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[ { "id": "PMID-7641319__text", "type": "abstract", "text": [ "Characterization of 5' end of human thromboxane receptor gene. Organizational analysis and mapping of protein kinase C--responsive elements regulating expression in platelets. \nPlatelet thromboxane receptors are acutely and reversibly upregulated after acute myocardial infarction. To determine if platelet thromboxane receptors are under transcriptional control, we isolated and characterized human genomic DNA clones containing the 5' flanking region of the thromboxane receptor gene. The exon-intron structure of the 5' portion of the thromboxane receptor gene was determined initially by comparing the nucleotide sequence of the 5' flanking genomic clone with that of a novel human uterine thromboxane receptor cDNA that extended the mRNA 141 bp further upstream than the previously identified human placental cDNA. A major transcription initiation site was located in three human tissues approximately 560 bp upstream from the translation initiation codon and 380 bp upstream from any previously identified transcription initiation site. The thromboxane receptor gene has neither a TATA nor a CAAT consensus site. Promoter function of the 5' flanking region of the thromboxane receptor gene was evaluated by transfection of thromboxane receptor gene promoter/chloramphenicol acetyltransferase (CAT) chimera plasmids into platelet-like K562 cells. Thromboxane receptor promoter activity, as assessed by CAT expression, was relatively weak but was significantly enhanced by phorbol ester treatment. Functional analysis of 5' deletion constructs in transfected K562 cells and gel mobility shift localized the major phorbol ester-responsive motifs in the thromboxane receptor gene promoter to a cluster of activator protein-2 (AP-2) binding consensus sites located approximately 1.8 kb 5' from the transcription initiation site. These studies are the first to determine the structure and organization of the 5' end of the thromboxane receptor gene and demonstrate that thromboxane receptor gene expression can be regulated by activation of protein kinase C via induction of an AP-2-like nuclear factor binding to upstream promoter elements. These findings strongly suggest that the mechanism for previously described upregulation of platelet thromboxane receptors after acute myocardial infarction is increased thromboxane receptor gene transcription in platelet-progenitor cells. " ], "offsets": [ [ 0, 2382 ] ] } ]

[ { "id": "PMID-7641319_T1", "type": "Protein", "text": [ "thromboxane receptor" ], "offsets": [ [ 36, 56 ] ], "normalized": [] }, { "id": "PMID-7641319_T2", "type": "Protein", "text": [ "thromboxane receptors" ], "offsets": [ [ 186, 207 ] ], "normalized": [] }, { "id": "PMID-7641319_T3", "type": "Protein", "text": [ "thromboxane receptors" ], "offsets": [ [ 307, 328 ] ], "normalized": [] }, { "id": "PMID-7641319_T4", "type": "Protein", "text": [ "thromboxane receptor" ], "offsets": [ [ 460, 480 ] ], "normalized": [] }, { "id": "PMID-7641319_T5", "type": "Protein", "text": [ "thromboxane receptor" ], "offsets": [ [ 538, 558 ] ], "normalized": [] }, { "id": "PMID-7641319_T6", "type": "Protein", "text": [ "thromboxane receptor" ], "offsets": [ [ 694, 714 ] ], "normalized": [] }, { "id": "PMID-7641319_T7", "type": "Protein", "text": [ "thromboxane receptor" ], "offsets": [ [ 1047, 1067 ] ], "normalized": [] }, { "id": "PMID-7641319_T8", "type": "Protein", "text": [ "thromboxane receptor" ], "offsets": [ [ 1170, 1190 ] ], "normalized": [] }, { "id": "PMID-7641319_T9", "type": "Protein", "text": [ "thromboxane receptor" ], "offsets": [ [ 1229, 1249 ] ], "normalized": [] }, { "id": "PMID-7641319_T10", "type": "Protein", "text": [ "chloramphenicol acetyltransferase" ], "offsets": [ [ 1264, 1297 ] ], "normalized": [] }, { "id": "PMID-7641319_T11", "type": "Protein", "text": [ "CAT" ], "offsets": [ [ 1299, 1302 ] ], "normalized": [] }, { "id": "PMID-7641319_T12", "type": "Protein", "text": [ "Thromboxane receptor" ], "offsets": [ [ 1352, 1372 ] ], "normalized": [] }, { "id": "PMID-7641319_T13", "type": "Protein", "text": [ "CAT" ], "offsets": [ [ 1407, 1410 ] ], "normalized": [] }, { "id": "PMID-7641319_T14", "type": "Protein", "text": [ "thromboxane receptor" ], "offsets": [ [ 1656, 1676 ] ], "normalized": [] }, { "id": "PMID-7641319_T15", "type": "Protein", "text": [ "thromboxane receptor" ], "offsets": [ [ 1923, 1943 ] ], "normalized": [] }, { "id": "PMID-7641319_T16", "type": "Protein", "text": [ "thromboxane receptor" ], "offsets": [ [ 1970, 1990 ] ], "normalized": [] }, { "id": "PMID-7641319_T17", "type": "Protein", "text": [ "thromboxane receptors" ], "offsets": [ [ 2243, 2264 ] ], "normalized": [] }, { "id": "PMID-7641319_T18", "type": "Protein", "text": [ "thromboxane receptor" ], "offsets": [ [ 2312, 2332 ] ], "normalized": [] }, { "id": "PMID-7641319_T25", "type": "Entity", "text": [ "5' flanking region" ], "offsets": [ [ 1144, 1162 ] ], "normalized": [] }, { "id": "PMID-7641319_T26", "type": "Entity", "text": [ "promoter" ], "offsets": [ [ 1373, 1381 ] ], "normalized": [] } ]

[ { "id": "PMID-7641319_E1", "type": "Regulation", "trigger": { "text": [ "regulating" ], "offsets": [ [ 140, 150 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "PMID-7641319_E2" } ] }, { "id": "PMID-7641319_E2", "type": "Gene_expression", "trigger": { "text": [ "expression" ], "offsets": [ [ 151, 161 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "PMID-7641319_T1" } ] }, { "id": "PMID-7641319_E3", "type": "Positive_regulation", "trigger": { "text": [ "upregulated" ], "offsets": [ [ 235, 246 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "PMID-7641319_T2" } ] }, { "id": "PMID-7641319_E4", "type": "Regulation", "trigger": { "text": [ "under transcriptional control" ], "offsets": [ [ 333, 362 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "PMID-7641319_T3" } ] }, { "id": "PMID-7641319_E5", "type": "Transcription", "trigger": { "text": [ "mRNA" ], "offsets": [ [ 738, 742 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "PMID-7641319_T6" } ] }, { "id": "PMID-7641319_E6", "type": "Positive_regulation", "trigger": { "text": [ "Promoter function" ], "offsets": [ [ 1119, 1136 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "PMID-7641319_T8" }, { "role": "Site", "ref_id": "PMID-7641319_T25" } ] }, { "id": "PMID-7641319_E7", "type": "Gene_expression", "trigger": { "text": [ "expression" ], "offsets": [ [ 1411, 1421 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "PMID-7641319_T13" } ] }, { "id": "PMID-7641319_E8", "type": "Positive_regulation", "trigger": { "text": [ "enhanced" ], "offsets": [ [ 1465, 1473 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "PMID-7641319_T12" }, { "role": "Site", "ref_id": "PMID-7641319_T26" } ] }, { "id": "PMID-7641319_E9", "type": "Gene_expression", "trigger": { "text": [ "expression" ], "offsets": [ [ 1996, 2006 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "PMID-7641319_T16" } ] }, { "id": "PMID-7641319_E10", "type": "Regulation", "trigger": { "text": [ "regulated" ], "offsets": [ [ 2014, 2023 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "PMID-7641319_E9" } ] }, { "id": "PMID-7641319_E11", "type": "Positive_regulation", "trigger": { "text": [ "mechanism" ], "offsets": [ [ 2183, 2192 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "PMID-7641319_E12" }, { "role": "Cause", "ref_id": "PMID-7641319_E13" } ] }, { "id": "PMID-7641319_E12", "type": "Positive_regulation", "trigger": { "text": [ "upregulation" ], "offsets": [ [ 2218, 2230 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "PMID-7641319_T17" } ] }, { "id": "PMID-7641319_E13", "type": "Positive_regulation", "trigger": { "text": [ "increased" ], "offsets": [ [ 2302, 2311 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "PMID-7641319_E14" } ] }, { "id": "PMID-7641319_E14", "type": "Transcription", "trigger": { "text": [ "transcription" ], "offsets": [ [ 2338, 2351 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "PMID-7641319_T18" } ] } ]

