } ]

[ { "id": "PMID-14654789_E1", "type": "RegulatoryProcess", "trigger": { "text": [ "mediated" ], "offsets": [ [ 93, 101 ] ] }, "arguments": [ { "role": "hasAgent", "ref_id": "PMID-14654789_T4" }, { "role": "hasPatient", "ref_id": "PMID-14654789_E2" } ] }, { "id": "PMID-14654789_E2", "type": "CellDeath", "trigger": { "text": [ "apoptosis pathway" ], "offsets": [ [ 102, 119 ] ] }, "arguments": [] }, { "id": "PMID-14654789_E3", "type": "RegulatoryProcess", "trigger": { "text": [ "mediated" ], "offsets": [ [ 187, 195 ] ] }, "arguments": [ { "role": "hasAgent", "ref_id": "PMID-14654789_T10" }, { "role": "hasPatient", "ref_id": "PMID-14654789_E4" } ] }, { "id": "PMID-14654789_E4", "type": "CellDeath", "trigger": { "text": [ "apoptosis" ], "offsets": [ [ 196, 205 ] ] }, "arguments": [] }, { "id": "PMID-14654789_E5", "type": "CellDeath", "trigger": { "text": [ "cell death" ], "offsets": [ [ 269, 279 ] ] }, "arguments": [] }, { "id": "PMID-14654789_E6", "type": "BindingToProtein", "trigger": { "text": [ "interacted" ], "offsets": [ [ 320, 330 ] ] }, "arguments": [ { "role": "hasPatient", "ref_id": "PMID-14654789_T20" }, { "role": "hasPatient2", "ref_id": "PMID-14654789_T17" } ] }, { "id": "PMID-14654789_E7", "type": "Localization", "trigger": { "text": [ "localized" ], "offsets": [ [ 395, 404 ] ] }, "arguments": [ { "role": "hasPatient", "ref_id": "PMID-14654789_T21" } ] }, { "id": "PMID-14654789_E8", "type": "Localization", "trigger": { "text": [ "relocalization" ], "offsets": [ [ 582, 596 ] ] }, "arguments": [ { "role": "hasPatient", "ref_id": "PMID-14654789_T27" } ] }, { "id": "PMID-14654789_E9", "type": "GeneExpression", "trigger": { "text": [ "Coexpression" ], "offsets": [ [ 632, 644 ] ] }, "arguments": [ { "role": "hasPatient", "ref_id": "PMID-14654789_T31" } ] }, { "id": "PMID-14654789_E10", "type": "Increase", "trigger": { "text": [ "enhanced" ], "offsets": [ [ 664, 672 ] ] }, "arguments": [ { "role": "hasPatient", "ref_id": "PMID-14654789_E13" }, { "role": "hasAgent", "ref_id": "PMID-14654789_E9" } ] }, { "id": "PMID-14654789_E11", "type": "Mutation", "trigger": { "text": [ "damage" ], "offsets": [ [ 677, 683 ] ] }, "arguments": [ { "role": "hasPatient", "ref_id": "PMID-14654789_T34" } ] }, { "id": "PMID-14654789_E12", "type": "PositiveRegulation", "trigger": { "text": [ "induced" ], "offsets": [ [ 684, 691 ] ] }, "arguments": [ { "role": "hasAgent", "ref_id": "PMID-14654789_E11" }, { "role": "hasPatient", "ref_id": "PMID-14654789_E13" } ] }, { "id": "PMID-14654789_E13", "type": "CellDeath", "trigger": { "text": [ "apoptosis" ], "offsets": [ [ 692, 701 ] ] }, "arguments": [] }, { "id": "PMID-14654789_E14", "type": "GeneExpression", "trigger": { "text": [ "expressing" ], "offsets": [ [ 756, 766 ] ] }, "arguments": [ { "role": "hasPatient", "ref_id": "PMID-14654789_T43" } ] }, { "id": "PMID-14654789_E15", "type": "PositiveRegulation", "trigger": { "text": [ "induced" ], "offsets": [ [ 886, 893 ] ] }, "arguments": [ { "role": "hasAgent", "ref_id": "PMID-14654789_T44" }, { "role": "hasPatient", "ref_id": "PMID-14654789_T46" } ] }, { "id": "PMID-14654789_E16", "type": "PositiveRegulation", "trigger": { "text": [ "inducing" ], "offsets": [ [ 916, 924 ] ] }, "arguments": [ { "role": "hasPatient", "ref_id": "PMID-14654789_E17" } ] }, { "id": "PMID-14654789_E17", "type": "CellDeath", "trigger": { "text": [ "apoptosis" ], "offsets": [ [ 925, 934 ] ] }, "arguments": [] }, { "id": "PMID-14654789_E18", "type": "GeneExpression", "trigger": { "text": [ "expressed" ], "offsets": [ [ 959, 968 ] ] }, "arguments": [ { "role": "hasPatient", "ref_id": "PMID-14654789_T50" } ] }, { "id": "PMID-14654789_E19", "type": "Mutation", "trigger": { "text": [ "damaged" ], "offsets": [ [ 976, 983 ] ] }, "arguments": [ { "role": "hasPatient", "ref_id": "PMID-14654789_T52" } ] }, { "id": "PMID-14654789_E20", "type": "RegulatoryProcess", "trigger": { "text": [ "mediated" ], "offsets": [ [ 1057, 1065 ] ] }, "arguments": [ { "role": "hasAgent", "ref_id": "PMID-14654789_T58" }, { "role": "hasPatient", "ref_id": "PMID-14654789_E22" } ] }, { "id": "PMID-14654789_E21", "type": "Mutation", "trigger": { "text": [ "damage" ], "offsets": [ [ 1086, 1092 ] ] }, "arguments": [ { "role": "hasPatient", "ref_id": "PMID-14654789_T60" } ] }, { "id": "PMID-14654789_E22", "type": "CellDeath", "trigger": { "text": [ "apoptosis" ], "offsets": [ [ 1105, 1114 ] ] }, "arguments": [] }, { "id": "PMID-14654789_E23", "type": "BindingToProtein", "trigger": { "text": [ "associated" ], "offsets": [ [ 54, 64 ] ] }, "arguments": [ { "role": "hasPatient", "ref_id": "PMID-14654789_T3" }, { "role": "hasPatient2", "ref_id": "PMID-14654789_T2" } ] }, { "id": "PMID-14654789_E24", "type": "BindingToProtein", "trigger": { "text": [ "associated" ], "offsets": [ [ 152, 162 ] ] }, "arguments": [ { "role": "hasPatient", "ref_id": "PMID-14654789_T8" }, { "role": "hasPatient2", "ref_id": "PMID-14654789_T9" } ] }, { "id": "PMID-14654789_E25", "type": "SignalingPathway", "trigger": { "text": [ "signals" ], "offsets": [ [ 1093, 1100 ] ] }, "arguments": [] }, { "id": "PMID-14654789_E26", "type": "GeneExpression", "trigger": { "text": [ "Coexpression" ], "offsets": [ [ 632, 644 ] ] }, "arguments": [ { "role": "hasPatient", "ref_id": "PMID-14654789_T32" } ] }, { "id": "PMID-14654789_E27", "type": "RegulatoryProcess", "trigger": { "text": [ "mediated" ], "offsets": [ [ 1057, 1065 ] ] }, "arguments": [ { "role": "hasAgent", "ref_id": "PMID-14654789_T58" }, { "role": "hasPatient", "ref_id": "PMID-14654789_E25" } ] }, { "id": "PMID-14654789_E28", "type": "Increase", "trigger": { "text": [ "enhanced" ], "offsets": [ [ 664, 672 ] ] }, "arguments": [ { "role": "hasPatient", "ref_id": "PMID-14654789_E13" }, { "role": "hasAgent", "ref_id": "PMID-14654789_E26" } ] } ]

[]

[ { "id": "PMID-14654789_R1", "type": "hasPart", "arg1_id": "PMID-14654789_T13", "arg2_id": "PMID-14654789_T14", "normalized": [] }, { "id": "PMID-14654789_R2", "type": "hasPart", "arg1_id": "PMID-14654789_T16", "arg2_id": "PMID-14654789_T14", "normalized": [] }, { "id": "PMID-14654789_R3", "type": "hasPart", "arg1_id": "PMID-14654789_T19", "arg2_id": "PMID-14654789_T20", "normalized": [] }, { "id": "PMID-14654789_R8", "type": "fromSpecies", "arg1_id": "PMID-14654789_T39", "arg2_id": "PMID-14654789_T38", "normalized": [] }, { "id": "PMID-14654789_R9", "type": "locatedIn", "arg1_id": "PMID-14654789_T40", "arg2_id": "PMID-14654789_T41", "normalized": [] }, { "id": "PMID-14654789_R11", "type": "fromSpecies", "arg1_id": "PMID-14654789_T50", "arg2_id": "PMID-14654789_T49", "normalized": [] } ]

[ { "id": "PMID-14667815__text", "type": "abstract", "text": [ "Regulation of aldehyde reductase expression by STAF and CHOP. Aldehyde reductase is involved in the reductive detoxification of reactive aldehydes that can modify cellular macromolecules. To analyze the mechanism of basal regulation of aldehyde reductase expression, we cloned the murine gene and adjacent regulatory region and compared it to the human gene. The mouse enzyme exhibits substrate specificity similar to that of the human enzyme, but with a 2-fold higher catalytic efficiency. In contrast to the mouse gene, the human aldehyde reductase gene has two alternatively spliced transcripts. A fragment of 57 bp is sufficient for 25% of human promoter activity and consists of two elements. The 3' element binds transcription factors of the Sp1 family. Gel-shift assays and chromatin immunoprecipitation as well as deletion/mutation analysis reveal that selenocysteine tRNA transcription activating factor (STAF) binds to the 5' element and drives constitutive expression of both mouse and human aldehyde reductase. Aldehyde reductase thus becomes the fourth protein-encoding gene regulated by STAF. The human, but not the mouse, promoter also binds C/EBP homologous protein (CHOP), which competes with STAF for the same binding site. Transfection of the human promoter into ethoxyquin-treated mouse 3T3 cells induces a 3.5-fold increase in promoter activity and a CHOP-C/EBP band appears on gel shifts performed with the 5' probe from the human aldehyde reductase promoter. Induction is attenuated in similar transfection studies of the mouse promoter. Mutation of the CHOP-binding site in the human promoter abolishes CHOP binding and significantly reduces ethoxyquin induction, suggesting that CHOP mediates stimulated expression in response to antioxidants in the human. This subtle difference in the human promoter suggests a further evolution of the promoter toward responsiveness to exogenous stress and/or toxins.\n" ], "offsets": [ [ 0, 1929 ] ] } ]

[ { "id": "PMID-14667815_T2", "type": "Enzyme", "text": [ "aldehyde reductase" ], "offsets": [ [ 14, 32 ] ], "normalized": [] }, { "id": "PMID-14667815_T4", "type": "Protein", "text": [ "STAF" ], "offsets": [ [ 47, 51 ] ], "normalized": [] }, { "id": "PMID-14667815_T5", "type": "Protein", "text": [ "CHOP" ], "offsets": [ [ 56, 60 ] ], "normalized": [] }, { "id": "PMID-14667815_T6", "type": "Enzyme", "text": [ "Aldehyde reductase" ], "offsets": [ [ 62, 80 ] ], "normalized": [] }, { "id": "PMID-14667815_T7", "type": "Chemical", "text": [ "aldehydes" ], "offsets": [ [ 137, 146 ] ], "normalized": [] }, { "id": "PMID-14667815_T9", "type": "MolecularEntity", "text": [ "cellular macromolecules" ], "offsets": [ [ 163, 186 ] ], "normalized": [] }, { "id": "PMID-14667815_T11", "type": "Enzyme", "text": [ "aldehyde reductase" ], "offsets": [ [ 236, 254 ] ], "normalized": [] }, { "id": "PMID-14667815_T13", "type": "Eukaryote", "text": [ "murine" ], "offsets": [ [ 281, 287 ] ], "normalized": [] }, { "id": "PMID-14667815_T14", "type": "Gene", "text": [ "gene" ], "offsets": [ [ 288, 292 ] ], "normalized": [] }, { "id": "PMID-14667815_T15", "type": "Eukaryote", "text": [ "human" ], "offsets": [ [ 347, 352 ] ], "normalized": [] }, { "id": "PMID-14667815_T16", "type": "Gene", "text": [ "gene" ], "offsets": [ [ 353, 357 ] ], "normalized": [] }, { "id": "PMID-14667815_T17", "type": "Eukaryote", "text": [ "mouse" ], "offsets": [ [ 363, 368 ] ], "normalized": [] }, { "id": "PMID-14667815_T18", "type": "Enzyme", "text": [ "enzyme" ], "offsets": [ [ 369, 375 ] ], "normalized": [] }, { "id": "PMID-14667815_T19", "type": "Eukaryote", "text": [ "human" ], "offsets": [ [ 430, 435 ] ], "normalized": [] }, { "id": "PMID-14667815_T20", "type": "Enzyme", "text": [ "enzyme" ], "offsets": [ [ 436, 442 ] ], "normalized": [] }, { "id": "PMID-14667815_T21", "type": "Eukaryote", "text": [ "mouse" ], "offsets": [ [ 510, 515 ] ], "normalized": [] }, { "id": "PMID-14667815_T22", "type": "Gene", "text": [ "gene" ], "offsets": [ [ 516, 520 ] ], "normalized": [] }, { "id": "PMID-14667815_T23", "type": "Eukaryote", "text": [ "human" ], "offsets": [ [ 526, 531 ] ], "normalized": [] }, { "id": "PMID-14667815_T24", "type": "Enzyme", "text": [ "aldehyde reductase" ], "offsets": [ [ 532, 550 ] ], "normalized": [] }, { "id": "PMID-14667815_T25", "type": "Gene", "text": [ "gene" ], "offsets": [ [ 551, 555 ] ], "normalized": [] }, { "id": "PMID-14667815_T26", "type": "Transcript", "text": [ "transcripts" ], "offsets": [ [ 586, 597 ] ], "normalized": [] }, { "id": "PMID-14667815_T27", "type": "DNAFragment", "text": [ "fragment" ], "offsets": [ [ 601, 609 ] ], "normalized": [] }, { "id": "PMID-14667815_T28", "type": "Eukaryote", "text": [ "human" ], "offsets": [ [ 644, 649 ] ], "normalized": [] }, { "id": "PMID-14667815_T29", "type": "Promoter", "text": [ "promoter" ], "offsets": [ [ 650, 658 ] ], "normalized": [] }, { "id": "PMID-14667815_T30", "type": "RegulatoryDNARegion", "text": [ "3' element" ], "offsets": [ [ 702, 712 ] ], "normalized": [] }, { "id": "PMID-14667815_T32", "type": "TranscriptionFactor", "text": [ "transcription factors" ], "offsets": [ [ 719, 740 ] ], "normalized": [] }, { "id": "PMID-14667815_T33", "type": "Protein", "text": [ "Sp1 family" ], "offsets": [ [ 748, 758 ] ], "normalized": [] }, { "id": "PMID-14667815_T34", "type": "TranscriptionActivator", "text": [ "selenocysteine tRNA transcription activating factor" ], "offsets": [ [ 861, 912 ] ], "normalized": [] }, { "id": "PMID-14667815_T35", "type": "TranscriptionActivator", "text": [ "STAF" ], "offsets": [ [ 914, 918 ] ], "normalized": [] }, { "id": "PMID-14667815_T37", "type": "RegulatoryDNARegion", "text": [ "5' element" ], "offsets": [ [ 933, 943 ] ], "normalized": [] }, { "id": "PMID-14667815_T40", "type": "Eukaryote", "text": [ "mouse" ], "offsets": [ [ 987, 992 ] ], "normalized": [] }, { "id": "PMID-14667815_T41", "type": "Eukaryote", "text": [ "human" ], "offsets": [ [ 997, 1002 ] ], "normalized": [] }, { "id": "PMID-14667815_T42", "type": "Enzyme", "text": [ "aldehyde reductase" ], "offsets": [ [ 1003, 1021 ] ], "normalized": [] }, { "id": "PMID-14667815_T43", "type": "Gene", "text": [ "Aldehyde reductase" ], "offsets": [ [ 1023, 1041 ] ], "normalized": [] }, { "id": "PMID-14667815_T44", "type": "Protein", "text": [ "protein" ], "offsets": [ [ 1066, 1073 ] ], "normalized": [] }, { "id": "PMID-14667815_T45", "type": "Gene", "text": [ "gene" ], "offsets": [ [ 1083, 1087 ] ], "normalized": [] }, { "id": "PMID-14667815_T47", "type": "Protein", "text": [ "STAF" ], "offsets": [ [ 1101, 1105 ] ], "normalized": [] }, { "id": "PMID-14667815_T48", "type": "Eukaryote", "text": [ "human" ], "offsets": [ [ 1111, 1116 ] ], "normalized": [] }, { "id": "PMID-14667815_T49", "type": "Eukaryote", "text": [ "mouse" ], "offsets": [ [ 1130, 1135 ] ], "normalized": [] }, { "id": "PMID-14667815_T50", "type": "Promoter", "text": [ "promoter" ], "offsets": [ [ 1137, 1145 ] ], "normalized": [] }, { "id": "PMID-14667815_T52", "type": "Protein", "text": [ "C/EBP homologous protein" ], "offsets": [ [ 1157, 1181 ] ], "normalized": [] }, { "id": "PMID-14667815_T53", "type": "Protein", "text": [ "CHOP" ], "offsets": [ [ 1183, 1187 ] ], "normalized": [] }, { "id": "PMID-14667815_T54", "type": "Protein", "text": [ "STAF" ], "offsets": [ [ 1210, 1214 ] ], "normalized": [] }, { "id": "PMID-14667815_T55", "type": "ProteinBindingSiteOfDNA", "text": [ "binding site" ], "offsets": [ [ 1228, 1240 ] ], "normalized": [] }, { "id": "PMID-14667815_T56", "type": "Eukaryote", "text": [ "human" ], "offsets": [ [ 1262, 1267 ] ], "normalized": [] }, { "id": "PMID-14667815_T57", "type": "Promoter", "text": [ "promoter" ], "offsets": [ [ 1268, 1276 ] ], "normalized": [] }, { "id": "PMID-14667815_T58", "type": "Chemical", "text": [ "ethoxyquin" ], "offsets": [ [ 1282, 1292 ] ], "normalized": [] }, { "id": "PMID-14667815_T59", "type": "Eukaryote", "text": [ "mouse" ], "offsets": [ [ 1301, 1306 ] ], "normalized": [] }, { "id": "PMID-14667815_T60", "type": "Cell", "text": [ "3T3 cells" ], "offsets": [ [ 1307, 1316 ] ], "normalized": [] }, { "id": "PMID-14667815_T61", "type": "Promoter", "text": [ "promoter" ], "offsets": [ [ 1348, 1356 ] ], "normalized": [] }, { "id": "PMID-14667815_T62", "type": "Eukaryote", "text": [ "human" ], "offsets": [ [ 1447, 1452 ] ], "normalized": [] }, { "id": "PMID-14667815_T63", "type": "Gene", "text": [ "aldehyde reductase" ], "offsets": [ [ 1453, 1471 ] ], "normalized": [] }, { "id": "PMID-14667815_T64", "type": "Promoter", "text": [ "promoter" ], "offsets": [ [ 1472, 1480 ] ], "normalized": [] }, { "id": "PMID-14667815_T67", "type": "Eukaryote", "text": [ "mouse" ], "offsets": [ [ 1545, 1550 ] ], "normalized": [] }, { "id": "PMID-14667815_T68", "type": "Promoter", "text": [ "promoter" ], "offsets": [ [ 1551, 1559 ] ], "normalized": [] }, { "id": "PMID-14667815_T70", "type": "ProteinBindingSiteOfDNA", "text": [ "CHOP-binding site" ], "offsets": [ [ 1577, 1594 ] ], "normalized": [] }, { "id": "PMID-14667815_T71", "type": "Eukaryote", "text": [ "human" ], "offsets": [ [ 1602, 1607 ] ], "normalized": [] }, { "id": "PMID-14667815_T72", "type": "Promoter", "text": [ "promoter" ], "offsets": [ [ 1608, 1616 ] ], "normalized": [] }, { "id": "PMID-14667815_T74", "type": "Protein", "text": [ "CHOP" ], "offsets": [ [ 1627, 1631 ] ], "normalized": [] }, { "id": "PMID-14667815_T77", "type": "Chemical", "text": [ "ethoxyquin" ], "offsets": [ [ 1666, 1676 ] ], "normalized": [] }, { "id": "PMID-14667815_T79", "type": "Protein", "text": [ "CHOP" ], "offsets": [ [ 1704, 1708 ] ], "normalized": [] }, { "id": "PMID-14667815_T83", "type": "Chemical", "text": [ "antioxidants" ], "offsets": [ [ 1755, 1767 ] ], "normalized": [] }, { "id": "PMID-14667815_T84", "type": "Eukaryote", "text": [ "human" ], "offsets": [ [ 1775, 1780 ] ], "normalized": [] }, { "id": "PMID-14667815_T85", "type": "Eukaryote", "text": [ "human" ], "offsets": [ [ 1812, 1817 ] ], "normalized": [] }, { "id": "PMID-14667815_T86", "type": "Promoter", "text": [ "promoter" ], "offsets": [ [ 1818, 1826 ] ], "normalized": [] }, { "id": "PMID-14667815_T87", "type": "Promoter", "text": [ "promoter" ], "offsets": [ [ 1863, 1871 ] ], "normalized": [] }, { "id": "PMID-14667815_T89", "type": "Stress", "text": [ "stress" ], "offsets": [ [ 1907, 1913 ] ], "normalized": [] }, { "id": "PMID-14667815_T90", "type": "Chemical", "text": [ "toxins" ], "offsets": [ [ 1921, 1927 ] ], "normalized": [] }, { "id": "PMID-14667815_T91", "type": "RegulatoryDNARegion", "text": [ "regulatory region" ], "offsets": [ [ 306, 323 ] ], "normalized": [] }, { "id": "PMID-14667815_T92", "type": "Substrate", "text": [ "substrate" ], "offsets": [ [ 385, 394 ] ], "normalized": [] }, { "id": "PMID-14667815_T93", "type": "CatalyticActivity", "text": [ "catalytic" ], "offsets": [ [ 469, 478 ] ], "normalized": [] } ]

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"expression" ], "offsets": [ [ 255, 265 ] ] }, "arguments": [ { "role": "hasPatient", "ref_id": "PMID-14667815_T11" } ] }, { "id": "PMID-14667815_E6", "type": "BindingOfTFToTFBindingSiteOfDNA", "trigger": { "text": [ "binds" ], "offsets": [ [ 713, 718 ] ] }, "arguments": [ { "role": "hasAgent", "ref_id": "PMID-14667815_T32" }, { "role": "hasPatient", "ref_id": "PMID-14667815_T30" } ] }, { "id": "PMID-14667815_E7", "type": "BindingOfTFToTFBindingSiteOfDNA", "trigger": { "text": [ "binds" ], "offsets": [ [ 920, 925 ] ] }, "arguments": [ { "role": "hasAgent", "ref_id": "PMID-14667815_T34" }, { "role": "hasPatient", "ref_id": "PMID-14667815_T37" } ] }, { "id": "PMID-14667815_E8", "type": "PositiveRegulation", "trigger": { "text": [ "drives" ], "offsets": [ [ 948, 954 ] ] }, "arguments": [ { "role": "hasAgent", "ref_id": "PMID-14667815_T34" }, { "role": "hasPatient", "ref_id": "PMID-14667815_E9" } ] }, { "id": "PMID-14667815_E9", "type": "GeneExpression", "trigger": { "text": [ "expression" ], "offsets": [ [ 968, 978 ] ] }, "arguments": [ { "role": "hasPatient", "ref_id": "PMID-14667815_T42" } ] }, { "id": "PMID-14667815_E10", "type": "RegulatoryProcess", "trigger": { "text": [ "regulated" ], "offsets": [ [ 1088, 1097 ] ] }, "arguments": [ { "role": "hasAgent", "ref_id": "PMID-14667815_T47" }, { "role": "hasPatient", "ref_id": "PMID-14667815_T45" } ] }, { "id": "PMID-14667815_E11", "type": "BindingOfProteinToDNA", "trigger": { "text": [ "binds" ], "offsets": [ [ 1151, 1156 ] ] }, "arguments": [ { "role": "hasAgent", "ref_id": "PMID-14667815_T52" }, { "role": "hasPatient", "ref_id": "PMID-14667815_T50" } ] }, { "id": "PMID-14667815_E12", "type": "PositiveRegulation", "trigger": { "text": [ "Induction" ], "offsets": [ [ 1482, 1491 ] ] }, "arguments": [] }, { "id": "PMID-14667815_E13", "type": "Decrease", "trigger": { "text": [ "attenuated" ], "offsets": [ [ 1495, 1505 ] ] }, "arguments": [] }, { "id": "PMID-14667815_E14", "type": "Mutation", "trigger": { "text": [ 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"hasAgent", "ref_id": "PMID-14667815_T77" } ] }, { "id": "PMID-14667815_E19", "type": "RegulatoryProcess", "trigger": { "text": [ "mediates" ], "offsets": [ [ 1709, 1717 ] ] }, "arguments": [ { "role": "hasAgent", "ref_id": "PMID-14667815_T79" }, { "role": "hasPatient", "ref_id": "PMID-14667815_E20" } ] }, { "id": "PMID-14667815_E20", "type": "GeneExpression", "trigger": { "text": [ "expression" ], "offsets": [ [ 1729, 1739 ] ] }, "arguments": [] }, { "id": "PMID-14667815_E21", "type": "ResponseToChemicalStimulus", "trigger": { "text": [ "response" ], "offsets": [ [ 1743, 1751 ] ] }, "arguments": [ { "role": "hasAgent", "ref_id": "PMID-14667815_T83" } ] }, { "id": "PMID-14667815_E22", "type": "ResponseProcess", "trigger": { "text": [ "responsiveness" ], "offsets": [ [ 1879, 1893 ] ] }, "arguments": [ { "role": "hasAgent", "ref_id": "PMID-14667815_T89" } ] }, { "id": "PMID-14667815_E23", "type": "Splicing", "trigger": { "text": [ "spliced" ], "offsets": [ [ 578, 585 ] ] }, "arguments": [ { "role": "hasPatient", "ref_id": "PMID-14667815_T26" } ] }, { "id": "PMID-14667815_E24", "type": "RegulatoryProcess", "trigger": { "text": [ "Regulation" ], "offsets": [ [ 0, 10 ] ] }, "arguments": [ { "role": "hasPatient", "ref_id": "PMID-14667815_E2" }, { "role": "hasAgent", "ref_id": "PMID-14667815_T5" } ] }, { "id": "PMID-14667815_E25", "type": "ResponseProcess", "trigger": { "text": [ "responsiveness" ], "offsets": [ [ 1879, 1893 ] ] }, "arguments": [ { "role": "hasAgent", "ref_id": "PMID-14667815_T90" } ] } ]

[]

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[ { "id": "PMID-1493333__text", "type": "abstract", "text": [ "I kappa B/MAD-3 masks the nuclear localization signal of NF-kappa B p65 and requires the transactivation domain to inhibit NF-kappa B p65 DNA binding. The active nuclear form of the NF-kappa B transcription factor complex is composed of two DNA binding subunits, NF-kappa B p65 and NF-kappa B p50, both of which share extensive N-terminal sequence homology with the v-rel oncogene product. The NF-kappa B p65 subunit provides the transactivation activity in this complex and serves as an intracellular receptor for a cytoplasmic inhibitor of NF-kappa B, termed I kappa B. In contrast, NF-kappa B p50 alone fails to stimulate kappa B-directed transcription, and based on prior in vitro studies, is not directly regulated by I kappa B. To investigate the molecular basis for the critical regulatory interaction between NF-kappa B and I kappa B/MAD-3, a series of human NF-kappa B p65 mutants was identified that functionally segregated DNA binding, I kappa B-mediated inhibition, and I kappa B-induced nuclear exclusion of this transcription factor. Results from in vivo expression studies performed with these NF-kappa B p65 mutants revealed the following: 1) I kappa B/MAD-3 completely inhibits NF-kappa B p65-dependent transcriptional activation mediated through the human immunodeficiency virus type 1 kappa B enhancer in human T lymphocytes, 2) the binding of I kappa B/MAD-3 to NF-kappa B p65 is sufficient to retarget NF-kappa B p65 from the nucleus to the cytoplasm, 3) selective deletion of the functional nuclear localization signal present in the Rel homology domain of NF-kappa B p65 disrupts its ability to engage I kappa B/MAD-3, and 4) the unique C-terminus of NF-kappa B p65 attenuates its own nuclear localization and contains sequences that are required for I kappa B-mediated inhibition of NF-kappa B p65 DNA binding activity. Together, these findings suggest that the nuclear localization signal and transactivation domain of NF-kappa B p65 constitute a bipartite system that is critically involved in the inhibitory function of I kappa B/MAD-3. Unexpectedly, our in vivo studies also demonstrate that I kappa B/MAD-3 binds directly to NF-kappa B p50. This interaction is functional as it leads to retargeting of NF-kappa B p50 from the nucleus to the cytoplasm. However, no loss of DNA binding activity is observed, presumably reflecting the unique C-terminal domain that is distinct from that present in NF-kappa B p65.\n" ], "offsets": [ [ 0, 2440 ] ] } ]

[ { "id": "PMID-1493333_T1", "type": "Protein", "text": [ "I kappa B/MAD-3" ], "offsets": [ [ 0, 15 ] ], "normalized": [] }, { "id": "PMID-1493333_T2", "type": "ProteinSubunit", "text": [ "NF-kappa B p65" ], "offsets": [ [ 57, 71 ] ], "normalized": [] }, { "id": "PMID-1493333_T3", "type": "ProteinDomain", "text": [ "transactivation domain" ], "offsets": [ [ 89, 111 ] ], "normalized": [] }, { "id": "PMID-1493333_T5", "type": "ProteinSubunit", "text": [ "NF-kappa B p65" ], "offsets": [ [ 123, 137 ] ], "normalized": [] }, { "id": "PMID-1493333_T6", "type": "DNA", "text": [ "DNA" ], "offsets": [ [ 138, 141 ] ], "normalized": [] }, { "id": "PMID-1493333_T8", "type": "TranscriptionFactorComplex", "text": [ "NF-kappa B" ], "offsets": [ [ 182, 192 ] ], "normalized": [] }, { "id": "PMID-1493333_T9", "type": "TranscriptionFactorComplex", "text": [ "transcription factor complex" ], "offsets": [ [ 193, 221 ] ], "normalized": [] }, { "id": "PMID-1493333_T10", "type": "DNA", "text": [ "DNA" ], "offsets": [ [ 241, 244 ] ], "normalized": [] }, { "id": "PMID-1493333_T12", "type": "ProteinSubunit", "text": [ "subunits" ], "offsets": [ [ 253, 261 ] ], "normalized": [] }, { "id": "PMID-1493333_T13", "type": "ProteinSubunit", "text": [ "NF-kappa B p65" ], "offsets": [ [ 263, 277 ] ], "normalized": [] }, { "id": "PMID-1493333_T14", "type": "ProteinSubunit", "text": [ "NF-kappa B p50" ], "offsets": [ [ 282, 296 ] ], "normalized": [] }, { "id": "PMID-1493333_T15", "type": "Gene", "text": [ "v-rel oncogene" ], "offsets": [ [ 366, 380 ] ], "normalized": [] }, { "id": "PMID-1493333_T16", "type": "GeneProduct", "text": [ "product" ], "offsets": [ [ 381, 388 ] ], "normalized": [] }, { "id": "PMID-1493333_T17", "type": "ProteinSubunit", "text": [ "NF-kappa B p65" ], "offsets": [ [ 394, 408 ] ], "normalized": [] }, { "id": "PMID-1493333_T18", "type": "TranscriptionFactorComplex", "text": [ "this complex" ], "offsets": [ [ 458, 470 ] ], "normalized": [] }, { "id": "PMID-1493333_T19", "type": "CellComponent", "text": [ "cytoplasmic" ], "offsets": [ [ 517, 528 ] ], "normalized": [] }, { "id": "PMID-1493333_T21", "type": "TranscriptionFactorComplex", "text": [ "NF-kappa B" ], "offsets": [ [ 542, 552 ] ], "normalized": [] }, { "id": "PMID-1493333_T22", "type": "Protein", "text": [ "I kappa B" ], "offsets": [ [ 561, 570 ] ], "normalized": [] }, { "id": "PMID-1493333_T24", "type": "TranscriptionFactorComplex", "text": [ "NF-kappa B" ], "offsets": [ [ 817, 827 ] ], "normalized": [] }, { "id": "PMID-1493333_T25", "type": "Protein", "text": [ "I kappa B/MAD-3" ], "offsets": [ [ 832, 847 ] ], "normalized": [] }, { "id": "PMID-1493333_T26", "type": "Eukaryote", "text": [ "human" ], "offsets": [ [ 861, 866 ] ], "normalized": [] }, { "id": "PMID-1493333_T27", "type": "MutantProtein", "text": [ "NF-kappa B p65 mutants" ], "offsets": [ [ 867, 889 ] ], "normalized": [] }, { "id": "PMID-1493333_T28", "type": "DNA", "text": [ "DNA" ], "offsets": [ [ 934, 937 ] ], "normalized": [] }, { "id": "PMID-1493333_T30", "type": "Protein", "text": [ "I kappa B" ], "offsets": [ [ 947, 956 ] ], "normalized": [] }, { "id": "PMID-1493333_T33", "type": "Protein", "text": [ "I kappa B" ], "offsets": [ [ 982, 991 ] ], "normalized": [] }, { "id": "PMID-1493333_T35", "type": "Nucleus", "text": [ "nuclear" ], "offsets": [ [ 1000, 1007 ] ], "normalized": [] }, { "id": "PMID-1493333_T37", "type": "TranscriptionFactor", "text": [ "transcription factor" ], "offsets": [ [ 1026, 1046 ] ], "normalized": [] }, { "id": "PMID-1493333_T38", "type": "MutantProtein", "text": [ "NF-kappa B p65 mutants" ], "offsets": [ [ 1109, 1131 ] ], "normalized": [] }, { "id": "PMID-1493333_T39", "type": "Protein", "text": [ "I kappa B/MAD-3" ], "offsets": [ [ 1159, 1174 ] ], "normalized": [] }, { "id": "PMID-1493333_T41", "type": "ProteinSubunit", "text": [ "NF-kappa B p65" ], "offsets": [ [ 1195, 1209 ] ], "normalized": [] }, { "id": "PMID-1493333_T45", "type": "Virus", "text": [ "human immunodeficiency virus type 1" ], "offsets": [ [ 1268, 1303 ] ], "normalized": [] }, { "id": "PMID-1493333_T46", "type": "Enhancer", "text": [ "kappa B enhancer" ], "offsets": [ [ 1304, 1320 ] ], "normalized": [] }, { "id": "PMID-1493333_T47", "type": "Eukaryote", "text": [ "human" ], "offsets": [ [ 1324, 1329 ] ], "normalized": [] }, { "id": "PMID-1493333_T48", "type": "Cell", "text": [ "T lymphocytes" ], "offsets": [ [ 1330, 1343 ] ], "normalized": [] }, { "id": "PMID-1493333_T50", "type": "Protein", "text": [ "I kappa B/MAD-3" ], "offsets": [ [ 1363, 1378 ] ], "normalized": [] }, { "id": "PMID-1493333_T51", "type": "ProteinSubunit", "text": [ "NF-kappa B p65" ], "offsets": [ [ 1382, 1396 ] ], "normalized": [] }, { "id": "PMID-1493333_T53", "type": "ProteinSubunit", "text": [ "NF-kappa B p65" ], "offsets": [ [ 1423, 1437 ] ], "normalized": [] }, { "id": "PMID-1493333_T54", "type": "Nucleus", "text": [ "nucleus" ], "offsets": [ [ 1447, 1454 ] ], "normalized": [] }, { "id": "PMID-1493333_T55", "type": "CellComponent", "text": [ "cytoplasm" ], "offsets": [ [ 1462, 1471 ] ], "normalized": [] }, { "id": "PMID-1493333_T56", "type": "GeneProduct", "text": [ "Rel" ], "offsets": [ [ 1556, 1559 ] ], "normalized": [] }, { "id": "PMID-1493333_T57", "type": "ProteinDomain", "text": [ "homology domain" ], "offsets": [ [ 1560, 1575 ] ], "normalized": [] }, { "id": "PMID-1493333_T58", "type": "ProteinSubunit", "text": [ "NF-kappa B p65" ], "offsets": [ [ 1579, 1593 ] ], "normalized": [] }, { "id": "PMID-1493333_T59", "type": "Protein", "text": [ "I kappa B/MAD-3" ], "offsets": [ [ 1625, 1640 ] ], "normalized": [] }, { "id": "PMID-1493333_T60", "type": "ProteinDomain", "text": [ "C-terminus" ], "offsets": [ [ 1660, 1670 ] ], "normalized": [] }, { "id": "PMID-1493333_T61", "type": "ProteinSubunit", "text": [ "NF-kappa B p65" ], "offsets": [ [ 1674, 1688 ] ], "normalized": [] }, { "id": "PMID-1493333_T63", "type": "Nucleus", "text": [ "nuclear" ], "offsets": [ [ 1708, 1715 ] ], "normalized": [] }, { "id": "PMID-1493333_T65", "type": "Sequence", "text": [ "sequences" ], "offsets": [ [ 1742, 1751 ] ], "normalized": [] }, { "id": "PMID-1493333_T66", "type": "Protein", "text": [ "I kappa B" ], "offsets": [ [ 1774, 1783 ] ], "normalized": [] }, { "id": "PMID-1493333_T69", "type": "ProteinSubunit", "text": [ "NF-kappa B p65" ], "offsets": [ [ 1807, 1821 ] ], "normalized": [] }, { "id": "PMID-1493333_T70", "type": "DNA", "text": [ "DNA" ], "offsets": [ [ 1822, 1825 ] ], "normalized": [] }, { "id": "PMID-1493333_T72", "type": "ProteinDomain", "text": [ "transactivation domain" ], "offsets": [ [ 1918, 1940 ] ], "normalized": [] }, { "id": "PMID-1493333_T73", "type": "ProteinSubunit", "text": [ "NF-kappa B p65" ], "offsets": [ [ 1944, 1958 ] ], "normalized": [] }, { "id": "PMID-1493333_T74", "type": "Function", "text": [ "inhibitory function" ], "offsets": [ [ 2024, 2043 ] ], "normalized": [] }, { "id": "PMID-1493333_T75", "type": "Protein", "text": [ "I kappa B/MAD-3" ], "offsets": [ [ 2047, 2062 ] ], "normalized": [] }, { "id": "PMID-1493333_T76", "type": "Protein", "text": [ "I kappa B/MAD-3" ], "offsets": [ [ 2120, 2135 ] ], "normalized": [] }, { "id": "PMID-1493333_T78", "type": "ProteinSubunit", "text": [ "NF-kappa B p50" ], "offsets": [ [ 2154, 2168 ] ], "normalized": [] }, { "id": "PMID-1493333_T81", "type": "ProteinSubunit", "text": [ "NF-kappa B p50" ], "offsets": [ [ 2231, 2245 ] ], "normalized": [] }, { "id": "PMID-1493333_T82", "type": "Nucleus", "text": [ "nucleus" ], "offsets": [ [ 2255, 2262 ] ], "normalized": [] }, { "id": "PMID-1493333_T83", "type": "CellComponent", "text": [ "cytoplasm" ], "offsets": [ [ 2270, 2279 ] ], "normalized": [] }, { "id": "PMID-1493333_T84", "type": "ProteinDomain", "text": [ "domain" ], "offsets": [ [ 2379, 2385 ] ], "normalized": [] }, { "id": "PMID-1493333_T85", "type": "ProteinSubunit", "text": [ "NF-kappa B p65" ], "offsets": [ [ 2424, 2438 ] ], "normalized": [] }, { "id": "PMID-1493333_T86", "type": "Nucleus", "text": [ "nuclear" ], "offsets": [ [ 26, 33 ] ], "normalized": [] }, { "id": "PMID-1493333_T43", "type": "Nucleus", "text": [ "nuclear" ], "offsets": [ [ 1513, 1520 ] ], "normalized": [] }, { "id": "PMID-1493333_T91", "type": "Peptide", "text": [ "signal" ], "offsets": [ [ 1534, 1540 ] ], "normalized": [] }, { "id": "PMID-1493333_T93", "type": "ProteinSubunit", "text": [ "its" ], "offsets": [ [ 1603, 1606 ] ], "normalized": [] }, { "id": "PMID-1493333_T95", "type": "Nucleus", "text": [ "nuclear" ], "offsets": [ [ 1886, 1893 ] ], "normalized": [] } ]