[ { "id": "PMID-7641319_1", "entity_ids": [ "PMID-7641319_T10", "PMID-7641319_T11" ] } ]

[]

[ { "id": "PMID-7641692__text", "type": "abstract", "text": [ "IL-2 gene expression and NF-kappa B activation through CD28 requires reactive oxygen production by 5-lipoxygenase. \nActivation of the CD28 surface receptor provides a major costimulatory signal for T cell activation resulting in enhanced production of interleukin-2 (IL-2) and cell proliferation. In primary T lymphocytes we show that CD28 ligation leads to the rapid intracellular formation of reactive oxygen intermediates (ROIs) which are required for CD28-mediated activation of the NF-kappa B/CD28-responsive complex and IL-2 expression. Delineation of the CD28 signaling cascade was found to involve protein tyrosine kinase activity, followed by the activation of phospholipase A2 and 5-lipoxygenase. Our data suggest that lipoxygenase metabolites activate ROI formation which then induce IL-2 expression via NF-kappa B activation. These findings should be useful for therapeutic strategies and the development of immunosuppressants targeting the CD28 costimulatory pathway. " ], "offsets": [ [ 0, 981 ] ] } ]

[ { "id": "PMID-7641692_T1", "type": "Protein", "text": [ "IL-2" ], "offsets": [ [ 0, 4 ] ], "normalized": [] }, { "id": "PMID-7641692_T2", "type": "Protein", "text": [ "CD28" ], "offsets": [ [ 55, 59 ] ], "normalized": [] }, { "id": "PMID-7641692_T3", "type": "Protein", "text": [ "CD28" ], "offsets": [ [ 134, 138 ] ], "normalized": [] }, { "id": "PMID-7641692_T4", "type": "Protein", "text": [ "interleukin-2" ], "offsets": [ [ 252, 265 ] ], "normalized": [] }, { "id": "PMID-7641692_T5", "type": "Protein", "text": [ "IL-2" ], "offsets": [ [ 267, 271 ] ], "normalized": [] }, { "id": "PMID-7641692_T6", "type": "Protein", "text": [ "CD28" ], "offsets": [ [ 335, 339 ] ], "normalized": [] }, { "id": "PMID-7641692_T7", "type": "Protein", "text": [ "CD28" ], "offsets": [ [ 455, 459 ] ], "normalized": [] }, { "id": "PMID-7641692_T8", "type": "Protein", "text": [ "CD28" ], "offsets": [ [ 498, 502 ] ], "normalized": [] }, { "id": "PMID-7641692_T9", "type": "Protein", "text": [ "IL-2" ], "offsets": [ [ 526, 530 ] ], "normalized": [] }, { "id": "PMID-7641692_T10", "type": "Protein", "text": [ "CD28" ], "offsets": [ [ 562, 566 ] ], "normalized": [] }, { "id": "PMID-7641692_T11", "type": "Protein", "text": [ "IL-2" ], "offsets": [ [ 795, 799 ] ], "normalized": [] }, { "id": "PMID-7641692_T12", "type": "Protein", "text": [ "CD28" ], "offsets": [ [ 953, 957 ] ], "normalized": [] } ]

[ { "id": "PMID-7641692_E1", "type": "Gene_expression", "trigger": { "text": [ "expression" ], "offsets": [ [ 10, 20 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "PMID-7641692_T1" } ] }, { "id": "PMID-7641692_E2", "type": "Positive_regulation", "trigger": { "text": [ "activation" ], "offsets": [ [ 36, 46 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "PMID-7641692_E1" }, { "role": "Cause", "ref_id": "PMID-7641692_T2" } ] }, { "id": "PMID-7641692_E3", "type": "Positive_regulation", "trigger": { "text": [ "requires" ], "offsets": [ [ 60, 68 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "PMID-7641692_E2" } ] }, { "id": "PMID-7641692_E4", "type": "Positive_regulation", "trigger": { "text": [ "enhanced" ], "offsets": [ [ 229, 237 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "PMID-7641692_E5" } ] }, { "id": "PMID-7641692_E5", "type": "Gene_expression", "trigger": { "text": [ "production" ], "offsets": [ [ 238, 248 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "PMID-7641692_T5" } ] }, { "id": "PMID-7641692_E6", "type": "Positive_regulation", "trigger": { "text": [ "required" ], "offsets": [ [ 442, 450 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "PMID-7641692_E8" } ] }, { "id": "PMID-7641692_E7", "type": "Positive_regulation", "trigger": { "text": [ "required" ], "offsets": [ [ 442, 450 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "PMID-7641692_E9" } ] }, { "id": "PMID-7641692_E8", "type": "Positive_regulation", "trigger": { "text": [ "activation" ], "offsets": [ [ 469, 479 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "PMID-7641692_T8" }, { "role": "Cause", "ref_id": "PMID-7641692_T7" } ] }, { "id": "PMID-7641692_E9", "type": "Gene_expression", "trigger": { "text": [ "expression" ], "offsets": [ [ 531, 541 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "PMID-7641692_T9" } ] }, { "id": "PMID-7641692_E10", "type": "Positive_regulation", "trigger": { "text": [ "induce" ], "offsets": [ [ 788, 794 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "PMID-7641692_E11" } ] }, { "id": "PMID-7641692_E11", "type": "Gene_expression", "trigger": { "text": [ "expression" ], "offsets": [ [ 800, 810 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "PMID-7641692_T11" } ] } ]

[ { "id": "PMID-7641692_1", "entity_ids": [ "PMID-7641692_T5", "PMID-7641692_T4" ] } ]

[]

[ { "id": "PMID-7645208__text", "type": "abstract", "text": [ "Infection and replication of Tat- human immunodeficiency viruses: genetic analyses of LTR and tat mutations in primary and long-term human lymphoid cells. \nTat is an essential regulatory protein for the replication of human immunodeficiency virus (HIV). Mutations in the tat gene have been shown to block HIV replication in human T cells. Several studies have established that Tat releases an elongation block to the transcription of HIV long terminal repeat (LTR); however, it is not known whether this mechanism alone is sufficient to explain the block to HIV replication in human T cells when Tat is absent. It is possible that Tat is also needed for other functions during HIV replication. To test these hypotheses, we studied several tat mutants, including two stop codon mutants and one deletion mutant using replication-competent HIV-1 constructs carrying wild-type or mutant LTRs with modifications in the NF-kappa B and/or Sp1 binding sites. In this study, we show that Tat- HIV-1 with wild-type LTRs can replicate in HeLa cells, and the virus produced from HeLa cells can infect primary peripheral blood lymphocytes and macrophages. It was found that the propagation of the Tat mutants containing wild-type LTRs was less efficient than that of the LTR-modified Tat mutants. Large amounts of viral RNA and particles were synthesized in infections established using the tat mutants that contain modified LTRs. However, this efficient propagation of the LTR-modified tat mutants was restricted to some lymphoid cell lines that have been transformed with other viruses. Thus, despite its essential role for releasing an elongation block, Tat is not otherwise absolutely required for synthesis of full-length HIV transcripts and assembly of virus particles. Direct sequencing of the viral genomes and reinfection kinetics showed no evidence of wild-type reversion even after prolonged infection with the Tat- virus. The implications for in vivo HIV-1 replication and potential application of this system to the study of alternative Tat function are discussed. " ], "offsets": [ [ 0, 2065 ] ] } ]

[ { "id": "PMID-7645208_T1", "type": "Protein", "text": [ "Tat" ], "offsets": [ [ 29, 32 ] ], "normalized": [] }, { "id": "PMID-7645208_T2", "type": "Protein", "text": [ "tat" ], "offsets": [ [ 94, 97 ] ], "normalized": [] }, { "id": "PMID-7645208_T3", "type": "Protein", "text": [ "Tat" ], "offsets": [ [ 156, 159 ] ], "normalized": [] }, { "id": "PMID-7645208_T4", "type": "Protein", "text": [ "tat" ], "offsets": [ [ 271, 274 ] ], "normalized": [] }, { "id": "PMID-7645208_T5", "type": "Protein", "text": [ "Tat" ], "offsets": [ [ 377, 380 ] ], "normalized": [] }, { "id": "PMID-7645208_T6", "type": "Protein", "text": [ "Tat" ], "offsets": [ [ 596, 599 ] ], "normalized": [] }, { "id": "PMID-7645208_T7", "type": "Protein", "text": [ "Tat" ], "offsets": [ [ 631, 634 ] ], "normalized": [] }, { "id": "PMID-7645208_T8", "type": "Protein", "text": [ "tat" ], "offsets": [ [ 739, 742 ] ], "normalized": [] }, { "id": "PMID-7645208_T9", "type": "Protein", "text": [ "Sp1" ], "offsets": [ [ 932, 935 ] ], "normalized": [] }, { "id": "PMID-7645208_T10", "type": "Protein", "text": [ "Tat" ], "offsets": [ [ 979, 982 ] ], "normalized": [] }, { "id": "PMID-7645208_T11", "type": "Protein", "text": [ "Tat" ], "offsets": [ [ 1184, 1187 ] ], "normalized": [] }, { "id": "PMID-7645208_T12", "type": "Protein", "text": [ "Tat" ], "offsets": [ [ 1271, 1274 ] ], "normalized": [] }, { "id": "PMID-7645208_T13", "type": "Protein", "text": [ "tat" ], "offsets": [ [ 1378, 1381 ] ], "normalized": [] }, { "id": "PMID-7645208_T14", "type": "Protein", "text": [ "tat" ], "offsets": [ [ 1474, 1477 ] ], "normalized": [] }, { "id": "PMID-7645208_T15", "type": "Protein", "text": [ "Tat" ], "offsets": [ [ 1644, 1647 ] ], "normalized": [] }, { "id": "PMID-7645208_T16", "type": "Protein", "text": [ "Tat" ], "offsets": [ [ 1909, 1912 ] ], "normalized": [] }, { "id": "PMID-7645208_T17", "type": "Protein", "text": [ "Tat" ], "offsets": [ [ 2037, 2040 ] ], "normalized": [] } ]

[ { "id": "PMID-7645208_E1", "type": "Negative_regulation", "trigger": { "text": [ "absent" ], "offsets": [ [ 603, 609 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "PMID-7645208_T6" } ] } ]

[]

[]

[ { "id": "PMID-7650486__text", "type": "abstract", "text": [ "Activation and expression of the nuclear factors of activated T cells, NFATp and NFATc, in human natural killer cells: regulation upon CD16 ligand binding. \nThe putative factors that couple the signal transduction from surface receptors to the activation of cytokine synthesis in natural killer (NK) cells have not been elucidated. We report here that the nuclear factor of activated T cells (NFATp), a cyclosporin A (CsA)-sensitive factor that regulates the transcription of several cytokines, mediates CD16-induced activation of cytokine genes in human NK cells. CD16 (Fc gamma RIIIA)-induced expression of cytokine mRNA in NK cells occurs via a CsA-sensitive and Ca(2+)-dependent mechanism. Stimulation of NK cells with CD16 ligands induces NFAT-like DNA binding activity in the nuclear extracts from these cells, as detected in electrophoretic mobility shift assays. This occurs with fast kinetics after stimulation, via a CsA-sensitive and Ca(2+)-dependent mechanism that does not require de novo protein synthesis. NK cell NFAT is present in the cytosol of nonstimulated cells, migrates to the nucleus upon stimulation, and can associate with AP-1. Two distinct molecules, NFATp and NFATc, have been reported to mediate NFAT activity. The results of supershift assays using NFATp- and NFATc- specific antibodies indicate that NK cell activation early after CD16 ligand binding involves primarily, if not exclusively, NFATp, and Western blot analysis shows that this has the same electrophoretic mobility (approximately 120 kD) as that of T lymphocytes. NK cells do not express NFATc constitutively, but NFATc mRNA accumulation is induced in these cells within 2 h of stimulation with CD16 ligands. However, supershift assays using the available mAb recognizing the T cell NFATc revealed no detectable NFATc protein in nuclear and cytoplasmic extracts from CD16- or phorbol ester-stimulated cells at any time tested, up to 4 h. These results provide the first direct evidence that both CsA-sensitive transcription factors, NFATp and NFATc, are expressed in human NK cells, and that their activation and/or expression can be regulated in primary cells by a single stimulus, that, in the case of CD16 in NK cells, results in early activation of NFATp and subsequently induced expression of NFATc mRNA. " ], "offsets": [ [ 0, 2305 ] ] } ]