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"BindingOfProteinToDNA", "trigger": { "text": [ "binding" ], "offsets": [ [ 938, 945 ] ] }, "arguments": [ { "role": "hasPatient", "ref_id": "PMID-1493333_T28" } ] }, { "id": "PMID-1493333_E7", "type": "RegulatoryProcess", "trigger": { "text": [ "mediated" ], "offsets": [ [ 957, 965 ] ] }, "arguments": [ { "role": "hasAgent", "ref_id": "PMID-1493333_T30" }, { "role": "hasPatient", "ref_id": "PMID-1493333_E8" } ] }, { "id": "PMID-1493333_E8", "type": "NegativeRegulation", "trigger": { "text": [ "inhibition" ], "offsets": [ [ 966, 976 ] ] }, "arguments": [] }, { "id": "PMID-1493333_E9", "type": "PositiveRegulation", "trigger": { "text": [ "induced" ], "offsets": [ [ 992, 999 ] ] }, "arguments": [ { "role": "hasAgent", "ref_id": "PMID-1493333_T33" }, { "role": "hasPatient", "ref_id": "PMID-1493333_E10" } ] }, { "id": "PMID-1493333_E10", "type": "Transport", "trigger": { "text": [ "exclusion" ], "offsets": [ [ 1008, 1017 ] ] }, "arguments": [ { "role": "hasPatient", "ref_id": "PMID-1493333_T37" } ] }, { "id": "PMID-1493333_E11", "type": "NegativeRegulation", "trigger": { "text": [ "inhibits" ], "offsets": [ [ 1186, 1194 ] ] }, "arguments": [ { "role": "hasAgent", "ref_id": "PMID-1493333_T39" }, { "role": "hasPatient", "ref_id": "PMID-1493333_E12" } ] }, { "id": "PMID-1493333_E14", "type": "RegulatoryProcess", "trigger": { "text": [ "mediated" ], "offsets": [ [ 1247, 1255 ] ] }, "arguments": [ { "role": "hasAgent", "ref_id": "PMID-1493333_T46" }, { "role": "hasPatient", "ref_id": "PMID-1493333_E12" } ] }, { "id": "PMID-1493333_E15", "type": "BindingToProtein", "trigger": { "text": [ "binding" ], "offsets": [ [ 1352, 1359 ] ] }, "arguments": [ { "role": "hasPatient", "ref_id": "PMID-1493333_T51" }, { "role": "hasPatient2", "ref_id": "PMID-1493333_T50" } ] }, { "id": "PMID-1493333_E16", "type": "ProteinTargeting", "trigger": { "text": [ "retarget" ], "offsets": [ [ 1414, 1422 ] ] }, "arguments": [ { "role": "hasAgent", "ref_id": "PMID-1493333_E15" }, { "role": "hasPatient", "ref_id": "PMID-1493333_T53" } ] }, { "id": "PMID-1493333_E17", "type": "NegativeRegulation", "trigger": { "text": [ "attenuates" ], "offsets": [ [ 1689, 1699 ] ] }, "arguments": [ { "role": "hasAgent", "ref_id": "PMID-1493333_T60" }, { "role": "hasPatient", "ref_id": "PMID-1493333_E18" } ] }, { "id": "PMID-1493333_E18", "type": "Localization", "trigger": { "text": [ "localization" ], "offsets": [ [ 1716, 1728 ] ] }, "arguments": [] }, { "id": "PMID-1493333_E19", "type": "RegulatoryProcess", "trigger": { "text": [ "mediated" ], "offsets": [ [ 1784, 1792 ] ] }, "arguments": [ { "role": "hasAgent", "ref_id": "PMID-1493333_T66" }, { "role": "hasPatient", "ref_id": "PMID-1493333_E20" } ] }, { "id": "PMID-1493333_E20", "type": "NegativeRegulation", "trigger": { "text": [ "inhibition" ], "offsets": [ [ 1793, 1803 ] ] }, "arguments": [ { "role": "hasPatient", "ref_id": "PMID-1493333_E21" } ] }, { "id": "PMID-1493333_E21", "type": "BindingOfProteinToDNA", "trigger": { "text": [ "binding activity" ], "offsets": [ [ 1826, 1842 ] ] }, "arguments": [ { "role": "hasAgent", "ref_id": "PMID-1493333_T69" }, { "role": "hasPatient", "ref_id": "PMID-1493333_T70" } ] }, { "id": "PMID-1493333_E22", "type": "BindingToProtein", "trigger": { "text": [ "binds" ], "offsets": [ [ 2136, 2141 ] ] }, "arguments": [ { "role": "hasPatient", "ref_id": "PMID-1493333_T78" }, { "role": "hasPatient2", "ref_id": "PMID-1493333_T76" } ] }, { "id": "PMID-1493333_E23", "type": "BindingToProtein", "trigger": { "text": [ "interaction" ], "offsets": [ [ 2175, 2186 ] ] }, "arguments": [] }, { "id": "PMID-1493333_E24", "type": "ProteinTargeting", "trigger": { "text": [ "retargeting" ], "offsets": [ [ 2216, 2227 ] ] }, "arguments": [ { "role": "hasPatient", "ref_id": "PMID-1493333_T81" } ] }, { "id": "PMID-1493333_E25", "type": "Localization", "trigger": { "text": [ "localization" ], "offsets": [ [ 34, 46 ] ] }, "arguments": [ { "role": "hasPatient", "ref_id": "PMID-1493333_T2" } ] }, { "id": "PMID-1493333_E5", "type": "RegulatoryProcess", "trigger": { "text": [ "regulatory" ], "offsets": [ [ 786, 796 ] ] }, "arguments": [ { "role": "hasAgent", "ref_id": "PMID-1493333_E26" } ] }, { "id": "PMID-1493333_E26", "type": "BindingToProtein", "trigger": { "text": [ "interaction" ], "offsets": [ [ 797, 808 ] ] }, "arguments": [ { "role": "hasPatient", "ref_id": "PMID-1493333_T24" }, { "role": "hasPatient2", "ref_id": "PMID-1493333_T25" } ] }, { "id": "PMID-1493333_E12", "type": "PositiveRegulationOfTranscription", "trigger": { "text": [ "transcriptional activation" ], "offsets": [ [ 1220, 1246 ] ] }, "arguments": [] }, { "id": "PMID-1493333_E13", "type": "Localization", "trigger": { "text": [ "localization" ], "offsets": [ [ 1521, 1533 ] ] }, "arguments": [] }, { "id": "PMID-1493333_E27", "type": "Mutation", "trigger": { "text": [ "deletion" ], "offsets": [ [ 1486, 1494 ] ] }, "arguments": [ { "role": "hasPatient", "ref_id": "PMID-1493333_T91" } ] }, { "id": "PMID-1493333_E28", "type": "NegativeRegulation", "trigger": { "text": [ "disrupts" ], "offsets": [ [ 1594, 1602 ] ] }, "arguments": [ { "role": "hasAgent", "ref_id": "PMID-1493333_E27" }, { "role": "hasPatient", "ref_id": "PMID-1493333_E29" } ] }, { "id": "PMID-1493333_E29", "type": "BindingToProtein", "trigger": { "text": [ "engage" ], "offsets": [ [ 1618, 1624 ] ] }, "arguments": [ { "role": "hasPatient", "ref_id": "PMID-1493333_T93" }, { "role": "hasPatient2", "ref_id": "PMID-1493333_T59" } ] }, { "id": "PMID-1493333_E30", "type": "Localization", "trigger": { "text": [ "localization" ], "offsets": [ [ 1894, 1906 ] ] }, "arguments": [ { "role": "hasPatient", "ref_id": "PMID-1493333_T73" } ] } ]

[]

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[ { "id": "PMID-1502157__text", "type": "abstract", "text": [ "MAZ, a zinc finger protein, binds to c-MYC and C2 gene sequences regulating transcriptional initiation and termination. ME1a1, a 16-base-pair nuclear factor binding site residing between the c-MYC P1 and P2 transcription initiation sites, is required for P2 activity. A cDNA encoding a 477-amino acid zinc finger protein designated MAZ (MYC-associated zinc finger protein) was cloned from a HeLa lambda gt11 library by screening with a concatamerized ME1a1 binding site probe. In addition to six potential zinc fingers of the Cys2His2 type, MAZ contains an amino-terminal proline-rich domain and several polyalanine tracts. Its mRNA was present in all human tissues tested except for kidney, as a doublet of approximately 2.5 and 2.7 kilobases, along with differentially expressed minor species. MAZ bound specifically to the wild-type ME1a1 sequence but not to a ME1a1 mutant that also failed to yield P2 activity. When expressed as a fusion protein in a pMAL-c vector, MAZ binds with specificity to a GA box sequence (GGGAGGG) found in the c-MYC P2 promoter, to the P2 attenuator region within the gene's first exon, and to a related sequence involved in the transcriptional termination of the C2 gene. MAZ may encode a transcription factor with dual roles in transcription initiation and termination.\n" ], "offsets": [ [ 0, 1304 ] ] } ]

[ { "id": "PMID-1502157_T1", "type": "Protein", "text": [ "MAZ" ], "offsets": [ [ 0, 3 ] ], "normalized": [] }, { "id": "PMID-1502157_T2", "type": "Protein", "text": [ "zinc finger protein" ], "offsets": [ [ 7, 26 ] ], "normalized": [] }, { "id": "PMID-1502157_T4", "type": "Gene", "text": [ "c-MYC" ], "offsets": [ [ 37, 42 ] ], "normalized": [] }, { "id": "PMID-1502157_T5", "type": "Gene", "text": [ "C2 gene" ], "offsets": [ [ 47, 54 ] ], "normalized": [] }, { "id": "PMID-1502157_T9", "type": "ProteinBindingSiteOfDNA", "text": [ "ME1a1" ], "offsets": [ [ 120, 125 ] ], "normalized": [] }, { "id": "PMID-1502157_T10", "type": "Protein", "text": [ "nuclear factor" ], "offsets": [ [ 142, 156 ] ], "normalized": [] }, { "id": "PMID-1502157_T11", "type": "ProteinBindingSiteOfDNA", "text": [ "binding site" ], "offsets": [ [ 157, 169 ] ], "normalized": [] }, { "id": "PMID-1502157_T12", "type": "Gene", "text": [ "c-MYC" ], "offsets": [ [ 191, 196 ] ], "normalized": [] }, { "id": "PMID-1502157_T13", "type": "Promoter", "text": [ "P1" ], "offsets": [ [ 197, 199 ] ], "normalized": [] }, { "id": "PMID-1502157_T14", "type": "Promoter", "text": [ "P2" ], "offsets": [ [ 204, 206 ] ], "normalized": [] }, { "id": "PMID-1502157_T15", "type": "Promoter", "text": [ "P2" ], "offsets": [ [ 255, 257 ] ], "normalized": [] }, { "id": "PMID-1502157_T16", "type": "DNA", "text": [ "cDNA" ], "offsets": [ [ 270, 274 ] ], "normalized": [] }, { "id": "PMID-1502157_T17", "type": "AminoAcid", "text": [ "amino acid" ], "offsets": [ [ 290, 300 ] ], "normalized": [] }, { "id": "PMID-1502157_T18", "type": "Protein", "text": [ "zinc finger protein" ], "offsets": [ [ 301, 320 ] ], "normalized": [] }, { "id": "PMID-1502157_T19", "type": "Protein", "text": [ "MAZ" ], "offsets": [ [ 332, 335 ] ], "normalized": [] }, { "id": "PMID-1502157_T20", "type": "Cell", "text": [ "HeLa" ], "offsets": [ [ 391, 395 ] ], "normalized": [] }, { "id": "PMID-1502157_T21", "type": "ProteinBindingSiteOfDNA", "text": [ "ME1a1 binding site" ], "offsets": [ [ 451, 469 ] ], "normalized": [] }, { "id": "PMID-1502157_T22", "type": "Protein", "text": [ "MAZ" ], "offsets": [ [ 541, 544 ] ], "normalized": [] }, { "id": "PMID-1502157_T23", "type": "ProteinDomain", "text": [ "proline-rich domain" ], "offsets": [ [ 572, 591 ] ], "normalized": [] }, { "id": "PMID-1502157_T24", "type": "Sequence", "text": [ "polyalanine tracts" ], "offsets": [ [ 604, 622 ] ], "normalized": [] }, { "id": "PMID-1502157_T25", "type": "MessengerRNA", "text": [ "mRNA" ], "offsets": [ [ 628, 632 ] ], "normalized": [] }, { "id": "PMID-1502157_T26", "type": "Eukaryote", "text": [ "human" ], "offsets": [ [ 652, 657 ] ], "normalized": [] }, { "id": "PMID-1502157_T27", "type": "Tissue", "text": [ "tissues" ], "offsets": [ [ 658, 665 ] ], "normalized": [] }, { "id": "PMID-1502157_T29", "type": "Protein", "text": [ "MAZ" ], "offsets": [ [ 796, 799 ] ], "normalized": [] }, { "id": "PMID-1502157_T31", "type": "ProteinBindingSiteOfDNA", "text": [ "ME1a1" ], "offsets": [ [ 836, 841 ] ], "normalized": [] }, { "id": "PMID-1502157_T32", "type": "Protein", "text": [ "fusion protein" ], "offsets": [ [ 936, 950 ] ], "normalized": [] }, { "id": "PMID-1502157_T33", "type": "DNA", "text": [ "pMAL-c vector" ], "offsets": [ [ 956, 969 ] ], "normalized": [] }, { "id": "PMID-1502157_T34", "type": "Protein", "text": [ "MAZ" ], "offsets": [ [ 971, 974 ] ], "normalized": [] }, { "id": "PMID-1502157_T36", "type": "Sequence", "text": [ "GA box sequence (GGGAGGG)" ], "offsets": [ [ 1003, 1028 ] ], "normalized": [] }, { "id": "PMID-1502157_T37", "type": "Gene", "text": [ "c-MYC" ], "offsets": [ [ 1042, 1047 ] ], "normalized": [] }, { "id": "PMID-1502157_T38", "type": "Promoter", "text": [ "P2 promoter" ], "offsets": [ [ 1048, 1059 ] ], "normalized": [] }, { "id": "PMID-1502157_T39", "type": "Promoter", "text": [ "P2" ], "offsets": [ [ 1068, 1070 ] ], "normalized": [] }, { "id": "PMID-1502157_T40", "type": "Attenuator", "text": [ "attenuator region" ], "offsets": [ [ 1071, 1088 ] ], "normalized": [] }, { "id": "PMID-1502157_T41", "type": "Gene", "text": [ "gene's" ], "offsets": [ [ 1100, 1106 ] ], "normalized": [] }, { "id": "PMID-1502157_T42", "type": "Exon", "text": [ "exon" ], "offsets": [ [ 1113, 1117 ] ], "normalized": [] }, { "id": "PMID-1502157_T43", "type": "Sequence", "text": [ "sequence" ], "offsets": [ [ 1136, 1144 ] ], "normalized": [] }, { "id": "PMID-1502157_T45", "type": "Gene", "text": [ "C2 gene" ], "offsets": [ [ 1196, 1203 ] ], "normalized": [] }, { "id": "PMID-1502157_T46", "type": "Gene", "text": [ "MAZ" ], "offsets": [ [ 1205, 1208 ] ], "normalized": [] }, { "id": "PMID-1502157_T47", "type": "TranscriptionFactor", "text": [ "transcription factor" ], "offsets": [ [ 1222, 1242 ] ], "normalized": [] }, { "id": "PMID-1502157_T50", "type": "ZincCoordinatingDomain", "text": [ "zinc fingers of the Cys2His2 type" ], "offsets": [ [ 506, 539 ] ], "normalized": [] } ]

[ { "id": "PMID-1502157_E1", "type": "BindingOfProteinToDNA", "trigger": { "text": [ "binds" ], "offsets": [ [ 28, 33 ] ] }, "arguments": [ { "role": "hasAgent", "ref_id": "PMID-1502157_T1" }, { "role": "hasPatient", "ref_id": "PMID-1502157_T4" } ] }, { "id": "PMID-1502157_E2", "type": "RegulatoryProcess", "trigger": { "text": [ "regulating" ], "offsets": [ [ 65, 75 ] ] }, "arguments": [ { "role": "hasPatient", "ref_id": "PMID-1502157_E3" }, { "role": "hasAgent", "ref_id": "PMID-1502157_E1" } ] }, { "id": "PMID-1502157_E3", "type": "TranscriptionInitiation", "trigger": { "text": [ "transcriptional initiation" ], "offsets": [ [ 76, 102 ] ] }, "arguments": [] }, { "id": "PMID-1502157_E5", "type": "TranscriptionOfGene", "trigger": { "text": [ "expressed" ], "offsets": [ [ 771, 780 ] ] }, "arguments": [ { "role": "hasPatient", "ref_id": "PMID-1502157_T25" } ] }, { "id": "PMID-1502157_E6", "type": "BindingOfProteinToDNA", "trigger": { "text": [ "bound" ], "offsets": [ [ 800, 805 ] ] }, "arguments": [ { "role": "hasAgent", "ref_id": "PMID-1502157_T29" }, { "role": "hasPatient", "ref_id": "PMID-1502157_T31" } ] }, { "id": "PMID-1502157_E7", "type": "BindingOfProteinToDNA", "trigger": { "text": [ "binds" ], "offsets": [ [ 975, 980 ] ] }, "arguments": [ { "role": "hasAgent", "ref_id": "PMID-1502157_T34" }, { "role": "hasPatient", "ref_id": "PMID-1502157_T36" } ] }, { "id": "PMID-1502157_E8", "type": "TranscriptionTermination", "trigger": { "text": [ "transcriptional termination" ], "offsets": [ [ 1161, 1188 ] ] }, "arguments": [ { "role": "hasPatient", "ref_id": "PMID-1502157_T45" } ] }, { "id": "PMID-1502157_E9", "type": "TranscriptionInitiation", "trigger": { "text": [ "transcription initiation" ], "offsets": [ [ 1262, 1286 ] ] }, "arguments": [] }, { "id": "PMID-1502157_E4", "type": "TranscriptionTermination", "trigger": { "text": [ "termination" ], "offsets": [ [ 107, 118 ] ] }, "arguments": [] }, { "id": "PMID-1502157_E11", "type": "GeneExpression", "trigger": { "text": [ "expressed" ], "offsets": [ [ 921, 930 ] ] }, "arguments": [ { "role": "hasPatient", "ref_id": "PMID-1502157_T32" } ] }, { "id": "PMID-1502157_E10", "type": "TranscriptionTermination", "trigger": { "text": [ "termination" ], "offsets": [ [ 1291, 1302 ] ] }, "arguments": [] }, { "id": "PMID-1502157_E12", "type": "RegulatoryProcess", "trigger": { "text": [ "regulating" ], "offsets": [ [ 65, 75 ] ] }, "arguments": [ { "role": "hasPatient", "ref_id": "PMID-1502157_E4" }, { "role": "hasAgent", "ref_id": "PMID-1502157_E1" } ] }, { "id": "PMID-1502157_E13", "type": "BindingOfProteinToDNA", "trigger": { "text": [ "binds" ], "offsets": [ [ 28, 33 ] ] }, "arguments": [ { "role": "hasAgent", "ref_id": "PMID-1502157_T1" }, { "role": "hasPatient", "ref_id": "PMID-1502157_T5" } ] }, { "id": "PMID-1502157_E14", "type": "RegulatoryProcess", "trigger": { "text": [ "regulating" ], "offsets": [ [ 65, 75 ] ] }, "arguments": [ { "role": "hasPatient", "ref_id": "PMID-1502157_E4" }, { "role": "hasAgent", "ref_id": "PMID-1502157_E13" } ] }, { "id": "PMID-1502157_E15", "type": "RegulatoryProcess", "trigger": { "text": [ "regulating" ], "offsets": [ [ 65, 75 ] ] }, "arguments": [ { "role": "hasPatient", "ref_id": "PMID-1502157_E3" }, { "role": "hasAgent", "ref_id": "PMID-1502157_E13" } ] }, { "id": "PMID-1502157_E16", "type": "BindingOfProteinToDNA", "trigger": { "text": [ "binds" ], "offsets": [ [ 975, 980 ] ] }, "arguments": [ { "role": "hasAgent", "ref_id": "PMID-1502157_T34" }, { "role": "hasPatient", "ref_id": "PMID-1502157_T40" } ] }, { "id": "PMID-1502157_E17", "type": "BindingOfProteinToDNA", "trigger": { "text": [ "binds" ], "offsets": [ [ 975, 980 ] ] }, "arguments": [ { "role": "hasAgent", "ref_id": "PMID-1502157_T34" }, { "role": "hasPatient", "ref_id": "PMID-1502157_T43" } ] } ]

[]

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[ { "id": "PMID-15195100__text", "type": "abstract", "text": [ "PML regulates p53 stability by sequestering Mdm2 to the nucleolus. The promyelocytic leukaemia (PML) tumour-suppressor protein potentiates p53 function by regulating post-translational modifications, such as CBP-dependent acetylation and Chk2-dependent phosphorylation, in the PML-Nuclear Body (NB). PML was recently shown to interact with the p53 ubiquitin-ligase Mdm2 (refs 4-6); however, the mechanism by which PML regulates Mdm2 remains unclear. Here, we show that PML enhances p53 stability by sequestering Mdm2 to the nucleolus. We found that after DNA damage, PML and Mdm2 accumulate in the nucleolus in an Arf-independent manner. In addition, we found that the nucleolar localization of PML is dependent on ATR activation and phosphorylation of PML by ATR. Notably, in Pml(-/-) cells, sequestration of Mdm2 to the nucleolus was impaired, as well as p53 stabilization and the induction of apoptosis. Furthermore, we demonstrate that PML physically associates with the nucleolar protein L11, and that L11 knockdown impairs the ability of PML to localize to nucleoli after DNA damage. These findings demonstrate an unexpected role of PML in the nucleolar network for tumour suppression.\n" ], "offsets": [ [ 0, 1192 ] ] } ]

[ { "id": "PMID-15195100_T1", "type": "Protein", "text": [ "PML" ], "offsets": [ [ 0, 3 ] ], "normalized": [] }, { "id": "PMID-15195100_T3", "type": "Protein", "text": [ "p53" ], "offsets": [ [ 14, 17 ] ], "normalized": [] }, { "id": "PMID-15195100_T5", "type": "Enzyme", "text": [ "Mdm2" ], "offsets": [ [ 44, 48 ] ], "normalized": [] }, { "id": "PMID-15195100_T6", "type": "Nucleus", "text": [ "nucleolus" ], "offsets": [ [ 56, 65 ] ], "normalized": [] }, { "id": "PMID-15195100_T7", "type": "Protein", "text": [ "promyelocytic leukaemia (PML) tumour-suppressor protein" ], "offsets": [ [ 71, 126 ] ], "normalized": [] }, { "id": "PMID-15195100_T10", "type": "Protein", "text": [ "p53" ], "offsets": [ [ 139, 142 ] ], "normalized": [] }, { "id": "PMID-15195100_T11", "type": "Function", "text": [ "function" ], "offsets": [ [ 143, 151 ] ], "normalized": [] }, { "id": "PMID-15195100_T14", "type": "Protein", "text": [ "CBP" ], "offsets": [ [ 208, 211 ] ], "normalized": [] }, { "id": "PMID-15195100_T16", "type": "Enzyme", "text": [ "Chk2" ], "offsets": [ [ 238, 242 ] ], "normalized": [] }, { "id": "PMID-15195100_T18", "type": "Nucleus", "text": [ "PML-Nuclear Body" ], "offsets": [ [ 277, 293 ] ], "normalized": [] }, { "id": "PMID-15195100_T19", "type": "Nucleus", "text": [ "NB" ], "offsets": [ [ 295, 297 ] ], "normalized": [] }, { "id": "PMID-15195100_T20", "type": "Protein", "text": [ "PML" ], "offsets": [ [ 300, 303 ] ], "normalized": [] }, { "id": "PMID-15195100_T25", "type": "Enzyme", "text": [ "Mdm2" ], "offsets": [ [ 365, 369 ] ], "normalized": [] }, { "id": "PMID-15195100_T26", "type": "Protein", "text": [ "PML" ], "offsets": [ [ 414, 417 ] ], "normalized": [] }, { "id": "PMID-15195100_T28", "type": "Enzyme", "text": [ "Mdm2" ], "offsets": [ [ 428, 432 ] ], "normalized": [] }, { "id": "PMID-15195100_T29", "type": "Protein", "text": [ "PML" ], "offsets": [ [ 469, 472 ] ], "normalized": [] }, { "id": "PMID-15195100_T31", "type": "Protein", "text": [ "p53" ], "offsets": [ [ 482, 485 ] ], "normalized": [] }, { "id": "PMID-15195100_T33", "type": "Enzyme", "text": [ "Mdm2" ], "offsets": [ [ 512, 516 ] ], "normalized": [] }, { "id": "PMID-15195100_T34", "type": "Nucleus", "text": [ "nucleolus" ], "offsets": [ [ 524, 533 ] ], "normalized": [] }, { "id": "PMID-15195100_T35", "type": "DNA", "text": [ "DNA" ], "offsets": [ [ 555, 558 ] ], "normalized": [] }, { "id": "PMID-15195100_T37", "type": "Protein", "text": [ "PML" ], "offsets": [ [ 567, 570 ] ], "normalized": [] }, { "id": "PMID-15195100_T38", "type": "Enzyme", "text": [ "Mdm2" ], "offsets": [ [ 575, 579 ] ], "normalized": [] }, { "id": "PMID-15195100_T40", "type": "Nucleus", "text": [ "nucleolus" ], "offsets": [ [ 598, 607 ] ], "normalized": [] }, { "id": "PMID-15195100_T41", "type": "Protein", "text": [ "Arf" ], "offsets": [ [ 614, 617 ] ], "normalized": [] }, { "id": "PMID-15195100_T42", "type": "Nucleus", "text": [ "nucleolar" ], "offsets": [ [ 669, 678 ] ], "normalized": [] }, { "id": "PMID-15195100_T44", "type": "Protein", "text": [ "PML" ], "offsets": [ [ 695, 698 ] ], "normalized": [] }, { "id": "PMID-15195100_T45", "type": "Enzyme", "text": [ "ATR" ], "offsets": [ [ 715, 718 ] ], "normalized": [] }, { "id": "PMID-15195100_T48", "type": "Protein", "text": [ "PML" ], "offsets": [ [ 753, 756 ] ], "normalized": [] }, { "id": "PMID-15195100_T49", "type": "Enzyme", "text": [ "ATR" ], "offsets": [ [ 760, 763 ] ], "normalized": [] }, { "id": "PMID-15195100_T50", "type": "Cell", "text": [ "Pml(-/-) cells" ], "offsets": [ [ 777, 791 ] ], "normalized": [] }, { "id": "PMID-15195100_T52", "type": "Enzyme", "text": [ "Mdm2" ], "offsets": [ [ 810, 814 ] ], "normalized": [] }, { "id": "PMID-15195100_T53", "type": "Nucleus", "text": [ "nucleolus" ], "offsets": [ [ 822, 831 ] ], "normalized": [] }, { "id": "PMID-15195100_T55", "type": "Protein", "text": [ "p53" ], "offsets": [ [ 857, 860 ] ], "normalized": [] }, { "id": "PMID-15195100_T58", "type": "Protein", "text": [ "PML" ], "offsets": [ [ 940, 943 ] ], "normalized": [] }, { "id": "PMID-15195100_T60", "type": "Protein", "text": [ "nucleolar protein L11" ], "offsets": [ [ 975, 996 ] ], "normalized": [] }, { "id": "PMID-15195100_T61", "type": "Protein", "text": [ "L11" ], "offsets": [ [ 1007, 1010 ] ], "normalized": [] }, { "id": "PMID-15195100_T64", "type": "Protein", "text": [ "PML" ], "offsets": [ [ 1044, 1047 ] ], "normalized": [] }, { "id": "PMID-15195100_T66", "type": "Nucleus", "text": [ "nucleoli" ], "offsets": [ [ 1063, 1071 ] ], "normalized": [] }, { "id": "PMID-15195100_T67", "type": "DNA", "text": [ "DNA" ], "offsets": [ [ 1078, 1081 ] ], "normalized": [] }, { "id": "PMID-15195100_T69", "type": "Protein", "text": [ "PML" ], "offsets": [ [ 1139, 1142 ] ], "normalized": [] }, { "id": "PMID-15195100_T70", "type": "Nucleus", "text": [ "nucleolar" ], "offsets": [ [ 1150, 1159 ] ], "normalized": [] }, { "id": "PMID-15195100_T8", "type": "Enzyme", "text": [ "p53 ubiquitin-ligase" ], "offsets": [ [ 344, 364 ] ], "normalized": [] } ]

[ { "id": "PMID-15195100_E1", "type": "RegulatoryProcess", "trigger": { "text": [ "regulates" ], "offsets": [ [ 4, 13 ] ] }, "arguments": [ { "role": "hasAgent", "ref_id": "PMID-15195100_T1" }, { "role": "hasPatient", "ref_id": "PMID-15195100_T3" } ] }, { "id": "PMID-15195100_E2", "type": "Localization", "trigger": { "text": [ "sequestering" ], "offsets": [ [ 31, 43 ] ] }, "arguments": [ { "role": "hasPatient", "ref_id": "PMID-15195100_T5" } ] }, { "id": "PMID-15195100_E3", "type": "RegulationOfFunction", "trigger": { "text": [ "potentiates" ], "offsets": [ [ 127, 138 ] ] }, "arguments": [ { "role": "hasAgent", "ref_id": "PMID-15195100_T7" }, { "role": "hasPatient", "ref_id": "PMID-15195100_T11" } ] }, { "id": "PMID-15195100_E4", "type": "RegulatoryProcess", "trigger": { "text": [ "regulating" ], "offsets": [ [ 155, 165 ] ] }, "arguments": [ { "role": "hasPatient", "ref_id": "PMID-15195100_E5" } ] }, { "id": "PMID-15195100_E5", "type": "PosttranslationalModification", "trigger": { "text": [ "post-translational modifications" ], "offsets": [ [ 166, 198 ] ] }, "arguments": [] }, { "id": "PMID-15195100_E6", "type": "Acetylation", "trigger": { "text": [ "acetylation" ], "offsets": [ [ 222, 233 ] ] }, "arguments": [] }, { "id": "PMID-15195100_E7", "type": "Phosphorylation", "trigger": { "text": [ "phosphorylation" ], "offsets": [ [ 253, 268 ] ] }, "arguments": [] }, { "id": "PMID-15195100_E8", "type": "BindingToProtein", "trigger": { "text": [ "interact" ], "offsets": [ [ 326, 334 ] ] }, "arguments": [ { "role": "hasPatient", "ref_id": "PMID-15195100_T25" }, { "role": "hasPatient2", "ref_id": "PMID-15195100_T20" } ] }, { "id": "PMID-15195100_E9", "type": "RegulatoryProcess", "trigger": { "text": [ "regulates" ], "offsets": [ [ 418, 427 ] ] }, "arguments": [ { "role": "hasAgent", "ref_id": "PMID-15195100_T26" }, { "role": "hasPatient", "ref_id": "PMID-15195100_T28" } ] }, { "id": "PMID-15195100_E10", "type": "Increase", "trigger": { "text": [ "enhances" ], "offsets": [ [ 473, 481 ] ] }, "arguments": [ { "role": "hasAgent", "ref_id": "PMID-15195100_T29" }, { "role": "hasPatient", "ref_id": "PMID-15195100_T31" } ] }, { "id": "PMID-15195100_E11", "type": "Localization", "trigger": { "text": [ "sequestering" ], "offsets": [ [ 499, 511 ] ] }, "arguments": [ { "role": "hasPatient", "ref_id": "PMID-15195100_T33" } ] }, { "id": "PMID-15195100_E12", "type": "Mutation", "trigger": { "text": [ "damage" ], "offsets": [ [ 559, 565 ] ] }, "arguments": [ { "role": "hasPatient", "ref_id": "PMID-15195100_T35" } ] }, { "id": "PMID-15195100_E13", "type": "Localization", "trigger": { "text": [ "accumulate" ], "offsets": [ [ 580, 590 ] ] }, "arguments": [ { "role": "hasPatient", "ref_id": "PMID-15195100_T37" } ] }, { "id": "PMID-15195100_E14", "type": "Localization", "trigger": { "text": [ "localization" ], "offsets": [ [ 679, 691 ] ] }, "arguments": [ { "role": "hasPatient", "ref_id": "PMID-15195100_T44" }, { "role": "hasAgent", "ref_id": "PMID-15195100_E15" } ] }, { "id": "PMID-15195100_E15", "type": "PositiveRegulation", "trigger": { "text": [ "activation" ], "offsets": [ [ 719, 729 ] ] }, "arguments": [ { "role": "hasPatient", "ref_id": "PMID-15195100_T45" } ] }, { "id": "PMID-15195100_E16", "type": "Phosphorylation", "trigger": { "text": [ "phosphorylation" ], "offsets": [ [ 734, 749 ] ] }, "arguments": [ { "role": "hasAgent", "ref_id": "PMID-15195100_T49" }, { "role": "hasPatient", "ref_id": "PMID-15195100_T48" } ] }, { "id": "PMID-15195100_E17", "type": "Localization", "trigger": { "text": [ "sequestration" ], "offsets": [ [ 793, 806 ] ] }, "arguments": [ { "role": "hasPatient", "ref_id": "PMID-15195100_T52" } ] }, { "id": "PMID-15195100_E18", "type": "NegativeRegulation", "trigger": { "text": [ "impaired" ], "offsets": [ [ 836, 844 ] ] }, "arguments": [ { "role": "hasPatient2", "ref_id": "PMID-15195100_E17" } ] }, { "id": "PMID-15195100_E19", "type": "PositiveRegulation", "trigger": { "text": [ "induction" ], "offsets": [ [ 883, 892 ] ] }, "arguments": [ { "role": "hasPatient", "ref_id": "PMID-15195100_E20" } ] }, { "id": "PMID-15195100_E20", "type": "CellDeath", "trigger": { "text": [ "apoptosis" ], "offsets": [ [ 896, 905 ] ] }, "arguments": [] }, { "id": "PMID-15195100_E21", "type": "BindingToProtein", "trigger": { "text": [ "associates" ], "offsets": [ [ 955, 965 ] ] }, "arguments": [ { "role": "hasPatient", "ref_id": "PMID-15195100_T58" }, { "role": "hasPatient2", "ref_id": "PMID-15195100_T60" } ] }, { "id": "PMID-15195100_E22", "type": "ExperimentalIntervention", "trigger": { "text": [ "knockdown" ], "offsets": [ [ 1011, 1020 ] ] }, "arguments": [ { "role": "hasPatient", "ref_id": "PMID-15195100_T61" } ] }, { "id": "PMID-15195100_E23", "type": "NegativeRegulation", "trigger": { "text": [ "impairs" ], "offsets": [ [ 1021, 1028 ] ] }, "arguments": [ { "role": "hasAgent", "ref_id": "PMID-15195100_E22" }, { "role": "hasPatient", "ref_id": "PMID-15195100_E24" } ] }, { "id": "PMID-15195100_E24", "type": "Localization", "trigger": { "text": [ "localize" ], "offsets": [ [ 1051, 1059 ] ] }, "arguments": [ { "role": "hasPatient", "ref_id": "PMID-15195100_T64" } ] }, { "id": "PMID-15195100_E25", "type": "Mutation", "trigger": { "text": [ "damage" ], "offsets": [ [ 1082, 1088 ] ] }, "arguments": [ { "role": "hasPatient", "ref_id": "PMID-15195100_T67" } ] }, { "id": "PMID-15195100_E26", "type": "Localization", "trigger": { "text": [ "accumulate" ], "offsets": [ [ 580, 590 ] ] }, "arguments": [ { "role": "hasPatient", "ref_id": "PMID-15195100_T38" } ] }, { "id": "PMID-15195100_E27", "type": "Localization", "trigger": { "text": [ "localization" ], "offsets": [ [ 679, 691 ] ] }, "arguments": [ { "role": "hasPatient", "ref_id": "PMID-15195100_T44" }, { "role": "hasAgent", "ref_id": "PMID-15195100_E16" } ] } ]

[]

[ { "id": "PMID-15195100_R3", "type": "hasFunction", "arg1_id": "PMID-15195100_T10", "arg2_id": "PMID-15195100_T11", "normalized": [] } ]

[ { "id": "PMID-15215856__text", "type": "abstract", "text": [ "A membrane protein complex mediates retro-translocation from the ER lumen into the cytosol. Elimination of misfolded proteins from the endoplasmic reticulum (ER) by retro-translocation is an important physiological adaptation to ER stress. This process requires recognition of a substrate in the ER lumen and its subsequent movement through the membrane by the cytosolic p97 ATPase. Here we identify a p97-interacting membrane protein complex in the mammalian ER that links these two events. The central component of the complex, Derlin-1, is a homologue of Der1, a yeast protein whose inactivation prevents the elimination of misfolded luminal ER proteins. Derlin-1 associates with different substrates as they move through the membrane, and inactivation of Derlin-1 in C. elegans causes ER stress. Derlin-1 interacts with US11, a virally encoded ER protein that specifically targets MHC class I heavy chains for export from the ER, as well as with VIMP, a novel membrane protein that recruits the p97 ATPase and its cofactor.\n" ], "offsets": [ [ 0, 1028 ] ] } ]

[ { "id": "PMID-15215856_T1", "type": "CellComponent", "text": [ "membrane" ], "offsets": [ [ 2, 10 ] ], "normalized": [] }, { "id": "PMID-15215856_T2", "type": "ProteinComplex", "text": [ "protein complex" ], "offsets": [ [ 11, 26 ] ], "normalized": [] }, { "id": "PMID-15215856_T5", "type": "CellComponent", "text": [ "ER lumen" ], "offsets": [ [ 65, 73 ] ], "normalized": [] }, { "id": "PMID-15215856_T6", "type": "CellComponent", "text": [ "cytosol" ], "offsets": [ [ 83, 90 ] ], "normalized": [] }, { "id": "PMID-15215856_T8", "type": "Protein", "text": [ "misfolded proteins" ], "offsets": [ [ 107, 125 ] ], "normalized": [] }, { "id": "PMID-15215856_T9", "type": "CellComponent", "text": [ "endoplasmic reticulum" ], "offsets": [ [ 135, 156 ] ], "normalized": [] }, { "id": "PMID-15215856_T10", "type": "CellComponent", "text": [ "ER" ], "offsets": [ [ 158, 160 ] ], "normalized": [] }, { "id": "PMID-15215856_T12", "type": "Stress", "text": [ "ER stress" ], "offsets": [ [ 229, 238 ] ], "normalized": [] }, { "id": "PMID-15215856_T13", "type": "Substrate", "text": [ "substrate" ], "offsets": [ [ 279, 288 ] ], "normalized": [] }, { "id": "PMID-15215856_T14", "type": "CellComponent", "text": [ "ER lumen" ], "offsets": [ [ 296, 304 ] ], "normalized": [] }, { "id": "PMID-15215856_T16", "type": "CellComponent", "text": [ "membrane" ], "offsets": [ [ 345, 353 ] ], "normalized": [] }, { "id": "PMID-15215856_T17", "type": "CellComponent", "text": [ "cytosolic" ], "offsets": [ [ 361, 370 ] ], "normalized": [] }, { "id": "PMID-15215856_T18", "type": "Enzyme", "text": [ "p97 ATPase" ], "offsets": [ [ 371, 381 ] ], "normalized": [] }, { "id": "PMID-15215856_T19", "type": "Protein", "text": [ "p97" ], "offsets": [ [ 402, 405 ] ], "normalized": [] }, { "id": "PMID-15215856_T21", "type": "CellComponent", "text": [ "membrane" ], "offsets": [ [ 418, 426 ] ], "normalized": [] }, { "id": "PMID-15215856_T22", "type": "ProteinComplex", "text": [ "protein complex" ], "offsets": [ [ 427, 442 ] ], "normalized": [] }, { "id": "PMID-15215856_T23", "type": "Eukaryote", "text": [ "mammalian" ], "offsets": [ [ 450, 459 ] ], "normalized": [] }, { "id": "PMID-15215856_T24", "type": "CellComponent", "text": [ "ER" ], "offsets": [ [ 460, 462 ] ], "normalized": [] }, { "id": "PMID-15215856_T25", "type": "ProteinComplex", "text": [ "the complex" ], "offsets": [ [ 517, 528 ] ], "normalized": [] }, { "id": "PMID-15215856_T26", "type": "Protein", "text": [ "Derlin-1" ], "offsets": [ [ 530, 538 ] ], "normalized": [] }, { "id": "PMID-15215856_T27", "type": "Protein", "text": [ "Der1" ], "offsets": [ [ 558, 562 ] ], "normalized": [] }, { "id": "PMID-15215856_T28", "type": "Eukaryote", "text": [ "yeast" ], "offsets": [ [ 566, 571 ] ], "normalized": [] }, { "id": "PMID-15215856_T29", "type": "Protein", "text": [ "protein" ], "offsets": [ [ 572, 579 ] ], "normalized": [] }, { "id": "PMID-15215856_T33", "type": "CellComponent", "text": [ "luminal ER" ], "offsets": [ [ 637, 647 ] ], "normalized": [] }, { "id": "PMID-15215856_T34", "type": "Protein", "text": [ "proteins" ], "offsets": [ [ 648, 656 ] ], "normalized": [] }, { "id": "PMID-15215856_T35", "type": "Protein", "text": [ "Derlin-1" ], "offsets": [ [ 658, 666 ] ], "normalized": [] }, { "id": "PMID-15215856_T37", "type": "Substrate", "text": [ "substrates" ], "offsets": [ [ 693, 703 ] ], "normalized": [] }, { "id": "PMID-15215856_T39", "type": "CellComponent", "text": [ "membrane" ], "offsets": [ [ 729, 737 ] ], "normalized": [] }, { "id": "PMID-15215856_T41", "type": "Protein", "text": [ "Derlin-1" ], "offsets": [ [ 759, 767 ] ], "normalized": [] }, { "id": "PMID-15215856_T42", "type": "Eukaryote", "text": [ "C. elegans" ], "offsets": [ [ 771, 781 ] ], "normalized": [] }, { "id": "PMID-15215856_T43", "type": "Stress", "text": [ "ER stress" ], "offsets": [ [ 789, 798 ] ], "normalized": [] }, { "id": "PMID-15215856_T44", "type": "Protein", "text": [ "Derlin-1" ], "offsets": [ [ 800, 808 ] ], "normalized": [] }, { "id": "PMID-15215856_T46", "type": "Protein", "text": [ "US11" ], "offsets": [ [ 824, 828 ] ], "normalized": [] }, { "id": "PMID-15215856_T47", "type": "Virus", "text": [ "virally" ], "offsets": [ [ 832, 839 ] ], "normalized": [] }, { "id": "PMID-15215856_T48", "type": "CellComponent", "text": [ "ER" ], "offsets": [ [ 848, 850 ] ], "normalized": [] }, { "id": "PMID-15215856_T49", "type": "Protein", "text": [ "protein" ], "offsets": [ [ 851, 858 ] ], "normalized": [] }, { "id": "PMID-15215856_T51", "type": "CellComponent", "text": [ "ER" ], "offsets": [ [ 930, 932 ] ], "normalized": [] }, { "id": "PMID-15215856_T52", "type": "Protein", "text": [ "VIMP" ], "offsets": [ [ 950, 954 ] ], "normalized": [] }, { "id": "PMID-15215856_T53", "type": "CellComponent", "text": [ "membrane" ], "offsets": [ [ 964, 972 ] ], "normalized": [] }, { "id": "PMID-15215856_T54", "type": "Protein", "text": [ "protein" ], "offsets": [ [ 973, 980 ] ], "normalized": [] }, { "id": "PMID-15215856_T55", "type": "Enzyme", "text": [ "p97 ATPase" ], "offsets": [ [ 999, 1009 ] ], "normalized": [] }, { "id": "PMID-15215856_T56", "type": "Protein", "text": [ "cofactor" ], "offsets": [ [ 1018, 1026 ] ], "normalized": [] }, { "id": "PMID-15215856_T57", "type": "Protein", "text": [ "MHC class I heavy chains" ], "offsets": [ [ 885, 909 ] ], "normalized": [] } ]