[ { "id": "PMID-7650486_T1", "type": "Protein", "text": [ "NFATp" ], "offsets": [ [ 71, 76 ] ], "normalized": [] }, { "id": "PMID-7650486_T2", "type": "Protein", "text": [ "NFATc" ], "offsets": [ [ 81, 86 ] ], "normalized": [] }, { "id": "PMID-7650486_T3", "type": "Protein", "text": [ "NFATp" ], "offsets": [ [ 393, 398 ] ], "normalized": [] }, { "id": "PMID-7650486_T4", "type": "Protein", "text": [ "Fc gamma RIIIA" ], "offsets": [ [ 571, 585 ] ], "normalized": [] }, { "id": "PMID-7650486_T5", "type": "Protein", "text": [ "NFATp" ], "offsets": [ [ 1179, 1184 ] ], "normalized": [] }, { "id": "PMID-7650486_T6", "type": "Protein", "text": [ "NFATc" ], "offsets": [ [ 1189, 1194 ] ], "normalized": [] }, { "id": "PMID-7650486_T7", "type": "Protein", "text": [ "NFATp" ], "offsets": [ [ 1280, 1285 ] ], "normalized": [] }, { "id": "PMID-7650486_T8", "type": "Protein", "text": [ "NFATc" ], "offsets": [ [ 1291, 1296 ] ], "normalized": [] }, { "id": "PMID-7650486_T9", "type": "Protein", "text": [ "NFATp" ], "offsets": [ [ 1423, 1428 ] ], "normalized": [] }, { "id": "PMID-7650486_T10", "type": "Protein", "text": [ "NFATc" ], "offsets": [ [ 1583, 1588 ] ], "normalized": [] }, { "id": "PMID-7650486_T11", "type": "Protein", "text": [ "NFATc" ], "offsets": [ [ 1609, 1614 ] ], "normalized": [] }, { "id": "PMID-7650486_T12", "type": "Protein", "text": [ "NFATc" ], "offsets": [ [ 1778, 1783 ] ], "normalized": [] }, { "id": "PMID-7650486_T13", "type": "Protein", "text": [ "NFATc" ], "offsets": [ [ 1807, 1812 ] ], "normalized": [] }, { "id": "PMID-7650486_T14", "type": "Protein", "text": [ "NFATp" ], "offsets": [ [ 2028, 2033 ] ], "normalized": [] }, { "id": "PMID-7650486_T15", "type": "Protein", "text": [ "NFATc" ], "offsets": [ [ 2038, 2043 ] ], "normalized": [] }, { "id": "PMID-7650486_T16", "type": "Protein", "text": [ "NFATp" ], "offsets": [ [ 2248, 2253 ] ], "normalized": [] }, { "id": "PMID-7650486_T17", "type": "Protein", "text": [ "NFATc" ], "offsets": [ [ 2293, 2298 ] ], "normalized": [] } ]

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"Regulation", "trigger": { "text": [ "regulation" ], "offsets": [ [ 119, 129 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "PMID-7650486_E4" } ] }, { "id": "PMID-7650486_E7", "type": "Regulation", "trigger": { "text": [ "regulation" ], "offsets": [ [ 119, 129 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "PMID-7650486_E3" } ] }, { "id": "PMID-7650486_E8", "type": "Regulation", "trigger": { "text": [ "regulation" ], "offsets": [ [ 119, 129 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "PMID-7650486_E2" } ] }, { "id": "PMID-7650486_E9", "type": "Regulation", "trigger": { "text": [ "sensitive" ], "offsets": [ [ 423, 432 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "PMID-7650486_T3" } ] }, { "id": "PMID-7650486_E10", "type": "Gene_expression", "trigger": { "text": [ "express" ], "offsets": [ [ 1575, 1582 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "PMID-7650486_T10" } ] }, { "id": "PMID-7650486_E11", "type": "Positive_regulation", "trigger": { "text": [ "accumulation" ], "offsets": [ [ 1620, 1632 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "PMID-7650486_T11" } ] }, { "id": "PMID-7650486_E12", "type": "Positive_regulation", "trigger": { "text": [ "induced" ], "offsets": [ [ 1636, 1643 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "PMID-7650486_E11" } ] }, { "id": "PMID-7650486_E13", "type": "Gene_expression", "trigger": { "text": [ "detectable" ], "offsets": [ [ 1796, 1806 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "PMID-7650486_T13" } ] }, { "id": "PMID-7650486_E14", "type": "Regulation", "trigger": { "text": [ "sensitive" ], "offsets": [ [ 1995, 2004 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "PMID-7650486_T14" } ] }, { "id": "PMID-7650486_E15", "type": "Regulation", "trigger": { "text": [ "sensitive" ], "offsets": [ [ 1995, 2004 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "PMID-7650486_T15" } ] }, { "id": "PMID-7650486_E16", "type": "Gene_expression", "trigger": { "text": [ "expressed" ], "offsets": [ [ 2049, 2058 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "PMID-7650486_T14" } ] }, { "id": "PMID-7650486_E17", "type": "Gene_expression", "trigger": { "text": [ "expressed" ], "offsets": [ [ 2049, 2058 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "PMID-7650486_T15" } ] }, { "id": "PMID-7650486_E18", "type": "Positive_regulation", "trigger": { "text": [ "activation" ], "offsets": [ [ 2093, 2103 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "PMID-7650486_T15" } ] }, { "id": "PMID-7650486_E19", "type": "Positive_regulation", "trigger": { "text": [ "activation" ], "offsets": [ [ 2093, 2103 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "PMID-7650486_T14" } ] }, { "id": "PMID-7650486_E20", "type": "Gene_expression", "trigger": { "text": [ "expression" ], "offsets": [ [ 2111, 2121 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "PMID-7650486_T14" } ] }, { "id": "PMID-7650486_E21", "type": "Gene_expression", "trigger": { "text": [ "expression" ], "offsets": [ [ 2111, 2121 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "PMID-7650486_T15" } ] }, { "id": "PMID-7650486_E22", "type": "Regulation", "trigger": { "text": [ "regulated" ], "offsets": [ [ 2129, 2138 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "PMID-7650486_E18" } ] }, { "id": "PMID-7650486_E23", "type": "Regulation", "trigger": { "text": [ "regulated" ], "offsets": [ [ 2129, 2138 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "PMID-7650486_E19" } ] }, { "id": "PMID-7650486_E24", "type": "Regulation", "trigger": { "text": [ "regulated" ], "offsets": [ [ 2129, 2138 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "PMID-7650486_E21" } ] }, { "id": "PMID-7650486_E25", "type": "Regulation", "trigger": { "text": [ "regulated" ], "offsets": [ [ 2129, 2138 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "PMID-7650486_E20" } ] }, { "id": "PMID-7650486_E26", "type": "Positive_regulation", "trigger": { "text": [ "results" ], "offsets": [ [ 2217, 2224 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "PMID-7650486_E30" }, { "role": "Cause", "ref_id": "PMID-7650486_E22" } ] }, { "id": "PMID-7650486_E27", "type": "Positive_regulation", "trigger": { "text": [ "results" ], "offsets": [ [ 2217, 2224 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "PMID-7650486_E30" }, { "role": "Cause", "ref_id": "PMID-7650486_E23" } ] }, { "id": "PMID-7650486_E28", "type": "Positive_regulation", "trigger": { "text": [ "results" ], "offsets": [ [ 2217, 2224 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "PMID-7650486_E30" }, { "role": "Cause", "ref_id": "PMID-7650486_E25" } ] }, { "id": "PMID-7650486_E29", "type": "Positive_regulation", "trigger": { "text": [ "results" ], "offsets": [ [ 2217, 2224 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "PMID-7650486_E30" }, { "role": "Cause", "ref_id": "PMID-7650486_E24" } ] }, { "id": "PMID-7650486_E30", "type": "Positive_regulation", "trigger": { "text": [ "activation" ], "offsets": [ [ 2234, 2244 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "PMID-7650486_T16" } ] }, { "id": "PMID-7650486_E31", "type": "Positive_regulation", "trigger": { "text": [ "induced" ], "offsets": [ [ 2271, 2278 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "PMID-7650486_E35" }, { "role": "Cause", "ref_id": "PMID-7650486_E27" } ] }, { "id": "PMID-7650486_E32", "type": "Positive_regulation", "trigger": { "text": [ "induced" ], "offsets": [ [ 2271, 2278 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "PMID-7650486_E35" }, { "role": "Cause", "ref_id": "PMID-7650486_E29" } ] }, { "id": "PMID-7650486_E33", "type": "Positive_regulation", "trigger": { "text": [ "induced" ], "offsets": [ [ 2271, 2278 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "PMID-7650486_E35" }, { "role": "Cause", "ref_id": "PMID-7650486_E26" } ] }, { "id": "PMID-7650486_E34", "type": "Positive_regulation", "trigger": { "text": [ "induced" ], "offsets": [ [ 2271, 2278 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "PMID-7650486_E35" }, { "role": "Cause", "ref_id": "PMID-7650486_E28" } ] }, { "id": "PMID-7650486_E35", "type": "Transcription", "trigger": { "text": [ "expression" ], "offsets": [ [ 2279, 2289 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "PMID-7650486_T17" } ] } ]