[ { "id": "PMID-15215856_E1", "type": "RegulatoryProcess", "trigger": { "text": [ "mediates" ], "offsets": [ [ 27, 35 ] ] }, "arguments": [ { "role": "hasAgent", "ref_id": "PMID-15215856_T2" }, { "role": "hasPatient", "ref_id": "PMID-15215856_E2" } ] }, { "id": "PMID-15215856_E2", "type": "Transport", "trigger": { "text": [ "retro-translocation" ], "offsets": [ [ 36, 55 ] ] }, "arguments": [] }, { "id": "PMID-15215856_E3", "type": "Decrease", "trigger": { "text": [ "Elimination" ], "offsets": [ [ 92, 103 ] ] }, "arguments": [ { "role": "hasPatient", "ref_id": "PMID-15215856_T8" } ] }, { "id": "PMID-15215856_E4", "type": "Transport", "trigger": { "text": [ "retro-translocation" ], "offsets": [ [ 165, 184 ] ] }, "arguments": [] }, { "id": "PMID-15215856_E5", "type": "Transport", "trigger": { "text": [ "movement" ], "offsets": [ [ 324, 332 ] ] }, "arguments": [ { "role": "hasPatient", "ref_id": "PMID-15215856_T13" } ] }, { "id": "PMID-15215856_E6", "type": "BindingToProtein", "trigger": { "text": [ "interacting" ], "offsets": [ [ 406, 417 ] ] }, "arguments": [ { "role": "hasPatient", "ref_id": "PMID-15215856_T19" }, { "role": "hasPatient2", "ref_id": "PMID-15215856_T22" } ] }, { "id": "PMID-15215856_E7", "type": "NegativeRegulation", "trigger": { "text": [ "inactivation" ], "offsets": [ [ 586, 598 ] ] }, "arguments": [ { "role": "hasPatient", "ref_id": "PMID-15215856_T29" } ] }, { "id": "PMID-15215856_E8", "type": "NegativeRegulation", "trigger": { "text": [ "prevents" ], "offsets": [ [ 599, 607 ] ] }, "arguments": [ { "role": "hasAgent", "ref_id": "PMID-15215856_E7" }, { "role": "hasPatient", "ref_id": "PMID-15215856_E9" } ] }, { "id": "PMID-15215856_E9", "type": "Decrease", "trigger": { "text": [ "elimination" ], "offsets": [ [ 612, 623 ] ] }, "arguments": [ { "role": "hasPatient", "ref_id": "PMID-15215856_T34" } ] }, { "id": "PMID-15215856_E10", "type": "BindingToProtein", "trigger": { "text": [ "associates" ], "offsets": [ [ 667, 677 ] ] }, "arguments": [ { "role": "hasPatient", "ref_id": "PMID-15215856_T35" } ] }, { "id": "PMID-15215856_E11", "type": "Transport", "trigger": { "text": [ "move" ], "offsets": [ [ 712, 716 ] ] }, "arguments": [ { "role": "hasPatient", "ref_id": "PMID-15215856_T37" } ] }, { "id": "PMID-15215856_E12", "type": "NegativeRegulation", "trigger": { "text": [ "inactivation" ], "offsets": [ [ 743, 755 ] ] }, "arguments": [ { "role": "hasPatient", "ref_id": "PMID-15215856_T41" } ] }, { "id": "PMID-15215856_E13", "type": "BindingToProtein", "trigger": { "text": [ "interacts" ], "offsets": [ [ 809, 818 ] ] }, "arguments": [ { "role": "hasPatient", "ref_id": "PMID-15215856_T44" }, { "role": "hasPatient2", "ref_id": "PMID-15215856_T46" } ] }, { "id": "PMID-15215856_E14", "type": "Transport", "trigger": { "text": [ "export" ], "offsets": [ [ 914, 920 ] ] }, "arguments": [ { "role": "hasPatient", "ref_id": "PMID-15215856_T57" } ] } ]

[]

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[ { "id": "PMID-1527846__text", "type": "abstract", "text": [ "A novel Ets-related transcription factor, Elf-1, binds to human immunodeficiency virus type 2 regulatory elements that are required for inducible trans activation in T cells. Human immunodeficiency virus type 1 (HIV-1) and HIV-2 are structurally related retroviruses which both cause AIDS in humans. Although both viruses establish latency in quiescent human-peripheral-blood T cells, the asymptomatic phase of HIV-2 infection may be more prolonged than that of HIV-1. The latent phases of both HIV-1 and HIV-2 infection have been shown to be disrupted by T-cell activation, a process that requires host cell transcription factors. In the case of HIV-1, the transcription factor NF-kappa B is sufficient for inducible transcriptional activation. In contrast, factors in addition to NF-kappa B are required to activate HIV-2 transcription in infected T cells. In this report, we demonstrate that a novel Ets-related transcription factor, Elf-1, binds specifically to two purine-rich motifs in the HIV-2 enhancer. Mutagenesis experiments demonstrated that these Elf-1 binding sites are required for induction of HIV-2 transcription following T-cell-receptor-mediated T-cell activation. Moreover, Elf-1 is the only factor present in activated T-cell nuclear extracts that binds to these sites in electrophoretic mobility shift assays. Thus, Elf-1 is a novel transcription factor that appears to be required for the T-cell-receptor-mediated trans activation of HIV-2 gene expression. These results may explain differences in the clinical spectra of diseases caused by HIV-1 and HIV-2 and may also have implications for the design of therapeutic approaches to HIV-2 infection.\n" ], "offsets": [ [ 0, 1672 ] ] } ]

[ { "id": "PMID-1527846_T1", "type": "TranscriptionFactor", "text": [ "Ets-related transcription factor" ], "offsets": [ [ 8, 40 ] ], "normalized": [] }, { "id": "PMID-1527846_T2", "type": "TranscriptionFactor", "text": [ "Elf-1" ], "offsets": [ [ 42, 47 ] ], "normalized": [] }, { "id": "PMID-1527846_T4", "type": "Virus", "text": [ "human immunodeficiency virus type 2" ], "offsets": [ [ 58, 93 ] ], "normalized": [] }, { "id": "PMID-1527846_T5", "type": "RegulatoryDNARegion", "text": [ "regulatory elements" ], "offsets": [ [ 94, 113 ] ], "normalized": [] }, { "id": "PMID-1527846_T7", "type": "Cell", "text": [ "T cells" ], "offsets": [ [ 166, 173 ] ], "normalized": [] }, { "id": "PMID-1527846_T8", "type": "Virus", "text": [ "Human immunodeficiency virus type 1" ], "offsets": [ [ 175, 210 ] ], "normalized": [] }, { "id": "PMID-1527846_T9", "type": "Virus", "text": [ "HIV-1" ], "offsets": [ [ 212, 217 ] ], "normalized": [] }, { "id": "PMID-1527846_T10", "type": "Virus", "text": [ "HIV-2" ], "offsets": [ [ 223, 228 ] ], "normalized": [] }, { "id": "PMID-1527846_T11", "type": "Virus", "text": [ "retroviruses" ], "offsets": [ [ 254, 266 ] ], "normalized": [] }, { "id": "PMID-1527846_T13", "type": "Eukaryote", "text": [ "humans" ], "offsets": [ [ 292, 298 ] ], "normalized": [] }, { "id": "PMID-1527846_T14", "type": "Virus", "text": [ "viruses" ], "offsets": [ [ 314, 321 ] ], "normalized": [] }, { "id": "PMID-1527846_T17", "type": "Virus", "text": [ "HIV-2" ], "offsets": [ [ 411, 416 ] ], "normalized": [] }, { "id": "PMID-1527846_T18", "type": "Virus", "text": [ "HIV-1" ], "offsets": [ [ 462, 467 ] ], "normalized": [] }, { "id": "PMID-1527846_T19", "type": "Virus", "text": [ "HIV-1" ], "offsets": [ [ 495, 500 ] ], "normalized": [] }, { "id": "PMID-1527846_T20", "type": "Virus", "text": [ "HIV-2" ], "offsets": [ [ 505, 510 ] ], "normalized": [] }, { "id": "PMID-1527846_T21", "type": "Cell", "text": [ "T-cell" ], "offsets": [ [ 556, 562 ] ], "normalized": [] }, { "id": "PMID-1527846_T23", "type": "Cell", "text": [ "host cell" ], "offsets": [ [ 599, 608 ] ], "normalized": [] }, { "id": "PMID-1527846_T24", "type": "TranscriptionFactor", "text": [ "transcription factors" ], "offsets": [ [ 609, 630 ] ], "normalized": [] }, { "id": "PMID-1527846_T25", "type": "Virus", "text": [ "HIV-1" ], "offsets": [ [ 647, 652 ] ], "normalized": [] }, { "id": "PMID-1527846_T26", "type": "TranscriptionFactor", "text": [ "transcription factor" ], "offsets": [ [ 658, 678 ] ], "normalized": [] }, { "id": "PMID-1527846_T27", "type": "TranscriptionFactor", "text": [ "NF-kappa B" ], "offsets": [ [ 679, 689 ] ], "normalized": [] }, { "id": "PMID-1527846_T30", "type": "TranscriptionFactor", "text": [ "factors" ], "offsets": [ [ 759, 766 ] ], "normalized": [] }, { "id": "PMID-1527846_T31", "type": "TranscriptionFactor", "text": [ "NF-kappa B" ], "offsets": [ [ 782, 792 ] ], "normalized": [] }, { "id": "PMID-1527846_T33", "type": "Virus", "text": [ "HIV-2" ], "offsets": [ [ 818, 823 ] ], "normalized": [] }, { "id": "PMID-1527846_T35", "type": "Cell", "text": [ "T cells" ], "offsets": [ [ 850, 857 ] ], "normalized": [] }, { "id": "PMID-1527846_T36", "type": "TranscriptionFactor", "text": [ "Ets-related transcription factor" ], "offsets": [ [ 903, 935 ] ], "normalized": [] }, { "id": "PMID-1527846_T37", "type": "TranscriptionFactor", "text": [ "Elf-1" ], "offsets": [ [ 937, 942 ] ], "normalized": [] }, { "id": "PMID-1527846_T39", "type": "DNARegion", "text": [ "purine-rich motifs" ], "offsets": [ [ 970, 988 ] ], "normalized": [] }, { "id": "PMID-1527846_T40", "type": "Virus", "text": [ "HIV-2" ], "offsets": [ [ 996, 1001 ] ], "normalized": [] }, { "id": "PMID-1527846_T41", "type": "Enhancer", "text": [ "enhancer" ], "offsets": [ [ 1002, 1010 ] ], "normalized": [] }, { "id": "PMID-1527846_T42", "type": "TranscriptionFactor", "text": [ "Elf-1" ], "offsets": [ [ 1060, 1065 ] ], "normalized": [] }, { "id": "PMID-1527846_T44", "type": "DNABindingSite", "text": [ "sites" ], "offsets": [ [ 1074, 1079 ] ], "normalized": [] }, { "id": "PMID-1527846_T46", "type": "Virus", "text": [ "HIV-2" ], "offsets": [ [ 1110, 1115 ] ], "normalized": [] }, { "id": "PMID-1527846_T48", "type": "Cell", "text": [ "T-cell" ], "offsets": [ [ 1140, 1146 ] ], "normalized": [] }, { "id": "PMID-1527846_T49", "type": "Protein", "text": [ "receptor" ], "offsets": [ [ 1147, 1155 ] ], "normalized": [] }, { "id": "PMID-1527846_T51", "type": "Cell", "text": [ "T-cell" ], "offsets": [ [ 1165, 1171 ] ], "normalized": [] }, { "id": "PMID-1527846_T53", "type": "TranscriptionFactor", "text": [ "Elf-1" ], "offsets": [ [ 1194, 1199 ] ], "normalized": [] }, { "id": "PMID-1527846_T54", "type": "TranscriptionFactor", "text": [ "factor" ], "offsets": [ [ 1212, 1218 ] ], "normalized": [] }, { "id": "PMID-1527846_T56", "type": "Cell", "text": [ "T-cell" ], "offsets": [ [ 1240, 1246 ] ], "normalized": [] }, { "id": "PMID-1527846_T57", "type": "Nucleus", "text": [ "nuclear extracts" ], "offsets": [ [ 1247, 1263 ] ], "normalized": [] }, { "id": "PMID-1527846_T59", "type": "DNABindingSite", "text": [ "these sites" ], "offsets": [ [ 1278, 1289 ] ], "normalized": [] }, { "id": "PMID-1527846_T60", "type": "TranscriptionFactor", "text": [ "Elf-1" ], "offsets": [ [ 1338, 1343 ] ], "normalized": [] }, { "id": "PMID-1527846_T61", "type": "TranscriptionFactor", "text": [ "transcription factor" ], "offsets": [ [ 1355, 1375 ] ], "normalized": [] }, { "id": "PMID-1527846_T62", "type": "Cell", "text": [ "T-cell" ], "offsets": [ [ 1412, 1418 ] ], "normalized": [] }, { "id": "PMID-1527846_T63", "type": "Protein", "text": [ "receptor" ], "offsets": [ [ 1419, 1427 ] ], "normalized": [] }, { "id": "PMID-1527846_T66", "type": "Virus", "text": [ "HIV-2" ], "offsets": [ [ 1457, 1462 ] ], "normalized": [] }, { "id": "PMID-1527846_T68", "type": "Virus", "text": [ "HIV-1" ], "offsets": [ [ 1564, 1569 ] ], "normalized": [] }, { "id": "PMID-1527846_T69", "type": "Virus", "text": [ "HIV-2" ], "offsets": [ [ 1574, 1579 ] ], "normalized": [] }, { "id": "PMID-1527846_T70", "type": "Virus", "text": [ "HIV-2" ], "offsets": [ [ 1655, 1660 ] ], "normalized": [] }, { "id": "PMID-1527846_T15", "type": "EukaryoticCell", "text": [ "human-peripheral-blood T cells" ], "offsets": [ [ 353, 383 ] ], "normalized": [] } ]

[ { "id": "PMID-1527846_E1", "type": "BindingOfProteinToDNA", "trigger": { "text": [ "binds" ], "offsets": [ [ 49, 54 ] ] }, "arguments": [ { "role": "hasAgent", "ref_id": "PMID-1527846_T1" }, { "role": "hasPatient", "ref_id": "PMID-1527846_T5" } ] }, { "id": "PMID-1527846_E2", "type": "PositiveRegulationOfGeneExpression", "trigger": { "text": [ "trans activation" ], "offsets": [ [ 146, 162 ] ] }, "arguments": [] }, { "id": "PMID-1527846_E3", "type": "Disease", "trigger": { "text": [ "AIDS" ], "offsets": [ [ 284, 288 ] ] }, "arguments": [] }, { "id": "PMID-1527846_E4", "type": "PositiveRegulation", "trigger": { "text": [ "activation" ], "offsets": [ [ 563, 573 ] ] }, "arguments": [ { "role": "hasAgent", "ref_id": "PMID-1527846_T24" }, { "role": "hasPatient", "ref_id": "PMID-1527846_T21" } ] }, { "id": "PMID-1527846_E5", "type": "Transcription", "trigger": { "text": [ "transcriptional" ], "offsets": [ [ 718, 733 ] ] }, "arguments": [] }, { "id": "PMID-1527846_E6", "type": "PositiveRegulation", "trigger": { "text": [ "activation" ], "offsets": [ [ 734, 744 ] ] }, "arguments": [ { "role": "hasAgent", "ref_id": "PMID-1527846_T27" }, { "role": "hasPatient", "ref_id": "PMID-1527846_E5" } ] }, { "id": "PMID-1527846_E7", "type": "PositiveRegulation", "trigger": { "text": [ "activate" ], "offsets": [ [ 809, 817 ] ] }, "arguments": [ { "role": "hasPatient", "ref_id": "PMID-1527846_E8" }, { "role": "hasAgent", "ref_id": "PMID-1527846_T30" } ] }, { "id": "PMID-1527846_E8", "type": "Transcription", "trigger": { "text": [ "transcription" ], "offsets": [ [ 824, 837 ] ] }, "arguments": [] }, { "id": "PMID-1527846_E9", "type": "BindingOfProteinToDNA", "trigger": { "text": [ "binds" ], "offsets": [ [ 944, 949 ] ] }, "arguments": [ { "role": "hasAgent", "ref_id": "PMID-1527846_T36" }, { "role": "hasPatient", "ref_id": "PMID-1527846_T39" } ] }, { "id": "PMID-1527846_E10", "type": "BindingOfTFToTFBindingSiteOfDNA", "trigger": { "text": [ "binding" ], "offsets": [ [ 1066, 1073 ] ] }, "arguments": [ { "role": "hasAgent", "ref_id": "PMID-1527846_T42" }, { "role": "hasPatient", "ref_id": "PMID-1527846_T44" } ] }, { "id": "PMID-1527846_E11", "type": "PositiveRegulation", "trigger": { "text": [ "induction" ], "offsets": [ [ 1097, 1106 ] ] }, "arguments": [ { "role": "hasPatient", "ref_id": "PMID-1527846_E12" } ] }, { "id": "PMID-1527846_E12", "type": "Transcription", "trigger": { "text": [ "transcription" ], "offsets": [ [ 1116, 1129 ] ] }, "arguments": [] }, { "id": "PMID-1527846_E13", "type": "RegulatoryProcess", "trigger": { "text": [ "mediated" ], "offsets": [ [ 1156, 1164 ] ] }, "arguments": [ { "role": "hasAgent", "ref_id": "PMID-1527846_T49" }, { "role": "hasPatient", "ref_id": "PMID-1527846_E14" } ] }, { "id": "PMID-1527846_E14", "type": "PositiveRegulation", "trigger": { "text": [ "activation" ], "offsets": [ [ 1172, 1182 ] ] }, "arguments": [ { "role": "hasPatient", "ref_id": "PMID-1527846_T51" } ] }, { "id": "PMID-1527846_E15", "type": "PositiveRegulation", "trigger": { "text": [ "activated" ], "offsets": [ [ 1230, 1239 ] ] }, "arguments": [ { "role": "hasPatient", "ref_id": "PMID-1527846_T56" } ] }, { "id": "PMID-1527846_E16", "type": "BindingOfTFToTFBindingSiteOfDNA", "trigger": { "text": [ "binds" ], "offsets": [ [ 1269, 1274 ] ] }, "arguments": [ { "role": "hasAgent", "ref_id": "PMID-1527846_T53" }, { "role": "hasPatient", "ref_id": "PMID-1527846_T59" } ] }, { "id": "PMID-1527846_E17", "type": "RegulatoryProcess", "trigger": { "text": [ "mediated" ], "offsets": [ [ 1428, 1436 ] ] }, "arguments": [ { "role": "hasAgent", "ref_id": "PMID-1527846_T63" }, { "role": "hasPatient", "ref_id": "PMID-1527846_E18" } ] }, { "id": "PMID-1527846_E18", "type": "PositiveRegulation", "trigger": { "text": [ "trans activation" ], "offsets": [ [ 1437, 1453 ] ] }, "arguments": [ { "role": "hasAgent", "ref_id": "PMID-1527846_T60" }, { "role": "hasPatient", "ref_id": "PMID-1527846_E19" } ] }, { "id": "PMID-1527846_E19", "type": "GeneExpression", "trigger": { "text": [ "gene expression" ], "offsets": [ [ 1463, 1478 ] ] }, "arguments": [] }, { "id": "PMID-1527846_E20", "type": "PositiveRegulation", "trigger": { "text": [ "activate" ], "offsets": [ [ 809, 817 ] ] }, "arguments": [ { "role": "hasPatient", "ref_id": "PMID-1527846_E8" }, { "role": "hasAgent", "ref_id": "PMID-1527846_T31" } ] } ]

[]

[ { "id": "PMID-1527846_R1", "type": "fromSpecies", "arg1_id": "PMID-1527846_T5", "arg2_id": "PMID-1527846_T4", "normalized": [] }, { "id": "PMID-1527846_R2", "type": "locatedIn", "arg1_id": "PMID-1527846_T24", "arg2_id": "PMID-1527846_T23", "normalized": [] }, { "id": "PMID-1527846_R4", "type": "fromSpecies", "arg1_id": "PMID-1527846_T41", "arg2_id": "PMID-1527846_T40", "normalized": [] }, { "id": "PMID-1527846_R5", "type": "hasPart", "arg1_id": "PMID-1527846_T41", "arg2_id": "PMID-1527846_T39", "normalized": [] }, { "id": "PMID-1527846_R6", "type": "locatedIn", "arg1_id": "PMID-1527846_T49", "arg2_id": "PMID-1527846_T48", "normalized": [] }, { "id": "PMID-1527846_R8", "type": "locatedIn", "arg1_id": "PMID-1527846_T57", "arg2_id": "PMID-1527846_T56", "normalized": [] }, { "id": "PMID-1527846_R9", "type": "hasPart", "arg1_id": "PMID-1527846_T57", "arg2_id": "PMID-1527846_T53", "normalized": [] }, { "id": "PMID-1527846_R10", "type": "locatedIn", "arg1_id": "PMID-1527846_T63", "arg2_id": "PMID-1527846_T62", "normalized": [] } ]

[ { "id": "PMID-15577913__text", "type": "abstract", "text": [ "The BCL6 proto-oncogene suppresses p53 expression in germinal-centre B cells. The human proto-oncogene BCL6 encodes a BTB/POZ-zinc-finger transcriptional repressor that is necessary for germinal-centre formation and is implicated in the pathogenesis of B-cell lymphoma. The precise function of BCL6 in germinal-centre development and lymphomagenesis is unclear because very few direct BCL6 target genes have been identified. Here we report that BCL6 suppresses the expression of the p53 (also known as tp53) tumour suppressor gene and modulates DNA damage-induced apoptotic responses in germinal-centre B cells. BCL6 represses p53 transcription by binding two specific DNA sites within the p53 promoter region and, accordingly, p53 expression is absent in germinal-centre B cells where BCL6 is highly expressed. Suppression of BCL6 expression via specific short interfering RNA leads to increased levels of p53 messenger RNA and protein both under basal conditions and in response to DNA damage. Most notably, constitutive expression of BCL6 protects B cell lines from apoptosis induced by DNA damage. These results suggest that an important function of BCL6 is to allow germinal-centre B cells to tolerate the physiological DNA breaks required for immunoglobulin class switch recombination and somatic hypermutation without inducing a p53-dependent apoptotic response. These findings also imply that deregulated BCL6 expression contributes to lymphomagenesis in part by functional inactivation of p53.\n" ], "offsets": [ [ 0, 1503 ] ] } ]

[ { "id": "PMID-15577913_T1", "type": "Gene", "text": [ "BCL6" ], "offsets": [ [ 4, 8 ] ], "normalized": [] }, { "id": "PMID-15577913_T2", "type": "Gene", "text": [ "proto-oncogene" ], "offsets": [ [ 9, 23 ] ], "normalized": [] }, { "id": "PMID-15577913_T4", "type": "Gene", "text": [ "p53" ], "offsets": [ [ 35, 38 ] ], "normalized": [] }, { "id": "PMID-15577913_T6", "type": "Cell", "text": [ "germinal-centre B cells" ], "offsets": [ [ 53, 76 ] ], "normalized": [] }, { "id": "PMID-15577913_T7", "type": "Eukaryote", "text": [ "human" ], "offsets": [ [ 82, 87 ] ], "normalized": [] }, { "id": "PMID-15577913_T8", "type": "Gene", "text": [ "proto-oncogene" ], "offsets": [ [ 88, 102 ] ], "normalized": [] }, { "id": "PMID-15577913_T9", "type": "Gene", "text": [ "BCL6" ], "offsets": [ [ 103, 107 ] ], "normalized": [] }, { "id": "PMID-15577913_T10", "type": "ZincCoordinatingDomain", "text": [ "BTB/POZ-zinc-finger" ], "offsets": [ [ 118, 137 ] ], "normalized": [] }, { "id": "PMID-15577913_T11", "type": "TranscriptionRepressor", "text": [ "transcriptional repressor" ], "offsets": [ [ 138, 163 ] ], "normalized": [] }, { "id": "PMID-15577913_T14", "type": "Gene", "text": [ "BCL6" ], "offsets": [ [ 294, 298 ] ], "normalized": [] }, { "id": "PMID-15577913_T17", "type": "Gene", "text": [ "BCL6" ], "offsets": [ [ 385, 389 ] ], "normalized": [] }, { "id": "PMID-15577913_T18", "type": "Gene", "text": [ "genes" ], "offsets": [ [ 397, 402 ] ], "normalized": [] }, { "id": "PMID-15577913_T19", "type": "Gene", "text": [ "BCL6" ], "offsets": [ [ 445, 449 ] ], "normalized": [] }, { "id": "PMID-15577913_T22", "type": "Gene", "text": [ "p53" ], "offsets": [ [ 483, 486 ] ], "normalized": [] }, { "id": "PMID-15577913_T23", "type": "Gene", "text": [ "tp53" ], "offsets": [ [ 502, 506 ] ], "normalized": [] }, { "id": "PMID-15577913_T24", "type": "Gene", "text": [ "gene" ], "offsets": [ [ 526, 530 ] ], "normalized": [] }, { "id": "PMID-15577913_T26", "type": "DNA", "text": [ "DNA" ], "offsets": [ [ 545, 548 ] ], "normalized": [] }, { "id": "PMID-15577913_T28", "type": "Cell", "text": [ "germinal-centre B cells" ], "offsets": [ [ 587, 610 ] ], "normalized": [] }, { "id": "PMID-15577913_T29", "type": "Protein", "text": [ "BCL6" ], "offsets": [ [ 612, 616 ] ], "normalized": [] }, { "id": "PMID-15577913_T31", "type": "Gene", "text": [ "p53" ], "offsets": [ [ 627, 630 ] ], "normalized": [] }, { "id": "PMID-15577913_T34", "type": "ProteinBindingSiteOfDNA", "text": [ "DNA sites" ], "offsets": [ [ 669, 678 ] ], "normalized": [] }, { "id": "PMID-15577913_T35", "type": "Gene", "text": [ "p53" ], "offsets": [ [ 690, 693 ] ], "normalized": [] }, { "id": "PMID-15577913_T36", "type": "Promoter", "text": [ "promoter region" ], "offsets": [ [ 694, 709 ] ], "normalized": [] }, { "id": "PMID-15577913_T37", "type": "Gene", "text": [ "p53" ], "offsets": [ [ 728, 731 ] ], "normalized": [] }, { "id": "PMID-15577913_T39", "type": "Cell", "text": [ "germinal-centre B cells" ], "offsets": [ [ 756, 779 ] ], "normalized": [] }, { "id": "PMID-15577913_T40", "type": "Gene", "text": [ "BCL6" ], "offsets": [ [ 786, 790 ] ], "normalized": [] }, { "id": "PMID-15577913_T43", "type": "Gene", "text": [ "BCL6" ], "offsets": [ [ 827, 831 ] ], "normalized": [] }, { "id": "PMID-15577913_T47", "type": "Gene", "text": [ "p53" ], "offsets": [ [ 907, 910 ] ], "normalized": [] }, { "id": "PMID-15577913_T48", "type": "MessengerRNA", "text": [ "messenger RNA" ], "offsets": [ [ 911, 924 ] ], "normalized": [] }, { "id": "PMID-15577913_T49", "type": "Protein", "text": [ "protein" ], "offsets": [ [ 929, 936 ] ], "normalized": [] }, { "id": "PMID-15577913_T50", "type": "DNA", "text": [ "DNA" ], "offsets": [ [ 984, 987 ] ], "normalized": [] }, { "id": "PMID-15577913_T52", "type": "Gene", "text": [ "BCL6" ], "offsets": [ [ 1037, 1041 ] ], "normalized": [] }, { "id": "PMID-15577913_T53", "type": "Cell", "text": [ "B cell lines" ], "offsets": [ [ 1051, 1063 ] ], "normalized": [] }, { "id": "PMID-15577913_T55", "type": "DNA", "text": [ "DNA" ], "offsets": [ [ 1090, 1093 ] ], "normalized": [] }, { "id": "PMID-15577913_T56", "type": "Gene", "text": [ "BCL6" ], "offsets": [ [ 1154, 1158 ] ], "normalized": [] }, { "id": "PMID-15577913_T57", "type": "Cell", "text": [ "germinal-centre B cells" ], "offsets": [ [ 1171, 1194 ] ], "normalized": [] }, { "id": "PMID-15577913_T58", "type": "DNA", "text": [ "DNA" ], "offsets": [ [ 1225, 1228 ] ], "normalized": [] }, { "id": "PMID-15577913_T60", "type": "Gene", "text": [ "p53" ], "offsets": [ [ 1336, 1339 ] ], "normalized": [] }, { "id": "PMID-15577913_T62", "type": "Gene", "text": [ "BCL6" ], "offsets": [ [ 1413, 1417 ] ], "normalized": [] }, { "id": "PMID-15577913_T65", "type": "Gene", "text": [ "p53" ], "offsets": [ [ 1498, 1501 ] ], "normalized": [] }, { "id": "PMID-15577913_T45", "type": "SmallInterferingRNA", "text": [ "short interfering RNA" ], "offsets": [ [ 856, 877 ] ], "normalized": [] } ]

[ { "id": "PMID-15577913_E1", "type": "NegativeRegulation", "trigger": { "text": [ "suppresses" ], "offsets": [ [ 24, 34 ] ] }, "arguments": [ { "role": "hasAgent", "ref_id": "PMID-15577913_T1" }, { "role": "hasPatient", "ref_id": "PMID-15577913_E2" } ] }, { "id": "PMID-15577913_E2", "type": "GeneExpression", "trigger": { "text": [ "expression" ], "offsets": [ [ 39, 49 ] ] }, "arguments": [ { "role": "hasPatient", "ref_id": "PMID-15577913_T4" } ] }, { "id": "PMID-15577913_E3", "type": "CellularDevelopmentalProcess", "trigger": { "text": [ "germinal-centre formation" ], "offsets": [ [ 186, 211 ] ] }, "arguments": [] }, { "id": "PMID-15577913_E4", "type": "CellularDevelopmentalProcess", "trigger": { "text": [ "germinal-centre development" ], "offsets": [ [ 302, 329 ] ] }, "arguments": [] }, { "id": "PMID-15577913_E5", "type": "CellularDevelopmentalProcess", "trigger": { "text": [ "lymphomagenesis" ], "offsets": [ [ 334, 349 ] ] }, "arguments": [] }, { "id": "PMID-15577913_E6", "type": "NegativeRegulation", "trigger": { "text": [ "suppresses" ], "offsets": [ [ 450, 460 ] ] }, "arguments": [ { "role": "hasAgent", "ref_id": "PMID-15577913_T19" }, { "role": "hasPatient", "ref_id": "PMID-15577913_E7" } ] }, { "id": "PMID-15577913_E7", "type": "GeneExpression", "trigger": { "text": [ "expression" ], "offsets": [ [ 465, 475 ] ] }, "arguments": [ { "role": "hasPatient", "ref_id": "PMID-15577913_T22" } ] }, { "id": "PMID-15577913_E8", "type": "RegulatoryProcess", "trigger": { "text": [ "modulates" ], "offsets": [ [ 535, 544 ] ] }, "arguments": [ { "role": "hasAgent", "ref_id": "PMID-15577913_T19" }, { "role": "hasPatient", "ref_id": "PMID-15577913_E9" } ] }, { "id": "PMID-15577913_E9", "type": "CellDeath", "trigger": { "text": [ "apoptotic responses" ], "offsets": [ [ 564, 583 ] ] }, "arguments": [] }, { "id": "PMID-15577913_E10", "type": "NegativeRegulation", "trigger": { "text": [ "represses" ], "offsets": [ [ 617, 626 ] ] }, "arguments": [ { "role": "hasAgent", "ref_id": "PMID-15577913_T29" }, { "role": "hasPatient", "ref_id": "PMID-15577913_E11" } ] }, { "id": "PMID-15577913_E11", "type": "Transcription", "trigger": { "text": [ "transcription" ], "offsets": [ [ 631, 644 ] ] }, "arguments": [ { "role": "hasPatient", "ref_id": "PMID-15577913_T31" } ] }, { "id": "PMID-15577913_E12", "type": "BindingOfProteinToDNA", "trigger": { "text": [ "binding" ], "offsets": [ [ 648, 655 ] ] }, "arguments": [ { "role": "hasAgent", "ref_id": "PMID-15577913_T29" }, { "role": "hasPatient", "ref_id": "PMID-15577913_T34" } ] }, { "id": "PMID-15577913_E13", "type": "GeneExpression", "trigger": { "text": [ "expression" ], "offsets": [ [ 732, 742 ] ] }, "arguments": [ { "role": "hasPatient", "ref_id": "PMID-15577913_T37" } ] }, { "id": "PMID-15577913_E14", "type": "GeneExpression", "trigger": { "text": [ "expressed" ], "offsets": [ [ 801, 810 ] ] }, "arguments": [ { "role": "hasPatient", "ref_id": "PMID-15577913_T40" } ] }, { "id": "PMID-15577913_E15", "type": "NegativeRegulation", "trigger": { "text": [ "Suppression" ], "offsets": [ [ 812, 823 ] ] }, "arguments": [ { "role": "hasPatient", "ref_id": "PMID-15577913_E16" } ] }, { "id": "PMID-15577913_E16", "type": "GeneExpression", "trigger": { "text": [ "expression" ], "offsets": [ [ 832, 842 ] ] }, "arguments": [ { "role": "hasPatient", "ref_id": "PMID-15577913_T43" } ] }, { "id": "PMID-15577913_E17", "type": "Increase", "trigger": { "text": [ "increased" ], "offsets": [ [ 887, 896 ] ] }, "arguments": [ { "role": "hasAgent", "ref_id": "PMID-15577913_E15" }, { "role": "hasPatient", "ref_id": "PMID-15577913_T48" } ] }, { "id": "PMID-15577913_E18", "type": "GeneExpression", "trigger": { "text": [ "expression" ], "offsets": [ [ 1023, 1033 ] ] }, "arguments": [ { "role": "hasPatient", "ref_id": "PMID-15577913_T52" } ] }, { "id": "PMID-15577913_E19", "type": "CellDeath", "trigger": { "text": [ "apoptosis" ], "offsets": [ [ 1069, 1078 ] ] }, "arguments": [] }, { "id": "PMID-15577913_E20", "type": "Mutation", "trigger": { "text": [ "hypermutation" ], "offsets": [ [ 1303, 1316 ] ] }, "arguments": [] }, { "id": "PMID-15577913_E21", "type": "CellDeath", "trigger": { "text": [ "apoptotic response" ], "offsets": [ [ 1350, 1368 ] ] }, "arguments": [] }, { "id": "PMID-15577913_E22", "type": "GeneExpression", "trigger": { "text": [ "expression" ], "offsets": [ [ 1418, 1428 ] ] }, "arguments": [ { "role": "hasPatient", "ref_id": "PMID-15577913_T62" } ] }, { "id": "PMID-15577913_E23", "type": "CellularDevelopmentalProcess", "trigger": { "text": [ "lymphomagenesis" ], "offsets": [ [ 1444, 1459 ] ] }, "arguments": [] }, { "id": "PMID-15577913_E24", "type": "Disease", "trigger": { "text": [ "B-cell lymphoma" ], "offsets": [ [ 253, 268 ] ] }, "arguments": [] }, { "id": "PMID-15577913_E25", "type": "RegulatoryProcess", "trigger": { "text": [ "response" ], "offsets": [ [ 972, 980 ] ] }, "arguments": [] }, { "id": "PMID-15577913_E26", "type": "CellularProcess", "trigger": { "text": [ "immunoglobulin class switch recombination" ], "offsets": [ [ 1249, 1290 ] ] }, "arguments": [] }, { "id": "PMID-15577913_E27", "type": "Increase", "trigger": { "text": [ "increased" ], "offsets": [ [ 887, 896 ] ] }, "arguments": [ { "role": "hasAgent", "ref_id": "PMID-15577913_E15" }, { "role": "hasPatient", "ref_id": "PMID-15577913_T49" } ] } ]

[]

[ { "id": "PMID-15577913_R2", "type": "fromSpecies", "arg1_id": "PMID-15577913_T8", "arg2_id": "PMID-15577913_T7", "normalized": [] }, { "id": "PMID-15577913_R3", "type": "encodes", "arg1_id": "PMID-15577913_T9", "arg2_id": "PMID-15577913_T11", "normalized": [] }, { "id": "PMID-15577913_R4", "type": "hasPart", "arg1_id": "PMID-15577913_T11", "arg2_id": "PMID-15577913_T10", "normalized": [] }, { "id": "PMID-15577913_R7", "type": "hasPart", "arg1_id": "PMID-15577913_T35", "arg2_id": "PMID-15577913_T36", "normalized": [] }, { "id": "PMID-15577913_R8", "type": "hasPart", "arg1_id": "PMID-15577913_T36", "arg2_id": "PMID-15577913_T34", "normalized": [] }, { "id": "PMID-15577913_R10", "type": "encodes", "arg1_id": "PMID-15577913_T47", "arg2_id": "PMID-15577913_T48", "normalized": [] }, { "id": "PMID-15577913_R11", "type": "encodes", "arg1_id": "PMID-15577913_T47", "arg2_id": "PMID-15577913_T49", "normalized": [] } ]

[ { "id": "PMID-1569101__text", "type": "abstract", "text": [ "The human T cell transcription factor-1 gene. Structure, localization, and promoter characterization. We have recently isolated cDNA clones representing four alternative splice forms of a T cell-specific transcription factor, TCF-1. Here we report the characterization of the human gene encoding this factor. The TCF-1 gene is contained in 10 exons including an untranslated first exon. The DNA-binding high mobility group (HMG) box of TCF-1 is encoded by the closely spaced exons VI and VII. Differential splicing involves an alternative exon (IX) and three splice acceptor sites in exon X. Based on comparison of sequence and on the placement of an alternative exon, TCF-1 appears closely related to the recently characterized HMG box transcription factor TCF-1 alpha/LEF. In particular, the HMG boxes encoded by the two TCF genes are virtually identical. The TCF-1 gene resides on chromosome 5 band q31.1. The TCF-1 promoter coincides with a CpG island. As determined by chloramphenicol acetyltransferase analysis, the promoter is preferentially active in T cells. The promoter does not contain TCF-1/TCF-1 alpha binding sites and is therefore not autoregulated. This observation implies the existence of yet uncharacterized T cell transcription factors that are active during early T cell differentiation.\n" ], "offsets": [ [ 0, 1310 ] ] } ]

[ { "id": "PMID-1569101_T1", "type": "Eukaryote", "text": [ "human" ], "offsets": [ [ 4, 9 ] ], "normalized": [] }, { "id": "PMID-1569101_T2", "type": "TranscriptionFactor", "text": [ "T cell transcription factor-1" ], "offsets": [ [ 10, 39 ] ], "normalized": [] }, { "id": "PMID-1569101_T3", "type": "Gene", "text": [ "gene" ], "offsets": [ [ 40, 44 ] ], "normalized": [] }, { "id": "PMID-1569101_T4", "type": "DNA", "text": [ "cDNA clones" ], "offsets": [ [ 128, 139 ] ], "normalized": [] }, { "id": "PMID-1569101_T5", "type": "TranscriptionFactor", "text": [ "T cell-specific transcription factor" ], "offsets": [ [ 188, 224 ] ], "normalized": [] }, { "id": "PMID-1569101_T6", "type": "TranscriptionFactor", "text": [ "TCF-1" ], "offsets": [ [ 226, 231 ] ], "normalized": [] }, { "id": "PMID-1569101_T7", "type": "Eukaryote", "text": [ "human" ], "offsets": [ [ 276, 281 ] ], "normalized": [] }, { "id": "PMID-1569101_T8", "type": "Gene", "text": [ "gene" ], "offsets": [ [ 282, 286 ] ], "normalized": [] }, { "id": "PMID-1569101_T9", "type": "TranscriptionFactor", "text": [ "this factor" ], "offsets": [ [ 296, 307 ] ], "normalized": [] }, { "id": "PMID-1569101_T10", "type": "Gene", "text": [ "TCF-1 gene" ], "offsets": [ [ 313, 323 ] ], "normalized": [] }, { "id": "PMID-1569101_T11", "type": "Exon", "text": [ "exons" ], "offsets": [ [ 343, 348 ] ], "normalized": [] }, { "id": "PMID-1569101_T12", "type": "Exon", "text": [ "exon" ], "offsets": [ [ 381, 385 ] ], "normalized": [] }, { "id": "PMID-1569101_T13", "type": "DNA", "text": [ "DNA" ], "offsets": [ [ 391, 394 ] ], "normalized": [] }, { "id": "PMID-1569101_T15", "type": "HMG", "text": [ "HMG" ], "offsets": [ [ 424, 427 ] ], "normalized": [] }, { "id": "PMID-1569101_T16", "type": "TranscriptionFactor", "text": [ "TCF-1" ], "offsets": [ [ 436, 441 ] ], "normalized": [] }, { "id": "PMID-1569101_T17", "type": "Exon", "text": [ "exons", "VII" ], "offsets": [ [ 475, 480 ], [ 488, 491 ] ], "normalized": [] }, { "id": "PMID-1569101_T18", "type": "Exon", "text": [ "exons VI" ], "offsets": [ [ 475, 483 ] ], "normalized": [] }, { "id": "PMID-1569101_T20", "type": "Exon", "text": [ "exon (IX)" ], "offsets": [ [ 539, 548 ] ], "normalized": [] }, { "id": "PMID-1569101_T21", "type": "Nucleotide", "text": [ "splice acceptor sites" ], "offsets": [ [ 559, 580 ] ], "normalized": [] }, { "id": "PMID-1569101_T22", "type": "Exon", "text": [ "exon X" ], "offsets": [ [ 584, 590 ] ], "normalized": [] }, { "id": "PMID-1569101_T23", "type": "Sequence", "text": [ "sequence" ], "offsets": [ [ 615, 623 ] ], "normalized": [] }, { "id": "PMID-1569101_T24", "type": "Exon", "text": [ "exon" ], "offsets": [ [ 663, 667 ] ], "normalized": [] }, { "id": "PMID-1569101_T25", "type": "TranscriptionFactor", "text": [ "TCF-1" ], "offsets": [ [ 669, 674 ] ], "normalized": [] }, { "id": "PMID-1569101_T26", "type": "HMG", "text": [ "HMG box" ], "offsets": [ [ 729, 736 ] ], "normalized": [] }, { "id": "PMID-1569101_T27", "type": "TranscriptionFactor", "text": [ "transcription factor TCF-1 alpha/LEF" ], "offsets": [ [ 737, 773 ] ], "normalized": [] }, { "id": "PMID-1569101_T28", "type": "HMG", "text": [ "HMG boxes" ], "offsets": [ [ 794, 803 ] ], "normalized": [] }, { "id": "PMID-1569101_T29", "type": "Gene", "text": [ "TCF genes" ], "offsets": [ [ 823, 832 ] ], "normalized": [] }, { "id": "PMID-1569101_T30", "type": "Gene", "text": [ "TCF-1 gene" ], "offsets": [ [ 862, 872 ] ], "normalized": [] }, { "id": "PMID-1569101_T31", "type": "Chromosome", "text": [ "chromosome 5 band q31.1" ], "offsets": [ [ 884, 907 ] ], "normalized": [] }, { "id": "PMID-1569101_T32", "type": "Gene", "text": [ "TCF-1" ], "offsets": [ [ 913, 918 ] ], "normalized": [] }, { "id": "PMID-1569101_T33", "type": "Promoter", "text": [ "promoter" ], "offsets": [ [ 919, 927 ] ], "normalized": [] }, { "id": "PMID-1569101_T34", "type": "CpGIsland", "text": [ "CpG island" ], "offsets": [ [ 945, 955 ] ], "normalized": [] }, { "id": "PMID-1569101_T35", "type": "ExperimentalMethod", "text": [ "chloramphenicol acetyltransferase analysis" ], "offsets": [ [ 974, 1016 ] ], "normalized": [] }, { "id": "PMID-1569101_T36", "type": "Promoter", "text": [ "promoter" ], "offsets": [ [ 1022, 1030 ] ], "normalized": [] }, { "id": "PMID-1569101_T38", "type": "Cell", "text": [ "T cells" ], "offsets": [ [ 1059, 1066 ] ], "normalized": [] }, { "id": "PMID-1569101_T39", "type": "Cell", "text": [ "T cell" ], "offsets": [ [ 1228, 1234 ] ], "normalized": [] }, { "id": "PMID-1569101_T40", "type": "TranscriptionFactor", "text": [ "transcription factors" ], "offsets": [ [ 1235, 1256 ] ], "normalized": [] }, { "id": "PMID-1569101_T42", "type": "Cell", "text": [ "T cell" ], "offsets": [ [ 1286, 1292 ] ], "normalized": [] }, { "id": "PMID-1569101_T44", "type": "Promoter", "text": [ "promoter" ], "offsets": [ [ 75, 83 ] ], "normalized": [] } ]

[ { "id": "PMID-1569101_E1", "type": "BindingOfTranscriptionFactorToDNA", "trigger": { "text": [ "binding" ], "offsets": [ [ 395, 402 ] ] }, "arguments": [ { "role": "hasPatient2", "ref_id": "PMID-1569101_T13" }, { "role": "hasAgent", "ref_id": "PMID-1569101_T15" } ] }, { "id": "PMID-1569101_E2", "type": "RNASplicing", "trigger": { "text": [ "Differential splicing" ], "offsets": [ [ 493, 514 ] ] }, "arguments": [] }, { "id": "PMID-1569101_E3", "type": "PositiveRegulation", "trigger": { "text": [ "active" ], "offsets": [ [ 1049, 1055 ] ] }, "arguments": [ { "role": "hasPatient", "ref_id": "PMID-1569101_T36" } ] }, { "id": "PMID-1569101_E4", "type": "PositiveRegulation", "trigger": { "text": [ "active" ], "offsets": [ [ 1266, 1272 ] ] }, "arguments": [ { "role": "hasPatient", "ref_id": "PMID-1569101_T40" } ] }, { "id": "PMID-1569101_E5", "type": "CellDifferentiation", "trigger": { "text": [ "differentiation" ], "offsets": [ [ 1293, 1308 ] ] }, "arguments": [ { "role": "hasPatient", "ref_id": "PMID-1569101_T42" } ] }, { "id": "PMID-1569101_E6", "type": "Splicing", "trigger": { "text": [ "alternative splice forms" ], "offsets": [ [ 158, 182 ] ] }, "arguments": [ { "role": "hasPatient", "ref_id": "PMID-1569101_T5" } ] } ]

[]

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[ { "id": "PMID-15705585__text", "type": "abstract", "text": [ "CATERPILLER 16.2 (CLR16.2), a novel NBD/LRR family member that negatively regulates T cell function. The newly discovered mammalian CATERPILLER (NOD, NALP, PAN) family of proteins share similarities with the NBD-LRR superfamily of plant disease resistance (R) proteins and are predicted to mediate important immune regulatory function. This report describes the first cloning and characterization of a novel CATERPILLER gene, CLR16.2 that is located on human chromosome 16. The protein encoded by this gene has a typical NBD-LRR configuration. Analysis of CLR16.2 suggests the highest expression among T lymphocytes. Cellular localization studies of CLR16.2 revealed that it is a cytoplasmic protein. Querying microarray studies in the public data base showed that CLR16.2 was significantly (>90%) down-regulated 6 h after anti-CD3 and anti-CD28 stimulation of primary T lymphocytes. Its reduction upon T cell stimulation is consistent with a potential negative regulatory role. Indeed CLR16.2 decreased NF-kappaB, NFAT, and AP-1 induction of reporter gene constructs in response to T cell activation by anti-CD3 and anti-CD28 antibodies or PMA and ionomycin. Following T cell stimulation, the presence of CLR16.2 reduced the levels of the endogenous transcripts for the IL-2 and CD25 proteins that are central in maintaining T cell activation and preventing T cell anergy. This reduction was accompanied by a delay of IkappaBalpha degradation. We propose that CLR16.2 serves to attenuate T cell activation via TCR and co-stimulatory molecules, and its reduction during T cell stimulation allows the ensuing cellular activation.\n" ], "offsets": [ [ 0, 1629 ] ] } ]

[ { "id": "PMID-15705585_T1", "type": "Protein", "text": [ "CLR16.2" ], "offsets": [ [ 18, 25 ] ], "normalized": [] }, { "id": "PMID-15705585_T2", "type": "Protein", "text": [ "NBD/LRR family" ], "offsets": [ [ 36, 50 ] ], "normalized": [] }, { "id": "PMID-15705585_T5", "type": "Cell", "text": [ "T cell" ], "offsets": [ [ 84, 90 ] ], "normalized": [] }, { "id": "PMID-15705585_T6", "type": "Function", "text": [ "function" ], "offsets": [ [ 91, 99 ] ], "normalized": [] }, { "id": "PMID-15705585_T7", "type": "Eukaryote", "text": [ "mammalian" ], "offsets": [ [ 122, 131 ] ], "normalized": [] }, { "id": "PMID-15705585_T8", "type": "Protein", "text": [ "CATERPILLER (NOD, NALP, PAN) family" ], "offsets": [ [ 132, 167 ] ], "normalized": [] }, { "id": "PMID-15705585_T9", "type": "Protein", "text": [ "proteins" ], "offsets": [ [ 171, 179 ] ], "normalized": [] }, { "id": "PMID-15705585_T10", "type": "Protein", "text": [ "NBD-LRR superfamily" ], "offsets": [ [ 208, 227 ] ], "normalized": [] }, { "id": "PMID-15705585_T11", "type": "Eukaryote", "text": [ "plant" ], "offsets": [ [ 231, 236 ] ], "normalized": [] }, { "id": "PMID-15705585_T17", "type": "Function", "text": [ "function" ], "offsets": [ [ 326, 334 ] ], "normalized": [] }, { "id": "PMID-15705585_T18", "type": "ExperimentalMethod", "text": [ "cloning" ], "offsets": [ [ 368, 375 ] ], "normalized": [] }, { "id": "PMID-15705585_T19", "type": "Gene", "text": [ "CATERPILLER gene" ], "offsets": [ [ 408, 424 ] ], "normalized": [] }, { "id": "PMID-15705585_T20", "type": "Gene", "text": [ "CLR16.2" ], "offsets": [ [ 426, 433 ] ], "normalized": [] }, { "id": "PMID-15705585_T22", "type": "Eukaryote", "text": [ "human" ], "offsets": [ [ 453, 458 ] ], "normalized": [] }, { "id": "PMID-15705585_T23", "type": "Chromosome", "text": [ "chromosome 16" ], "offsets": [ [ 459, 472 ] ], "normalized": [] }, { "id": "PMID-15705585_T24", "type": "Protein", "text": [ "protein" ], "offsets": [ [ 478, 485 ] ], "normalized": [] }, { "id": "PMID-15705585_T25", "type": "Gene", "text": [ "gene" ], "offsets": [ [ 502, 506 ] ], "normalized": [] }, { "id": "PMID-15705585_T26", "type": "Protein", "text": [ "NBD-LRR configuration" ], "offsets": [ [ 521, 542 ] ], "normalized": [] }, { "id": "PMID-15705585_T27", "type": "Gene", "text": [ "CLR16.2" ], "offsets": [ [ 556, 563 ] ], "normalized": [] }, { "id": "PMID-15705585_T29", "type": "Cell", "text": [ "T lymphocytes" ], "offsets": [ [ 602, 615 ] ], "normalized": [] }, { "id": "PMID-15705585_T30", "type": "Cell", "text": [ "Cellular" ], "offsets": [ [ 617, 625 ] ], "normalized": [] }, { "id": "PMID-15705585_T32", "type": "Protein", "text": [ "CLR16.2" ], "offsets": [ [ 650, 657 ] ], "normalized": [] }, { "id": "PMID-15705585_T33", "type": "CellComponent", "text": [ "cytoplasmic" ], "offsets": [ [ 680, 691 ] ], "normalized": [] }, { "id": "PMID-15705585_T34", "type": "Protein", "text": [ "protein" ], "offsets": [ [ 692, 699 ] ], "normalized": [] }, { "id": "PMID-15705585_T35", "type": "Protein", "text": [ "CLR16.2" ], "offsets": [ [ 765, 772 ] ], "normalized": [] }, { "id": "PMID-15705585_T37", "type": "Protein", "text": [ "anti-CD3" ], "offsets": [ [ 823, 831 ] ], "normalized": [] }, { "id": "PMID-15705585_T38", "type": "Protein", "text": [ "anti-CD28" ], "offsets": [ [ 836, 845 ] ], "normalized": [] }, { "id": "PMID-15705585_T40", "type": "Cell", "text": [ "primary T lymphocytes" ], "offsets": [ [ 861, 882 ] ], "normalized": [] }, { "id": "PMID-15705585_T42", "type": "Cell", "text": [ "T cell" ], "offsets": [ [ 903, 909 ] ], "normalized": [] }, { "id": "PMID-15705585_T46", "type": "Protein", "text": [ "CLR16.2" ], "offsets": [ [ 986, 993 ] ], "normalized": [] }, { "id": "PMID-15705585_T48", "type": "Protein", "text": [ "NF-kappaB" ], "offsets": [ [ 1004, 1013 ] ], "normalized": [] }, { "id": "PMID-15705585_T49", "type": "Protein", "text": [ "NFAT" ], "offsets": [ [ 1015, 1019 ] ], "normalized": [] }, { "id": "PMID-15705585_T50", "type": "Protein", "text": [ "AP-1" ], "offsets": [ [ 1025, 1029 ] ], "normalized": [] }, { "id": "PMID-15705585_T52", "type": "ReporterGeneConstruction", "text": [ "reporter gene constructs" ], "offsets": [ [ 1043, 1067 ] ], "normalized": [] }, { "id": "PMID-15705585_T53", "type": "AP2EREBPRelatedDomain", "text": [ "T cell" ], "offsets": [ [ 1083, 1089 ] ], "normalized": [] }, { "id": "PMID-15705585_T55", "type": "Protein", "text": [ "anti-CD3" ], "offsets": [ [ 1104, 1112 ] ], "normalized": [] }, { "id": "PMID-15705585_T56", "type": "Protein", "text": [ "anti-CD28" ], "offsets": [ [ 1117, 1126 ] ], "normalized": [] }, { "id": "PMID-15705585_T57", "type": "Protein", "text": [ "antibodies" ], "offsets": [ [ 1127, 1137 ] ], "normalized": [] }, { "id": "PMID-15705585_T58", "type": "Protein", "text": [ "PMA" ], "offsets": [ [ 1141, 1144 ] ], "normalized": [] }, { "id": "PMID-15705585_T59", "type": "Protein", "text": [ "ionomycin" ], "offsets": [ [ 1149, 1158 ] ], "normalized": [] }, { "id": "PMID-15705585_T60", "type": "Cell", "text": [ "T cell" ], "offsets": [ [ 1170, 1176 ] ], "normalized": [] }, { "id": "PMID-15705585_T62", "type": "Protein", "text": [ "CLR16.2" ], "offsets": [ [ 1206, 1213 ] ], "normalized": [] }, { "id": "PMID-15705585_T64", "type": "Transcript", "text": [ "transcripts" ], "offsets": [ [ 1251, 1262 ] ], "normalized": [] }, { "id": "PMID-15705585_T65", "type": "Protein", "text": [ "IL-2" ], "offsets": [ [ 1271, 1275 ] ], "normalized": [] }, { "id": "PMID-15705585_T66", "type": "Protein", "text": [ "CD25 proteins" ], "offsets": [ [ 1280, 1293 ] ], "normalized": [] }, { "id": "PMID-15705585_T68", "type": "Cell", "text": [ "T cell" ], "offsets": [ [ 1326, 1332 ] ], "normalized": [] }, { "id": "PMID-15705585_T75", "type": "AP2EREBPRelatedDomain", "text": [ "IkappaBalpha" ], "offsets": [ [ 1419, 1431 ] ], "normalized": [] }, { "id": "PMID-15705585_T77", "type": "Protein", "text": [ "CLR16.2" ], "offsets": [ [ 1461, 1468 ] ], "normalized": [] }, { "id": "PMID-15705585_T79", "type": "Cell", "text": [ "T cell" ], "offsets": [ [ 1489, 1495 ] ], "normalized": [] }, { "id": "PMID-15705585_T81", "type": "Protein", "text": [ "TCR" ], "offsets": [ [ 1511, 1514 ] ], "normalized": [] }, { "id": "PMID-15705585_T82", "type": "MolecularEntity", "text": [ "co-stimulatory molecules" ], "offsets": [ [ 1519, 1543 ] ], "normalized": [] }, { "id": "PMID-15705585_T84", "type": "Cell", "text": [ "T cell" ], "offsets": [ [ 1570, 1576 ] ], "normalized": [] }, { "id": "PMID-15705585_T86", "type": "Cell", "text": [ "cellular" ], "offsets": [ [ 1608, 1616 ] ], "normalized": [] }, { "id": "PMID-15705585_T4", "type": "Protein", "text": [ "disease resistance (R) proteins" ], "offsets": [ [ 237, 268 ] ], "normalized": [] } ]

[ { "id": "PMID-15705585_E3", "type": "RegulatoryProcess", "trigger": { "text": [ "mediate" ], "offsets": [ [ 290, 297 ] ] }, "arguments": [ { "role": "hasAgent", "ref_id": "PMID-15705585_T8" }, { "role": "hasPatient", "ref_id": "PMID-15705585_T17" } ] }, { "id": "PMID-15705585_E4", "type": "CellularProcess", "trigger": { "text": [ "immune" ], "offsets": [ [ 308, 314 ] ] }, "arguments": [] }, { "id": "PMID-15705585_E5", "type": "RegulatoryProcess", "trigger": { "text": [ "regulatory" ], "offsets": [ [ 315, 325 ] ] }, "arguments": [ { "role": "hasPatient", "ref_id": "PMID-15705585_E4" } ] }, { "id": "PMID-15705585_E7", "type": "GeneExpression", "trigger": { "text": [ "expression" ], "offsets": [ [ 585, 595 ] ] }, "arguments": [ { "role": "hasPatient", "ref_id": "PMID-15705585_T27" } ] }, { "id": "PMID-15705585_E8", "type": "Localization", "trigger": { "text": [ "localization" ], "offsets": [ [ 626, 638 ] ] }, "arguments": [ { "role": "hasPatient", "ref_id": "PMID-15705585_T32" } ] }, { "id": "PMID-15705585_E9", "type": "NegativeRegulation", "trigger": { "text": [ "down-regulated" ], "offsets": [ [ 798, 812 ] ] }, "arguments": [ { "role": "hasPatient", "ref_id": "PMID-15705585_T35" } ] }, { "id": "PMID-15705585_E10", "type": "PositiveRegulation", "trigger": { "text": [ "stimulation" ], "offsets": [ [ 846, 857 ] ] }, "arguments": [ { "role": "hasPatient", "ref_id": "PMID-15705585_T40" }, { "role": "hasAgent", "ref_id": "PMID-15705585_T37" } ] }, { "id": "PMID-15705585_E11", "type": "Decrease", "trigger": { "text": [ "reduction" ], "offsets": [ [ 888, 897 ] ] }, "arguments": [ { "role": "hasPatient", "ref_id": "PMID-15705585_T35" } ] }, { "id": "PMID-15705585_E12", "type": "PositiveRegulation", "trigger": { "text": [ "stimulation" ], "offsets": [ [ 910, 921 ] ] }, "arguments": [ { "role": "hasPatient", "ref_id": "PMID-15705585_T42" } ] }, { "id": "PMID-15705585_E14", "type": "Decrease", "trigger": { "text": [ "decreased" ], "offsets": [ [ 994, 1003 ] ] }, "arguments": [ { "role": "hasAgent", "ref_id": "PMID-15705585_T46" }, { "role": "hasPatient", "ref_id": "PMID-15705585_E15" } ] }, { "id": "PMID-15705585_E15", "type": "PositiveRegulation", "trigger": { "text": [ "induction" ], "offsets": [ [ 1030, 1039 ] ] }, "arguments": [ { "role": "hasPatient", "ref_id": "PMID-15705585_T52" }, { "role": "hasAgent", "ref_id": "PMID-15705585_T48" } ] }, { "id": "PMID-15705585_E16", "type": "PositiveRegulation", "trigger": { "text": [ "activation" ], "offsets": [ [ 1090, 1100 ] ] }, "arguments": [ { "role": "hasPatient", "ref_id": "PMID-15705585_T53" }, { "role": "hasAgent", "ref_id": "PMID-15705585_T57" } ] }, { "id": "PMID-15705585_E17", "type": "PositiveRegulation", "trigger": { "text": [ "stimulation" ], "offsets": [ [ 1177, 1188 ] ] }, "arguments": [ { "role": "hasPatient", "ref_id": "PMID-15705585_T60" } ] }, { "id": "PMID-15705585_E18", "type": "Decrease", "trigger": { "text": [ "reduced" ], "offsets": [ [ 1214, 1221 ] ] }, "arguments": [ { "role": 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[]

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[ { "id": "PMID-15788408__text", "type": "abstract", "text": [ "The oxidative stressor arsenite activates vascular endothelial growth factor mRNA transcription by an ATF4-dependent mechanism. Aberrant retinal expression of vascular endothelial growth factor (VEGF) leading to neovascularization is a central feature of age-related macular degeneration and diabetic retinopathy, two leading causes of vision loss. Oxidative stress is suggested to occur in retinal tissue during age-related macular degeneration and diabetic retinopathy and is suspected in the mechanism of VEGF expression in these diseases. Arsenite, a thiol-reactive oxidative stressor, induces VEGF expression by a HIF-1alpha-independent mechanism. Previously, we demonstrated that homocysteine, an endoplasmic reticulum stressor, increases VEGF transcription by a mechanism dependent upon activating transcription factor ATF4. Because ATF4 is expressed in response to oxidative stress, we hypothesized that ATF4 was also responsible for increased VEGF transcription in response to arsenite. We now show that arsenite increased steady state levels of VEGF mRNA and activated transcription from a VEGF promoter construct. Arsenite induced eIF2alpha phosphorylation, resulting in increased ATF4 protein levels. Inactivation or loss of ATF4 greatly diminished the VEGF response to arsenite treatment. Overexpression of ATF4 was sufficient to activate the VEGF promoter, and arsenite cooperated with exogenous ATF4 to further activate the promoter. A complex containing ATF4 binds a DNA element at +1767 bp relative to the VEGF transcription start site, and DNA binding activity is increased by arsenite treatment. In addition, the ability of a thiol antioxidant, N-acetylcysteine, to inhibit the effect of arsenite on VEGF expression coincided with its ability to inhibit phosphorylation of eIF2alpha and ATF4 protein expression. Thus, arsenite-induced up-regulation of VEGF gene transcription occurs by an ATF4-dependent mechanism.\n" ], "offsets": [ [ 0, 1934 ] ] } ]

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}, { "id": "PMID-15788408_T15", "type": "Tissue", "text": [ "retinal tissue" ], "offsets": [ [ 391, 405 ] ], "normalized": [] }, { "id": "PMID-15788408_T18", "type": "Protein", "text": [ "VEGF" ], "offsets": [ [ 508, 512 ] ], "normalized": [] }, { "id": "PMID-15788408_T21", "type": "Chemical", "text": [ "Arsenite" ], "offsets": [ [ 543, 551 ] ], "normalized": [] }, { "id": "PMID-15788408_T22", "type": "Chemical", "text": [ "oxidative stressor" ], "offsets": [ [ 570, 588 ] ], "normalized": [] }, { "id": "PMID-15788408_T24", "type": "Protein", "text": [ "VEGF" ], "offsets": [ [ 598, 602 ] ], "normalized": [] }, { "id": "PMID-15788408_T26", "type": "Protein", "text": [ "HIF-1alpha" ], "offsets": [ [ 619, 629 ] ], "normalized": [] }, { "id": "PMID-15788408_T27", "type": "AminoAcid", "text": [ "homocysteine" ], "offsets": [ [ 686, 698 ] ], "normalized": [] }, { "id": "PMID-15788408_T28", "type": "CellComponent", "text": [ "endoplasmic reticulum" ], "offsets": [ [ 703, 724 ] ], "normalized": [] }, { "id": "PMID-15788408_T29", "type": "Chemical", "text": [ "stressor" ], "offsets": [ [ 725, 733 ] ], "normalized": [] }, { "id": "PMID-15788408_T31", "type": "Protein", "text": [ "VEGF" ], "offsets": [ [ 745, 749 ] ], "normalized": [] }, { "id": "PMID-15788408_T34", "type": "TranscriptionFactor", "text": [ "transcription factor ATF4" ], "offsets": [ [ 805, 830 ] ], "normalized": [] }, { "id": "PMID-15788408_T35", "type": "TranscriptionFactor", "text": [ "ATF4" ], "offsets": [ [ 840, 844 ] ], "normalized": [] }, { "id": "PMID-15788408_T37", "type": "Stress", "text": [ "oxidative stress" ], "offsets": [ [ 873, 889 ] ], "normalized": [] }, { "id": "PMID-15788408_T38", "type": "TranscriptionFactor", "text": [ "ATF4" ], "offsets": [ [ 912, 916 ] ], "normalized": [] }, { "id": "PMID-15788408_T40", "type": "Protein", "text": [ "VEGF" ], "offsets": [ [ 952, 956 ] ], "normalized": [] }, { "id": "PMID-15788408_T42", "type": "Chemical", "text": [ "arsenite" ], "offsets": [ [ 986, 994 ] ], 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"normalized": [] }, { "id": "PMID-15788408_T58", "type": "TranscriptionFactor", "text": [ "ATF4" ], "offsets": [ [ 1237, 1241 ] ], "normalized": [] }, { "id": "PMID-15788408_T60", "type": "Protein", "text": [ "VEGF" ], "offsets": [ [ 1265, 1269 ] ], "normalized": [] }, { "id": "PMID-15788408_T62", "type": "Chemical", "text": [ "arsenite" ], "offsets": [ [ 1282, 1290 ] ], "normalized": [] }, { "id": "PMID-15788408_T64", "type": "TranscriptionFactor", "text": [ "ATF4" ], "offsets": [ [ 1320, 1324 ] ], "normalized": [] }, { "id": "PMID-15788408_T66", "type": "Gene", "text": [ "VEGF" ], "offsets": [ [ 1356, 1360 ] ], "normalized": [] }, { "id": "PMID-15788408_T67", "type": "Promoter", "text": [ "promoter" ], "offsets": [ [ 1361, 1369 ] ], "normalized": [] }, { "id": "PMID-15788408_T68", "type": "Chemical", "text": [ "arsenite" ], "offsets": [ [ 1375, 1383 ] ], "normalized": [] }, { "id": "PMID-15788408_T69", "type": "TranscriptionFactor", "text": [ "ATF4" ], "offsets": [ [ 1410, 1414 ] ], 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"hasPatient", "ref_id": "PMID-15788408_T35" } ] }, { "id": "PMID-15788408_E17", "type": "Increase", "trigger": { "text": [ "increased" ], "offsets": [ [ 942, 951 ] ] }, "arguments": [ { "role": "hasAgent", "ref_id": "PMID-15788408_T38" }, { "role": "hasPatient", "ref_id": "PMID-15788408_E18" } ] }, { "id": "PMID-15788408_E18", "type": "Transcription", "trigger": { "text": [ "transcription" ], "offsets": [ [ 957, 970 ] ] }, "arguments": [ { "role": "hasPatient", "ref_id": "PMID-15788408_T40" } ] }, { "id": "PMID-15788408_E19", "type": "Increase", "trigger": { "text": [ "increased" ], "offsets": [ [ 1022, 1031 ] ] }, "arguments": [ { "role": "hasAgent", "ref_id": "PMID-15788408_T43" }, { "role": "hasPatient", "ref_id": "PMID-15788408_T46" } ] }, { "id": "PMID-15788408_E20", "type": "PositiveRegulation", "trigger": { "text": [ "activated" ], "offsets": [ [ 1069, 1078 ] ] }, "arguments": [ { "role": "hasAgent", "ref_id": "PMID-15788408_T43" }, { "role": "hasPatient", "ref_id": 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"text": [ "expression" ], "offsets": [ [ 1819, 1829 ] ] }, "arguments": [ { "role": "hasPatient", "ref_id": "PMID-15788408_T90" } ] }, { "id": "PMID-15788408_E39", "type": "PositiveRegulation", "trigger": { "text": [ "induced" ], "offsets": [ [ 1846, 1853 ] ] }, "arguments": [ { "role": "hasAgent", "ref_id": "PMID-15788408_T92" }, { "role": "hasPatient", "ref_id": "PMID-15788408_E40" } ] }, { "id": "PMID-15788408_E40", "type": "PositiveRegulation", "trigger": { "text": [ "up-regulation" ], "offsets": [ [ 1854, 1867 ] ] }, "arguments": [ { "role": "hasAgent", "ref_id": "PMID-15788408_T92" }, { "role": "hasPatient", "ref_id": "PMID-15788408_E41" } ] }, { "id": "PMID-15788408_E41", "type": "Transcription", "trigger": { "text": [ "gene transcription" ], "offsets": [ [ 1876, 1894 ] ] }, "arguments": [ { "role": "hasPatient", "ref_id": "PMID-15788408_T95" } ] }, { "id": "PMID-15788408_E42", "type": "Disease", "trigger": { "text": [ "vision loss" ], "offsets": [ [ 336, 347 ] ] }, "arguments": [] }, { "id": "PMID-15788408_E43", "type": "PositiveRegulation", "trigger": { "text": [ "activate" ], "offsets": [ [ 1426, 1434 ] ] }, "arguments": [ { "role": "hasPatient", "ref_id": "PMID-15788408_T71" }, { "role": "hasAgent", "ref_id": "PMID-15788408_T69" } ] }, { "id": "PMID-15788408_E44", "type": "NegativeRegulation", "trigger": { "text": [ "inhibit" ], "offsets": [ [ 1765, 1772 ] ] }, "arguments": [ { "role": "hasAgent", "ref_id": "PMID-15788408_T81" }, { "role": "hasPatient", "ref_id": "PMID-15788408_E38" } ] } ]

[]

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[ { "id": "PMID-15790729__text", "type": "abstract", "text": [ "Role of 14-3-3 eta as a positive regulator of the glucocorticoid receptor transcriptional activation. The glucocorticoid receptor (GR), a member of the nuclear receptor superfamily, mediates the effects of glucocorticoids. It is known that 14-3-3 family proteins interact with GR and regulate its transcriptional activity. They also bind to several molecules and influence many cellular events by altering their subcellular localization and/or acting as a chaperone. Recently, it has been proposed that ligand-activated degradation of GR occurs via the ubiquitin-proteasomal degradation pathway and that inhibition of proteasomal activity induces up-regulation of GR and enhances the transcriptional activity of GR. To examine the function of 14-3-3eta in the glucocorticoid-dependent signal pathway, we studied the regulatory role of 14-3-3eta in ligand-induced GR transcriptional activation. 14-3-3eta Enhanced the transcriptional activity of GR, and the levels of GR were higher in cells transfected with the 14-3-3eta expression vector in response to glucocorticoid. The GR level increased in both cytosol and nucleus, and endogenous GR was also elevated by 14-3-3eta in HeLa cells. 14-3-3eta Inhibited ligand-induced down-regulation of GR. Proteasomal inhibition did not induce any synergistic effect on the 14-3-3eta-induced increase in GR in response to glucocorticoid, and inhibition of translation did not block elevation of GR by 14-3-3eta, indicating that 14-3-3eta induces stabilization of GR. These results suggest that 14-3-3eta functions as a positive regulator in the glucocorticoid signal pathway by blocking the degradation of GR and inducing an elevation of GR, thus enhancing the transcriptional activity of GR.\n" ], "offsets": [ [ 0, 1732 ] ] } ]

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{ "id": "PMID-15790729_T14", "type": "Protein", "text": [ "GR" ], "offsets": [ [ 277, 279 ] ], "normalized": [] }, { "id": "PMID-15790729_T19", "type": "MolecularEntity", "text": [ "molecules" ], "offsets": [ [ 349, 358 ] ], "normalized": [] }, { "id": "PMID-15790729_T23", "type": "Cell", "text": [ "subcellular" ], "offsets": [ [ 412, 423 ] ], "normalized": [] }, { "id": "PMID-15790729_T25", "type": "Protein", "text": [ "chaperone" ], "offsets": [ [ 456, 465 ] ], "normalized": [] }, { "id": "PMID-15790729_T26", "type": "Ligand", "text": [ "ligand" ], "offsets": [ [ 503, 509 ] ], "normalized": [] }, { "id": "PMID-15790729_T29", "type": "Protein", "text": [ "GR" ], "offsets": [ [ 535, 537 ] ], "normalized": [] }, { "id": "PMID-15790729_T30", "type": "Enzyme", "text": [ "ubiquitin-proteasomal" ], "offsets": [ [ 553, 574 ] ], "normalized": [] }, { "id": "PMID-15790729_T33", "type": "Enzyme", "text": [ "proteasomal" ], "offsets": [ [ 618, 629 ] ], "normalized": [] }, { "id": "PMID-15790729_T34", "type": "CatalyticActivity", "text": [ "activity" ], "offsets": [ [ 630, 638 ] ], "normalized": [] }, { "id": "PMID-15790729_T38", "type": "Protein", "text": [ "GR" ], "offsets": [ [ 664, 666 ] ], "normalized": [] }, { "id": "PMID-15790729_T41", "type": "Protein", "text": [ "GR" ], "offsets": [ [ 712, 714 ] ], "normalized": [] }, { "id": "PMID-15790729_T42", "type": "Protein", "text": [ "14-3-3eta" ], "offsets": [ [ 743, 752 ] ], "normalized": [] }, { "id": "PMID-15790729_T43", "type": "Lipid", "text": [ "glucocorticoid" ], "offsets": [ [ 760, 774 ] ], "normalized": [] }, { "id": "PMID-15790729_T45", "type": "Protein", "text": [ "14-3-3eta" ], "offsets": [ [ 835, 844 ] ], "normalized": [] }, { "id": "PMID-15790729_T46", "type": "Ligand", "text": [ "ligand" ], "offsets": [ [ 848, 854 ] ], "normalized": [] }, { "id": "PMID-15790729_T48", "type": "Protein", "text": [ "GR" ], "offsets": [ [ 863, 865 ] ], "normalized": [] }, { "id": "PMID-15790729_T51", "type": "Protein", "text": [ "14-3-3eta" ], "offsets": [ [ 894, 903 ] ], "normalized": [] }, { "id": "PMID-15790729_T54", "type": "Protein", "text": [ "GR" ], "offsets": [ [ 945, 947 ] ], "normalized": [] }, { "id": "PMID-15790729_T55", "type": "Protein", "text": [ "GR" ], "offsets": [ [ 967, 969 ] ], "normalized": [] }, { "id": "PMID-15790729_T56", "type": "Cell", "text": [ "cells" ], "offsets": [ [ 985, 990 ] ], "normalized": [] }, { "id": "PMID-15790729_T57", "type": "Protein", "text": [ "14-3-3eta" ], "offsets": [ [ 1012, 1021 ] ], "normalized": [] }, { "id": "PMID-15790729_T58", "type": "Lipid", "text": [ "glucocorticoid" ], "offsets": [ [ 1055, 1069 ] ], "normalized": [] }, { "id": "PMID-15790729_T59", "type": "Protein", "text": [ "GR" ], "offsets": [ [ 1075, 1077 ] ], "normalized": [] }, { "id": "PMID-15790729_T61", "type": "CellComponent", "text": [ "cytosol" ], "offsets": [ [ 1102, 1109 ] ], "normalized": [] }, { "id": "PMID-15790729_T62", "type": "Nucleus", "text": [ "nucleus" ], "offsets": [ [ 1114, 1121 ] ], "normalized": [] }, { "id": "PMID-15790729_T63", "type": "Protein", "text": [ "GR" ], "offsets": [ [ 1138, 1140 ] ], "normalized": [] }, { "id": "PMID-15790729_T65", "type": "Protein", "text": [ "14-3-3eta" ], "offsets": [ [ 1162, 1171 ] ], "normalized": [] }, { "id": "PMID-15790729_T66", "type": "Cell", "text": [ "HeLa cells" ], "offsets": [ [ 1175, 1185 ] ], "normalized": [] }, { "id": "PMID-15790729_T67", "type": "Protein", "text": [ "14-3-3eta" ], "offsets": [ [ 1187, 1196 ] ], "normalized": [] }, { "id": "PMID-15790729_T69", "type": "Ligand", "text": [ "ligand" ], "offsets": [ [ 1207, 1213 ] ], "normalized": [] }, { "id": "PMID-15790729_T72", "type": "Protein", "text": [ "GR" ], "offsets": [ [ 1241, 1243 ] ], "normalized": [] }, { "id": "PMID-15790729_T73", "type": "Protein", "text": [ "14-3-3eta" ], "offsets": [ [ 1533, 1542 ] ], "normalized": [] }, { "id": "PMID-15790729_T75", "type": "Lipid", "text": [ "glucocorticoid" ], "offsets": [ [ 1584, 1598 ] ], "normalized": [] }, { "id": "PMID-15790729_T79", "type": "Protein", "text": [ "GR" ], "offsets": [ [ 1645, 1647 ] ], "normalized": [] }, { "id": "PMID-15790729_T82", "type": "Protein", "text": [ "GR" ], "offsets": [ [ 1677, 1679 ] ], "normalized": [] }, { "id": "PMID-15790729_T85", "type": "Protein", "text": [ "GR" ], "offsets": [ [ 1728, 1730 ] ], "normalized": [] }, { "id": "PMID-15790729_T2", "type": "PositiveTranscriptionRegulator", "text": [ "positive regulator" ], "offsets": [ [ 24, 42 ] ], "normalized": [] }, { "id": "PMID-15790729_T37", "type": "TranscriptionRegulator", "text": [ "transcriptional activity" ], "offsets": [ [ 1700, 1724 ] ], "normalized": [] } ]

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"type": "RegulatoryProcess", "trigger": { "text": [ "regulate" ], "offsets": [ [ 284, 292 ] ] }, "arguments": [ { "role": "hasAgent", "ref_id": "PMID-15790729_T12" }, { "role": "hasPatient", "ref_id": "PMID-15790729_E6" } ] }, { "id": "PMID-15790729_E6", "type": "Transcription", "trigger": { "text": [ "transcriptional activity" ], "offsets": [ [ 297, 321 ] ] }, "arguments": [ { "role": "hasPatient", "ref_id": "PMID-15790729_T14" } ] }, { "id": "PMID-15790729_E7", "type": "BindingToMolecularEntity", "trigger": { "text": [ "bind" ], "offsets": [ [ 333, 337 ] ] }, "arguments": [ { "role": "hasPatient", "ref_id": "PMID-15790729_T19" } ] }, { "id": "PMID-15790729_E8", "type": "RegulatoryProcess", "trigger": { "text": [ "influence" ], "offsets": [ [ 363, 372 ] ] }, "arguments": [ { "role": "hasPatient", "ref_id": "PMID-15790729_E9" } ] }, { "id": "PMID-15790729_E9", "type": "CellularProcess", "trigger": { "text": [ "cellular events" ], "offsets": [ [ 378, 393 ] ] }, "arguments": [] }, { "id": "PMID-15790729_E10", "type": "RegulatoryProcess", "trigger": { "text": [ "altering" ], "offsets": [ [ 397, 405 ] ] }, "arguments": [ { "role": "hasPatient", "ref_id": "PMID-15790729_E11" } ] }, { "id": "PMID-15790729_E11", "type": "Localization", "trigger": { "text": [ "localization" ], "offsets": [ [ 424, 436 ] ] }, "arguments": [ { "role": "hasPatient", "ref_id": "PMID-15790729_T19" } ] }, { "id": "PMID-15790729_E12", "type": "PositiveRegulation", "trigger": { "text": [ "activated" ], "offsets": [ [ 510, 519 ] ] }, "arguments": [ { "role": "hasAgent", "ref_id": "PMID-15790729_T26" }, { "role": "hasPatient", "ref_id": "PMID-15790729_E13" } ] }, { "id": "PMID-15790729_E13", "type": "ProteinCatabolism", "trigger": { "text": [ "degradation" ], "offsets": [ [ 520, 531 ] ] }, "arguments": [ { "role": "hasPatient", "ref_id": "PMID-15790729_T29" } ] }, { "id": "PMID-15790729_E14", "type": "MetabolicPathway", "trigger": { "text": [ "degradation pathway" ], "offsets": [ [ 575, 594 ] ] }, "arguments": [] }, { "id": "PMID-15790729_E15", "type": "NegativeRegulation", "trigger": { "text": [ "inhibition" ], "offsets": [ [ 604, 614 ] ] }, "arguments": [ { "role": "hasPatient", "ref_id": "PMID-15790729_T34" } ] }, { "id": "PMID-15790729_E16", "type": "PositiveRegulation", "trigger": { "text": [ "induces" ], "offsets": [ [ 639, 646 ] ] }, "arguments": [ { "role": "hasAgent", "ref_id": "PMID-15790729_E15" } ] }, { "id": "PMID-15790729_E18", "type": "PositiveRegulationOfTranscription", "trigger": { "text": [ "enhances" ], "offsets": [ [ 671, 679 ] ] }, "arguments": [ { "role": "hasAgent", "ref_id": "PMID-15790729_E15" }, { "role": "hasPatient", "ref_id": "PMID-15790729_E19" } ] }, { "id": "PMID-15790729_E19", "type": "Transcription", "trigger": { "text": [ "transcriptional activity" ], "offsets": [ [ 684, 708 ] ] }, "arguments": [ { "role": "hasPatient", "ref_id": "PMID-15790729_T41" } ] }, { "id": "PMID-15790729_E20", "type": "SignalingPathway", "trigger": { "text": [ "signal pathway" ], "offsets": [ [ 785, 799 ] ] }, "arguments": [] }, { "id": "PMID-15790729_E21", "type": "PositiveRegulation", "trigger": { "text": [ "induced" ], "offsets": [ [ 855, 862 ] ] }, "arguments": [ { "role": "hasAgent", "ref_id": "PMID-15790729_T46" }, { "role": "hasPatient", "ref_id": "PMID-15790729_E23" } ] }, { "id": "PMID-15790729_E22", "type": "Transcription", "trigger": { "text": [ "transcriptional" ], "offsets": [ [ 866, 881 ] ] }, "arguments": [ { "role": "hasPatient", "ref_id": "PMID-15790729_T48" } ] }, { "id": "PMID-15790729_E23", "type": "PositiveRegulation", "trigger": { "text": [ "activation" ], "offsets": [ [ 882, 892 ] ] }, "arguments": [ { "role": "hasPatient", "ref_id": "PMID-15790729_E22" } ] }, { "id": "PMID-15790729_E24", "type": "Increase", "trigger": { "text": [ "Enhanced" ], "offsets": [ [ 904, 912 ] ] }, "arguments": [ { "role": "hasAgent", "ref_id": "PMID-15790729_T51" }, { "role": "hasPatient", "ref_id": "PMID-15790729_E25" } ] }, { "id": "PMID-15790729_E25", "type": "Transcription", "trigger": { "text": [ "transcriptional activity" ], "offsets": [ [ 917, 941 ] ] }, "arguments": [ { "role": "hasPatient", "ref_id": "PMID-15790729_T54" } ] }, { "id": "PMID-15790729_E26", "type": "Increase", "trigger": { "text": [ "increased" ], "offsets": [ [ 1084, 1093 ] ] }, "arguments": [] }, { "id": "PMID-15790729_E27", "type": "Increase", "trigger": { "text": [ "elevated" ], "offsets": [ [ 1150, 1158 ] ] }, "arguments": [ { "role": "hasAgent", "ref_id": "PMID-15790729_T65" }, { "role": "hasPatient", "ref_id": "PMID-15790729_T63" } ] }, { "id": "PMID-15790729_E28", "type": "NegativeRegulation", "trigger": { "text": [ "Inhibited" ], "offsets": [ [ 1197, 1206 ] ] }, "arguments": [ { "role": "hasAgent", "ref_id": "PMID-15790729_T67" }, { "role": "hasPatient", "ref_id": "PMID-15790729_E30" } ] }, { "id": "PMID-15790729_E29", "type": "PositiveRegulation", "trigger": { "text": [ "induced" ], "offsets": [ [ 1214, 1221 ] ] }, "arguments": [ { "role": "hasAgent", "ref_id": "PMID-15790729_T69" }, { "role": "hasPatient", "ref_id": "PMID-15790729_E30" } ] }, { "id": "PMID-15790729_E30", "type": "NegativeRegulation", "trigger": { "text": [ "down-regulation" ], "offsets": [ [ 1222, 1237 ] ] }, "arguments": [ { "role": "hasPatient", "ref_id": "PMID-15790729_T72" } ] }, { "id": "PMID-15790729_E32", "type": "SignalingPathway", "trigger": { "text": [ "signal pathway" ], "offsets": [ [ 1599, 1613 ] ] }, "arguments": [] }, { "id": "PMID-15790729_E33", "type": "NegativeRegulation", "trigger": { "text": [ "blocking" ], "offsets": [ [ 1617, 1625 ] ] }, "arguments": [ { "role": "hasPatient", "ref_id": "PMID-15790729_E34" } ] }, { "id": "PMID-15790729_E34", "type": "ProteinMetabolism", "trigger": { "text": [ "degradation" ], "offsets": [ [ 1630, 1641 ] ] }, "arguments": [ { "role": "hasPatient", "ref_id": "PMID-15790729_T79" } ] }, { "id": "PMID-15790729_E35", "type": "PositiveRegulation", "trigger": { "text": [ "inducing" ], "offsets": [ [ 1652, 1660 ] ] }, "arguments": [ { "role": "hasPatient", "ref_id": "PMID-15790729_E36" } ] }, { "id": "PMID-15790729_E36", "type": "Increase", "trigger": { "text": [ "elevation" ], "offsets": [ [ 1664, 1673 ] ] }, "arguments": [ { "role": "hasPatient", "ref_id": "PMID-15790729_T82" } ] }, { "id": "PMID-15790729_E37", "type": "Increase", "trigger": { "text": [ "enhancing" ], "offsets": [ [ 1686, 1695 ] ] }, "arguments": [ { "role": "hasPatient", "ref_id": "PMID-15790729_T37" } ] }, { "id": "PMID-15790729_E17", "type": "PositiveRegulation", "trigger": { "text": [ "up-regulation" ], "offsets": [ [ 647, 660 ] ] }, "arguments": [ { "role": "hasPatient", "ref_id": "PMID-15790729_T38" }, { "role": "hasAgent", "ref_id": "PMID-15790729_E16" } ] }, { "id": "PMID-15790729_E31", "type": "PositiveRegulation", "trigger": { "text": [ "positive regulator" ], "offsets": [ [ 1558, 1576 ] ] }, "arguments": [ { "role": "hasAgent", "ref_id": "PMID-15790729_T73" }, { "role": "hasPatient", "ref_id": "PMID-15790729_E32" } ] } ]