[]

[]

[ { "id": "PMID-7657825__text", "type": "abstract", "text": [ "Constitutive activation of different Jak tyrosine kinases in human T cell leukemia virus type 1 (HTLV-1) tax protein or virus-transformed cells. \nHTLV-1 infection causes an adult T cell leukemia in humans. The viral encoded protein tax, is thought to play an important role in oncogenesis. Our previous data obtained from a tax transgenic mouse model revealed that tax transforms mouse fibroblasts but not thymocytes, despite comparable levels of tax expression in both tissues. Constitutive tyrosine phosphorylation of a 130-kD protein(s) was observed in the tax transformed fibroblast B line and in HTLV-1 transformed human lymphoid lines, but not in thymocytes from Thy-tax transgenic mice. Phosphotyrosine immunoprecipitation followed by Western blot analysis with a set of Jak kinase specific antibodies, identified p130 as Jak2 in the tax transformed mouse fibroblastic cell line and Jak3 in HTLV-1 transformed human T cell lines. Phosphorylation of Jak2 in tax transformed cells resulted from high expression of IL-6. Tyrosine phosphorylation of this protein could also be induced in Balb/c3T3 cells using a supernatant from the B line, which was associated with induction of cell proliferation. Both phosphorylation and proliferation were inhibited by IL-6 neutralizing antibodies. Constitutive phosphorylation of Jak kinases may facilitate tumor growth in both HTLV-1 infected human T cells and the transgenic mouse model. " ], "offsets": [ [ 0, 1432 ] ] } ]

[ { "id": "PMID-7657825_T1", "type": "Protein", "text": [ "tax" ], "offsets": [ [ 105, 108 ] ], "normalized": [] }, { "id": "PMID-7657825_T2", "type": "Protein", "text": [ "tax" ], "offsets": [ [ 232, 235 ] ], "normalized": [] }, { "id": "PMID-7657825_T3", "type": "Protein", "text": [ "tax" ], "offsets": [ [ 324, 327 ] ], "normalized": [] }, { "id": "PMID-7657825_T4", "type": "Protein", "text": [ "tax" ], "offsets": [ [ 365, 368 ] ], "normalized": [] }, { "id": "PMID-7657825_T5", "type": "Protein", "text": [ "tax" ], "offsets": [ [ 447, 450 ] ], "normalized": [] }, { "id": "PMID-7657825_T6", "type": "Protein", "text": [ "tax" ], "offsets": [ [ 560, 563 ] ], "normalized": [] }, { "id": "PMID-7657825_T7", "type": "Protein", "text": [ "Jak2" ], "offsets": [ [ 829, 833 ] ], "normalized": [] }, { "id": "PMID-7657825_T8", "type": "Protein", "text": [ "tax" ], "offsets": [ [ 841, 844 ] ], "normalized": [] }, { "id": "PMID-7657825_T9", "type": "Protein", "text": [ "Jak3" ], "offsets": [ [ 890, 894 ] ], "normalized": [] }, { "id": "PMID-7657825_T10", "type": "Protein", "text": [ "Jak2" ], "offsets": [ [ 956, 960 ] ], "normalized": [] }, { "id": "PMID-7657825_T11", "type": "Protein", "text": [ "tax" ], "offsets": [ [ 964, 967 ] ], "normalized": [] }, { "id": "PMID-7657825_T12", "type": "Protein", "text": [ "IL-6" ], "offsets": [ [ 1019, 1023 ] ], "normalized": [] }, { "id": "PMID-7657825_T13", "type": "Protein", "text": [ "IL-6" ], "offsets": [ [ 1260, 1264 ] ], "normalized": [] }, { "id": "PMID-7657825_T19", "type": "Entity", "text": [ "Tyrosine" ], "offsets": [ [ 1025, 1033 ] ], "normalized": [] } ]

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[]

[]

[ { "id": "PMID-7659529__text", "type": "abstract", "text": [ "Regulation of transcription of the human erythropoietin receptor gene by proteins binding to GATA-1 and Sp1 motifs. \nErythropoietin (Epo), the primary regulator of the production of erythroid cells, acts by binding to a cell surface receptor (EpoR) on erythroid progenitors. We used deletion analysis and transfection assays with reporter gene constructs to examine the transcription control elements in the 5' flanking region of the human EpoR gene. In erythroid cells most of the transcription activity was contained in a 150 bp promoter fragment with binding sites for transcription factors AP2, Sp1 and the erythroid-specific GATA-1. The 150 bp hEpoR promoter exhibited high and low activity in erythroid OCIM1 and K562 cells, respectively, reflecting the high and low levels of constitutive hEpoR expression. The GATA-1 and Sp1 binding sites in this promoter lacking a TATA sequence were necessary for a high level of transcription activation. Protein-DNA binding studies suggested that Sp1 and two other CCGCCC binding proteins from erythroid and non-erythroid cells could bind to the Sp1 binding motif. By increasing GATA-1 levels via co-transfection, we were able to transactivate the hEpoR promoter in K562 cells and non-erythroid cells, but not in the highly active OCIM1 cells, although GATA-1 mRNA levels were comparable in OCIM1 and K562. Interestingly, when we mutated the Sp1 site, resulting in a marked decrease in hEpoR promoter activity, we could restore transactivation by increasing GATA-1 levels in OCIM1 cells. These data suggest that while GATA-1 can transactivate the EpoR promoter, the level of hEpoR gene expression does not depend on GATA-1 alone. Rather, hEpoR transcription activity depends on coordination between Sp1 and GATA-1 with other cell-specific factors, including possibly other Sp1-like binding proteins, to provide high level, tissue-specific expression. " ], "offsets": [ [ 0, 1896 ] ] } ]