[]

[ { "id": "PMID-15790729_R1", "type": "locatedIn", "arg1_id": "PMID-15790729_T8", "arg2_id": "PMID-15790729_T7", "normalized": [] }, { "id": "PMID-15790729_R3", "type": "hasFunction", "arg1_id": "PMID-15790729_T11", "arg2_id": "PMID-15790729_T10", "normalized": [] }, { "id": "PMID-15790729_R5", "type": "hasFunction", "arg1_id": "PMID-15790729_T33", "arg2_id": "PMID-15790729_T34", "normalized": [] }, { "id": "PMID-15790729_R12", "type": "hasFunction", "arg1_id": "PMID-15790729_T1", "arg2_id": "PMID-15790729_T2", "normalized": [] }, { "id": "PMID-15790729_R2", "type": "hasFunction", "arg1_id": "PMID-15790729_T85", "arg2_id": "PMID-15790729_T37", "normalized": [] } ]

[ { "id": "PMID-1620116__text", "type": "abstract", "text": [ "Transcriptional repression by a novel member of the bZIP family of transcription factors. We describe here a novel member of the bZIP family of DNA-binding proteins, designated E4BP4, that displays an unusual DNA-binding specificity which overlaps that of the activating transcription factor family of factors. When expressed in a transient transfection assay with a suitable reporter plasmid, E4BP4 strongly repressed transcription in a DNA-binding-site-dependent manner. Examination of a series of deletion mutants revealed that sequences responsible for the repressing potential of E4BP4 lie within the carboxyl-terminal region of the protein. No similarity was found between this region and the repressing domains of other known eukaryotic transcriptional repressors.\n" ], "offsets": [ [ 0, 772 ] ] } ]

[ { "id": "PMID-1620116_T3", "type": "bZIPTF", "text": [ "bZIP family" ], "offsets": [ [ 52, 63 ] ], "normalized": [] }, { "id": "PMID-1620116_T4", "type": "TranscriptionFactor", "text": [ "transcription factors" ], "offsets": [ [ 67, 88 ] ], "normalized": [] }, { "id": "PMID-1620116_T5", "type": "bZIPTF", "text": [ "bZIP family" ], "offsets": [ [ 129, 140 ] ], "normalized": [] }, { "id": "PMID-1620116_T9", "type": "TranscriptionFactor", "text": [ "E4BP4" ], "offsets": [ [ 177, 182 ] ], "normalized": [] }, { "id": "PMID-1620116_T10", "type": "DNA", "text": [ "DNA" ], "offsets": [ [ 209, 212 ] ], "normalized": [] }, { "id": "PMID-1620116_T13", "type": "TranscriptionFactor", "text": [ "transcription factor family" ], "offsets": [ [ 271, 298 ] ], "normalized": [] }, { "id": "PMID-1620116_T15", "type": "ExperimentalMethod", "text": [ "transient transfection assay" ], "offsets": [ [ 331, 359 ] ], "normalized": [] }, { "id": "PMID-1620116_T16", "type": "ReporterGene", "text": [ "reporter plasmid" ], "offsets": [ [ 376, 392 ] ], "normalized": [] }, { "id": "PMID-1620116_T17", "type": "TranscriptionFactor", "text": [ "E4BP4" ], "offsets": [ [ 394, 399 ] ], "normalized": [] }, { "id": "PMID-1620116_T20", "type": "DNABindingSite", "text": [ "DNA-binding-site" ], "offsets": [ [ 438, 454 ] ], "normalized": [] }, { "id": "PMID-1620116_T21", "type": "Sequence", "text": [ "sequences" ], "offsets": [ [ 531, 540 ] ], "normalized": [] }, { "id": "PMID-1620116_T23", "type": "TranscriptionFactor", "text": [ "E4BP4" ], "offsets": [ [ 585, 590 ] ], "normalized": [] }, { "id": "PMID-1620116_T24", "type": "ProteinSubunit", "text": [ "carboxyl-terminal region" ], "offsets": [ [ 606, 630 ] ], "normalized": [] }, { "id": "PMID-1620116_T25", "type": "Protein", "text": [ "protein" ], "offsets": [ [ 638, 645 ] ], "normalized": [] }, { "id": "PMID-1620116_T27", "type": "ProteinDomain", "text": [ "domains" ], "offsets": [ [ 710, 717 ] ], "normalized": [] }, { "id": "PMID-1620116_T28", "type": "Eukaryote", "text": [ "eukaryotic" ], "offsets": [ [ 733, 743 ] ], "normalized": [] }, { "id": "PMID-1620116_T29", "type": "TranscriptionRepressor", "text": [ "transcriptional repressors" ], "offsets": [ [ 744, 770 ] ], "normalized": [] }, { "id": "PMID-1620116_T6", "type": "Protein", "text": [ "DNA-binding proteins" ], "offsets": [ [ 144, 164 ] ], "normalized": [] } ]

[ { "id": "PMID-1620116_E2", "type": "NegativeRegulationOfTranscription", "trigger": { "text": [ "Transcriptional repression" ], "offsets": [ [ 0, 26 ] ] }, "arguments": [ { "role": "hasAgent", "ref_id": "PMID-1620116_T3" } ] }, { "id": "PMID-1620116_E4", "type": "BindingOfProteinToDNA", "trigger": { "text": [ "binding" ], "offsets": [ [ 213, 220 ] ] }, "arguments": [ { "role": "hasAgent", "ref_id": "PMID-1620116_T9" }, { "role": "hasPatient", "ref_id": "PMID-1620116_T10" } ] }, { "id": "PMID-1620116_E5", "type": "PositiveRegulation", "trigger": { "text": [ "activating" ], "offsets": [ [ 260, 270 ] ] }, "arguments": [ { "role": "hasAgent", "ref_id": "PMID-1620116_T13" } ] }, { "id": "PMID-1620116_E6", "type": "GeneExpression", "trigger": { "text": [ "expressed" ], "offsets": [ [ 316, 325 ] ] }, "arguments": [ { "role": "hasPatient", "ref_id": "PMID-1620116_T16" } ] }, { "id": "PMID-1620116_E7", "type": "NegativeRegulation", "trigger": { "text": [ "repressed" ], "offsets": [ [ 409, 418 ] ] }, "arguments": [ { "role": "hasAgent", "ref_id": "PMID-1620116_T17" }, { "role": "hasPatient", "ref_id": "PMID-1620116_E8" } ] }, { "id": "PMID-1620116_E8", "type": "Transcription", "trigger": { "text": [ "transcription" ], "offsets": [ [ 419, 432 ] ] }, "arguments": [] }, { "id": "PMID-1620116_E9", "type": "NegativeRegulation", "trigger": { "text": [ "repressing" ], "offsets": [ [ 561, 571 ] ] }, "arguments": [ { "role": "hasAgent", "ref_id": "PMID-1620116_T21" } ] }, { "id": "PMID-1620116_E10", "type": "NegativeRegulation", "trigger": { "text": [ "repressing" ], "offsets": [ [ 699, 709 ] ] }, "arguments": [ { "role": "hasAgent", "ref_id": "PMID-1620116_T27" } ] } ]

[]

[ { "id": "PMID-1620116_R1", "type": "hasPart", "arg1_id": "PMID-1620116_T4", "arg2_id": "PMID-1620116_T3", "normalized": [] }, { "id": "PMID-1620116_R2", "type": "hasPart", "arg1_id": "PMID-1620116_T5", "arg2_id": "PMID-1620116_T9", "normalized": [] }, { "id": "PMID-1620116_R4", "type": "hasPart", "arg1_id": "PMID-1620116_T23", "arg2_id": "PMID-1620116_T21", "normalized": [] }, { "id": "PMID-1620116_R5", "type": "hasPart", "arg1_id": "PMID-1620116_T25", "arg2_id": "PMID-1620116_T24", "normalized": [] }, { "id": "PMID-1620116_R6", "type": "fromSpecies", "arg1_id": "PMID-1620116_T29", "arg2_id": "PMID-1620116_T28", "normalized": [] }, { "id": "PMID-1620116_R7", "type": "hasPart", "arg1_id": "PMID-1620116_T29", "arg2_id": "PMID-1620116_T27", "normalized": [] } ]

[ { "id": "PMID-1630447__text", "type": "abstract", "text": [ "Subunit of an alpha-interferon-responsive transcription factor is related to interferon regulatory factor and Myb families of DNA-binding proteins. Alpha interferon stimulates transcription by converting the positive transcriptional regulator ISGF3 from a latent to an active form. This receptor-mediated event occurs in the cytoplasm, with subsequent translocation of the activated factor to the nucleus. ISGF3 has two components, termed ISGF3 alpha and ISGF3 gamma. ISGF3 gamma serves as the DNA recognition subunit, while ISGF3 alpha, which appears to consist of three polypeptides, is a target for alpha interferon signaling and serves as a regulatory component whose activation is required to form ISGF3. ISGF3 gamma DNA-binding activity was identified as a 48-kDa polypeptide, and partial amino acid sequence has allowed isolation of cDNA clones. ISGF3 gamma translated in vitro from recombinant clones bound DNA with a specificity indistinguishable from that of ISGF3 gamma purified from HeLa cells. Sequencing of ISGF3 gamma cDNA clones revealed significant similarity to the interferon regulatory factor (IRF) family of DNA binding proteins in the amino-terminal 117 residues of ISGF3 gamma. The other IRF family proteins bind DNA with a specificity related to but distinct from that of ISGF3 gamma. We note sequence similarities between the related regions of IRF family proteins and the imperfect tryptophan repeats which constitute the DNA-binding domain of the c-myb oncoprotein. These sequence similarities suggest that ISGF3 gamma and IRF proteins and the c-myb oncoprotein use a common structural motif for DNA recognition. Recombinant ISGF3 gamma, like the natural protein, interacted with HeLa cell ISGF3 alpha to form the mature ISGF3 DNA-binding complex. We suggest that other IRF family members may participate in signaling pathways by interacting with as yet unidentified regulatory subunits analogous to ISGF3 alpha.\n" ], "offsets": [ [ 0, 1940 ] ] } ]

[ { "id": "PMID-1630447_T1", "type": "ProteinSubunit", "text": [ "Subunit" ], "offsets": [ [ 0, 7 ] ], "normalized": [] }, { "id": "PMID-1630447_T2", "type": "Protein", "text": [ "alpha-interferon" ], "offsets": [ [ 14, 30 ] ], "normalized": [] }, { "id": "PMID-1630447_T4", "type": "TranscriptionFactor", "text": [ "transcription factor" ], "offsets": [ [ 42, 62 ] ], "normalized": [] }, { "id": "PMID-1630447_T5", "type": "Protein", "text": [ "interferon regulatory factor" ], "offsets": [ [ 77, 105 ] ], "normalized": [] }, { "id": "PMID-1630447_T6", "type": "Protein", "text": [ "Myb families of DNA-binding proteins" ], "offsets": [ [ 110, 146 ] ], "normalized": [] }, { "id": "PMID-1630447_T9", "type": "Protein", "text": [ "Alpha interferon" ], "offsets": [ [ 148, 164 ] ], "normalized": [] }, { "id": "PMID-1630447_T14", "type": "TranscriptionFactor", "text": [ "transcriptional regulator ISGF3" ], "offsets": [ [ 217, 248 ] ], "normalized": [] }, { "id": "PMID-1630447_T16", "type": "Protein", "text": [ "receptor" ], "offsets": [ [ 287, 295 ] ], "normalized": [] }, { "id": "PMID-1630447_T17", "type": "CellComponent", "text": [ "cytoplasm" ], "offsets": [ [ 325, 334 ] ], "normalized": [] }, { "id": "PMID-1630447_T20", "type": "Protein", "text": [ "factor" ], "offsets": [ [ 383, 389 ] ], "normalized": [] }, { "id": "PMID-1630447_T21", "type": "Nucleus", "text": [ "nucleus" ], "offsets": [ [ 397, 404 ] ], "normalized": [] }, { "id": "PMID-1630447_T22", "type": "TranscriptionFactor", "text": [ "ISGF3" ], "offsets": [ [ 406, 411 ] ], "normalized": [] }, { "id": "PMID-1630447_T23", "type": "ProteinSubunit", "text": [ "ISGF3 alpha" ], "offsets": [ [ 439, 450 ] ], "normalized": [] }, { "id": "PMID-1630447_T24", "type": "ProteinSubunit", "text": [ "ISGF3 gamma" ], "offsets": [ [ 455, 466 ] ], "normalized": [] }, { "id": "PMID-1630447_T25", "type": "ProteinSubunit", "text": [ "ISGF3 gamma" ], "offsets": [ [ 468, 479 ] ], "normalized": [] }, { "id": "PMID-1630447_T26", "type": "DNA", "text": [ "DNA" ], "offsets": [ [ 494, 497 ] ], "normalized": [] }, { "id": "PMID-1630447_T27", "type": "ProteinSubunit", "text": [ "subunit" ], "offsets": [ [ 510, 517 ] ], "normalized": [] }, { "id": "PMID-1630447_T28", "type": "ProteinSubunit", "text": [ "ISGF3 alpha" ], "offsets": [ [ 525, 536 ] ], "normalized": [] }, { "id": "PMID-1630447_T29", "type": "Peptide", "text": [ "polypeptides" ], "offsets": [ [ 572, 584 ] ], "normalized": [] }, { "id": "PMID-1630447_T30", "type": "Protein", "text": [ "alpha interferon" ], "offsets": [ [ 602, 618 ] ], "normalized": [] }, { "id": "PMID-1630447_T34", "type": "TranscriptionFactor", "text": [ "ISGF3" ], "offsets": [ [ 703, 708 ] ], "normalized": [] }, { "id": "PMID-1630447_T35", "type": "ProteinSubunit", "text": [ "ISGF3 gamma" ], "offsets": [ [ 710, 721 ] ], "normalized": [] }, { "id": "PMID-1630447_T36", "type": "DNA", "text": [ "DNA" ], "offsets": [ [ 722, 725 ] ], "normalized": [] }, { "id": "PMID-1630447_T38", "type": "Peptide", "text": [ "polypeptide" ], "offsets": [ [ 770, 781 ] ], "normalized": [] }, { "id": "PMID-1630447_T39", "type": "AminoAcid", "text": [ "amino acid" ], "offsets": [ [ 795, 805 ] ], "normalized": [] }, { "id": "PMID-1630447_T40", "type": "Sequence", "text": [ "sequence" ], "offsets": [ [ 806, 814 ] ], "normalized": [] }, { "id": "PMID-1630447_T41", "type": "DNA", "text": [ "cDNA clones" ], "offsets": [ [ 840, 851 ] ], "normalized": [] }, { "id": "PMID-1630447_T42", "type": "ProteinSubunit", "text": [ "ISGF3 gamma" ], "offsets": [ [ 853, 864 ] ], "normalized": [] }, { "id": "PMID-1630447_T44", "type": "DNA", "text": [ "DNA" ], "offsets": [ [ 915, 918 ] ], "normalized": [] }, { "id": "PMID-1630447_T45", "type": "ProteinSubunit", "text": [ "ISGF3 gamma" ], "offsets": [ [ 969, 980 ] ], "normalized": [] }, { "id": "PMID-1630447_T46", "type": "Cell", "text": [ "HeLa cells" ], "offsets": [ [ 995, 1005 ] ], "normalized": [] }, { "id": "PMID-1630447_T47", "type": "SequenceHomologyAnalysis", "text": [ "Sequencing" ], "offsets": [ [ 1007, 1017 ] ], "normalized": [] }, { "id": "PMID-1630447_T48", "type": "ProteinSubunit", "text": [ "ISGF3 gamma" ], "offsets": [ [ 1021, 1032 ] ], "normalized": [] }, { "id": "PMID-1630447_T49", "type": "DNA", "text": [ "cDNA clones" ], "offsets": [ [ 1033, 1044 ] ], "normalized": [] }, { "id": "PMID-1630447_T50", "type": "Protein", "text": [ "IRF" ], "offsets": [ [ 1114, 1117 ] ], "normalized": [] }, { "id": "PMID-1630447_T54", "type": "AminoAcid", "text": [ "residues" ], "offsets": [ [ 1176, 1184 ] ], "normalized": [] }, { "id": "PMID-1630447_T55", "type": "ProteinSubunit", "text": [ "ISGF3 gamma" ], "offsets": [ [ 1188, 1199 ] ], "normalized": [] }, { "id": "PMID-1630447_T56", "type": "Protein", "text": [ "IRF family proteins" ], "offsets": [ [ 1211, 1230 ] ], "normalized": [] }, { "id": "PMID-1630447_T58", "type": "DNA", "text": [ "DNA" ], "offsets": [ [ 1236, 1239 ] ], "normalized": [] }, { "id": "PMID-1630447_T59", "type": "ProteinSubunit", "text": [ "ISGF3 gamma" ], "offsets": [ [ 1296, 1307 ] ], "normalized": [] }, { "id": "PMID-1630447_T60", "type": "SequenceHomologyAnalysis", "text": [ "sequence similarities" ], "offsets": [ [ 1317, 1338 ] ], "normalized": [] }, { "id": "PMID-1630447_T61", "type": "Protein", "text": [ "IRF family proteins" ], "offsets": [ [ 1370, 1389 ] ], "normalized": [] }, { "id": "PMID-1630447_T62", "type": "PrimaryStructure", "text": [ "tryptophan repeats" ], "offsets": [ [ 1408, 1426 ] ], "normalized": [] }, { "id": "PMID-1630447_T63", "type": "DNABindingDomainOfProtein", "text": [ "DNA-binding domain" ], "offsets": [ [ 1448, 1466 ] ], "normalized": [] }, { "id": "PMID-1630447_T64", "type": "Protein", "text": [ "c-myb oncoprotein" ], "offsets": [ [ 1474, 1491 ] ], "normalized": [] }, { "id": "PMID-1630447_T65", "type": "ProteinSubunit", "text": [ "ISGF3 gamma" ], "offsets": [ [ 1534, 1545 ] ], "normalized": [] }, { "id": "PMID-1630447_T66", "type": "Protein", "text": [ "IRF proteins" ], "offsets": [ [ 1550, 1562 ] ], "normalized": [] }, { "id": "PMID-1630447_T67", "type": "Protein", "text": [ "c-myb oncoprotein" ], "offsets": [ [ 1571, 1588 ] ], "normalized": [] }, { "id": "PMID-1630447_T68", "type": "PrimaryStructure", "text": [ "structural motif" ], "offsets": [ [ 1602, 1618 ] ], "normalized": [] }, { "id": "PMID-1630447_T69", "type": "DNA", "text": [ "DNA" ], "offsets": [ [ 1623, 1626 ] ], "normalized": [] }, { "id": "PMID-1630447_T70", "type": "ProteinSubunit", "text": [ "ISGF3 gamma" ], "offsets": [ [ 1652, 1663 ] ], "normalized": [] }, { "id": "PMID-1630447_T72", "type": "Cell", "text": [ "HeLa cell" ], "offsets": [ [ 1707, 1716 ] ], "normalized": [] }, { "id": "PMID-1630447_T73", "type": "ProteinSubunit", "text": [ "ISGF3 alpha" ], "offsets": [ [ 1717, 1728 ] ], "normalized": [] }, { "id": "PMID-1630447_T75", "type": "ProteinComplex", "text": [ "ISGF3 DNA-binding complex" ], "offsets": [ [ 1748, 1773 ] ], "normalized": [] }, { "id": "PMID-1630447_T78", "type": "Protein", "text": [ "IRF family" ], "offsets": [ [ 1797, 1807 ] ], "normalized": [] }, { "id": "PMID-1630447_T81", "type": "ProteinSubunit", "text": [ "subunits" ], "offsets": [ [ 1905, 1913 ] ], "normalized": [] }, { "id": "PMID-1630447_T82", "type": "ProteinSubunit", "text": [ "ISGF3 alpha" ], "offsets": [ [ 1927, 1938 ] ], "normalized": [] }, { "id": "PMID-1630447_T8", "type": "Protein", "text": [ "DNA binding proteins" ], "offsets": [ [ 1129, 1149 ] ], "normalized": [] } ]

[ { "id": "PMID-1630447_E1", "type": "ResponseProcess", "trigger": { "text": [ "responsive" ], "offsets": [ [ 31, 41 ] ] }, "arguments": [ { "role": "hasAgent2", "ref_id": "PMID-1630447_T2" }, { "role": "hasPatient", "ref_id": "PMID-1630447_T4" } ] }, { "id": "PMID-1630447_E3", "type": "Increase", "trigger": { "text": [ "stimulates" ], "offsets": [ [ 165, 175 ] ] }, "arguments": [ { "role": "hasAgent", "ref_id": "PMID-1630447_T9" }, { "role": "hasPatient", "ref_id": "PMID-1630447_E4" } ] }, { "id": "PMID-1630447_E4", "type": "Transcription", "trigger": { "text": [ "transcription" ], "offsets": [ [ 176, 189 ] ] }, "arguments": [] }, { "id": "PMID-1630447_E5", "type": "RegulatoryProcess", "trigger": { "text": [ "converting" ], "offsets": [ [ 193, 203 ] ] }, "arguments": [ { "role": "hasPatient", "ref_id": "PMID-1630447_T14" } ] }, { "id": "PMID-1630447_E7", "type": "Localization", "trigger": { "text": [ "translocation" ], "offsets": [ [ 352, 365 ] ] }, "arguments": [ { "role": "hasPatient", "ref_id": "PMID-1630447_T20" } ] }, { "id": "PMID-1630447_E8", "type": "PositiveRegulation", "trigger": { "text": [ "activated" ], "offsets": [ [ 373, 382 ] ] }, "arguments": [ { "role": "hasPatient", "ref_id": "PMID-1630447_T20" } ] }, { "id": "PMID-1630447_E9", "type": "SignalingPathway", "trigger": { "text": [ "signaling" ], "offsets": [ [ 619, 628 ] ] }, "arguments": [] }, { "id": "PMID-1630447_E10", "type": "PositiveRegulation", "trigger": { "text": [ "activation" ], "offsets": [ [ 672, 682 ] ] }, "arguments": [] }, { "id": "PMID-1630447_E11", "type": "FormationOfTranscriptionFactorComplex", "trigger": { "text": [ "form" ], "offsets": [ [ 698, 702 ] ] }, "arguments": [ { "role": "hasPatient", "ref_id": "PMID-1630447_T34" } ] }, { "id": "PMID-1630447_E12", "type": "BindingOfProteinToDNA", "trigger": { "text": [ "binding" ], "offsets": [ [ 726, 733 ] ] }, "arguments": [ { "role": "hasAgent", "ref_id": "PMID-1630447_T35" }, { "role": "hasPatient", "ref_id": "PMID-1630447_T36" } ] }, { "id": "PMID-1630447_E13", "type": "BindingOfProteinToDNA", "trigger": { "text": [ "bound" ], "offsets": [ [ 909, 914 ] ] }, "arguments": [ { "role": "hasAgent", "ref_id": "PMID-1630447_T42" }, { "role": "hasPatient", "ref_id": "PMID-1630447_T44" } ] }, { "id": "PMID-1630447_E15", "type": "BindingOfProteinToDNA", "trigger": { "text": [ "bind" ], "offsets": [ [ 1231, 1235 ] ] }, "arguments": [ { "role": "hasAgent", "ref_id": "PMID-1630447_T56" }, { "role": "hasPatient", "ref_id": "PMID-1630447_T58" } ] }, { "id": "PMID-1630447_E16", "type": "BindingToProtein", "trigger": { "text": [ "interacted" ], "offsets": [ [ 1691, 1701 ] ] }, "arguments": [ { "role": "hasPatient", "ref_id": "PMID-1630447_T70" }, { "role": "hasPatient2", "ref_id": "PMID-1630447_T73" } ] }, { "id": "PMID-1630447_E19", "type": "SignalingPathway", "trigger": { "text": [ "signaling pathways" ], "offsets": [ [ 1835, 1853 ] ] }, "arguments": [] }, { "id": "PMID-1630447_E20", "type": "BindingToProtein", "trigger": { "text": [ "interacting" ], "offsets": [ [ 1857, 1868 ] ] }, "arguments": [ { "role": "hasPatient", "ref_id": "PMID-1630447_T78" }, { "role": "hasPatient2", "ref_id": "PMID-1630447_T81" } ] }, { "id": "PMID-1630447_E2", "type": "RegulatoryProcess", "trigger": { "text": [ "mediated" ], "offsets": [ [ 296, 304 ] ] }, "arguments": [ { "role": "hasAgent", "ref_id": "PMID-1630447_T16" } ] } ]

[]

[ { "id": "PMID-1630447_R1", "type": "hasPart", "arg1_id": "PMID-1630447_T4", "arg2_id": "PMID-1630447_T1", "normalized": [] }, { "id": "PMID-1630447_R6", "type": "hasPart", "arg1_id": "PMID-1630447_T22", "arg2_id": "PMID-1630447_T24", "normalized": [] }, { "id": "PMID-1630447_R7", "type": "hasPart", "arg1_id": "PMID-1630447_T22", "arg2_id": "PMID-1630447_T23", "normalized": [] }, { "id": "PMID-1630447_R8", "type": "hasPart", "arg1_id": "PMID-1630447_T28", "arg2_id": "PMID-1630447_T29", "normalized": [] }, { "id": "PMID-1630447_R10", "type": "locatedIn", "arg1_id": "PMID-1630447_T45", "arg2_id": "PMID-1630447_T46", "normalized": [] }, { "id": "PMID-1630447_R11", "type": "encodes", "arg1_id": "PMID-1630447_T49", "arg2_id": "PMID-1630447_T48", "normalized": [] }, { "id": "PMID-1630447_R12", "type": "hasPart", "arg1_id": "PMID-1630447_T55", "arg2_id": "PMID-1630447_T54", "normalized": [] }, { "id": "PMID-1630447_R13", "type": "hasPart", "arg1_id": "PMID-1630447_T63", "arg2_id": "PMID-1630447_T62", "normalized": [] }, { "id": "PMID-1630447_R14", "type": "hasPart", "arg1_id": "PMID-1630447_T64", "arg2_id": "PMID-1630447_T63", "normalized": [] }, { "id": "PMID-1630447_R15", "type": "hasPart", "arg1_id": "PMID-1630447_T65", "arg2_id": "PMID-1630447_T68", "normalized": [] }, { "id": "PMID-1630447_R16", "type": "hasPart", "arg1_id": "PMID-1630447_T66", "arg2_id": "PMID-1630447_T68", "normalized": [] }, { "id": "PMID-1630447_R17", "type": "hasPart", "arg1_id": "PMID-1630447_T67", "arg2_id": "PMID-1630447_T68", "normalized": [] }, { "id": "PMID-1630447_R18", "type": "locatedIn", "arg1_id": "PMID-1630447_T73", "arg2_id": "PMID-1630447_T72", "normalized": [] }, { "id": "PMID-1630447_R4", "type": "hasPart", "arg1_id": "PMID-1630447_T35", "arg2_id": "PMID-1630447_T38", "normalized": [] }, { "id": "PMID-1630447_R9", "type": "hasPart", "arg1_id": "PMID-1630447_T75", "arg2_id": "PMID-1630447_T73", "normalized": [] }, { "id": "PMID-1630447_R20", "type": "hasPart", "arg1_id": "PMID-1630447_T75", "arg2_id": "PMID-1630447_T70", "normalized": [] } ]

[ { "id": "PMID-16384933__text", "type": "abstract", "text": [ "Expression of the Bcl-3 proto-oncogene suppresses p53 activation. While Bcl-3 expression in cancer was originally thought to be limited to B-cell lymphomas with a 14;19 chromosomal translocation, more recent evidence indicates that expression of this presumptive oncoprotein is significantly more widespread in cancer. However, an oncogenic role for Bcl-3 has not been clearly identified. Experiments presented here indicate that Bcl-3 is inducible by DNA damage and is required for the induction of Hdm2 gene expression and the suppression of persistent p53 activity. Furthermore, constitutive expression of Bcl-3 suppresses DNA damage-induced p53 activation and inhibits p53-induced apoptosis through a mechanism that is at least partly dependent on the up-regulation of Hdm2. The results provide insight into a mechanism whereby altered expression of Bcl-3 leads to tumorigenic potential. Since Bcl-3 is required for germinal center formation, these results suggest functional similarities with the unrelated Bcl-6 oncoprotein in suppressing potential p53-dependent cell cycle arrest and apoptosis in response to somatic hypermutation and class switch recombination.\n" ], "offsets": [ [ 0, 1170 ] ] } ]

[ { "id": "PMID-16384933_T2", "type": "Gene", "text": [ "Bcl-3 proto-oncogene" ], "offsets": [ [ 18, 38 ] ], "normalized": [] }, { "id": "PMID-16384933_T4", "type": "Protein", "text": [ "p53" ], "offsets": [ [ 50, 53 ] ], "normalized": [] }, { "id": "PMID-16384933_T6", "type": "Protein", "text": [ "Bcl-3" ], "offsets": [ [ 72, 77 ] ], "normalized": [] }, { "id": "PMID-16384933_T9", "type": "Cell", "text": [ "B-cell lymphomas" ], "offsets": [ [ 139, 155 ] ], "normalized": [] }, { "id": "PMID-16384933_T10", "type": "Chromosome", "text": [ "chromosomal" ], "offsets": [ [ 169, 180 ] ], "normalized": [] }, { "id": "PMID-16384933_T13", "type": "Protein", "text": [ "oncoprotein" ], "offsets": [ [ 263, 274 ] ], "normalized": [] }, { "id": "PMID-16384933_T15", "type": "Protein", "text": [ "Bcl-3" ], "offsets": [ [ 430, 435 ] ], "normalized": [] }, { "id": "PMID-16384933_T19", "type": "Gene", "text": [ "Hdm2" ], "offsets": [ [ 500, 504 ] ], "normalized": [] }, { "id": "PMID-16384933_T22", "type": "Protein", "text": [ "p53" ], "offsets": [ [ 555, 558 ] ], "normalized": [] }, { "id": "PMID-16384933_T23", "type": "Function", "text": [ "activity" ], "offsets": [ [ 559, 567 ] ], "normalized": [] }, { "id": "PMID-16384933_T25", "type": "Protein", "text": [ "Bcl-3" ], "offsets": [ [ 609, 614 ] ], "normalized": [] }, { "id": "PMID-16384933_T29", "type": "Protein", "text": [ "p53" ], "offsets": [ [ 645, 648 ] ], "normalized": [] }, { "id": "PMID-16384933_T32", "type": "Protein", "text": [ "p53" ], "offsets": [ [ 673, 676 ] ], "normalized": [] }, { "id": "PMID-16384933_T37", "type": "Gene", "text": [ "Hdm2" ], "offsets": [ [ 773, 777 ] ], "normalized": [] }, { "id": "PMID-16384933_T39", "type": "Protein", "text": [ "Bcl-3" ], "offsets": [ [ 854, 859 ] ], "normalized": [] }, { "id": "PMID-16384933_T40", "type": "Protein", "text": [ "Bcl-3" ], "offsets": [ [ 898, 903 ] ], "normalized": [] }, { "id": "PMID-16384933_T42", "type": "Protein", "text": [ "Bcl-6 oncoprotein" ], "offsets": [ [ 1012, 1029 ] ], "normalized": [] }, { "id": "PMID-16384933_T47", "type": "Cell", "text": [ "somatic" ], "offsets": [ [ 1116, 1123 ] ], "normalized": [] }, { "id": "PMID-16384933_T44", "type": "Protein", "text": [ "p53" ], "offsets": [ [ 1055, 1058 ] ], "normalized": [] } ]

[ { "id": "PMID-16384933_E1", "type": "GeneExpression", "trigger": { "text": [ "Expression" ], "offsets": [ [ 0, 10 ] ] }, "arguments": [ { "role": "hasPatient", "ref_id": "PMID-16384933_T2" } ] }, { "id": "PMID-16384933_E2", "type": "NegativeRegulation", "trigger": { "text": [ "suppresses" ], "offsets": [ [ 39, 49 ] ] }, "arguments": [ { "role": "hasAgent", "ref_id": "PMID-16384933_E1" }, { "role": "hasPatient", "ref_id": "PMID-16384933_E3" } ] }, { "id": "PMID-16384933_E3", "type": "PositiveRegulation", "trigger": { "text": [ "activation" ], "offsets": [ [ 54, 64 ] ] }, "arguments": [ { "role": "hasPatient", "ref_id": "PMID-16384933_T4" } ] }, { "id": "PMID-16384933_E4", "type": "GeneExpression", "trigger": { "text": [ "expression" ], "offsets": [ [ 78, 88 ] ] }, "arguments": [ { "role": "hasPatient", "ref_id": "PMID-16384933_T6" } ] }, { "id": "PMID-16384933_E5", "type": "Disease", "trigger": { "text": [ "cancer" ], "offsets": [ [ 92, 98 ] ] }, "arguments": [] }, { "id": "PMID-16384933_E6", "type": "GeneMutation", "trigger": { "text": [ "translocation" ], "offsets": [ [ 181, 194 ] ] }, "arguments": [ { "role": "hasPatient", "ref_id": "PMID-16384933_T10" } ] }, { "id": "PMID-16384933_E7", "type": "GeneExpression", "trigger": { "text": [ "expression" ], "offsets": [ [ 232, 242 ] ] }, "arguments": [ { "role": "hasPatient", "ref_id": "PMID-16384933_T13" } ] }, { "id": "PMID-16384933_E8", "type": "PositiveRegulation", "trigger": { "text": [ "inducible" ], "offsets": [ [ 439, 448 ] ] }, "arguments": [ { "role": "hasAgent", "ref_id": "PMID-16384933_E9" }, { "role": "hasPatient", "ref_id": "PMID-16384933_T15" } ] }, { "id": "PMID-16384933_E9", "type": "Mutation", "trigger": { "text": [ "DNA damage" ], "offsets": [ [ 452, 462 ] ] }, "arguments": [] }, { "id": "PMID-16384933_E10", "type": "PositiveRegulation", "trigger": { "text": [ "induction" ], "offsets": [ [ 487, 496 ] ] }, "arguments": [ { "role": "hasPatient", "ref_id": "PMID-16384933_E11" } ] }, { "id": "PMID-16384933_E11", "type": "GeneExpression", "trigger": { "text": [ "gene expression" ], "offsets": [ [ 505, 520 ] ] }, "arguments": [ { "role": "hasPatient", "ref_id": "PMID-16384933_T19" } ] }, { "id": "PMID-16384933_E12", "type": "NegativeRegulation", "trigger": { "text": [ "suppression" ], "offsets": [ [ 529, 540 ] ] }, "arguments": [ { "role": "hasPatient", "ref_id": "PMID-16384933_T23" } ] }, { "id": "PMID-16384933_E13", "type": "GeneExpression", "trigger": { "text": [ "expression" ], "offsets": [ [ 595, 605 ] ] }, "arguments": [ { "role": "hasPatient", "ref_id": "PMID-16384933_T25" } ] }, { "id": "PMID-16384933_E14", "type": "NegativeRegulation", "trigger": { "text": [ "suppresses" ], "offsets": [ [ 615, 625 ] ] }, "arguments": [ { "role": "hasAgent", "ref_id": "PMID-16384933_E13" }, { "role": "hasPatient", "ref_id": "PMID-16384933_E17" } ] }, { "id": "PMID-16384933_E15", "type": "Mutation", "trigger": { "text": [ "DNA damage" ], "offsets": [ [ 626, 636 ] ] }, "arguments": [] }, { "id": "PMID-16384933_E16", "type": "PositiveRegulation", "trigger": { "text": [ "induced" ], "offsets": [ [ 637, 644 ] ] }, "arguments": [ { "role": "hasAgent", "ref_id": "PMID-16384933_E15" }, { "role": "hasPatient", "ref_id": "PMID-16384933_E17" } ] }, { "id": "PMID-16384933_E17", "type": "PositiveRegulation", "trigger": { "text": [ "activation" ], "offsets": [ [ 649, 659 ] ] }, "arguments": [ { "role": "hasPatient", "ref_id": "PMID-16384933_T29" } ] }, { "id": "PMID-16384933_E18", "type": "NegativeRegulation", "trigger": { "text": [ "inhibits" ], "offsets": [ [ 664, 672 ] ] }, "arguments": [ { "role": "hasAgent", "ref_id": "PMID-16384933_E13" }, { "role": "hasPatient", "ref_id": "PMID-16384933_E20" } ] }, { "id": "PMID-16384933_E19", "type": "PositiveRegulation", "trigger": { "text": [ "induced" ], "offsets": [ [ 677, 684 ] ] }, "arguments": [ { "role": "hasAgent", "ref_id": "PMID-16384933_T32" }, { "role": "hasPatient", "ref_id": "PMID-16384933_E20" } ] }, { "id": "PMID-16384933_E20", "type": "CellDeath", "trigger": { "text": [ "apoptosis" ], "offsets": [ [ 685, 694 ] ] }, "arguments": [] }, { "id": "PMID-16384933_E22", "type": "GeneExpression", "trigger": { "text": [ "expression" ], "offsets": [ [ 840, 850 ] ] }, "arguments": [ { "role": "hasPatient", "ref_id": "PMID-16384933_T39" } ] }, { "id": "PMID-16384933_E23", "type": "CellularProcess", "trigger": { "text": [ "germinal center formation" ], "offsets": [ [ 920, 945 ] ] }, "arguments": [] }, { "id": "PMID-16384933_E24", "type": "NegativeRegulation", "trigger": { "text": [ "suppressing" ], "offsets": [ [ 1033, 1044 ] ] }, "arguments": [ { "role": "hasAgent", "ref_id": "PMID-16384933_T42" }, { "role": "hasPatient", "ref_id": "PMID-16384933_E26" } ] }, { "id": "PMID-16384933_E26", "type": "CellCyclePhaseTransition", "trigger": { "text": [ "cell cycle arrest" ], "offsets": [ [ 1069, 1086 ] ] }, "arguments": [] }, { "id": "PMID-16384933_E27", "type": "CellDeath", "trigger": { "text": [ "apoptosis" ], "offsets": [ [ 1091, 1100 ] ] }, "arguments": [] }, { "id": "PMID-16384933_E28", "type": "CellularProcess", "trigger": { "text": [ "hypermutation" ], "offsets": [ [ 1124, 1137 ] ] }, "arguments": [] }, { "id": "PMID-16384933_E29", "type": "CellularProcess", "trigger": { "text": [ "class switch recombination" ], "offsets": [ [ 1142, 1168 ] ] }, "arguments": [] }, { "id": "PMID-16384933_E30", "type": "Disease", "trigger": { "text": [ "cancer" ], "offsets": [ [ 311, 317 ] ] }, "arguments": [] }, { "id": "PMID-16384933_E21", "type": "PositiveRegulation", "trigger": { "text": [ "up-regulation" ], "offsets": [ [ 756, 769 ] ] }, "arguments": [ { "role": "hasPatient", "ref_id": "PMID-16384933_T37" } ] }, { "id": "PMID-16384933_E31", "type": "Disease", "trigger": { "text": [ "tumorigenic" ], "offsets": [ [ 869, 880 ] ] }, "arguments": [] }, { "id": "PMID-16384933_E25", "type": "NegativeRegulation", "trigger": { "text": [ "suppressing" ], "offsets": [ [ 1033, 1044 ] ] }, "arguments": [ { "role": "hasAgent", "ref_id": "PMID-16384933_T42" }, { "role": "hasPatient", "ref_id": "PMID-16384933_E27" } ] } ]

[]

[ { "id": "PMID-16384933_R4", "type": "hasFunction", "arg1_id": "PMID-16384933_T22", "arg2_id": "PMID-16384933_T23", "normalized": [] } ]

[ { "id": "PMID-1658795__text", "type": "abstract", "text": [ "Clone pAT 133 identifies a gene that encodes another human member of a class of growth factor-induced genes with almost identical zinc-finger domains. We report the structure and regulation of a gene represented by clone pAT 133, which is induced upon transition from a resting state (G0) through the early phase of the cell cycle (G1). The pAT 133 gene is immediately induced, with FOS-like kinetics, in human T cells and in fibroblasts. Primary structure analysis showed that the encoded protein contains three tandem zinc-finger sequences of the type Cys2-Xaa12-His2. This zinc-finger region, which is thought to bind DNA in a sequence-specific manner, is similar (greater than 80% on the amino acid level) to two previously described transcription factors pAT 225/EGR1 and pAT 591/EGR2. Except for the conserved zinc-finger domains, the amino acid sequences of the three proteins are distinct. This structural similarity suggests that the pAT 133 gene encodes a transcription factor with a specific biological function. Comparing the regulation of these related zinc-finger-encoding genes showed coordinate induction upon mitogenic stimulation of resting T lymphocytes and of resting fibroblasts. However, upon transition from a proliferating (G1) to a resting state of the cell cycle the three genes were differently regulated. In human histiocytic U937 cells mRNA of clone pAT 133 was constitutively expressed, whereas mRNA of pAT 225/EGR1 was induced upon induction of terminal differentiation. In contrast mRNA representing pAT 591/EGR2 was not expressed in these cells. This difference in gene regulation suggests distinct biological roles in the control of cell proliferation for the respective proteins.\n" ], "offsets": [ [ 0, 1715 ] ] } ]

[ { "id": "PMID-1658795_T10", "type": "DNA", "text": [ "pAT 133" ], "offsets": [ [ 221, 228 ] ], "normalized": [] }, { "id": "PMID-1658795_T19", "type": "Gene", "text": [ "gene" ], "offsets": [ [ 349, 353 ] ], "normalized": [] }, { "id": "PMID-1658795_T21", "type": "Eukaryote", "text": [ "human" ], "offsets": [ [ 405, 410 ] ], "normalized": [] }, { "id": "PMID-1658795_T22", "type": "Cell", "text": [ "T cells" ], "offsets": [ [ 411, 418 ] ], "normalized": [] }, { "id": "PMID-1658795_T23", "type": "Cell", "text": [ "fibroblasts" ], "offsets": [ [ 426, 437 ] ], "normalized": [] }, { "id": "PMID-1658795_T24", "type": "Protein", "text": [ "the encoded protein" ], "offsets": [ [ 478, 497 ] ], "normalized": [] }, { "id": "PMID-1658795_T25", "type": "ZincCoordinatingDomain", "text": [ "zinc-finger sequences" ], "offsets": [ [ 520, 541 ] ], "normalized": [] }, { "id": "PMID-1658795_T26", "type": "ZincCoordinatingDomain", "text": [ "zinc-finger region" ], "offsets": [ [ 576, 594 ] ], "normalized": [] }, { "id": "PMID-1658795_T28", "type": "DNA", "text": [ "DNA" ], "offsets": [ [ 621, 624 ] ], "normalized": [] }, { "id": "PMID-1658795_T42", "type": "Gene", "text": [ "these related zinc-finger-encoding genes" ], "offsets": [ [ 1052, 1092 ] ], "normalized": [] }, { "id": "PMID-1658795_T45", "type": "Cell", "text": [ "T lymphocytes" ], "offsets": [ [ 1159, 1172 ] ], "normalized": [] }, { "id": "PMID-1658795_T46", "type": "Cell", "text": [ "fibroblasts" ], "offsets": [ [ 1188, 1199 ] ], "normalized": [] }, { "id": "PMID-1658795_T52", "type": "Gene", "text": [ "the three genes" ], "offsets": [ [ 1289, 1304 ] ], "normalized": [] }, { "id": "PMID-1658795_T54", "type": "Eukaryote", "text": [ "human" ], "offsets": [ [ 1336, 1341 ] ], "normalized": [] }, { "id": "PMID-1658795_T55", "type": "Cell", "text": [ "histiocytic U937 cells" ], "offsets": [ [ 1342, 1364 ] ], "normalized": [] }, { "id": "PMID-1658795_T56", "type": "MessengerRNA", "text": [ "mRNA" ], "offsets": [ [ 1365, 1369 ] ], "normalized": [] }, { "id": "PMID-1658795_T59", "type": "MessengerRNA", "text": [ "mRNA" ], "offsets": [ [ 1425, 1429 ] ], "normalized": [] }, { "id": "PMID-1658795_T64", "type": "MessengerRNA", "text": [ "mRNA" ], "offsets": [ [ 1514, 1518 ] ], "normalized": [] }, { "id": "PMID-1658795_T65", "type": "TranscriptionFactor", "text": [ "pAT 591/EGR2" ], "offsets": [ [ 1532, 1544 ] ], "normalized": [] }, { "id": "PMID-1658795_T70", "type": "Protein", "text": [ "the respective proteins" ], "offsets": [ [ 1690, 1713 ] ], "normalized": [] }, { "id": "PMID-1658795_T12", "type": "Gene", "text": [ "gene" ], "offsets": [ [ 195, 199 ] ], "normalized": [] }, { "id": "PMID-1658795_T13", "type": "DNA", "text": [ "pAT 133" ], "offsets": [ [ 341, 348 ] ], "normalized": [] }, { "id": "PMID-1658795_T15", "type": "DNA", "text": [ "pAT 133" ], "offsets": [ [ 1379, 1386 ] ], "normalized": [] }, { "id": "PMID-1658795_T16", "type": "DNA", "text": [ "pAT 225/EGR1" ], "offsets": [ [ 1433, 1445 ] ], "normalized": [] }, { "id": "PMID-1658795_T1", "type": "Gene", "text": [ "gene" ], "offsets": [ [ 27, 31 ] ], "normalized": [] }, { "id": "PMID-1658795_T3", "type": "Gene", "text": [ "member of a class of growth factor-induced genes" ], "offsets": [ [ 59, 107 ] ], "normalized": [] }, { "id": "PMID-1658795_T4", "type": "Eukaryote", "text": [ "human" ], "offsets": [ [ 53, 58 ] ], "normalized": [] }, { "id": "PMID-1658795_T7", "type": "ZincCoordinatingDomain", "text": [ "zinc-finger domains" ], "offsets": [ [ 130, 149 ] ], "normalized": [] } ]

[ { "id": "PMID-1658795_E2", "type": "RegulatoryProcess", "trigger": { "text": [ "regulation" ], "offsets": [ [ 179, 189 ] ] }, "arguments": [ { "role": "hasPatient", "ref_id": "PMID-1658795_T12" } ] }, { "id": "PMID-1658795_E3", "type": "PositiveRegulation", "trigger": { "text": [ "induced" ], "offsets": [ [ 239, 246 ] ] }, "arguments": [ { "role": "hasPatient", "ref_id": "PMID-1658795_T12" } ] }, { "id": "PMID-1658795_E10", "type": "PositiveRegulation", "trigger": { "text": [ "induced" ], "offsets": [ [ 369, 376 ] ] }, "arguments": [ { "role": "hasPatient", "ref_id": "PMID-1658795_T19" } ] }, { "id": "PMID-1658795_E11", "type": "BindingOfDNABindingDomainOfProteinToDNA", "trigger": { "text": [ "bind" ], "offsets": [ [ 616, 620 ] ] }, "arguments": [ { "role": "hasPatient", "ref_id": "PMID-1658795_T28" }, { "role": "hasAgent", "ref_id": "PMID-1658795_T26" } ] }, { "id": "PMID-1658795_E12", "type": "RegulatoryProcess", "trigger": { "text": [ "regulation" ], "offsets": [ [ 1038, 1048 ] ] }, "arguments": [ { "role": "hasPatient", "ref_id": "PMID-1658795_T42" } ] }, { "id": "PMID-1658795_E19", "type": "RegulatoryProcess", "trigger": { "text": [ "regulated" ], "offsets": [ [ 1322, 1331 ] ] }, "arguments": [ { "role": "hasPatient", "ref_id": "PMID-1658795_T52" } ] }, { "id": "PMID-1658795_E20", "type": "TranscriptionOfGene", "trigger": { "text": [ "expressed" ], "offsets": [ [ 1406, 1415 ] ] }, "arguments": [ { "role": "hasPatient", "ref_id": "PMID-1658795_T56" } ] }, { "id": "PMID-1658795_E21", "type": "PositiveRegulation", "trigger": { "text": [ "induced" ], "offsets": [ [ 1450, 1457 ] ] }, "arguments": [ { "role": "hasPatient", "ref_id": "PMID-1658795_T59" }, { "role": "hasAgent", "ref_id": "PMID-1658795_E22" } ] }, { "id": "PMID-1658795_E22", "type": "PositiveRegulation", "trigger": { "text": [ "induction" ], "offsets": [ [ 1463, 1472 ] ] }, "arguments": [ { "role": "hasPatient", "ref_id": "PMID-1658795_E23" } ] }, { "id": "PMID-1658795_E23", "type": "CellDifferentiation", "trigger": { "text": [ "terminal differentiation" ], "offsets": [ [ 1476, 1500 ] ] }, "arguments": [] }, { "id": "PMID-1658795_E25", "type": "RegulatoryProcess", "trigger": { "text": [ "control" ], "offsets": [ [ 1656, 1663 ] ] }, "arguments": [ { "role": "hasAgent", "ref_id": "PMID-1658795_T70" }, { "role": "hasPatient", "ref_id": "PMID-1658795_E26" } ] }, { "id": "PMID-1658795_E26", "type": "CellGrowth", "trigger": { "text": [ "cell proliferation" ], "offsets": [ [ 1667, 1685 ] ] }, "arguments": [] }, { "id": "PMID-1658795_E1", "type": "CellCyclePhaseTransition", "trigger": { "text": [ "transition" ], "offsets": [ [ 252, 262 ] ] }, "arguments": [] }, { "id": "PMID-1658795_E4", "type": "PositiveRegulation", "trigger": { "text": [ "stimulation" ], "offsets": [ [ 1136, 1147 ] ] }, "arguments": [ { "role": "hasPatient", "ref_id": "PMID-1658795_E5" } ] }, { "id": "PMID-1658795_E5", "type": "CellGrowth", "trigger": { "text": [ "mitogenic" ], "offsets": [ [ 1126, 1135 ] ] }, "arguments": [ { "role": "hasPatient", "ref_id": "PMID-1658795_T45" } ] }, { "id": "PMID-1658795_E6", "type": "CellCyclePhaseTransition", "trigger": { "text": [ "transit" ], "offsets": [ [ 1215, 1222 ] ] }, "arguments": [] }, { "id": "PMID-1658795_E7", "type": "CellGrowth", "trigger": { "text": [ "mitogenic" ], "offsets": [ [ 1126, 1135 ] ] }, "arguments": [ { "role": "hasPatient", "ref_id": "PMID-1658795_T46" } ] }, { "id": "PMID-1658795_E8", "type": "PositiveRegulation", "trigger": { "text": [ "stimulation" ], "offsets": [ [ 1136, 1147 ] ] }, "arguments": [ { "role": "hasPatient", "ref_id": "PMID-1658795_E7" } ] } ]

[]

[ { "id": "PMID-1658795_R9", "type": "fromSpecies", "arg1_id": "PMID-1658795_T22", "arg2_id": "PMID-1658795_T21", "normalized": [] }, { "id": "PMID-1658795_R10", "type": "hasPart", "arg1_id": "PMID-1658795_T24", "arg2_id": "PMID-1658795_T25", "normalized": [] }, { "id": "PMID-1658795_R15", "type": "fromSpecies", "arg1_id": "PMID-1658795_T55", "arg2_id": "PMID-1658795_T54", "normalized": [] }, { "id": "PMID-1658795_R3", "type": "fromSpecies", "arg1_id": "PMID-1658795_T23", "arg2_id": "PMID-1658795_T21", "normalized": [] }, { "id": "PMID-1658795_R14", "type": "encodes", "arg1_id": "PMID-1658795_T64", "arg2_id": "PMID-1658795_T65", "normalized": [] }, { "id": "PMID-1658795_R2", "type": "fromSpecies", "arg1_id": "PMID-1658795_T3", "arg2_id": "PMID-1658795_T4", "normalized": [] }, { "id": "PMID-1658795_R5", "type": "locatedIn", "arg1_id": "PMID-1658795_T56", "arg2_id": "PMID-1658795_T55", "normalized": [] } ]

[ { "id": "PMID-16751106__text", "type": "abstract", "text": [ "A conserved MST-FOXO signaling pathway mediates oxidative-stress responses and extends life span. Oxidative stress influences cell survival and homeostasis, but the mechanisms underlying the biological effects of oxidative stress remain to be elucidated. Here, we demonstrate that the protein kinase MST1 mediates oxidative-stress-induced cell death in primary mammalian neurons by directly activating the FOXO transcription factors. MST1 phosphorylates FOXO proteins at a conserved site within the forkhead domain that disrupts their interaction with 14-3-3 proteins, promotes FOXO nuclear translocation, and thereby induces cell death in neurons. We also extend the MST-FOXO signaling link to nematodes. Knockdown of the C. elegans MST1 ortholog CST-1 shortens life span and accelerates tissue aging, while overexpression of cst-1 promotes life span and delays aging. The cst-1-induced life-span extension occurs in a daf-16-dependent manner. The identification of the FOXO transcription factors as major and evolutionarily conserved targets of MST1 suggests that MST kinases play important roles in diverse biological processes including cellular responses to oxidative stress and longevity.\n" ], "offsets": [ [ 0, 1195 ] ] } ]

[ { "id": "PMID-16751106_T1", "type": "Enzyme", "text": [ "MST" ], "offsets": [ [ 12, 15 ] ], "normalized": [] }, { "id": "PMID-16751106_T2", "type": "TranscriptionFactor", "text": [ "FOXO" ], "offsets": [ [ 16, 20 ] ], "normalized": [] }, { "id": "PMID-16751106_T5", "type": "OxidativeStress", "text": [ "oxidative-stress" ], "offsets": [ [ 48, 64 ] ], "normalized": [] }, { "id": "PMID-16751106_T7", "type": "OxidativeStress", "text": [ "Oxidative stress" ], "offsets": [ [ 98, 114 ] ], "normalized": [] }, { "id": "PMID-16751106_T10", "type": "OxidativeStress", "text": [ "oxidative stress" ], "offsets": [ [ 213, 229 ] ], "normalized": [] }, { "id": "PMID-16751106_T11", "type": "Enzyme", "text": [ "protein kinase MST1" ], "offsets": [ [ 285, 304 ] ], "normalized": [] }, { "id": "PMID-16751106_T13", "type": "OxidativeStress", "text": [ "oxidative-stress" ], "offsets": [ [ 314, 330 ] ], "normalized": [] }, { "id": "PMID-16751106_T16", "type": "Cell", "text": [ "neurons" ], "offsets": [ [ 371, 378 ] ], "normalized": [] }, { "id": "PMID-16751106_T19", "type": "TranscriptionFactor", "text": [ "FOXO transcription factors" ], "offsets": [ [ 406, 432 ] ], "normalized": [] }, { "id": "PMID-16751106_T20", "type": "Enzyme", "text": [ "MST1" ], "offsets": [ [ 434, 438 ] ], "normalized": [] }, { "id": "PMID-16751106_T22", "type": "TranscriptionFactor", "text": [ "FOXO proteins" ], "offsets": [ [ 454, 467 ] ], "normalized": [] }, { "id": "PMID-16751106_T23", "type": "ForkheadWingedHelix", "text": [ "forkhead domain" ], "offsets": [ [ 499, 514 ] ], "normalized": [] }, { "id": "PMID-16751106_T26", "type": "Protein", "text": [ "14-3-3 proteins" ], "offsets": [ [ 552, 567 ] ], "normalized": [] }, { "id": "PMID-16751106_T28", "type": "TranscriptionFactor", "text": [ "FOXO" ], "offsets": [ [ 578, 582 ] ], "normalized": [] }, { "id": "PMID-16751106_T29", "type": "Nucleus", "text": [ "nuclear" ], "offsets": [ [ 583, 590 ] ], "normalized": [] }, { "id": "PMID-16751106_T33", "type": "Cell", "text": [ "neurons" ], "offsets": [ [ 640, 647 ] ], "normalized": [] }, { "id": "PMID-16751106_T34", "type": "Enzyme", "text": [ "MST" ], "offsets": [ [ 668, 671 ] ], "normalized": [] }, { "id": "PMID-16751106_T35", "type": "TranscriptionFactor", "text": [ "FOXO" ], "offsets": [ [ 672, 676 ] ], "normalized": [] }, { "id": "PMID-16751106_T37", "type": "Eukaryote", "text": [ "nematodes" ], "offsets": [ [ 695, 704 ] ], "normalized": [] }, { "id": "PMID-16751106_T38", "type": "ExperimentalMethod", "text": [ "Knockdown" ], "offsets": [ [ 706, 715 ] ], "normalized": [] }, { "id": "PMID-16751106_T39", "type": "Eukaryote", "text": [ "C. elegans" ], "offsets": [ [ 723, 733 ] ], "normalized": [] }, { "id": "PMID-16751106_T40", "type": "Enzyme", "text": [ "MST1" ], "offsets": [ [ 734, 738 ] ], "normalized": [] }, { "id": "PMID-16751106_T41", "type": "Enzyme", "text": [ "CST-1" ], "offsets": [ [ 748, 753 ] ], "normalized": [] }, { "id": "PMID-16751106_T44", "type": "Tissue", "text": [ "tissue" ], "offsets": [ [ 789, 795 ] ], "normalized": [] }, { "id": "PMID-16751106_T51", "type": "Enzyme", "text": [ "cst-1" ], "offsets": [ [ 874, 879 ] ], "normalized": [] }, { "id": "PMID-16751106_T53", "type": "Gene", "text": [ "daf-16" ], "offsets": [ [ 920, 926 ] ], "normalized": [] }, { "id": "PMID-16751106_T54", "type": "TranscriptionFactor", "text": [ "FOXO transcription factors" ], "offsets": [ [ 971, 997 ] ], "normalized": [] }, { "id": "PMID-16751106_T55", "type": "Enzyme", "text": [ "MST1" ], "offsets": [ [ 1047, 1051 ] ], "normalized": [] }, { "id": "PMID-16751106_T56", "type": "Enzyme", "text": [ "MST" ], "offsets": [ [ 1066, 1069 ] ], "normalized": [] }, { "id": "PMID-16751106_T57", "type": "Enzyme", "text": [ "kinases" ], "offsets": [ [ 1070, 1077 ] ], "normalized": [] }, { "id": "PMID-16751106_T59", "type": "OxidativeStress", "text": [ "oxidative stress" ], "offsets": [ [ 1163, 1179 ] ], "normalized": [] }, { "id": "PMID-16751106_T17", "type": "Eukaryote", "text": [ "mammalian" ], "offsets": [ [ 361, 370 ] ], "normalized": [] } ]

[ { "id": "PMID-16751106_E1", "type": "SignalingPathway", "trigger": { "text": [ "signaling pathway" ], "offsets": [ [ 21, 38 ] ] }, "arguments": [] }, { "id": "PMID-16751106_E2", "type": "RegulatoryProcess", "trigger": { "text": [ "mediates" ], "offsets": [ [ 39, 47 ] ] }, "arguments": [ { "role": "hasAgent", "ref_id": "PMID-16751106_E1" }, { "role": "hasPatient", "ref_id": "PMID-16751106_E3" } ] }, { "id": "PMID-16751106_E3", "type": "ResponseProcess", "trigger": { "text": [ "responses" ], "offsets": [ [ 65, 74 ] ] }, "arguments": [ { "role": "hasAgent", "ref_id": "PMID-16751106_T5" } ] }, { "id": "PMID-16751106_E4", "type": "RegulatoryProcess", "trigger": { "text": [ "influences" ], "offsets": [ [ 115, 125 ] ] }, "arguments": [ { "role": "hasAgent", "ref_id": "PMID-16751106_T7" }, { "role": "hasPatient", "ref_id": "PMID-16751106_E5" } ] }, { "id": "PMID-16751106_E5", "type": "CellHomeostasis", "trigger": { "text": [ "homeostasis" ], "offsets": [ [ 144, 155 ] ] }, "arguments": [] }, { "id": "PMID-16751106_E6", "type": "RegulatoryProcess", "trigger": { "text": [ "mediates" ], "offsets": [ [ 305, 313 ] ] }, "arguments": [ { "role": "hasAgent", "ref_id": "PMID-16751106_T11" }, { "role": "hasPatient", "ref_id": "PMID-16751106_E8" } ] }, { "id": "PMID-16751106_E7", "type": "PositiveRegulation", "trigger": { "text": [ "induced" ], "offsets": [ [ 331, 338 ] ] }, "arguments": [ { "role": "hasAgent", "ref_id": "PMID-16751106_T13" }, { "role": "hasPatient", "ref_id": "PMID-16751106_E8" } ] }, { "id": "PMID-16751106_E8", "type": "CellDeath", "trigger": { "text": [ "cell death" ], "offsets": [ [ 339, 349 ] ] }, "arguments": [] }, { "id": "PMID-16751106_E9", "type": "PositiveRegulation", "trigger": { "text": [ "activating" ], "offsets": [ [ 391, 401 ] ] }, "arguments": [ { "role": "hasPatient", "ref_id": "PMID-16751106_T19" } ] }, { "id": "PMID-16751106_E10", "type": "Phosphorylation", "trigger": { "text": [ "phosphorylates" ], "offsets": [ [ 439, 453 ] ] }, "arguments": [ { "role": "hasAgent", "ref_id": "PMID-16751106_T20" }, { "role": "hasPatient", "ref_id": "PMID-16751106_T22" } ] }, { "id": "PMID-16751106_E11", "type": "NegativeRegulation", "trigger": { "text": [ "disrupts" ], "offsets": [ [ 520, 528 ] ] }, "arguments": [ { "role": "hasAgent", "ref_id": "PMID-16751106_E10" }, { "role": "hasPatient", "ref_id": "PMID-16751106_E12" } ] }, { "id": "PMID-16751106_E12", "type": "BindingToProtein", "trigger": { "text": [ "interaction" ], "offsets": [ [ 535, 546 ] ] }, "arguments": [ { "role": "hasPatient", "ref_id": "PMID-16751106_T26" } ] }, { "id": "PMID-16751106_E13", "type": "Increase", "trigger": { "text": [ "promotes" ], "offsets": [ [ 569, 577 ] ] }, "arguments": [ { "role": "hasAgent", "ref_id": "PMID-16751106_E10" }, { "role": "hasPatient", "ref_id": "PMID-16751106_E14" } ] }, { "id": "PMID-16751106_E14", "type": "Localization", "trigger": { "text": [ "translocation" ], "offsets": [ [ 591, 604 ] ] }, "arguments": [ { "role": "hasPatient", "ref_id": "PMID-16751106_T28" } ] }, { "id": "PMID-16751106_E15", "type": "PositiveRegulation", "trigger": { "text": [ "induces" ], "offsets": [ [ 618, 625 ] ] }, "arguments": [ { "role": "hasPatient", "ref_id": "PMID-16751106_E16" } ] }, { "id": "PMID-16751106_E16", "type": "CellDeath", "trigger": { "text": [ "cell death" ], "offsets": [ [ 626, 636 ] ] }, "arguments": [] }, { "id": "PMID-16751106_E17", "type": "SignalingPathway", "trigger": { "text": [ "signaling" ], "offsets": [ [ 677, 686 ] ] }, "arguments": [] }, { "id": "PMID-16751106_E18", "type": "Decrease", "trigger": { "text": [ "shortens" ], "offsets": [ [ 754, 762 ] ] }, "arguments": [ { "role": "hasAgent", "ref_id": "PMID-16751106_T38" } ] }, { "id": "PMID-16751106_E19", "type": "Increase", "trigger": { "text": [ "accelerates" ], "offsets": [ [ 777, 788 ] ] }, "arguments": [ { "role": "hasAgent", "ref_id": "PMID-16751106_T38" }, { "role": "hasPatient", "ref_id": "PMID-16751106_E20" } ] }, { "id": "PMID-16751106_E20", "type": "CellAging", "trigger": { "text": [ "aging" ], "offsets": [ [ 796, 801 ] ] }, "arguments": [] }, { "id": "PMID-16751106_E21", "type": "PositiveRegulationOfGeneExpression", "trigger": { "text": [ "overexpression" ], "offsets": [ [ 809, 823 ] ] }, "arguments": [ { "role": "hasPatient", "ref_id": "PMID-16751106_E22" } ] }, { "id": "PMID-16751106_E22", "type": "Acetylation", "trigger": { "text": [ "cst-1" ], "offsets": [ [ 827, 832 ] ] }, "arguments": [] }, { "id": "PMID-16751106_E23", "type": "Increase", "trigger": { "text": [ "promotes" ], "offsets": [ [ 833, 841 ] ] }, "arguments": [ { "role": "hasAgent", "ref_id": "PMID-16751106_E21" } ] }, { "id": "PMID-16751106_E24", "type": "Decrease", "trigger": { "text": [ "delays" ], "offsets": [ [ 856, 862 ] ] }, "arguments": [ { "role": "hasAgent", "ref_id": "PMID-16751106_E21" }, { "role": "hasPatient", "ref_id": "PMID-16751106_E25" } ] }, { "id": "PMID-16751106_E25", "type": "CellAging", "trigger": { "text": [ "aging" ], "offsets": [ [ 863, 868 ] ] }, "arguments": [] }, { "id": "PMID-16751106_E26", "type": "PositiveRegulation", "trigger": { "text": [ "induced" ], "offsets": [ [ 880, 887 ] ] }, "arguments": [ { "role": "hasAgent", "ref_id": "PMID-16751106_T51" } ] }, { "id": "PMID-16751106_E27", "type": "ResponseProcess", "trigger": { "text": [ "cellular responses" ], "offsets": [ [ 1141, 1159 ] ] }, "arguments": [ { "role": "hasAgent", "ref_id": "PMID-16751106_T59" } ] }, { "id": "PMID-16751106_E28", "type": "CellularProcess", "trigger": { "text": [ "cell survival" ], "offsets": [ [ 126, 139 ] ] }, "arguments": [] }, { "id": "PMID-16751106_E29", "type": "RegulatoryProcess", "trigger": { "text": [ "influences" ], "offsets": [ [ 115, 125 ] ] }, "arguments": [ { "role": "hasAgent", "ref_id": "PMID-16751106_T7" }, { "role": "hasPatient", "ref_id": "PMID-16751106_E28" } ] } ]

[]

[ { "id": "PMID-16751106_R5", "type": "hasPart", "arg1_id": "PMID-16751106_T22", "arg2_id": "PMID-16751106_T23", "normalized": [] }, { "id": "PMID-16751106_R10", "type": "fromSpecies", "arg1_id": "PMID-16751106_T41", "arg2_id": "PMID-16751106_T39", "normalized": [] }, { "id": "PMID-16751106_R2", "type": "fromSpecies", "arg1_id": "PMID-16751106_T16", "arg2_id": "PMID-16751106_T17", "normalized": [] } ]

[ { "id": "PMID-17071714__text", "type": "abstract", "text": [ "Identification of human tRNA:m5C methyltransferase catalysing intron-dependent m5C formation in the first position of the anticodon of the pre-tRNA Leu (CAA). We identified a human orthologue of tRNA:m5C methyltransferase from Saccharomyces cerevisiae, which has been previously shown to catalyse the specific modification of C34 in the intron-containing yeast pre-tRNA Leu (CAA). Using transcripts of intron-less and intron-containing human pre-tRNA Leu (CAA) genes as substrates, we have shown that m5C34 is introduced only in the intron-containing tRNA precursors when the substrates were incubated in the HeLa extract. m5C34 formation depends on the nucleotide sequence surrounding the wobble cytidine and on the structure of the prolongated anticodon stem. Expression of the human Trm4 (hTrm4) cDNA in yeast partially complements the lack of the endogenous Trm4p enzyme. The yeast extract prepared from the strain deprived of the endogenous TRM4 gene and transformed with hTrm4 cDNA exhibits the same activity and substrate specificity toward human pre-tRNALeu transcripts as the HeLa extract. The hTrm4 MTase has a much narrower specificity against the yeast substrates than its yeast orthologue: human enzyme is not able to form m5C at positions 48 and 49 of human and yeast tRNA precursors. To our knowledge, this is the first report showing intron-dependent methylation of humanpre-tRNA Leu (CAA) and identification of human gene encoding tRNA methylase responsible for this reaction.\n" ], "offsets": [ [ 0, 1494 ] ] } ]

[ { "id": "PMID-17071714_T1", "type": "Eukaryote", "text": [ "human" ], "offsets": [ [ 18, 23 ] ], "normalized": [] }, { "id": "PMID-17071714_T2", "type": "tRNA", "text": [ "tRNA:m5C" ], "offsets": [ [ 24, 32 ] ], "normalized": [] }, { "id": "PMID-17071714_T3", "type": "Enzyme", "text": [ "methyltransferase" ], "offsets": [ [ 33, 50 ] ], "normalized": [] }, { "id": "PMID-17071714_T4", "type": "CatalyticActivity", "text": [ "catalysing" ], "offsets": [ [ 51, 61 ] ], "normalized": [] }, { "id": "PMID-17071714_T5", "type": "Intron", "text": [ "intron" ], "offsets": [ [ 62, 68 ] ], "normalized": [] }, { "id": "PMID-17071714_T6", "type": "Chemical", "text": [ "m5C" ], "offsets": [ [ 79, 82 ] ], "normalized": [] }, { "id": "PMID-17071714_T10", "type": "Eukaryote", "text": [ "human" ], "offsets": [ [ 175, 180 ] ], "normalized": [] }, { "id": "PMID-17071714_T11", "type": "tRNA", "text": [ "tRNA:m5C" ], "offsets": [ [ 195, 203 ] ], "normalized": [] }, { "id": "PMID-17071714_T12", "type": "Enzyme", "text": [ "methyltransferase" ], "offsets": [ [ 204, 221 ] ], "normalized": [] }, { "id": "PMID-17071714_T13", "type": "Eukaryote", "text": [ "Saccharomyces cerevisiae" ], "offsets": [ [ 227, 251 ] ], "normalized": [] }, { "id": "PMID-17071714_T14", "type": "CatalyticActivity", "text": [ "catalyse" ], "offsets": [ [ 288, 296 ] ], "normalized": [] }, { "id": "PMID-17071714_T16", "type": "Chemical", "text": [ "C34" ], "offsets": [ [ 326, 329 ] ], "normalized": [] }, { "id": "PMID-17071714_T17", "type": "Intron", "text": [ "intron" ], "offsets": [ [ 337, 343 ] ], "normalized": [] }, { "id": "PMID-17071714_T18", "type": "Eukaryote", "text": [ "yeast" ], "offsets": [ [ 355, 360 ] ], "normalized": [] }, { "id": "PMID-17071714_T21", "type": "Transcript", "text": [ "transcripts" ], "offsets": [ [ 387, 398 ] ], "normalized": [] }, { "id": "PMID-17071714_T22", "type": "Intron", "text": [ "intron" ], "offsets": [ [ 402, 408 ] ], "normalized": [] }, { "id": "PMID-17071714_T23", "type": "Intron", "text": [ "intron" ], "offsets": [ [ 418, 424 ] ], "normalized": [] }, { "id": "PMID-17071714_T24", "type": "Eukaryote", "text": [ "human" ], "offsets": [ [ 436, 441 ] ], "normalized": [] }, { "id": "PMID-17071714_T25", "type": "tRNA", "text": [ "pre-tRNA" ], "offsets": [ [ 442, 450 ] ], "normalized": [] }, { "id": "PMID-17071714_T26", "type": "Gene", "text": [ "Leu (CAA) genes" ], "offsets": [ [ 451, 466 ] ], "normalized": [] }, { "id": "PMID-17071714_T27", "type": "Chemical", "text": [ "m5C34" ], "offsets": [ [ 501, 506 ] ], "normalized": [] }, { "id": "PMID-17071714_T29", "type": "Intron", "text": [ "intron" ], "offsets": [ [ 533, 539 ] ], "normalized": [] }, { "id": "PMID-17071714_T30", "type": "tRNA", "text": [ "tRNA precursors" ], "offsets": [ [ 551, 566 ] ], "normalized": [] }, { "id": "PMID-17071714_T31", "type": "Eukaryote", "text": [ "HeLa" ], "offsets": [ [ 609, 613 ] ], "normalized": [] }, { "id": "PMID-17071714_T32", "type": "Chemical", "text": [ "m5C34" ], "offsets": [ [ 623, 628 ] ], "normalized": [] }, { "id": "PMID-17071714_T34", "type": "Nucleotide", "text": [ "nucleotide" ], "offsets": [ [ 654, 664 ] ], "normalized": [] }, { "id": "PMID-17071714_T36", "type": "Eukaryote", "text": [ "human" ], "offsets": [ [ 780, 785 ] ], "normalized": [] }, { "id": "PMID-17071714_T37", "type": "Gene", "text": [ "hTrm4" ], "offsets": [ [ 792, 797 ] ], "normalized": [] }, { "id": "PMID-17071714_T38", "type": "DNA", "text": [ "cDNA" ], "offsets": [ [ 799, 803 ] ], "normalized": [] }, { "id": "PMID-17071714_T39", "type": "Eukaryote", "text": [ "yeast" ], "offsets": [ [ 807, 812 ] ], "normalized": [] }, { "id": "PMID-17071714_T40", "type": "Enzyme", "text": [ "Trm4p enzyme" ], "offsets": [ [ 862, 874 ] ], "normalized": [] }, { "id": "PMID-17071714_T41", "type": "Eukaryote", "text": [ "yeast" ], "offsets": [ [ 880, 885 ] ], "normalized": [] }, { "id": "PMID-17071714_T42", "type": "Gene", "text": [ "TRM4 gene" ], "offsets": [ [ 946, 955 ] ], "normalized": [] }, { "id": "PMID-17071714_T43", "type": "Gene", "text": [ "hTrm4" ], "offsets": [ [ 977, 982 ] ], "normalized": [] }, { "id": "PMID-17071714_T44", "type": "DNA", "text": [ "cDNA" ], "offsets": [ [ 983, 987 ] ], "normalized": [] }, { "id": "PMID-17071714_T45", "type": "Eukaryote", "text": [ "human" ], "offsets": [ [ 1048, 1053 ] ], "normalized": [] }, { "id": "PMID-17071714_T46", "type": "tRNA", "text": [ "pre-tRNALeu" ], "offsets": [ [ 1054, 1065 ] ], "normalized": [] }, { "id": "PMID-17071714_T47", "type": "Transcript", "text": [ "transcripts" ], "offsets": [ [ 1066, 1077 ] ], "normalized": [] }, { "id": "PMID-17071714_T48", "type": "EukaryoticCell", "text": [ "HeLa" ], "offsets": [ [ 1085, 1089 ] ], "normalized": [] }, { "id": "PMID-17071714_T49", "type": "Enzyme", "text": [ "hTrm4 MTase" ], "offsets": [ [ 1103, 1114 ] ], "normalized": [] }, { "id": "PMID-17071714_T50", "type": "Eukaryote", "text": [ "yeast" ], "offsets": [ [ 1159, 1164 ] ], "normalized": [] }, { "id": "PMID-17071714_T51", "type": "Eukaryote", "text": [ "yeast" ], "offsets": [ [ 1185, 1190 ] ], "normalized": [] }, { "id": "PMID-17071714_T52", "type": "Intron", "text": [ "intron" ], "offsets": [ [ 1350, 1356 ] ], "normalized": [] }, { "id": "PMID-17071714_T57", "type": "Eukaryote", "text": [ "human" ], "offsets": [ [ 1428, 1433 ] ], "normalized": [] }, { "id": "PMID-17071714_T58", "type": "Gene", "text": [ "gene" ], "offsets": [ [ 1434, 1438 ] ], "normalized": [] }, { "id": "PMID-17071714_T59", "type": "tRNA", "text": [ "tRNA" ], "offsets": [ [ 1448, 1452 ] ], "normalized": [] }, { "id": "PMID-17071714_T60", "type": "Enzyme", "text": [ "methylase" ], "offsets": [ [ 1453, 1462 ] ], "normalized": [] }, { "id": "PMID-17071714_T8", "type": "tRNA", "text": [ "pre-tRNA Leu (CAA)" ], "offsets": [ [ 139, 157 ] ], "normalized": [] }, { "id": "PMID-17071714_T9", "type": "tRNA", "text": [ "pre-tRNA Leu (CAA)" ], "offsets": [ [ 361, 379 ] ], "normalized": [] }, { "id": "PMID-17071714_T19", "type": "Eukaryote", "text": [ "human" ], "offsets": [ [ 1382, 1387 ] ], "normalized": [] }, { "id": "PMID-17071714_T20", "type": "tRNA", "text": [ "pre-tRNA Leu (CAA)" ], "offsets": [ [ 1387, 1405 ] ], "normalized": [] } ]

[ { "id": "PMID-17071714_E1", "type": "RNAProcessing", "trigger": { "text": [ "formation" ], "offsets": [ [ 83, 92 ] ] }, "arguments": [ { "role": "hasPatient", "ref_id": "PMID-17071714_T6" } ] }, { "id": "PMID-17071714_E2", "type": "Modification", "trigger": { "text": [ "modification" ], "offsets": [ [ 310, 322 ] ] }, "arguments": [ { "role": "hasPatient", "ref_id": "PMID-17071714_T16" } ] }, { "id": "PMID-17071714_E3", "type": "RNAProcessing", "trigger": { "text": [ "introduced" ], "offsets": [ [ 510, 520 ] ] }, "arguments": [ { "role": "hasAgent", "ref_id": "PMID-17071714_T27" }, { "role": "hasPatient", "ref_id": "PMID-17071714_T30" } ] }, { "id": "PMID-17071714_E4", "type": "MolecularProcess", "trigger": { "text": [ "formation" ], "offsets": [ [ 629, 638 ] ] }, "arguments": [ { "role": "hasPatient", "ref_id": "PMID-17071714_T32" } ] }, { "id": "PMID-17071714_E5", "type": "GeneExpression", "trigger": { "text": [ "Expression" ], "offsets": [ [ 762, 772 ] ] }, "arguments": [ { "role": "hasPatient", "ref_id": "PMID-17071714_T38" } ] }, { "id": "PMID-17071714_E6", "type": "Methylation", "trigger": { "text": [ "methylation" ], "offsets": [ [ 1367, 1378 ] ] }, "arguments": [ { "role": "hasPatient", "ref_id": "PMID-17071714_T20" } ] } ]

[]

[ { "id": "PMID-17071714_R1", "type": "fromSpecies", "arg1_id": "PMID-17071714_T3", "arg2_id": "PMID-17071714_T1", "normalized": [] }, { "id": "PMID-17071714_R4", "type": "fromSpecies", "arg1_id": "PMID-17071714_T12", "arg2_id": "PMID-17071714_T13", "normalized": [] }, { "id": "PMID-17071714_R8", "type": "encodes", "arg1_id": "PMID-17071714_T25", "arg2_id": "PMID-17071714_T21", "normalized": [] }, { "id": "PMID-17071714_R9", "type": "fromSpecies", "arg1_id": "PMID-17071714_T25", "arg2_id": "PMID-17071714_T24", "normalized": [] }, { "id": "PMID-17071714_R10", "type": "encodes", "arg1_id": "PMID-17071714_T26", "arg2_id": "PMID-17071714_T25", "normalized": [] }, { "id": "PMID-17071714_R12", "type": "hasPart", "arg1_id": "PMID-17071714_T30", "arg2_id": "PMID-17071714_T29", "normalized": [] }, { "id": "PMID-17071714_R14", "type": "fromSpecies", "arg1_id": "PMID-17071714_T37", "arg2_id": "PMID-17071714_T36", "normalized": [] }, { "id": "PMID-17071714_R15", "type": "fromSpecies", "arg1_id": "PMID-17071714_T42", "arg2_id": "PMID-17071714_T41", "normalized": [] }, { "id": "PMID-17071714_R17", "type": "fromSpecies", "arg1_id": "PMID-17071714_T46", "arg2_id": "PMID-17071714_T45", "normalized": [] }, { "id": "PMID-17071714_R20", "type": "encodes", "arg1_id": "PMID-17071714_T58", "arg2_id": "PMID-17071714_T60", "normalized": [] }, { "id": "PMID-17071714_R21", "type": "fromSpecies", "arg1_id": "PMID-17071714_T58", "arg2_id": "PMID-17071714_T57", "normalized": [] }, { "id": "PMID-17071714_R22", "type": "hasFunction", "arg1_id": "PMID-17071714_T3", "arg2_id": "PMID-17071714_T4", "normalized": [] }, { "id": "PMID-17071714_R3", "type": "fromSpecies", "arg1_id": "PMID-17071714_T9", "arg2_id": "PMID-17071714_T18", "normalized": [] }, { "id": "PMID-17071714_R6", "type": "hasPart", "arg1_id": "PMID-17071714_T9", "arg2_id": "PMID-17071714_T17", "normalized": [] }, { "id": "PMID-17071714_R7", "type": "fromSpecies", "arg1_id": "PMID-17071714_T20", "arg2_id": "PMID-17071714_T19", "normalized": [] } ]

[ { "id": "PMID-1719379__text", "type": "abstract", "text": [ "A human alpha-fetoprotein enhancer-binding protein, ATBF1, contains four homeodomains and seventeen zinc fingers. We have isolated a full-length cDNA encoding a protein (ATBF1) that binds to an AT-rich motif in the human alpha-fetoprotein gene enhancer. The amino acid sequence deduced from the cDNA revealed that this is the largest DNA-binding protein (306 kDa) known to date, containing four homeodomains, 17 zinc finger motifs, and a number of segments potentially involved in transcriptional regulation. Although the exact function of this protein has not been determined, these structural features suggest that ATBF1 plays a transcriptional regulatory role.\n" ], "offsets": [ [ 0, 664 ] ] } ]

[ { "id": "PMID-1719379_T1", "type": "Eukaryote", "text": [ "human" ], "offsets": [ [ 2, 7 ] ], "normalized": [] }, { "id": "PMID-1719379_T6", "type": "Protein", "text": [ "ATBF1" ], "offsets": [ [ 52, 57 ] ], "normalized": [] }, { "id": "PMID-1719379_T7", "type": "HomeoBox", "text": [ "homeodomains" ], "offsets": [ [ 73, 85 ] ], "normalized": [] }, { "id": "PMID-1719379_T8", "type": "ZincCoordinatingDomain", "text": [ "zinc fingers" ], "offsets": [ [ 100, 112 ] ], "normalized": [] }, { "id": "PMID-1719379_T9", "type": "DNA", "text": [ "cDNA" ], "offsets": [ [ 145, 149 ] ], "normalized": [] }, { "id": "PMID-1719379_T10", "type": "Protein", "text": [ "protein" ], "offsets": [ [ 161, 168 ] ], "normalized": [] }, { "id": "PMID-1719379_T11", "type": "Protein", "text": [ "ATBF1" ], "offsets": [ [ 170, 175 ] ], "normalized": [] }, { "id": "PMID-1719379_T13", "type": "DNARegion", "text": [ "AT-rich motif" ], "offsets": [ [ 194, 207 ] ], "normalized": [] }, { "id": "PMID-1719379_T14", "type": "Eukaryote", "text": [ "human" ], "offsets": [ [ 215, 220 ] ], "normalized": [] }, { "id": "PMID-1719379_T15", "type": "Gene", "text": [ "alpha-fetoprotein gene" ], "offsets": [ [ 221, 243 ] ], "normalized": [] }, { "id": "PMID-1719379_T16", "type": "Enhancer", "text": [ "enhancer" ], "offsets": [ [ 244, 252 ] ], "normalized": [] }, { "id": "PMID-1719379_T17", "type": "AminoAcid", "text": [ "amino acid" ], "offsets": [ [ 258, 268 ] ], "normalized": [] }, { "id": "PMID-1719379_T18", "type": "Sequence", "text": [ "sequence" ], "offsets": [ [ 269, 277 ] ], "normalized": [] }, { "id": "PMID-1719379_T19", "type": "DNA", "text": [ "cDNA" ], "offsets": [ [ 295, 299 ] ], "normalized": [] }, { "id": "PMID-1719379_T22", "type": "Protein", "text": [ "DNA-binding protein" ], "offsets": [ [ 334, 353 ] ], "normalized": [] }, { "id": "PMID-1719379_T23", "type": "HomeoBox", "text": [ "homeodomains" ], "offsets": [ [ 395, 407 ] ], "normalized": [] }, { "id": "PMID-1719379_T24", "type": "ZincCoordinatingDomain", "text": [ "zinc finger motifs" ], "offsets": [ [ 412, 430 ] ], "normalized": [] }, { "id": "PMID-1719379_T27", "type": "Protein", "text": [ "ATBF1" ], "offsets": [ [ 617, 622 ] ], "normalized": [] }, { "id": "PMID-1719379_T2", "type": "Protein", "text": [ "alpha-fetoprotein enhancer-binding protein" ], "offsets": [ [ 8, 50 ] ], "normalized": [] } ]