[ { "id": "PMID-7659529_T1", "type": "Protein", "text": [ "erythropoietin receptor" ], "offsets": [ [ 41, 64 ] ], "normalized": [] }, { "id": "PMID-7659529_T2", "type": "Protein", "text": [ "GATA-1" ], "offsets": [ [ 93, 99 ] ], "normalized": [] }, { "id": "PMID-7659529_T3", "type": "Protein", "text": [ "Sp1" ], "offsets": [ [ 104, 107 ] ], "normalized": [] }, { "id": "PMID-7659529_T4", "type": "Protein", "text": [ "Erythropoietin" ], "offsets": [ [ 117, 131 ] ], "normalized": [] }, { "id": "PMID-7659529_T5", "type": "Protein", "text": [ "Epo" ], "offsets": [ [ 133, 136 ] ], "normalized": [] }, { "id": "PMID-7659529_T6", "type": "Protein", "text": [ "EpoR" ], "offsets": [ [ 243, 247 ] ], "normalized": [] }, { "id": "PMID-7659529_T7", "type": "Protein", "text": [ "EpoR" ], "offsets": [ [ 440, 444 ] ], "normalized": [] }, { "id": "PMID-7659529_T8", "type": "Protein", "text": [ "Sp1" ], "offsets": [ [ 599, 602 ] ], "normalized": [] }, { "id": "PMID-7659529_T9", "type": "Protein", "text": [ "GATA-1" ], "offsets": [ [ 630, 636 ] ], "normalized": [] }, { "id": "PMID-7659529_T10", "type": "Protein", "text": [ "hEpoR" ], "offsets": [ [ 649, 654 ] ], "normalized": [] }, { "id": "PMID-7659529_T11", "type": "Protein", "text": [ "hEpoR" ], "offsets": [ [ 796, 801 ] ], "normalized": [] }, { "id": "PMID-7659529_T12", "type": "Protein", "text": [ "GATA-1" ], "offsets": [ [ 818, 824 ] ], "normalized": [] }, { "id": "PMID-7659529_T13", "type": "Protein", "text": [ "Sp1" ], "offsets": [ [ 829, 832 ] ], "normalized": [] }, { "id": "PMID-7659529_T14", "type": "Protein", "text": [ "Sp1" ], "offsets": [ [ 992, 995 ] ], "normalized": [] }, { "id": "PMID-7659529_T15", "type": "Protein", "text": [ "Sp1" ], "offsets": [ [ 1091, 1094 ] ], "normalized": [] }, { "id": "PMID-7659529_T16", "type": "Protein", "text": [ "GATA-1" ], "offsets": [ [ 1124, 1130 ] ], "normalized": [] }, { "id": "PMID-7659529_T17", "type": "Protein", "text": [ "hEpoR" ], "offsets": [ [ 1193, 1198 ] ], "normalized": [] }, { "id": "PMID-7659529_T18", "type": "Protein", "text": [ "GATA-1" ], "offsets": [ [ 1298, 1304 ] ], "normalized": [] }, { "id": "PMID-7659529_T19", "type": "Protein", "text": [ "Sp1" ], "offsets": [ [ 1387, 1390 ] ], "normalized": [] }, { "id": "PMID-7659529_T20", "type": "Protein", "text": [ "hEpoR" ], "offsets": [ [ 1431, 1436 ] ], "normalized": [] }, { "id": "PMID-7659529_T21", "type": "Protein", "text": [ "GATA-1" ], "offsets": [ [ 1503, 1509 ] ], "normalized": [] }, { "id": "PMID-7659529_T22", "type": "Protein", "text": [ "GATA-1" ], "offsets": [ [ 1563, 1569 ] ], "normalized": [] }, { "id": "PMID-7659529_T23", "type": "Protein", "text": [ "EpoR" ], "offsets": [ [ 1592, 1596 ] ], "normalized": [] }, { "id": "PMID-7659529_T24", "type": "Protein", "text": [ "hEpoR" ], "offsets": [ [ 1620, 1625 ] ], "normalized": [] }, { "id": "PMID-7659529_T25", "type": "Protein", "text": [ "GATA-1" ], "offsets": [ [ 1661, 1667 ] ], "normalized": [] }, { "id": "PMID-7659529_T26", "type": "Protein", "text": [ "hEpoR" ], "offsets": [ [ 1683, 1688 ] ], "normalized": [] }, { "id": "PMID-7659529_T27", "type": "Protein", "text": [ "Sp1" ], "offsets": [ [ 1744, 1747 ] ], "normalized": [] }, { "id": "PMID-7659529_T28", "type": "Protein", "text": [ "GATA-1" ], "offsets": [ [ 1752, 1758 ] ], "normalized": [] }, { "id": "PMID-7659529_T29", "type": "Protein", "text": [ "Sp1" ], "offsets": [ [ 1818, 1821 ] ], "normalized": [] }, { "id": "PMID-7659529_T37", "type": "Entity", "text": [ "promoter" ], "offsets": [ [ 1199, 1207 ] ], "normalized": [] }, { "id": "PMID-7659529_T40", "type": "Entity", "text": [ "promoter" ], "offsets": [ [ 1437, 1445 ] ], "normalized": [] }, { "id": "PMID-7659529_T43", "type": "Entity", "text": [ "promoter" ], "offsets": [ [ 1597, 1605 ] ], "normalized": [] } ]

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[]

[ { "id": "PMID-7662982__text", "type": "abstract", "text": [ "TCL1 oncogene activation in preleukemic T cells from a case of ataxia-telangiectasia. \nThe TCL1 oncogene on human chromosome 14q32.1 is involved in chromosome translocations [t(14;14)(q11;q32.1) and t(7;14)(q35;q32.1)] and inversions [inv14(q11;q32.1)] with TCR alpha/beta loci in T-cell leukemias, such as T-prolymphocytic (T-PLL). It is also involved in T- acute and- chronic leukemias arising in cases of ataxia-telangiectasia (AT), an immunodeficiency syndrome. Similar chromosomal rearrangements occur also in the clonally expanded T cells in AT patients before the appearance of the overt leukemia. We have analyzed the expression of TCL1 mRNA and protein in peripheral blood lymphocytes (PBLs) from four AT cases and from healthy controls. We found that the TCL1 gene was overexpressed in the PBLs of an AT patient with a large clonal T-cell population exhibiting the t(14;14) translocation but not in the lymphocytes of the other cases. Fluorescence in situ hybridization of the TCL1 genomic locus to lymphocyte metaphases from the AT patient with the T-cell clonal expansion showed that the breakpoint of the t(14;14) translocation lies within the TCL1 locus and is accompanied by an inverted duplication of the distal part of chromosome 14. These data indicate that TCL1 is activated in preleukemic clonal cells as a consequence of chromosome translocation involving sequences from the TCR locus at 14q11. Deregulation of TCL1 is the first event in the initiation of malignancy in these types of leukemias and represents a potential tool for clinical evaluation. " ], "offsets": [ [ 0, 1573 ] ] } ]

[ { "id": "PMID-7662982_T1", "type": "Protein", "text": [ "TCL1" ], "offsets": [ [ 0, 4 ] ], "normalized": [] }, { "id": "PMID-7662982_T2", "type": "Protein", "text": [ "TCL1" ], "offsets": [ [ 91, 95 ] ], "normalized": [] }, { "id": "PMID-7662982_T3", "type": "Protein", "text": [ "TCL1" ], "offsets": [ [ 640, 644 ] ], "normalized": [] }, { "id": "PMID-7662982_T4", "type": "Protein", "text": [ "TCL1" ], "offsets": [ [ 765, 769 ] ], "normalized": [] }, { "id": "PMID-7662982_T5", "type": "Protein", "text": [ "TCL1" ], "offsets": [ [ 987, 991 ] ], "normalized": [] }, { "id": "PMID-7662982_T6", "type": "Protein", "text": [ "TCL1" ], "offsets": [ [ 1157, 1161 ] ], "normalized": [] }, { "id": "PMID-7662982_T7", "type": "Protein", "text": [ "TCL1" ], "offsets": [ [ 1276, 1280 ] ], "normalized": [] }, { "id": "PMID-7662982_T8", "type": "Protein", "text": [ "TCL1" ], "offsets": [ [ 1432, 1436 ] ], "normalized": [] } ]

[ { "id": "PMID-7662982_E1", "type": "Positive_regulation", "trigger": { "text": [ "activation" ], "offsets": [ [ 14, 24 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "PMID-7662982_T1" } ] }, { "id": "PMID-7662982_E2", "type": "Gene_expression", "trigger": { "text": [ "expression" ], "offsets": [ [ 626, 636 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "PMID-7662982_T3" } ] }, { "id": "PMID-7662982_E3", "type": "Transcription", "trigger": { "text": [ "expression" ], "offsets": [ [ 626, 636 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "PMID-7662982_T3" } ] }, { "id": "PMID-7662982_E4", "type": "Positive_regulation", "trigger": { "text": [ "overexpressed" ], "offsets": [ [ 779, 792 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "PMID-7662982_E5" } ] }, { "id": "PMID-7662982_E5", "type": "Gene_expression", "trigger": { "text": [ "overexpressed" ], "offsets": [ [ 779, 792 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "PMID-7662982_T4" } ] }, { "id": "PMID-7662982_E6", "type": "Positive_regulation", "trigger": { "text": [ "activated" ], "offsets": [ [ 1284, 1293 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "PMID-7662982_T7" } ] }, { "id": "PMID-7662982_E7", "type": "Positive_regulation", "trigger": { "text": [ "as a consequence of" ], "offsets": [ [ 1322, 1341 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "PMID-7662982_E6" } ] }, { "id": "PMID-7662982_E8", "type": "Negative_regulation", "trigger": { "text": [ "Deregulation" ], "offsets": [ [ 1416, 1428 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "PMID-7662982_T8" } ] } ]

[]

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[ { "id": "PMID-7664781__text", "type": "abstract", "text": [ "Interleukin-2 promoter activity in Epstein-Barr virus-transformed B lymphocytes is controlled by nuclear factor-chi B. \nThe regulation of interleukin (IL)-2 gene expression has been investigated mainly in T lymphocytes, the predominant producers of IL-2. However, B cells can also synthesize IL-2. In the present study we analyzed the control of IL-2 promoter activity in Epstein-Barr virus (EBV)-transformed B cell clones which are capable of secreting IL-2 at a low level after stimulation with phorbol 12-myristate 13-acetate and the Ca2+ ionophore ionomycin. Transient transfections using reporter constructs with multiples of transcription factor binding sites from the IL-2 promoter [distal nuclear factor (NF)-AT, proximal NF-AT, AP-1/Octamer (UPS) or NF-chi B (TCEd) sites] were performed. In EBV-transformed B clones, the chi B site exerted the strongest inducible activity; the NF-AT binding sites showed either no or only weak activity compared to Jurkat T cells. An IL-2 promoter bearing a defective NF-chi B site was completely inactive in EBV-transformed B cells, while it still had activity in Jurkat T cells. In seven EBV-B cell clones or lines differing in their capacity to secrete IL-2, the activity of the IL-2 promoter correlated well with the status of IL-2 secretion. Similarly, a human immunodeficiency virus promoter, whose activity is controlled through chi B factors, was found to be active in the IL-2 producing EBV-B cells, but inactive in the non-IL-2-producing cells. Electrophoretic mobility shift assays using protein extracts from EBV-B cells and the IL-2 NF-chi B probe revealed the constitutive generation of chi B complexes in IL-2-secreting cells consisting mainly of heterodimeric p50/p65 complexes. A weaker chi B complex formation and faster-migrating complexes were detected in non-IL-2-secreting cells. These results demonstrate that the IL-2 NF-chi B site is indispensable for the activity of the IL-2 promoter in EBV-transformed B cells, whereas other transcription factors appear to be less important for IL-2 expression in these cells. " ], "offsets": [ [ 0, 2083 ] ] } ]

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[ { "id": "PMID-7664781_E1", "type": "Regulation", "trigger": { "text": [ "regulation" ], "offsets": [ [ 124, 134 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "PMID-7664781_E2" } ] }, { "id": "PMID-7664781_E2", "type": "Gene_expression", "trigger": { "text": [ "expression" ], "offsets": [ [ 162, 172 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "PMID-7664781_T2" } ] }, { "id": "PMID-7664781_E3", "type": "Gene_expression", "trigger": { "text": [ "producers" ], "offsets": [ [ 236, 245 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "PMID-7664781_T3" } ] }, { "id": "PMID-7664781_E4", "type": "Gene_expression", "trigger": { "text": [ "synthesize" ], "offsets": [ [ 281, 291 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "PMID-7664781_T4" } ] }, { "id": "PMID-7664781_E5", "type": "Localization", "trigger": { "text": [ "secreting" ], "offsets": [ [ 444, 453 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "PMID-7664781_T6" } ] }, { "id": "PMID-7664781_E6", "type": "Positive_regulation", "trigger": { "text": [ "after" ], "offsets": [ [ 474, 479 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "PMID-7664781_E5" } ] }, { "id": "PMID-7664781_E7", "type": "Localization", "trigger": { "text": [ "secrete" ], "offsets": [ [ 1192, 1199 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "PMID-7664781_T9" } ] }, { "id": "PMID-7664781_E8", "type": "Positive_regulation", "trigger": { "text": [ "activity" ], "offsets": [ [ 1210, 1218 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "PMID-7664781_T10" }, { "role": "Site", "ref_id": "PMID-7664781_T30" } ] }, { "id": "PMID-7664781_E9", "type": "Localization", "trigger": { "text": [ "secretion" ], "offsets": [ [ 1280, 1289 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "PMID-7664781_T11" } ] }, { "id": "PMID-7664781_E10", "type": "Gene_expression", "trigger": { "text": [ "producing" ], "offsets": [ [ 1430, 1439 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "PMID-7664781_T12" } ] }, { "id": "PMID-7664781_E11", "type": "Gene_expression", "trigger": { "text": [ "producing" ], "offsets": [ [ 1482, 1491 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "PMID-7664781_T13" } ] }, { "id": "PMID-7664781_E12", "type": "Positive_regulation", "trigger": { "text": [ "generation" ], "offsets": [ [ 1631, 1641 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "PMID-7664781_T16" } ] }, { "id": "PMID-7664781_E13", "type": "Positive_regulation", "trigger": { "text": [ "generation" ], "offsets": [ [ 1631, 1641 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "PMID-7664781_T17" } ] }, { "id": "PMID-7664781_E14", "type": "Localization", "trigger": { "text": [ "secreting" ], "offsets": [ [ 1669, 1678 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "PMID-7664781_T15" } ] }, { "id": "PMID-7664781_E15", "type": "Localization", "trigger": { "text": [ "secreting" ], "offsets": [ [ 1829, 1838 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "PMID-7664781_T18" } ] }, { "id": "PMID-7664781_E16", "type": "Positive_regulation", "trigger": { "text": [ "indispensable for the activity" ], "offsets": [ [ 1903, 1933 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "PMID-7664781_T20" }, { "role": "Site", "ref_id": "PMID-7664781_T38" } ] }, { "id": "PMID-7664781_E17", "type": "Regulation", "trigger": { "text": [ "less important" ], "offsets": [ [ 2032, 2046 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "PMID-7664781_E18" } ] }, { "id": "PMID-7664781_E18", "type": "Gene_expression", "trigger": { "text": [ "expression" ], "offsets": [ [ 2056, 2066 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "PMID-7664781_T21" } ] } ]

[]

[]