[ { "id": "PMID-1719379_E2", "type": "BindingOfProteinToProteinBindingSiteOfDNA", "trigger": { "text": [ "binds" ], "offsets": [ [ 182, 187 ] ] }, "arguments": [ { "role": "hasAgent", "ref_id": "PMID-1719379_T11" }, { "role": "hasPatient", "ref_id": "PMID-1719379_T13" } ] }, { "id": "PMID-1719379_E4", "type": "Transcription", "trigger": { "text": [ "transcriptional" ], "offsets": [ [ 481, 496 ] ] }, "arguments": [] }, { "id": "PMID-1719379_E5", "type": "RegulatoryProcess", "trigger": { "text": [ "regulation" ], "offsets": [ [ 497, 507 ] ] }, "arguments": [ { "role": "hasPatient", "ref_id": "PMID-1719379_E4" } ] }, { "id": "PMID-1719379_E6", "type": "Transcription", "trigger": { "text": [ "transcriptional" ], "offsets": [ [ 631, 646 ] ] }, "arguments": [] }, { "id": "PMID-1719379_E7", "type": "RegulatoryProcess", "trigger": { "text": [ "regulatory" ], "offsets": [ [ 647, 657 ] ] }, "arguments": [ { "role": "hasAgent", "ref_id": "PMID-1719379_T27" }, { "role": "hasPatient", "ref_id": "PMID-1719379_E6" } ] } ]

[]

[ { "id": "PMID-1719379_R3", "type": "hasPart", "arg1_id": "PMID-1719379_T6", "arg2_id": "PMID-1719379_T8", "normalized": [] }, { "id": "PMID-1719379_R4", "type": "hasPart", "arg1_id": "PMID-1719379_T6", "arg2_id": "PMID-1719379_T7", "normalized": [] }, { "id": "PMID-1719379_R5", "type": "encodes", "arg1_id": "PMID-1719379_T9", "arg2_id": "PMID-1719379_T10", "normalized": [] }, { "id": "PMID-1719379_R6", "type": "fromSpecies", "arg1_id": "PMID-1719379_T15", "arg2_id": "PMID-1719379_T14", "normalized": [] }, { "id": "PMID-1719379_R7", "type": "hasPart", "arg1_id": "PMID-1719379_T15", "arg2_id": "PMID-1719379_T16", "normalized": [] }, { "id": "PMID-1719379_R8", "type": "hasPart", "arg1_id": "PMID-1719379_T16", "arg2_id": "PMID-1719379_T13", "normalized": [] }, { "id": "PMID-1719379_R9", "type": "hasPart", "arg1_id": "PMID-1719379_T22", "arg2_id": "PMID-1719379_T23", "normalized": [] }, { "id": "PMID-1719379_R10", "type": "hasPart", "arg1_id": "PMID-1719379_T22", "arg2_id": "PMID-1719379_T24", "normalized": [] }, { "id": "PMID-1719379_R1", "type": "fromSpecies", "arg1_id": "PMID-1719379_T2", "arg2_id": "PMID-1719379_T1", "normalized": [] } ]

[ { "id": "PMID-17409385__text", "type": "abstract", "text": [ "Identification, molecular cloning, and characterization of the sixth subunit of human transcription factor TFIIIC. TFIIIC in yeast and humans is required for transcription of tRNA and 5 S RNA genes by RNA polymerase III. In the yeast Saccharomyces cerevisiae, TFIIIC is composed of six subunits, five of which are conserved in humans. We report the identification, molecular cloning, and characterization of the sixth subunit of human TFIIIC, TFIIIC35, which is related to the smallest subunit of yeast TFIIIC. Human TFIIIC35 does not contain the phosphoglycerate mutase domain of its yeast counterpart, and these two proteins display only limited homology within a 34-amino acid domain. Homologs of the sixth TFIIIC subunit are also identified in other eukaryotes, and their phylogenic evolution is analyzed. Affinity-purified human TFIIIC from an epitope-tagged TFIIIC35 cell line is active in binding to and in transcription of the VA1 gene in vitro. Furthermore, TFIIIC35 specifically interacts with the human TFIIIC subunits TFIIIC63 and, to a lesser extent, TFIIIC90 in vitro. Finally, we determined a limited region in the smallest subunit of yeast TFIIIC that is sufficient for interacting with the yeast TFIIIC subunit ScTfc1 (orthologous to TFIIIC63) and found it to be adjacent to and overlap the 34-amino acid domain that is conserved from yeast to humans.\n" ], "offsets": [ [ 0, 1369 ] ] } ]

[ { "id": "PMID-17409385_T1", "type": "ProteinSubunit", "text": [ "subunit" ], "offsets": [ [ 69, 76 ] ], "normalized": [] }, { "id": "PMID-17409385_T2", "type": "Eukaryote", "text": [ "human" ], "offsets": [ [ 80, 85 ] ], "normalized": [] }, { "id": "PMID-17409385_T3", "type": "TranscriptionFactor", "text": [ "transcription factor TFIIIC" ], "offsets": [ [ 86, 113 ] ], "normalized": [] }, { "id": "PMID-17409385_T4", "type": "TranscriptionFactor", "text": [ "TFIIIC" ], "offsets": [ [ 115, 121 ] ], "normalized": [] }, { "id": "PMID-17409385_T5", "type": "Eukaryote", "text": [ "yeast" ], "offsets": [ [ 125, 130 ] ], "normalized": [] }, { "id": "PMID-17409385_T6", "type": "Eukaryote", "text": [ "humans" ], "offsets": [ [ 135, 141 ] ], "normalized": [] }, { "id": "PMID-17409385_T8", "type": "tRNA", "text": [ "tRNA" ], "offsets": [ [ 175, 179 ] ], "normalized": [] }, { "id": "PMID-17409385_T9", "type": "RNA", "text": [ "5 S RNA" ], "offsets": [ [ 184, 191 ] ], "normalized": [] }, { "id": "PMID-17409385_T10", "type": "Gene", "text": [ "genes" ], "offsets": [ [ 192, 197 ] ], "normalized": [] }, { "id": "PMID-17409385_T11", "type": "RNAPolymerase", "text": [ "RNA polymerase III" ], "offsets": [ [ 201, 219 ] ], "normalized": [] }, { "id": "PMID-17409385_T12", "type": "Eukaryote", "text": [ "yeast" ], "offsets": [ [ 228, 233 ] ], "normalized": [] }, { "id": "PMID-17409385_T13", "type": "Eukaryote", "text": [ "Saccharomyces cerevisiae" ], "offsets": [ [ 234, 258 ] ], "normalized": [] }, { "id": "PMID-17409385_T14", "type": "TranscriptionFactor", "text": [ "TFIIIC" ], "offsets": [ [ 260, 266 ] ], "normalized": [] }, { "id": "PMID-17409385_T15", "type": "ProteinSubunit", "text": [ "subunits" ], "offsets": [ [ 286, 294 ] ], "normalized": [] }, { "id": "PMID-17409385_T16", "type": "Eukaryote", "text": [ "humans" ], "offsets": [ [ 327, 333 ] ], "normalized": [] }, { "id": "PMID-17409385_T17", "type": "ProteinSubunit", "text": [ "subunit" ], "offsets": [ [ 418, 425 ] ], "normalized": [] }, { "id": "PMID-17409385_T18", "type": "Eukaryote", "text": [ "human" ], "offsets": [ [ 429, 434 ] ], "normalized": [] }, { "id": "PMID-17409385_T19", "type": "TranscriptionFactor", "text": [ "TFIIIC" ], "offsets": [ [ 435, 441 ] ], "normalized": [] }, { "id": "PMID-17409385_T20", "type": "ProteinSubunit", "text": [ "TFIIIC35" ], "offsets": [ [ 443, 451 ] ], "normalized": [] }, { "id": "PMID-17409385_T21", "type": "ProteinSubunit", "text": [ "subunit" ], "offsets": [ [ 486, 493 ] ], "normalized": [] }, { "id": "PMID-17409385_T22", "type": "Eukaryote", "text": [ "yeast" ], "offsets": [ [ 497, 502 ] ], "normalized": [] }, { "id": "PMID-17409385_T23", "type": "TranscriptionFactor", "text": [ "TFIIIC" ], "offsets": [ [ 503, 509 ] ], "normalized": [] }, { "id": "PMID-17409385_T24", "type": "Protein", "text": [ "proteins" ], "offsets": [ [ 618, 626 ] ], "normalized": [] }, { "id": "PMID-17409385_T25", "type": "AminoAcid", "text": [ "amino acid" ], "offsets": [ [ 669, 679 ] ], "normalized": [] }, { "id": "PMID-17409385_T26", "type": "ProteinDomain", "text": [ "domain" ], "offsets": [ [ 680, 686 ] ], "normalized": [] }, { "id": "PMID-17409385_T27", "type": "TranscriptionFactor", "text": [ "TFIIIC" ], "offsets": [ [ 710, 716 ] ], "normalized": [] }, { "id": "PMID-17409385_T28", "type": "ProteinSubunit", "text": [ "subunit" ], "offsets": [ [ 717, 724 ] ], "normalized": [] }, { "id": "PMID-17409385_T29", "type": "Eukaryote", "text": [ "eukaryotes" ], "offsets": [ [ 754, 764 ] ], "normalized": [] }, { "id": "PMID-17409385_T30", "type": "Eukaryote", "text": [ "human" ], "offsets": [ [ 828, 833 ] ], "normalized": [] }, { "id": "PMID-17409385_T31", "type": "TranscriptionFactor", "text": [ "TFIIIC" ], "offsets": [ [ 834, 840 ] ], "normalized": [] }, { "id": "PMID-17409385_T32", "type": "ProteinSubunit", "text": [ "TFIIIC35" ], "offsets": [ [ 864, 872 ] ], "normalized": [] }, { "id": "PMID-17409385_T33", "type": "Cell", "text": [ "cell line" ], "offsets": [ [ 873, 882 ] ], "normalized": [] }, { "id": "PMID-17409385_T36", "type": "Gene", "text": [ "VA1" ], "offsets": [ [ 935, 938 ] ], "normalized": [] }, { "id": "PMID-17409385_T37", "type": "Gene", "text": [ "gene" ], "offsets": [ [ 939, 943 ] ], "normalized": [] }, { "id": "PMID-17409385_T38", "type": "ProteinSubunit", "text": [ "TFIIIC35" ], "offsets": [ [ 967, 975 ] ], "normalized": [] }, { "id": "PMID-17409385_T40", "type": "Eukaryote", "text": [ "human" ], "offsets": [ [ 1008, 1013 ] ], "normalized": [] }, { "id": "PMID-17409385_T41", "type": "TranscriptionFactor", "text": [ "TFIIIC" ], "offsets": [ [ 1014, 1020 ] ], "normalized": [] }, { "id": "PMID-17409385_T42", "type": "ProteinSubunit", "text": [ "subunits TFIIIC63" ], "offsets": [ [ 1021, 1038 ] ], "normalized": [] }, { "id": "PMID-17409385_T43", "type": "ProteinSubunit", "text": [ "TFIIIC90" ], "offsets": [ [ 1064, 1072 ] ], "normalized": [] }, { "id": "PMID-17409385_T44", "type": "ProteinSubunit", "text": [ "subunit" ], "offsets": [ [ 1139, 1146 ] ], "normalized": [] }, { "id": "PMID-17409385_T45", "type": "Eukaryote", "text": [ "yeast" ], "offsets": [ [ 1150, 1155 ] ], "normalized": [] }, { "id": "PMID-17409385_T46", "type": "TranscriptionFactor", "text": [ "TFIIIC" ], "offsets": [ [ 1156, 1162 ] ], "normalized": [] }, { "id": "PMID-17409385_T48", "type": "Eukaryote", "text": [ "yeast" ], "offsets": [ [ 1207, 1212 ] ], "normalized": [] }, { "id": "PMID-17409385_T49", "type": "TranscriptionFactor", "text": [ "TFIIIC" ], "offsets": [ [ 1213, 1219 ] ], "normalized": [] }, { "id": "PMID-17409385_T50", "type": "ProteinSubunit", "text": [ "subunit ScTfc1" ], "offsets": [ [ 1220, 1234 ] ], "normalized": [] }, { "id": "PMID-17409385_T51", "type": "ProteinSubunit", "text": [ "TFIIIC63" ], "offsets": [ [ 1251, 1259 ] ], "normalized": [] }, { "id": "PMID-17409385_T52", "type": "AminoAcid", "text": [ "amino acid" ], "offsets": [ [ 1311, 1321 ] ], "normalized": [] }, { "id": "PMID-17409385_T53", "type": "ProteinDomain", "text": [ "domain" ], "offsets": [ [ 1322, 1328 ] ], "normalized": [] }, { "id": "PMID-17409385_T54", "type": "Eukaryote", "text": [ "yeast" ], "offsets": [ [ 1352, 1357 ] ], "normalized": [] }, { "id": "PMID-17409385_T55", "type": "Eukaryote", "text": [ "humans" ], "offsets": [ [ 1361, 1367 ] ], "normalized": [] } ]

[ { "id": "PMID-17409385_E1", "type": "Transcription", "trigger": { "text": [ "transcription" ], "offsets": [ [ 158, 171 ] ] }, "arguments": [ { "role": "hasPatient2", "ref_id": "PMID-17409385_T10" }, { "role": "hasAgent", "ref_id": "PMID-17409385_T11" } ] }, { "id": "PMID-17409385_E2", "type": "BindingOfTranscriptionFactorToDNA", "trigger": { "text": [ "binding" ], "offsets": [ [ 896, 903 ] ] }, "arguments": [ { "role": "hasAgent", "ref_id": "PMID-17409385_T31" }, { "role": "hasPatient", "ref_id": "PMID-17409385_T36" } ] }, { "id": "PMID-17409385_E3", "type": "Transcription", "trigger": { "text": [ "transcription" ], "offsets": [ [ 914, 927 ] ] }, "arguments": [ { "role": "hasPatient", "ref_id": "PMID-17409385_T36" } ] }, { "id": "PMID-17409385_E4", "type": "BindingToProtein", "trigger": { "text": [ "interacts" ], "offsets": [ [ 989, 998 ] ] }, "arguments": [ { "role": "hasPatient", "ref_id": "PMID-17409385_T42" }, { "role": "hasPatient2", "ref_id": "PMID-17409385_T43" }, { "role": "hasPatient3", "ref_id": "PMID-17409385_T38" } ] }, { "id": "PMID-17409385_E5", "type": "BindingToProtein", "trigger": { "text": [ "interacting" ], "offsets": [ [ 1186, 1197 ] ] }, "arguments": [ { "role": "hasPatient", "ref_id": "PMID-17409385_T50" }, { "role": "hasPatient2", "ref_id": "PMID-17409385_T44" } ] } ]

[]

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[ { "id": "PMID-1760839__text", "type": "abstract", "text": [ "B cell lymphoma-associated chromosomal translocation involves candidate oncogene lyt-10, homologous to NF-kappa B p50. A B cell lymphoma-associated chromosomal translocation, t(10;14)(q24;q32), juxtaposes the immunoglobulin C alpha 1 locus to a novel gene, lyt-10. The normal lyt-10 cDNA codes for a 98 kd protein which displays amino-terminal homology with the rel (DNA-binding) domain of the NF-kappa B-rel family of transcription factors and carboxy-terminal homology with the NF-kappa B p50 precursor protein, including the putative proteolytic cleavage domain (poly-G) and the ankyrin-like repeat domains. The lyt-10 protein can bind to kappa B sequences in vitro, although with different specificity from NF-kappa B p50, and in vitro DNA-binding is activated by removal of the ankyrin domain. Chromosomal translocation generates an lyt-10-C alpha 1 fusion gene coding for a protein that retains the rel effector domain, lacks the ankyrin regulatory domain, and binds kappa B sequences in vitro, suggesting its constitutive activation in vivo. Analogous rearrangements of the lyt-10 gene have been found in an additional three cases of lymphoid neoplasia. The lyt-10 gene defines a new subfamily (rel/poly-G/ankyrin) of NF-kappa B-rel transcription factors with potential for oncogenic activation in human cancer.\n" ], "offsets": [ [ 0, 1319 ] ] } ]

[ { "id": "PMID-1760839_T1", "type": "Cell", "text": [ "B cell" ], "offsets": [ [ 0, 6 ] ], "normalized": [] }, { "id": "PMID-1760839_T3", "type": "Chromosome", "text": [ "chromosomal" ], "offsets": [ [ 27, 38 ] ], "normalized": [] }, { "id": "PMID-1760839_T5", "type": "Gene", "text": [ "oncogene lyt-10" ], "offsets": [ [ 72, 87 ] ], "normalized": [] }, { "id": "PMID-1760839_T6", "type": "Gene", "text": [ "NF-kappa B p50" ], "offsets": [ [ 103, 117 ] ], "normalized": [] }, { "id": "PMID-1760839_T7", "type": "Cell", "text": [ "B cell" ], "offsets": [ [ 121, 127 ] ], "normalized": [] }, { "id": "PMID-1760839_T9", "type": "Chromosome", "text": [ "chromosomal" ], "offsets": [ [ 148, 159 ] ], "normalized": [] }, { "id": "PMID-1760839_T11", "type": "Locus", "text": [ "immunoglobulin C alpha 1 locus" ], "offsets": [ [ 209, 239 ] ], "normalized": [] }, { "id": "PMID-1760839_T12", "type": "Gene", "text": [ "gene" ], "offsets": [ [ 251, 255 ] ], "normalized": [] }, { "id": "PMID-1760839_T13", "type": "Gene", "text": [ "lyt-10" ], "offsets": [ [ 257, 263 ] ], "normalized": [] }, { "id": "PMID-1760839_T14", "type": "Gene", "text": [ "lyt-10" ], "offsets": [ [ 276, 282 ] ], "normalized": [] }, { "id": "PMID-1760839_T15", "type": "DNA", "text": [ "cDNA" ], "offsets": [ [ 283, 287 ] ], "normalized": [] }, { "id": "PMID-1760839_T16", "type": "Protein", "text": [ "protein" ], "offsets": [ [ 306, 313 ] ], "normalized": [] }, { "id": "PMID-1760839_T17", "type": "ProteinDomain", "text": [ "rel (DNA-binding) domain" ], "offsets": [ [ 362, 386 ] ], "normalized": [] }, { "id": "PMID-1760839_T20", "type": "Protein", "text": [ "NF-kappa B-rel family" ], "offsets": [ [ 394, 415 ] ], "normalized": [] }, { "id": "PMID-1760839_T21", "type": "TranscriptionFactor", "text": [ "transcription factors" ], "offsets": [ [ 419, 440 ] ], "normalized": [] }, { "id": "PMID-1760839_T22", "type": "Protein", "text": [ "NF-kappa B p50" ], "offsets": [ [ 480, 494 ] ], "normalized": [] }, { "id": "PMID-1760839_T23", "type": "Protein", "text": [ "protein" ], "offsets": [ [ 505, 512 ] ], "normalized": [] }, { "id": "PMID-1760839_T24", "type": "ProteinDomain", "text": [ "proteolytic cleavage domain" ], "offsets": [ [ 537, 564 ] ], "normalized": [] }, { "id": "PMID-1760839_T25", "type": "ProteinDomain", "text": [ "ankyrin-like repeat domains" ], "offsets": [ [ 582, 609 ] ], "normalized": [] }, { "id": "PMID-1760839_T26", "type": "Protein", "text": [ "lyt-10 protein" ], "offsets": [ [ 615, 629 ] ], "normalized": [] }, { "id": "PMID-1760839_T28", "type": "DNARegion", "text": [ "kappa B sequences" ], "offsets": [ [ 642, 659 ] ], "normalized": [] }, { "id": "PMID-1760839_T29", "type": "Protein", "text": [ "NF-kappa B p50" ], "offsets": [ [ 711, 725 ] ], "normalized": [] }, { "id": "PMID-1760839_T30", "type": "DNA", "text": [ "DNA" ], "offsets": [ [ 740, 743 ] ], "normalized": [] }, { "id": "PMID-1760839_T34", "type": "ProteinDomain", "text": [ "ankyrin domain" ], "offsets": [ [ 783, 797 ] ], "normalized": [] }, { "id": "PMID-1760839_T35", "type": "Chromosome", "text": [ "Chromosomal" ], "offsets": [ [ 799, 810 ] ], "normalized": [] }, { "id": "PMID-1760839_T37", "type": "FusionGene", "text": [ "lyt-10-C alpha 1 fusion gene" ], "offsets": [ [ 838, 866 ] ], "normalized": [] }, { "id": "PMID-1760839_T38", "type": "Protein", "text": [ "protein" ], "offsets": [ [ 880, 887 ] ], "normalized": [] }, { "id": "PMID-1760839_T39", "type": "ProteinDomain", "text": [ "rel effector domain" ], "offsets": [ [ 905, 924 ] ], "normalized": [] }, { "id": "PMID-1760839_T40", "type": "ProteinDomain", "text": [ "ankyrin regulatory domain" ], "offsets": [ [ 936, 961 ] ], "normalized": [] }, { "id": "PMID-1760839_T42", "type": "DNARegion", "text": [ "kappa B sequences" ], "offsets": [ [ 973, 990 ] ], "normalized": [] }, { "id": "PMID-1760839_T45", "type": "Gene", "text": [ "lyt-10 gene" ], "offsets": [ [ 1081, 1092 ] ], "normalized": [] }, { "id": "PMID-1760839_T46", "type": "Gene", "text": [ "lyt-10 gene" ], "offsets": [ [ 1165, 1176 ] ], "normalized": [] }, { "id": "PMID-1760839_T47", "type": "Protein", "text": [ "rel/poly-G/ankyrin" ], "offsets": [ [ 1202, 1220 ] ], "normalized": [] }, { "id": "PMID-1760839_T52", "type": "Eukaryote", "text": [ "human" ], "offsets": [ [ 1305, 1310 ] ], "normalized": [] }, { "id": "PMID-1760839_T18", "type": "TranslationFactor", "text": [ "NF-kappa B-rel transcription factors" ], "offsets": [ [ 1225, 1261 ] ], "normalized": [] } ]

[ { "id": "PMID-1760839_E1", "type": "Disease", "trigger": { "text": [ "lymphoma" ], "offsets": [ [ 7, 15 ] ] }, "arguments": [] }, { "id": "PMID-1760839_E2", "type": "Mutation", "trigger": { "text": [ "translocation" ], "offsets": [ [ 39, 52 ] ] }, "arguments": [ { "role": "hasPatient", "ref_id": "PMID-1760839_T3" } ] }, { "id": "PMID-1760839_E3", "type": "Disease", "trigger": { "text": [ "lymphoma" ], "offsets": [ [ 128, 136 ] ] }, "arguments": [] }, { "id": "PMID-1760839_E4", "type": "Mutation", "trigger": { "text": [ "translocation" ], "offsets": [ [ 160, 173 ] ] }, "arguments": [ { "role": "hasPatient", "ref_id": "PMID-1760839_T9" } ] }, { "id": "PMID-1760839_E6", "type": "BindingOfProteinToDNA", "trigger": { "text": [ "bind" ], "offsets": [ [ 634, 638 ] ] }, "arguments": [ { "role": "hasAgent", "ref_id": "PMID-1760839_T26" }, { "role": "hasPatient", "ref_id": "PMID-1760839_T28" } ] }, { "id": "PMID-1760839_E7", "type": "BindingOfProteinToDNA", "trigger": { "text": [ "binding" ], "offsets": [ [ 744, 751 ] ] }, "arguments": [ { "role": "hasPatient", "ref_id": "PMID-1760839_T30" } ] }, { "id": "PMID-1760839_E8", "type": "PositiveRegulation", "trigger": { "text": [ "activated" ], "offsets": [ [ 755, 764 ] ] }, "arguments": [ { "role": "hasAgent", "ref_id": "PMID-1760839_E9" }, { "role": "hasPatient", "ref_id": "PMID-1760839_E7" } ] }, { "id": "PMID-1760839_E9", "type": "Decrease", "trigger": { "text": [ "removal" ], "offsets": [ [ 768, 775 ] ] }, "arguments": [ { "role": "hasPatient", "ref_id": "PMID-1760839_T34" } ] }, { "id": "PMID-1760839_E10", "type": "Mutation", "trigger": { "text": [ "translocation" ], "offsets": [ [ 811, 824 ] ] }, "arguments": [ { "role": "hasPatient", "ref_id": "PMID-1760839_T35" } ] }, { "id": "PMID-1760839_E11", "type": "BindingOfProteinToDNA", "trigger": { "text": [ "binds" ], "offsets": [ [ 967, 972 ] ] }, "arguments": [ { "role": "hasAgent", "ref_id": "PMID-1760839_T38" }, { "role": "hasPatient", "ref_id": "PMID-1760839_T42" } ] }, { "id": "PMID-1760839_E12", "type": "PositiveRegulation", "trigger": { "text": [ "activation" ], "offsets": [ [ 1029, 1039 ] ] }, "arguments": [] }, { "id": "PMID-1760839_E13", "type": "Mutation", "trigger": { "text": [ "rearrangements" ], "offsets": [ [ 1059, 1073 ] ] }, "arguments": [ { "role": "hasPatient", "ref_id": "PMID-1760839_T45" } ] }, { "id": "PMID-1760839_E14", "type": "PositiveRegulation", "trigger": { "text": [ "activation" ], "offsets": [ [ 1291, 1301 ] ] }, "arguments": [ { "role": "hasAgent", "ref_id": "PMID-1760839_T47" } ] }, { "id": "PMID-1760839_E15", "type": "Disease", "trigger": { "text": [ "cancer" ], "offsets": [ [ 1311, 1317 ] ] }, "arguments": [] } ]

[]

[ { "id": "PMID-1760839_R4", "type": "encodes", "arg1_id": "PMID-1760839_T15", "arg2_id": "PMID-1760839_T16", "normalized": [] }, { "id": "PMID-1760839_R5", "type": "hasPart", "arg1_id": "PMID-1760839_T20", "arg2_id": "PMID-1760839_T17", "normalized": [] }, { "id": "PMID-1760839_R6", "type": "hasPart", "arg1_id": "PMID-1760839_T22", "arg2_id": "PMID-1760839_T24", "normalized": [] }, { "id": "PMID-1760839_R7", "type": "hasPart", "arg1_id": "PMID-1760839_T22", "arg2_id": "PMID-1760839_T25", "normalized": [] }, { "id": "PMID-1760839_R9", "type": "encodes", "arg1_id": "PMID-1760839_T37", "arg2_id": "PMID-1760839_T38", "normalized": [] }, { "id": "PMID-1760839_R10", "type": "hasPart", "arg1_id": "PMID-1760839_T38", "arg2_id": "PMID-1760839_T39", "normalized": [] } ]

[ { "id": "PMID-1763325__text", "type": "abstract", "text": [ "Characterization of a cofactor that regulates dimerization of a mammalian homeodomain protein. Dimerization among transcription factors has become a recurrent theme in the regulation of eukaryotic gene expression. Hepatocyte nuclear factor-1 alpha (HNF-1 alpha) is a homeodomain-containing protein that functions as a dimer. A dimerization cofactor of HNF-1 alpha (DCoH) was identified that displayed a restricted tissue distribution and did not bind to DNA, but, rather, selectively stabilized HNF-1 alpha dimers. The formation of a stable tetrameric DCoH-HNF-1 alpha complex, which required the dimerization domain of HNF-1 alpha, did not change the DNA binding characteristics of HNF-1 alpha, but enhanced its transcriptional activity. However, DCoH did not confer transcriptional activation to the GAL4 DNA binding domain. These results indicate that DCoH regulates formation of transcriptionally active tetrameric complexes and may contribute to the developmental specificity of the complex.\n" ], "offsets": [ [ 0, 997 ] ] } ]

[ { "id": "PMID-1763325_T1", "type": "Protein", "text": [ "cofactor" ], "offsets": [ [ 22, 30 ] ], "normalized": [] }, { "id": "PMID-1763325_T4", "type": "Eukaryote", "text": [ "mammalian" ], "offsets": [ [ 64, 73 ] ], "normalized": [] }, { "id": "PMID-1763325_T5", "type": "ProteinDomain", "text": [ "homeodomain" ], "offsets": [ [ 74, 85 ] ], "normalized": [] }, { "id": "PMID-1763325_T6", "type": "Protein", "text": [ "protein" ], "offsets": [ [ 86, 93 ] ], "normalized": [] }, { "id": "PMID-1763325_T8", "type": "TranscriptionFactor", "text": [ "transcription factors" ], "offsets": [ [ 114, 135 ] ], "normalized": [] }, { "id": "PMID-1763325_T10", "type": "Eukaryote", "text": [ "eukaryotic" ], "offsets": [ [ 186, 196 ] ], "normalized": [] }, { "id": "PMID-1763325_T12", "type": "TranscriptionFactor", "text": [ "Hepatocyte nuclear factor-1 alpha" ], "offsets": [ [ 214, 247 ] ], "normalized": [] }, { "id": "PMID-1763325_T13", "type": "TranscriptionFactor", "text": [ "HNF-1 alpha" ], "offsets": [ [ 249, 260 ] ], "normalized": [] }, { "id": "PMID-1763325_T14", "type": "ProteinDomain", "text": [ "homeodomain" ], "offsets": [ [ 267, 278 ] ], "normalized": [] }, { "id": "PMID-1763325_T15", "type": "Protein", "text": [ "protein" ], "offsets": [ [ 290, 297 ] ], "normalized": [] }, { "id": "PMID-1763325_T16", "type": "Protein", "text": [ "HNF-1 alpha" ], "offsets": [ [ 352, 363 ] ], "normalized": [] }, { "id": "PMID-1763325_T17", "type": "Protein", "text": [ "DCoH" ], "offsets": [ [ 365, 369 ] ], "normalized": [] }, { "id": "PMID-1763325_T18", "type": "Tissue", "text": [ "tissue" ], "offsets": [ [ 414, 420 ] ], "normalized": [] }, { "id": "PMID-1763325_T21", "type": "TranscriptionFactor", "text": [ "HNF-1 alpha dimers" ], "offsets": [ [ 495, 513 ] ], "normalized": [] }, { "id": "PMID-1763325_T22", "type": "Protein", "text": [ "DCoH" ], "offsets": [ [ 552, 556 ] ], "normalized": [] }, { "id": "PMID-1763325_T23", "type": "TranscriptionFactor", "text": [ "HNF-1 alpha" ], "offsets": [ [ 557, 568 ] ], "normalized": [] }, { "id": "PMID-1763325_T24", "type": "ProteinComplex", "text": [ "complex" ], "offsets": [ [ 569, 576 ] ], "normalized": [] }, { "id": "PMID-1763325_T25", "type": "ProteinDomain", "text": [ "dimerization domain" ], "offsets": [ [ 597, 616 ] ], "normalized": [] }, { "id": "PMID-1763325_T26", "type": "TranscriptionFactor", "text": [ "HNF-1 alpha" ], "offsets": [ [ 620, 631 ] ], "normalized": [] }, { "id": "PMID-1763325_T29", "type": "Protein", "text": [ "DCoH" ], "offsets": [ [ 855, 859 ] ], "normalized": [] }, { "id": "PMID-1763325_T33", "type": "ProteinComplex", "text": [ "complexes" ], "offsets": [ [ 919, 928 ] ], "normalized": [] }, { "id": "PMID-1763325_T34", "type": "ProteinComplex", "text": [ "complex" ], "offsets": [ [ 988, 995 ] ], "normalized": [] } ]

[ { "id": "PMID-1763325_E1", "type": "RegulatoryProcess", "trigger": { "text": [ "regulates" ], "offsets": [ [ 36, 45 ] ] }, "arguments": [ { "role": "hasAgent", "ref_id": "PMID-1763325_T1" }, { "role": "hasPatient", "ref_id": "PMID-1763325_E2" } ] }, { "id": "PMID-1763325_E2", "type": "Dimerization", "trigger": { "text": [ "dimerization" ], "offsets": [ [ 46, 58 ] ] }, "arguments": [] }, { "id": "PMID-1763325_E3", "type": "Dimerization", "trigger": { "text": [ "Dimerization" ], "offsets": [ [ 95, 107 ] ] }, "arguments": [] }, { "id": "PMID-1763325_E4", "type": "RegulationOfGeneExpression", "trigger": { "text": [ "regulation" ], "offsets": [ [ 172, 182 ] ] }, "arguments": [ { "role": "hasPatient", "ref_id": "PMID-1763325_E5" } ] }, { "id": "PMID-1763325_E5", "type": "GeneExpression", "trigger": { "text": [ "gene expression" ], "offsets": [ [ 197, 212 ] ] }, "arguments": [] }, { "id": "PMID-1763325_E6", "type": "Localization", "trigger": { "text": [ "distribution" ], "offsets": [ [ 421, 433 ] ] }, "arguments": [] }, { "id": "PMID-1763325_E7", "type": "Stabilization", "trigger": { "text": [ "stabilized" ], "offsets": [ [ 484, 494 ] ] }, "arguments": [ { "role": "hasPatient", "ref_id": "PMID-1763325_T21" } ] }, { "id": "PMID-1763325_E8", "type": "Increase", "trigger": { "text": [ "enhanced" ], "offsets": [ [ 700, 708 ] ] }, "arguments": [ { "role": "hasPatient", "ref_id": "PMID-1763325_E9" } ] }, { "id": "PMID-1763325_E9", "type": "Transcription", "trigger": { "text": [ "transcriptional activity" ], "offsets": [ [ 713, 737 ] ] }, "arguments": [] }, { "id": "PMID-1763325_E10", "type": "RegulatoryProcess", "trigger": { "text": [ "regulates" ], "offsets": [ [ 860, 869 ] ] }, "arguments": [ { "role": "hasAgent", "ref_id": "PMID-1763325_T29" }, { "role": "hasPatient", "ref_id": "PMID-1763325_E11" } ] }, { "id": "PMID-1763325_E11", "type": "FormationOfTranscriptionFactorComplex", "trigger": { "text": [ "formation" ], "offsets": [ [ 870, 879 ] ] }, "arguments": [ { "role": "hasPatient", "ref_id": "PMID-1763325_T33" } ] }, { "id": "PMID-1763325_E12", "type": "Transcription", "trigger": { "text": [ "transcriptionally" ], "offsets": [ [ 883, 900 ] ] }, "arguments": [] }, { "id": "PMID-1763325_E13", "type": "DevelopmentalProcess", "trigger": { "text": [ "developmental" ], "offsets": [ [ 955, 968 ] ] }, "arguments": [] } ]

[]

[ { "id": "PMID-1763325_R1", "type": "hasPart", "arg1_id": "PMID-1763325_T6", "arg2_id": "PMID-1763325_T5", "normalized": [] }, { "id": "PMID-1763325_R2", "type": "fromSpecies", "arg1_id": "PMID-1763325_T6", "arg2_id": "PMID-1763325_T4", "normalized": [] }, { "id": "PMID-1763325_R4", "type": "hasPart", "arg1_id": "PMID-1763325_T15", "arg2_id": "PMID-1763325_T14", "normalized": [] }, { "id": "PMID-1763325_R6", "type": "hasPart", "arg1_id": "PMID-1763325_T24", "arg2_id": "PMID-1763325_T22", "normalized": [] }, { "id": "PMID-1763325_R7", "type": "hasPart", "arg1_id": "PMID-1763325_T24", "arg2_id": "PMID-1763325_T23", "normalized": [] }, { "id": "PMID-1763325_R8", "type": "hasPart", "arg1_id": "PMID-1763325_T26", "arg2_id": "PMID-1763325_T25", "normalized": [] } ]

[ { "id": "PMID-17875217__text", "type": "abstract", "text": [ "The DNA binding parvulin Par17 is targeted to the mitochondrial matrix by a recently evolved prepeptide uniquely present in Hominidae. The parvulin-type peptidyl prolyl cis/trans isomerase Par14 is highly conserved in all metazoans. The recently identified parvulin Par17 contains an additional N-terminal domain whose occurrence and function was the focus of the present study. Based on the observation that the human genome encodes Par17, but bovine and rodent genomes do not, Par17 exon sequences from 10 different primate species were cloned and sequenced. Par17 is encoded in the genomes of Hominidae species including humans, but is absent from other mammalian species. In contrast to Par14, endogenous Par17 was found in mitochondrial and membrane fractions of human cell lysates. Fluorescence of EGFP fusions of Par17, but not Par14, co-localized with mitochondrial staining. Par14 and Par17 associated with isolated human, rat and yeast mitochondria at low salt concentrations, but only the Par17 mitochondrial association was resistant to higher salt concentrations. Par17 was imported into mitochondria in a time and membrane potential-dependent manner, where it reached the mitochondrial matrix. Moreover, Par17 was shown to bind to double-stranded DNA under physiological salt conditions. Taken together, the DNA binding parvulin Par17 is targeted to the mitochondrial matrix by the most recently evolved mitochondrial prepeptide known to date, thus adding a novel protein constituent to the mitochondrial proteome of Hominidae.\n" ], "offsets": [ [ 0, 1542 ] ] } ]

[ { "id": "PMID-17875217_T4", "type": "Protein", "text": [ "Par17" ], "offsets": [ [ 25, 30 ] ], "normalized": [] }, { "id": "PMID-17875217_T6", "type": "CellComponent", "text": [ "mitochondrial matrix" ], "offsets": [ [ 50, 70 ] ], "normalized": [] }, { "id": "PMID-17875217_T7", "type": "Peptide", "text": [ "prepeptide" ], "offsets": [ [ 93, 103 ] ], "normalized": [] }, { "id": "PMID-17875217_T8", "type": "Eukaryote", "text": [ "Hominidae" ], "offsets": [ [ 124, 133 ] ], "normalized": [] }, { "id": "PMID-17875217_T9", "type": "Protein", "text": [ "parvulin" ], "offsets": [ [ 139, 147 ] ], "normalized": [] }, { "id": "PMID-17875217_T10", "type": "Enzyme", "text": [ "peptidyl prolyl cis/trans isomerase" ], "offsets": [ [ 153, 188 ] ], "normalized": [] }, { "id": "PMID-17875217_T11", "type": "Enzyme", "text": [ "Par14" ], "offsets": [ [ 189, 194 ] ], "normalized": [] }, { "id": "PMID-17875217_T12", "type": "Eukaryote", "text": [ "metazoans" ], "offsets": [ [ 222, 231 ] ], "normalized": [] }, { "id": "PMID-17875217_T13", "type": "Protein", "text": [ "parvulin" ], "offsets": [ [ 257, 265 ] ], "normalized": [] }, { "id": "PMID-17875217_T14", "type": "Protein", "text": [ "Par17" ], "offsets": [ [ 266, 271 ] ], "normalized": [] }, { "id": "PMID-17875217_T15", "type": "ProteinDomain", "text": [ "N-terminal domain" ], "offsets": [ [ 295, 312 ] ], "normalized": [] }, { "id": "PMID-17875217_T16", "type": "Eukaryote", "text": [ "human" ], "offsets": [ [ 413, 418 ] ], "normalized": [] }, { "id": "PMID-17875217_T17", "type": "Protein", "text": [ "Par17" ], "offsets": [ [ 434, 439 ] ], "normalized": [] }, { "id": "PMID-17875217_T18", "type": "Eukaryote", "text": [ "bovine" ], "offsets": [ [ 445, 451 ] ], "normalized": [] }, { "id": "PMID-17875217_T19", "type": "Eukaryote", "text": [ "rodent" ], "offsets": [ [ 456, 462 ] ], "normalized": [] }, { "id": "PMID-17875217_T20", "type": "Gene", "text": [ "Par17" ], "offsets": [ [ 479, 484 ] ], "normalized": [] }, { "id": "PMID-17875217_T21", "type": "Exon", "text": [ "exon" ], "offsets": [ [ 485, 489 ] ], "normalized": [] }, { "id": "PMID-17875217_T22", "type": "Eukaryote", "text": [ "primate species" ], "offsets": [ [ 518, 533 ] ], "normalized": [] }, { "id": "PMID-17875217_T23", "type": "Protein", "text": [ "Par17" ], "offsets": [ [ 561, 566 ] ], "normalized": [] }, { "id": "PMID-17875217_T24", "type": "Eukaryote", "text": [ "Hominidae species" ], "offsets": [ [ 596, 613 ] ], "normalized": [] }, { "id": "PMID-17875217_T25", "type": "Eukaryote", "text": [ "humans" ], "offsets": [ [ 624, 630 ] ], "normalized": [] }, { "id": "PMID-17875217_T26", "type": "Eukaryote", "text": [ "mammalian species" ], "offsets": [ [ 657, 674 ] ], "normalized": [] }, { "id": "PMID-17875217_T27", "type": "Enzyme", "text": [ "Par14" ], "offsets": [ [ 691, 696 ] ], "normalized": [] }, { "id": "PMID-17875217_T28", "type": "Protein", "text": [ "Par17" ], "offsets": [ [ 709, 714 ] ], "normalized": [] }, { "id": "PMID-17875217_T30", "type": "CellComponent", "text": [ "membrane fractions" ], "offsets": [ [ 746, 764 ] ], "normalized": [] }, { "id": "PMID-17875217_T31", "type": "Eukaryote", "text": [ "human" ], "offsets": [ [ 768, 773 ] ], "normalized": [] }, { "id": "PMID-17875217_T32", "type": "Cell", "text": [ "cell lysates" ], "offsets": [ [ 774, 786 ] ], "normalized": [] }, { "id": "PMID-17875217_T33", "type": "Protein", "text": [ "Par17" ], "offsets": [ [ 820, 825 ] ], "normalized": [] }, { "id": "PMID-17875217_T34", "type": "Enzyme", "text": [ "Par14" ], "offsets": [ [ 835, 840 ] ], "normalized": [] }, { "id": "PMID-17875217_T35", "type": "CellComponent", "text": [ "mitochondrial" ], "offsets": [ [ 860, 873 ] ], "normalized": [] }, { "id": "PMID-17875217_T36", "type": "Enzyme", "text": [ "Par14" ], "offsets": [ [ 884, 889 ] ], "normalized": [] }, { "id": "PMID-17875217_T37", "type": "Protein", "text": [ "Par17" ], "offsets": [ [ 894, 899 ] ], "normalized": [] }, { "id": "PMID-17875217_T39", "type": "Eukaryote", "text": [ "human" ], "offsets": [ [ 925, 930 ] ], "normalized": [] }, { "id": "PMID-17875217_T40", "type": "Eukaryote", "text": [ "rat" ], "offsets": [ [ 932, 935 ] ], "normalized": [] }, { "id": "PMID-17875217_T41", "type": "Eukaryote", "text": [ "yeast" ], "offsets": [ [ 940, 945 ] ], "normalized": [] }, { "id": "PMID-17875217_T42", "type": "CellComponent", "text": [ "mitochondria" ], "offsets": [ [ 946, 958 ] ], "normalized": [] }, { "id": "PMID-17875217_T43", "type": "Protein", "text": [ "Par17" ], "offsets": [ [ 1000, 1005 ] ], "normalized": [] }, { "id": "PMID-17875217_T44", "type": "CellComponent", "text": [ "mitochondrial" ], "offsets": [ [ 1006, 1019 ] ], "normalized": [] }, { "id": "PMID-17875217_T46", "type": "Protein", "text": [ "Par17" ], "offsets": [ [ 1077, 1082 ] ], "normalized": [] }, { "id": "PMID-17875217_T48", "type": "CellComponent", "text": [ "mitochondria" ], "offsets": [ [ 1101, 1113 ] ], "normalized": [] }, { "id": "PMID-17875217_T49", "type": "CellComponent", "text": [ "membrane" ], "offsets": [ [ 1128, 1136 ] ], "normalized": [] }, { "id": "PMID-17875217_T50", "type": "CellComponent", "text": [ "mitochondrial matrix" ], "offsets": [ [ 1186, 1206 ] ], "normalized": [] }, { "id": "PMID-17875217_T51", "type": "Protein", "text": [ "Par17" ], "offsets": [ [ 1218, 1223 ] ], "normalized": [] }, { "id": "PMID-17875217_T53", "type": "DoubleStrandDNA", "text": [ "double-stranded DNA" ], "offsets": [ [ 1245, 1264 ] ], "normalized": [] }, { "id": "PMID-17875217_T57", "type": "Protein", "text": [ "Par17" ], "offsets": [ [ 1343, 1348 ] ], "normalized": [] }, { "id": "PMID-17875217_T59", "type": "CellComponent", "text": [ "mitochondrial matrix" ], "offsets": [ [ 1368, 1388 ] ], "normalized": [] }, { "id": "PMID-17875217_T60", "type": "CellComponent", "text": [ "mitochondrial" ], "offsets": [ [ 1418, 1431 ] ], "normalized": [] }, { "id": "PMID-17875217_T61", "type": "Peptide", "text": [ "prepeptide" ], "offsets": [ [ 1432, 1442 ] ], "normalized": [] }, { "id": "PMID-17875217_T62", "type": "Protein", "text": [ "protein" ], "offsets": [ [ 1478, 1485 ] ], "normalized": [] }, { "id": "PMID-17875217_T63", "type": "CellComponent", "text": [ "mitochondrial" ], "offsets": [ [ 1505, 1518 ] ], "normalized": [] }, { "id": "PMID-17875217_T64", "type": "Eukaryote", "text": [ "Hominidae" ], "offsets": [ [ 1531, 1540 ] ], "normalized": [] }, { "id": "PMID-17875217_T1", "type": "Protein", "text": [ "DNA binding parvulin" ], "offsets": [ [ 4, 24 ] ], "normalized": [] }, { "id": "PMID-17875217_T2", "type": "CellComponent", "text": [ "mitochondrial" ], "offsets": [ [ 728, 741 ] ], "normalized": [] }, { "id": "PMID-17875217_T3", "type": "Protein", "text": [ "DNA binding parvulin" ], "offsets": [ [ 1322, 1342 ] ], "normalized": [] } ]

[ { "id": "PMID-17875217_E2", "type": "ProteinTargeting", "trigger": { "text": [ "targeted" ], "offsets": [ [ 34, 42 ] ] }, "arguments": [ { "role": "hasPatient", "ref_id": "PMID-17875217_T4" } ] }, { "id": "PMID-17875217_E3", "type": "Binding", "trigger": { "text": [ "associated" ], "offsets": [ [ 900, 910 ] ] }, "arguments": [ { "role": "hasPatient", "ref_id": "PMID-17875217_T42" } ] }, { "id": "PMID-17875217_E4", "type": "Binding", "trigger": { "text": [ "association" ], "offsets": [ [ 1020, 1031 ] ] }, "arguments": [ { "role": "hasPatient", "ref_id": "PMID-17875217_T44" } ] }, { "id": "PMID-17875217_E5", "type": "ProteinTransport", "trigger": { "text": [ "imported" ], "offsets": [ [ 1087, 1095 ] ] }, "arguments": [ { "role": "hasPatient", "ref_id": "PMID-17875217_T46" } ] }, { "id": "PMID-17875217_E6", "type": "BindingOfProteinToDNA", "trigger": { "text": [ "bind" ], "offsets": [ [ 1237, 1241 ] ] }, "arguments": [ { "role": "hasAgent", "ref_id": "PMID-17875217_T51" }, { "role": "hasPatient", "ref_id": "PMID-17875217_T53" } ] }, { "id": "PMID-17875217_E8", "type": "ProteinTargeting", "trigger": { "text": [ "targeted" ], "offsets": [ [ 1352, 1360 ] ] }, "arguments": [ { "role": "hasPatient", "ref_id": "PMID-17875217_T57" } ] }, { "id": "PMID-17875217_E1", "type": "Binding", "trigger": { "text": [ "associated" ], "offsets": [ [ 900, 910 ] ] }, "arguments": [ { "role": "hasPatient", "ref_id": "PMID-17875217_T36" } ] }, { "id": "PMID-17875217_E7", "type": "Binding", "trigger": { "text": [ "associated" ], "offsets": [ [ 900, 910 ] ] }, "arguments": [ { "role": "hasPatient", "ref_id": "PMID-17875217_T37" } ] }, { "id": "PMID-17875217_E9", "type": "Binding", "trigger": { "text": [ "association" ], "offsets": [ [ 1020, 1031 ] ] }, "arguments": [ { "role": "hasPatient", "ref_id": "PMID-17875217_T43" } ] } ]

[]

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[ { "id": "PMID-1850513__text", "type": "abstract", "text": [ "Human MyoD: cDNA and deduced amino acid sequence.\n" ], "offsets": [ [ 0, 50 ] ] } ]

[ { "id": "PMID-1850513_T1", "type": "Eukaryote", "text": [ "Human" ], "offsets": [ [ 0, 5 ] ], "normalized": [] }, { "id": "PMID-1850513_T2", "type": "Protein", "text": [ "MyoD" ], "offsets": [ [ 6, 10 ] ], "normalized": [] }, { "id": "PMID-1850513_T3", "type": "DNA", "text": [ "cDNA" ], "offsets": [ [ 12, 16 ] ], "normalized": [] }, { "id": "PMID-1850513_T4", "type": "AminoAcid", "text": [ "amino acid" ], "offsets": [ [ 29, 39 ] ], "normalized": [] }, { "id": "PMID-1850513_T5", "type": "Sequence", "text": [ "sequence" ], "offsets": [ [ 40, 48 ] ], "normalized": [] } ]

[]

[]

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[ { "id": "PMID-1903194__text", "type": "abstract", "text": [ "Structure and function of human jun-D. A jun related cDNA and its corresponding genomic fragment were cloned from human cells and sequenced. Polymerase chain reaction analysis showed that this gene is the human homologue of the mouse jun-D gene despite the fact that the degree of amino acid sequence conservation between the two is much poorer (77.3%) than that found between the homologues of c-jun and jun-B (95-98%). The product of this gene binds an AP-1 site and upon cotransfection stimulates the activity of a promoter that bears an AP-1 site. The level of activation is comparable to that of v-jun and the activity of both is further stimulated by v-fos. Deletion mutants of the gene that lack the best conserved region in the activating domain are poorly active. However, our data suggest that the activating domain is not confined exclusively to the conserved regions. Interestingly, at high concentrations human jun-D displays decreased activity which cannot be explained by a simple self squelching model.\n" ], "offsets": [ [ 0, 1019 ] ] } ]

[ { "id": "PMID-1903194_T1", "type": "Eukaryote", "text": [ "human" ], "offsets": [ [ 26, 31 ] ], "normalized": [] }, { "id": "PMID-1903194_T2", "type": "Protein", "text": [ "jun-D" ], "offsets": [ [ 32, 37 ] ], "normalized": [] }, { "id": "PMID-1903194_T3", "type": "DNA", "text": [ "jun related cDNA" ], "offsets": [ [ 41, 57 ] ], "normalized": [] }, { "id": "PMID-1903194_T4", "type": "DNAFragment", "text": [ "genomic fragment" ], "offsets": [ [ 80, 96 ] ], "normalized": [] }, { "id": "PMID-1903194_T5", "type": "Eukaryote", "text": [ "human" ], "offsets": [ [ 114, 119 ] ], "normalized": [] }, { "id": "PMID-1903194_T6", "type": "Cell", "text": [ "cells" ], "offsets": [ [ 120, 125 ] ], "normalized": [] }, { "id": "PMID-1903194_T7", "type": "ExperimentalMethod", "text": [ "sequenced" ], "offsets": [ [ 130, 139 ] ], "normalized": [] }, { "id": "PMID-1903194_T8", "type": "ExperimentalMethod", "text": [ "Polymerase chain reaction analysis" ], "offsets": [ [ 141, 175 ] ], "normalized": [] }, { "id": "PMID-1903194_T9", "type": "Gene", "text": [ "this gene" ], "offsets": [ [ 188, 197 ] ], "normalized": [] }, { "id": "PMID-1903194_T10", "type": "Eukaryote", "text": [ "human" ], "offsets": [ [ 205, 210 ] ], "normalized": [] }, { "id": "PMID-1903194_T11", "type": "Eukaryote", "text": [ "mouse" ], "offsets": [ [ 228, 233 ] ], "normalized": [] }, { "id": "PMID-1903194_T12", "type": "Gene", "text": [ "jun-D gene" ], "offsets": [ [ 234, 244 ] ], "normalized": [] }, { "id": "PMID-1903194_T13", "type": "AminoAcid", "text": [ "amino acid" ], "offsets": [ [ 281, 291 ] ], "normalized": [] }, { "id": "PMID-1903194_T14", "type": "Sequence", "text": [ "sequence" ], "offsets": [ [ 292, 300 ] ], "normalized": [] }, { "id": "PMID-1903194_T15", "type": "Gene", "text": [ "c-jun" ], "offsets": [ [ 395, 400 ] ], "normalized": [] }, { "id": "PMID-1903194_T16", "type": "Gene", "text": [ "jun-B" ], "offsets": [ [ 405, 410 ] ], "normalized": [] }, { "id": "PMID-1903194_T17", "type": "Protein", "text": [ "product" ], "offsets": [ [ 425, 432 ] ], "normalized": [] }, { "id": "PMID-1903194_T18", "type": "Gene", "text": [ "this gene" ], "offsets": [ [ 436, 445 ] ], "normalized": [] }, { "id": "PMID-1903194_T20", "type": "DNARegion", "text": [ "AP-1 site" ], "offsets": [ [ 455, 464 ] ], "normalized": [] }, { "id": "PMID-1903194_T22", "type": "Function", "text": [ "activity" ], "offsets": [ [ 504, 512 ] ], "normalized": [] }, { "id": "PMID-1903194_T23", "type": "Promoter", "text": [ "promoter" ], "offsets": [ [ 518, 526 ] ], "normalized": [] }, { "id": "PMID-1903194_T24", "type": "DNARegion", "text": [ "AP-1 site" ], "offsets": [ [ 541, 550 ] ], "normalized": [] }, { "id": "PMID-1903194_T26", "type": "Gene", "text": [ "v-jun" ], "offsets": [ [ 601, 606 ] ], "normalized": [] }, { "id": "PMID-1903194_T28", "type": "Gene", "text": [ "v-fos" ], "offsets": [ [ 657, 662 ] ], "normalized": [] }, { "id": "PMID-1903194_T29", "type": "Protein", "text": [ "jun-D" ], "offsets": [ [ 924, 929 ] ], "normalized": [] }, { "id": "PMID-1903194_T30", "type": "Eukaryote", "text": [ "human" ], "offsets": [ [ 918, 923 ] ], "normalized": [] } ]

[ { "id": "PMID-1903194_E1", "type": "BindingOfProteinToDNA", "trigger": { "text": [ "binds" ], "offsets": [ [ 446, 451 ] ] }, "arguments": [ { "role": "hasAgent", "ref_id": "PMID-1903194_T17" }, { "role": "hasPatient", "ref_id": "PMID-1903194_T20" } ] }, { "id": "PMID-1903194_E2", "type": "Increase", "trigger": { "text": [ "stimulates" ], "offsets": [ [ 489, 499 ] ] }, "arguments": [ { "role": "hasAgent", "ref_id": "PMID-1903194_T17" }, { "role": "hasPatient", "ref_id": "PMID-1903194_T22" } ] }, { "id": "PMID-1903194_E3", "type": "PositiveRegulation", "trigger": { "text": [ "activation" ], "offsets": [ [ 565, 575 ] ] }, "arguments": [] }, { "id": "PMID-1903194_E4", "type": "Increase", "trigger": { "text": [ "stimulated" ], "offsets": [ [ 643, 653 ] ] }, "arguments": [ { "role": "hasAgent", "ref_id": "PMID-1903194_T28" }, { "role": "hasPatient", "ref_id": "PMID-1903194_T26" } ] } ]

[]

[ { "id": "PMID-1903194_R1", "type": "fromSpecies", "arg1_id": "PMID-1903194_T2", "arg2_id": "PMID-1903194_T1", "normalized": [] }, { "id": "PMID-1903194_R2", "type": "locatedIn", "arg1_id": "PMID-1903194_T3", "arg2_id": "PMID-1903194_T6", "normalized": [] }, { "id": "PMID-1903194_R3", "type": "locatedIn", "arg1_id": "PMID-1903194_T4", "arg2_id": "PMID-1903194_T6", "normalized": [] }, { "id": "PMID-1903194_R4", "type": "fromSpecies", "arg1_id": "PMID-1903194_T6", "arg2_id": "PMID-1903194_T5", "normalized": [] }, { "id": "PMID-1903194_R5", "type": "fromSpecies", "arg1_id": "PMID-1903194_T9", "arg2_id": "PMID-1903194_T10", "normalized": [] }, { "id": "PMID-1903194_R6", "type": "fromSpecies", "arg1_id": "PMID-1903194_T12", "arg2_id": "PMID-1903194_T11", "normalized": [] }, { "id": "PMID-1903194_R7", "type": "encodes", "arg1_id": "PMID-1903194_T18", "arg2_id": "PMID-1903194_T17", "normalized": [] }, { "id": "PMID-1903194_R8", "type": "hasPart", "arg1_id": "PMID-1903194_T23", "arg2_id": "PMID-1903194_T24", "normalized": [] }, { "id": "PMID-1903194_R9", "type": "hasFunction", "arg1_id": "PMID-1903194_T23", "arg2_id": "PMID-1903194_T22", "normalized": [] }, { "id": "PMID-1903194_R10", "type": "fromSpecies", "arg1_id": "PMID-1903194_T29", "arg2_id": "PMID-1903194_T30", "normalized": [] } ]

[ { "id": "PMID-1916817__text", "type": "abstract", "text": [ "Localization of the gene for the DNA-binding protein AP-2 to human chromosome 6p22.3-pter. A variety of cellular proteins bind to cellular and viral enhancer elements. One such factor, known as AP-2, is a 52-kDa transcription factor identified by its interaction with the SV40 and metallothionein enhancers. In addition, it has been found that AP-2 binds to the SV40 T-antigen. AP-2 activity is mediated by both the state of cellular differentiation and changes in signal transduction pathways, suggesting a potential role of AP-2 in the regulation of diverse cellular processes. As part of an effort to examine the chromosomal organization of cellular genes encoding transcription factors, we report the mapping of the gene encoding AP-2 to human chromosome 6p22.3-24 by analysis of somatic cell hybrids and in situ hybridization to chromosomes.\n" ], "offsets": [ [ 0, 847 ] ] } ]

[ { "id": "PMID-1916817_T2", "type": "Gene", "text": [ "gene" ], "offsets": [ [ 20, 24 ] ], "normalized": [] }, { "id": "PMID-1916817_T5", "type": "Protein", "text": [ "DNA-binding protein AP-2" ], "offsets": [ [ 33, 57 ] ], "normalized": [] }, { "id": "PMID-1916817_T6", "type": "Eukaryote", "text": [ "human" ], "offsets": [ [ 61, 66 ] ], "normalized": [] }, { "id": "PMID-1916817_T7", "type": "Chromosome", "text": [ "chromosome 6p22.3-pter" ], "offsets": [ [ 67, 89 ] ], "normalized": [] }, { "id": "PMID-1916817_T8", "type": "Cell", "text": [ "cellular" ], "offsets": [ [ 104, 112 ] ], "normalized": [] }, { "id": "PMID-1916817_T9", "type": "Protein", "text": [ "proteins" ], "offsets": [ [ 113, 121 ] ], "normalized": [] }, { "id": "PMID-1916817_T11", "type": "Cell", "text": [ "cellular" ], "offsets": [ [ 130, 138 ] ], "normalized": [] }, { "id": "PMID-1916817_T12", "type": "Virus", "text": [ "viral" ], "offsets": [ [ 143, 148 ] ], "normalized": [] }, { "id": "PMID-1916817_T13", "type": "Enhancer", "text": [ "enhancer elements" ], "offsets": [ [ 149, 166 ] ], "normalized": [] }, { "id": "PMID-1916817_T14", "type": "TranscriptionFactor", "text": [ "AP-2" ], "offsets": [ [ 194, 198 ] ], "normalized": [] }, { "id": "PMID-1916817_T15", "type": "TranscriptionFactor", "text": [ "transcription factor" ], "offsets": [ [ 212, 232 ] ], "normalized": [] }, { "id": "PMID-1916817_T17", "type": "Virus", "text": [ "SV40" ], "offsets": [ [ 272, 276 ] ], "normalized": [] }, { "id": "PMID-1916817_T18", "type": "Gene", "text": [ "metallothionein" ], "offsets": [ [ 281, 296 ] ], "normalized": [] }, { "id": "PMID-1916817_T19", "type": "Enhancer", "text": [ "enhancers" ], "offsets": [ [ 297, 306 ] ], "normalized": [] }, { "id": "PMID-1916817_T20", "type": "TranscriptionFactor", "text": [ "AP-2" ], "offsets": [ [ 344, 348 ] ], "normalized": [] }, { "id": "PMID-1916817_T22", "type": "Virus", "text": [ "SV40" ], "offsets": [ [ 362, 366 ] ], "normalized": [] }, { "id": "PMID-1916817_T23", "type": "Gene", "text": [ "T-antigen" ], "offsets": [ [ 367, 376 ] ], "normalized": [] }, { "id": "PMID-1916817_T24", "type": "TranscriptionFactorActivity", "text": [ "AP-2 activity" ], "offsets": [ [ 378, 391 ] ], "normalized": [] }, { "id": "PMID-1916817_T28", "type": "TranscriptionFactor", "text": [ "AP-2" ], "offsets": [ [ 526, 530 ] ], "normalized": [] }, { "id": "PMID-1916817_T31", "type": "Chromosome", "text": [ "chromosomal" ], "offsets": [ [ 616, 627 ] ], "normalized": [] }, { "id": "PMID-1916817_T32", "type": "Gene", "text": [ "genes" ], "offsets": [ [ 653, 658 ] ], "normalized": [] }, { "id": "PMID-1916817_T33", "type": "TranscriptionFactor", "text": [ "transcription factors" ], "offsets": [ [ 668, 689 ] ], "normalized": [] }, { "id": "PMID-1916817_T34", "type": "Gene", "text": [ "gene" ], "offsets": [ [ 720, 724 ] ], "normalized": [] }, { "id": "PMID-1916817_T35", "type": "TranscriptionFactor", "text": [ "AP-2" ], "offsets": [ [ 734, 738 ] ], "normalized": [] }, { "id": "PMID-1916817_T36", "type": "Eukaryote", "text": [ "human" ], "offsets": [ [ 742, 747 ] ], "normalized": [] }, { "id": "PMID-1916817_T37", "type": "Chromosome", "text": [ "chromosome 6p22.3-24" ], "offsets": [ [ 748, 768 ] ], "normalized": [] }, { "id": "PMID-1916817_T38", "type": "Cell", "text": [ "somatic cell" ], "offsets": [ [ 784, 796 ] ], "normalized": [] }, { "id": "PMID-1916817_T39", "type": "Chromosome", "text": [ "chromosomes" ], "offsets": [ [ 834, 845 ] ], "normalized": [] } ]

[ { "id": "PMID-1916817_E3", "type": "BindingOfProteinToDNA", "trigger": { "text": [ "bind" ], "offsets": [ [ 122, 126 ] ] }, "arguments": [ { "role": "hasAgent", "ref_id": "PMID-1916817_T9" }, { "role": "hasPatient", "ref_id": "PMID-1916817_T13" } ] }, { "id": "PMID-1916817_E4", "type": "BindingOfTFToTFBindingSiteOfDNA", "trigger": { "text": [ "interaction" ], "offsets": [ [ 251, 262 ] ] }, "arguments": [ { "role": "hasAgent", "ref_id": "PMID-1916817_T15" }, { "role": "hasPatient", "ref_id": "PMID-1916817_T19" } ] }, { "id": "PMID-1916817_E5", "type": "BindingOfTFToTFBindingSiteOfDNA", "trigger": { "text": [ "binds" ], "offsets": [ [ 349, 354 ] ] }, "arguments": [ { "role": "hasAgent", "ref_id": "PMID-1916817_T20" }, { "role": "hasPatient", "ref_id": "PMID-1916817_T23" } ] }, { "id": "PMID-1916817_E6", "type": "RegulatoryProcess", "trigger": { "text": [ "mediated" ], "offsets": [ [ 395, 403 ] ] }, "arguments": [ { "role": "hasPatient", "ref_id": "PMID-1916817_T24" }, { "role": "hasAgent", "ref_id": "PMID-1916817_E7" } ] }, { "id": "PMID-1916817_E7", "type": "CellDifferentiation", "trigger": { "text": [ "cellular differentiation" ], "offsets": [ [ 425, 449 ] ] }, "arguments": [] }, { "id": "PMID-1916817_E8", "type": "SignalingPathway", "trigger": { "text": [ "signal transduction pathways" ], "offsets": [ [ 465, 493 ] ] }, "arguments": [] }, { "id": "PMID-1916817_E9", "type": "RegulatoryProcess", "trigger": { "text": [ "regulation" ], "offsets": [ [ 538, 548 ] ] }, "arguments": [ { "role": "hasAgent", "ref_id": "PMID-1916817_T28" }, { "role": "hasPatient", "ref_id": "PMID-1916817_E10" } ] }, { "id": "PMID-1916817_E10", "type": "CellularProcess", "trigger": { "text": [ "cellular processes" ], "offsets": [ [ 560, 578 ] ] }, "arguments": [] }, { "id": "PMID-1916817_E1", "type": "RegulatoryProcess", "trigger": { "text": [ "mediated" ], "offsets": [ [ 395, 403 ] ] }, "arguments": [ { "role": "hasPatient", "ref_id": "PMID-1916817_T24" }, { "role": "hasAgent", "ref_id": "PMID-1916817_E8" } ] } ]

[]

[ { "id": "PMID-1916817_R2", "type": "encodes", "arg1_id": "PMID-1916817_T2", "arg2_id": "PMID-1916817_T5", "normalized": [] }, { "id": "PMID-1916817_R3", "type": "fromSpecies", "arg1_id": "PMID-1916817_T7", "arg2_id": "PMID-1916817_T6", "normalized": [] }, { "id": "PMID-1916817_R4", "type": "locatedIn", "arg1_id": "PMID-1916817_T9", "arg2_id": "PMID-1916817_T8", "normalized": [] }, { "id": "PMID-1916817_R5", "type": "locatedIn", "arg1_id": "PMID-1916817_T13", "arg2_id": "PMID-1916817_T11", "normalized": [] }, { "id": "PMID-1916817_R6", "type": "locatedIn", "arg1_id": "PMID-1916817_T13", "arg2_id": "PMID-1916817_T12", "normalized": [] }, { "id": "PMID-1916817_R7", "type": "fromSpecies", "arg1_id": "PMID-1916817_T18", "arg2_id": "PMID-1916817_T17", "normalized": [] }, { "id": "PMID-1916817_R8", "type": "hasPart", "arg1_id": "PMID-1916817_T18", "arg2_id": "PMID-1916817_T19", "normalized": [] }, { "id": "PMID-1916817_R9", "type": "fromSpecies", "arg1_id": "PMID-1916817_T23", "arg2_id": "PMID-1916817_T22", "normalized": [] }, { "id": "PMID-1916817_R10", "type": "encodes", "arg1_id": "PMID-1916817_T32", "arg2_id": "PMID-1916817_T33", "normalized": [] }, { "id": "PMID-1916817_R11", "type": "locatedIn", "arg1_id": "PMID-1916817_T32", "arg2_id": "PMID-1916817_T31", "normalized": [] }, { "id": "PMID-1916817_R12", "type": "encodes", "arg1_id": "PMID-1916817_T34", "arg2_id": "PMID-1916817_T35", "normalized": [] }, { "id": "PMID-1916817_R13", "type": "locatedIn", "arg1_id": "PMID-1916817_T34", "arg2_id": "PMID-1916817_T37", "normalized": [] }, { "id": "PMID-1916817_R14", "type": "fromSpecies", "arg1_id": "PMID-1916817_T37", "arg2_id": "PMID-1916817_T36", "normalized": [] }, { "id": "PMID-1916817_R1", "type": "locatedIn", "arg1_id": "PMID-1916817_T2", "arg2_id": "PMID-1916817_T7", "normalized": [] } ]

[ { "id": "PMID-1946405__text", "type": "abstract", "text": [ "Isolation of a candidate repressor/activator, NF-E1 (YY-1, delta), that binds to the immunoglobulin kappa 3' enhancer and the immunoglobulin heavy-chain mu E1 site. We have determined that the developmental control of immunoglobulin kappa 3' enhancer (kappa E3') activity is the result of the combined influence of positive- and negative-acting elements. We show that a central core in the kappa E3' enhancer is active at the pre-B-cell stage but is repressed by flanking negative-acting elements. The negative-acting sequences repress enhancer activity in a position- and orientation-independent manner at the pre-B-cell stage. We have isolated a human cDNA clone encoding a zinc finger protein (NF-E1) that binds to the negative-acting segment of the kappa E3' enhancer. This protein also binds to the immunoglobulin heavy-chain enhancer mu E1 site. NF-E1 is encoded by the same gene as the YY-1 protein, which binds to the adeno-associated virus P5 promoter. NF-E1 is also the human homologue of the mouse delta protein, which binds to ribosomal protein gene promoters. The predicted amino acid sequence of this protein contains features characteristic of transcriptional activators as well as transcriptional repressors. Cotransfection studies with this cDNA indicate that it can repress basal promoter activity. The apparent dual function of this protein is discussed.\n" ], "offsets": [ [ 0, 1374 ] ] } ]

[ { "id": "PMID-1946405_T1", "type": "TranscriptionRegulator", "text": [ "repressor/activator" ], "offsets": [ [ 25, 44 ] ], "normalized": [] }, { "id": "PMID-1946405_T2", "type": "TranscriptionRegulator", "text": [ "NF-E1" ], "offsets": [ [ 46, 51 ] ], "normalized": [] }, { "id": "PMID-1946405_T3", "type": "TranscriptionRegulator", "text": [ "YY-1, delta" ], "offsets": [ [ 53, 64 ] ], "normalized": [] }, { "id": "PMID-1946405_T9", "type": "Enhancer", "text": [ "mu E1 site" ], "offsets": [ [ 153, 163 ] ], "normalized": [] }, { "id": "PMID-1946405_T13", "type": "Enhancer", "text": [ "kappa E3'" ], "offsets": [ [ 252, 261 ] ], "normalized": [] }, { "id": "PMID-1946405_T17", "type": "Enhancer", "text": [ "kappa E3' enhancer" ], "offsets": [ [ 390, 408 ] ], "normalized": [] }, { "id": "PMID-1946405_T19", "type": "Cell", "text": [ "pre-B-cell" ], "offsets": [ [ 426, 436 ] ], "normalized": [] }, { "id": "PMID-1946405_T26", "type": "Enhancer", "text": [ "enhancer activity" ], "offsets": [ [ 536, 553 ] ], "normalized": [] }, { "id": "PMID-1946405_T27", "type": "Cell", "text": [ "pre-B-cell" ], "offsets": [ [ 611, 621 ] ], "normalized": [] }, { "id": "PMID-1946405_T28", "type": "Eukaryote", "text": [ "human" ], "offsets": [ [ 648, 653 ] ], "normalized": [] }, { "id": "PMID-1946405_T29", "type": "DNA", "text": [ "cDNA clone" ], "offsets": [ [ 654, 664 ] ], "normalized": [] }, { "id": "PMID-1946405_T31", "type": "TranscriptionRegulator", "text": [ "zinc finger protein" ], "offsets": [ [ 676, 695 ] ], "normalized": [] }, { "id": "PMID-1946405_T32", "type": "TranscriptionRegulator", "text": [ "NF-E1" ], "offsets": [ [ 697, 702 ] ], "normalized": [] }, { "id": "PMID-1946405_T36", "type": "Enhancer", "text": [ "kappa E3' enhancer" ], "offsets": [ [ 753, 771 ] ], "normalized": [] }, { "id": "PMID-1946405_T37", "type": "TranscriptionRegulator", "text": [ "protein" ], "offsets": [ [ 778, 785 ] ], "normalized": [] }, { "id": "PMID-1946405_T41", "type": "Enhancer", "text": [ "enhancer" ], "offsets": [ [ 831, 839 ] ], "normalized": [] }, { "id": "PMID-1946405_T42", "type": "DNARegion", "text": [ "mu E1 site" ], "offsets": [ [ 840, 850 ] ], "normalized": [] }, { "id": "PMID-1946405_T43", "type": "TranscriptionRegulator", "text": [ "NF-E1" ], "offsets": [ [ 852, 857 ] ], "normalized": [] }, { "id": "PMID-1946405_T44", "type": "Gene", "text": [ "gene" ], "offsets": [ [ 881, 885 ] ], "normalized": [] }, { "id": "PMID-1946405_T45", "type": "TranscriptionRegulator", "text": [ "YY-1 protein" ], "offsets": [ [ 893, 905 ] ], "normalized": [] }, { "id": "PMID-1946405_T49", "type": "TranscriptionRegulator", "text": [ "NF-E1" ], "offsets": [ [ 962, 967 ] ], "normalized": [] }, { "id": "PMID-1946405_T50", "type": "Eukaryote", "text": [ "human" ], "offsets": [ [ 980, 985 ] ], "normalized": [] }, { "id": "PMID-1946405_T51", "type": "Eukaryote", "text": [ "mouse" ], "offsets": [ [ 1003, 1008 ] ], "normalized": [] }, { "id": "PMID-1946405_T52", "type": "Protein", "text": [ "delta protein" ], "offsets": [ [ 1009, 1022 ] ], "normalized": [] }, { "id": "PMID-1946405_T54", "type": "Protein", "text": [ "ribosomal protein" ], "offsets": [ [ 1039, 1056 ] ], "normalized": [] }, { "id": "PMID-1946405_T55", "type": "Gene", "text": [ "gene" ], "offsets": [ [ 1057, 1061 ] ], "normalized": [] }, { "id": "PMID-1946405_T56", "type": "Promoter", "text": [ "promoters" ], "offsets": [ [ 1062, 1071 ] ], "normalized": [] }, { "id": "PMID-1946405_T57", "type": "AminoAcid", "text": [ "amino acid" ], "offsets": [ [ 1087, 1097 ] ], "normalized": [] }, { "id": "PMID-1946405_T58", "type": "Sequence", "text": [ "sequence" ], "offsets": [ [ 1098, 1106 ] ], "normalized": [] }, { "id": "PMID-1946405_T59", "type": "TranscriptionRegulator", "text": [ "this protein" ], "offsets": [ [ 1110, 1122 ] ], "normalized": [] }, { "id": "PMID-1946405_T60", "type": "TranscriptionActivator", "text": [ "transcriptional activators" ], "offsets": [ [ 1159, 1185 ] ], "normalized": [] }, { "id": "PMID-1946405_T61", "type": "TranscriptionRepressor", "text": [ "transcriptional repressors" ], "offsets": [ [ 1197, 1223 ] ], "normalized": [] }, { "id": "PMID-1946405_T62", "type": "DNA", "text": [ "cDNA" ], "offsets": [ [ 1258, 1262 ] ], "normalized": [] }, { "id": "PMID-1946405_T64", "type": "Promoter", "text": [ "promoter activity" ], "offsets": [ [ 1298, 1315 ] ], "normalized": [] }, { "id": "PMID-1946405_T65", "type": "Function", "text": [ "function" ], "offsets": [ [ 1335, 1343 ] ], "normalized": [] }, { "id": "PMID-1946405_T66", "type": "TranscriptionRegulator", "text": [ "this protein" ], "offsets": [ [ 1347, 1359 ] ], "normalized": [] }, { "id": "PMID-1946405_T5", "type": "Gene", "text": [ "immunoglobulin kappa" ], "offsets": [ [ 85, 105 ] ], "normalized": [] }, { "id": "PMID-1946405_T6", "type": "Enhancer", "text": [ "3' enhancer" ], "offsets": [ [ 106, 117 ] ], "normalized": [] }, { "id": "PMID-1946405_T7", "type": "Gene", "text": [ "immunoglobulin heavy-chain" ], "offsets": [ [ 126, 152 ] ], "normalized": [] }, { "id": "PMID-1946405_T8", "type": "RegulatoryDNARegion", "text": [ "positive- and negative-acting elements" ], "offsets": [ [ 315, 353 ] ], "normalized": [] }, { "id": "PMID-1946405_T11", "type": "Gene", "text": [ "immunoglobulin kappa" ], "offsets": [ [ 218, 238 ] ], "normalized": [] }, { "id": "PMID-1946405_T12", "type": "Enhancer", "text": [ "3' enhancer" ], "offsets": [ [ 239, 250 ] ], "normalized": [] }, { "id": "PMID-1946405_T14", "type": "RegulatoryDNARegion", "text": [ "negative-acting elements" ], "offsets": [ [ 472, 496 ] ], "normalized": [] }, { "id": "PMID-1946405_T15", "type": "RegulatoryDNARegion", "text": [ "negative-acting sequences" ], "offsets": [ [ 502, 527 ] ], "normalized": [] }, { "id": "PMID-1946405_T16", "type": "RegulatoryDNARegion", "text": [ "negative-acting segment" ], "offsets": [ [ 722, 745 ] ], "normalized": [] }, { "id": "PMID-1946405_T21", "type": "Gene", "text": [ "immunoglobulin heavy-chain" ], "offsets": [ [ 804, 830 ] ], "normalized": [] }, { "id": "PMID-1946405_T22", "type": "Virus", "text": [ "adeno-associated virus" ], "offsets": [ [ 926, 948 ] ], "normalized": [] }, { "id": "PMID-1946405_T23", "type": "Promoter", "text": [ "P5 promoter" ], "offsets": [ [ 949, 960 ] ], "normalized": [] } ]

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[]

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[ { "id": "PMID-2105528__text", "type": "abstract", "text": [ "Two distinct transcription factors that bind the immunoglobulin enhancer microE5/kappa 2 motif. Activity of the immunoglobulin heavy and kappa light chain gene enhancers depends on a complex interplay of ubiquitous and developmentally regulated proteins. Two complementary DNAs were isolated that encode proteins, denoted ITF-1 and ITF-2, that are expressed in a variety of cell types and bind the microE5/kappa 2 motif found in both heavy and kappa light chain enhancers. The complementary DNAs are the products of distinct genes, yet both ITF-1 and ITF-2 are structurally and functionally similar. The two proteins interact with one another through their putative helix-loop-helix motifs and each possesses a distinct domain that dictates transcription activation.\n" ], "offsets": [ [ 0, 767 ] ] } ]

[ { "id": "PMID-2105528_T1", "type": "TranscriptionFactor", "text": [ "transcription factors" ], "offsets": [ [ 13, 34 ] ], "normalized": [] }, { "id": "PMID-2105528_T3", "type": "Gene", "text": [ "immunoglobulin" ], "offsets": [ [ 49, 63 ] ], "normalized": [] }, { "id": "PMID-2105528_T4", "type": "Enhancer", "text": [ "enhancer" ], "offsets": [ [ 64, 72 ] ], "normalized": [] }, { "id": "PMID-2105528_T5", "type": "DNARegion", "text": [ "microE5/kappa 2 motif" ], "offsets": [ [ 73, 94 ] ], "normalized": [] }, { "id": "PMID-2105528_T6", "type": "Protein", "text": [ "immunoglobulin" ], "offsets": [ [ 112, 126 ] ], "normalized": [] }, { "id": "PMID-2105528_T7", "type": "Peptide", "text": [ "heavy" ], "offsets": [ [ 127, 132 ] ], "normalized": [] }, { "id": "PMID-2105528_T8", "type": "Peptide", "text": [ "kappa light chain" ], "offsets": [ [ 137, 154 ] ], "normalized": [] }, { "id": "PMID-2105528_T9", "type": "Gene", "text": [ "gene" ], "offsets": [ [ 155, 159 ] ], "normalized": [] }, { "id": "PMID-2105528_T10", "type": "Enhancer", "text": [ "enhancers" ], "offsets": [ [ 160, 169 ] ], "normalized": [] }, { "id": "PMID-2105528_T12", "type": "Protein", "text": [ "proteins" ], "offsets": [ [ 245, 253 ] ], "normalized": [] }, { "id": "PMID-2105528_T13", "type": "DNA", "text": [ "complementary DNAs" ], "offsets": [ [ 259, 277 ] ], "normalized": [] }, { "id": "PMID-2105528_T14", "type": "Protein", "text": [ "proteins" ], "offsets": [ [ 304, 312 ] ], "normalized": [] }, { "id": "PMID-2105528_T15", "type": "TranscriptionFactor", "text": [ "ITF-1" ], "offsets": [ [ 322, 327 ] ], "normalized": [] }, { "id": "PMID-2105528_T16", "type": "TranscriptionFactor", "text": [ "ITF-2" ], "offsets": [ [ 332, 337 ] ], "normalized": [] }, { "id": "PMID-2105528_T18", "type": "Cell", "text": [ "cell" ], "offsets": [ [ 374, 378 ] ], "normalized": [] }, { "id": "PMID-2105528_T20", "type": "DNARegion", "text": [ "microE5/kappa 2 motif" ], "offsets": [ [ 398, 419 ] ], "normalized": [] }, { "id": "PMID-2105528_T21", "type": "Peptide", "text": [ "heavy" ], "offsets": [ [ 434, 439 ] ], "normalized": [] }, { "id": "PMID-2105528_T22", "type": "Peptide", "text": [ "kappa light chain" ], "offsets": [ [ 444, 461 ] ], "normalized": [] }, { "id": "PMID-2105528_T23", "type": "Enhancer", "text": [ "enhancers" ], "offsets": [ [ 462, 471 ] ], "normalized": [] }, { "id": "PMID-2105528_T24", "type": "DNA", "text": [ "complementary DNAs" ], "offsets": [ [ 477, 495 ] ], "normalized": [] }, { "id": "PMID-2105528_T25", "type": "Gene", "text": [ "genes" ], "offsets": [ [ 525, 530 ] ], "normalized": [] }, { "id": "PMID-2105528_T26", "type": "TranscriptionFactor", "text": [ "ITF-1" ], "offsets": [ [ 541, 546 ] ], "normalized": [] }, { "id": "PMID-2105528_T27", "type": "TranscriptionFactor", "text": [ "ITF-2" ], "offsets": [ [ 551, 556 ] ], "normalized": [] }, { "id": "PMID-2105528_T28", "type": "Protein", "text": [ "proteins" ], "offsets": [ [ 608, 616 ] ], "normalized": [] }, { "id": "PMID-2105528_T30", "type": "bHLH", "text": [ "helix-loop-helix motifs" ], "offsets": [ [ 666, 689 ] ], "normalized": [] }, { "id": "PMID-2105528_T31", "type": "ProteinDomain", "text": [ "domain" ], "offsets": [ [ 720, 726 ] ], "normalized": [] } ]

[ { "id": "PMID-2105528_E1", "type": "BindingOfTFToTFBindingSiteOfDNA", "trigger": { "text": [ "bind" ], "offsets": [ [ 40, 44 ] ] }, "arguments": [ { "role": "hasAgent", "ref_id": "PMID-2105528_T1" }, { "role": "hasPatient", "ref_id": "PMID-2105528_T5" } ] }, { "id": "PMID-2105528_E2", "type": "RegulatoryProcess", "trigger": { "text": [ "regulated" ], "offsets": [ [ 235, 244 ] ] }, "arguments": [ { "role": "hasPatient", "ref_id": "PMID-2105528_T12" } ] }, { "id": "PMID-2105528_E3", "type": "GeneExpression", "trigger": { "text": [ "expressed" ], "offsets": [ [ 348, 357 ] ] }, "arguments": [] }, { "id": "PMID-2105528_E4", "type": "BindingOfTFToTFBindingSiteOfDNA", "trigger": { "text": [ "bind" ], "offsets": [ [ 389, 393 ] ] }, "arguments": [ { "role": "hasPatient", "ref_id": "PMID-2105528_T20" } ] }, { "id": "PMID-2105528_E5", "type": "BindingToProtein", "trigger": { "text": [ "interact" ], "offsets": [ [ 617, 625 ] ] }, "arguments": [ { "role": "hasPatient", "ref_id": "PMID-2105528_T28" } ] }, { "id": "PMID-2105528_E6", "type": "RegulatoryProcess", "trigger": { "text": [ "dictates" ], "offsets": [ [ 732, 740 ] ] }, "arguments": [ { "role": "hasAgent", "ref_id": "PMID-2105528_T31" }, { "role": "hasPatient", "ref_id": "PMID-2105528_E8" } ] }, { "id": "PMID-2105528_E7", "type": "Transcription", "trigger": { "text": [ "transcription" ], "offsets": [ [ 741, 754 ] ] }, "arguments": [] }, { "id": "PMID-2105528_E8", "type": "PositiveRegulation", "trigger": { "text": [ "activation" ], "offsets": [ [ 755, 765 ] ] }, "arguments": [ { "role": "hasPatient", "ref_id": "PMID-2105528_E7" } ] } ]

[]

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