[ { "id": "PMID-7665588__text", "type": "abstract", "text": [ "Ubiquitin-mediated processing of NF-kappa B transcriptional activator precursor p105. Reconstitution of a cell-free system and identification of the ubiquitin-carrier protein, E2, and a novel ubiquitin-protein ligase, E3, involved in conjugation. \nIn most cases, the transcriptional factor NF-kappa B is a heterodimer consisting of two subunits, p50 and p65, which are encoded by two distinct genes of the Rel family. p50 is translated as a precursor of 105 kDa. The C-terminal domain of the precursor is rapidly degraded, forming the mature p50 subunit consisted of the N-terminal region of the molecule. The mechanism of generation of p50 is not known. It has been suggested that the ubiquitin-proteasome system is involved in the process; however, the specific enzymes involved and the mechanism of limited proteolysis, in which half of the molecule is spared, have been obscure. Palombella and colleagues (Palombella, V.J., Rando, O.J., Goldberg, A.L., and Maniatis, T.(1994) Cell 78, 773-785) have shown that ubiquitin is required for the processing in a cell-free system of a truncated, artificially constructed, 60-kDa precursor. They have also shown that proteasome inhibitors block the processing both in vitro and in vivo. In this study, we demonstrate reconstitution of a cell-free processing system and demonstrate directly that: (a) the ubiquitin-proteasome system is involved in processing of the intact p105 precursor, (b) conjugation of ubiquitin to the precursor is an essential intermediate step in the processing, (c) the recently discovered novel species of the ubiquitin-carrier protein, E2-F1, that is involved in the conjugation and degradation of p53, is also required for the limited processing of the p105 precursor, and (d) a novel, approximately 320-kDa species of ubiquitin-protein ligase, is involved in the process. This novel enzyme is distinct from E6-AP, the p53-conjugating ligase, and from E3 alpha, the \"N-end rule\" ligase. " ], "offsets": [ [ 0, 1961 ] ] } ]

[ { "id": "PMID-7665588_T1", "type": "Protein", "text": [ "Ubiquitin" ], "offsets": [ [ 0, 9 ] ], "normalized": [] }, { "id": "PMID-7665588_T2", "type": "Protein", "text": [ "p105" ], "offsets": [ [ 80, 84 ] ], "normalized": [] }, { "id": "PMID-7665588_T3", "type": "Protein", "text": [ "ubiquitin" ], "offsets": [ [ 149, 158 ] ], "normalized": [] }, { "id": "PMID-7665588_T4", "type": "Protein", "text": [ "E2" ], "offsets": [ [ 176, 178 ] ], "normalized": [] }, { "id": "PMID-7665588_T5", "type": "Protein", "text": [ "ubiquitin" ], "offsets": [ [ 192, 201 ] ], "normalized": [] }, { "id": "PMID-7665588_T6", "type": "Protein", "text": [ "E3" ], "offsets": [ [ 218, 220 ] ], "normalized": [] }, { "id": "PMID-7665588_T7", "type": "Protein", "text": [ "p50" ], "offsets": [ [ 346, 349 ] ], "normalized": [] }, { "id": "PMID-7665588_T8", "type": "Protein", "text": [ "p65" ], "offsets": [ [ 354, 357 ] ], "normalized": [] }, { "id": "PMID-7665588_T9", "type": "Protein", "text": [ "p50" ], "offsets": [ [ 418, 421 ] ], "normalized": [] }, { "id": "PMID-7665588_T10", "type": "Protein", "text": [ "p50" ], "offsets": [ [ 542, 545 ] ], "normalized": [] }, { "id": "PMID-7665588_T11", "type": "Protein", "text": [ "p50" ], "offsets": [ [ 637, 640 ] ], "normalized": [] }, { "id": "PMID-7665588_T12", "type": "Protein", "text": [ "ubiquitin" ], "offsets": [ [ 686, 695 ] ], "normalized": [] }, { "id": "PMID-7665588_T13", "type": "Protein", "text": [ "ubiquitin" ], "offsets": [ [ 1014, 1023 ] ], "normalized": [] }, { "id": "PMID-7665588_T14", "type": "Protein", "text": [ "ubiquitin" ], "offsets": [ [ 1350, 1359 ] ], "normalized": [] }, { "id": "PMID-7665588_T15", "type": "Protein", "text": [ "p105" ], "offsets": [ [ 1418, 1422 ] ], "normalized": [] }, { "id": "PMID-7665588_T16", "type": "Protein", "text": [ "ubiquitin" ], "offsets": [ [ 1582, 1591 ] ], "normalized": [] }, { "id": "PMID-7665588_T17", "type": "Protein", "text": [ "E2-F1" ], "offsets": [ [ 1609, 1614 ] ], "normalized": [] }, { "id": "PMID-7665588_T18", "type": "Protein", "text": [ "p53" ], "offsets": [ [ 1671, 1674 ] ], "normalized": [] }, { "id": "PMID-7665588_T19", "type": "Protein", "text": [ "p105" ], "offsets": [ [ 1727, 1731 ] ], "normalized": [] }, { "id": "PMID-7665588_T20", "type": "Protein", "text": [ "ubiquitin" ], "offsets": [ [ 1793, 1802 ] ], "normalized": [] }, { "id": "PMID-7665588_T21", "type": "Protein", "text": [ "E6-AP" ], "offsets": [ [ 1882, 1887 ] ], "normalized": [] }, { "id": "PMID-7665588_T22", "type": "Protein", "text": [ "p53" ], "offsets": [ [ 1893, 1896 ] ], "normalized": [] }, { "id": "PMID-7665588_T23", "type": "Protein", "text": [ "E3 alpha" ], "offsets": [ [ 1926, 1934 ] ], "normalized": [] } ]

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[]

[]

[ { "id": "PMID-7670114__text", "type": "abstract", "text": [ "The hematopoietic transcription factor PU.1 is downregulated in human multiple myeloma cell lines. \nPU.1 is a hematopoietic transcription factor belonging to the Ets-family. It is identical to the Spi-1 oncogene, which is implicated in spleen focus-forming virus-induced murine erythroleukemias. PU.1 seems to be required for early development of multiple hematopoietic lineages, but its expression in mature cells is preferentially observed in cells of the B-cell-and monocyte/macrophage-differentiation lineage. It binds the so-called Pu box, an important tissue-specific regulatory DNA element present in a number of genes expressed in these cell lineages. We have analyzed the expression and activity of PU.1 during human B-cell development using a panel of B-cell lines representing different stages of maturation, from early precursors to differentiated plasma cells. PU.1 mRNA expression and PU.1 DNA binding activity, as measured by Northern blot analysis and electrophoretic mobility shift assay, respectively, were evident in cell lines representing pro-B, pre-B, and mature B cells. We could also show Pu box-dependent transactivation of a reporter gene in transient transfections in these cell lines. In contrast, in a number of multiple myeloma cell lines, representing differentiated, plasma cell-like B cells, PU.1 DNA binding activity, mRNA expression, and Pu box-dependent transactivation were absent or detectable at a very low level. In lymphoblastoid cell lines, which exemplify an intermediate stage of B-cell differentiation, a reduced expression and activity were observed. The findings in the human multiple myeloma cell lines represent the first examples of B cells with downregulated PU.1 expression and apparently contradict observations in the murine system in which PU.1 is expressed and active in plasmacytoma cell lines. At present, it is unclear whether the lack of PU.1 expression and activity in human multiple myeloma cell lines represents a malignancy-associated defect in these cells or exemplifies a normal developmental regulation in terminally differentiated B cells. " ], "offsets": [ [ 0, 2108 ] ] } ]

[ { "id": "PMID-7670114_T1", "type": "Protein", "text": [ "PU.1" ], "offsets": [ [ 39, 43 ] ], "normalized": [] }, { "id": "PMID-7670114_T2", "type": "Protein", "text": [ "PU.1" ], "offsets": [ [ 100, 104 ] ], "normalized": [] }, { "id": "PMID-7670114_T3", "type": "Protein", "text": [ "Spi-1" ], "offsets": [ [ 197, 202 ] ], "normalized": [] }, { "id": "PMID-7670114_T4", "type": "Protein", "text": [ "PU.1" ], "offsets": [ [ 296, 300 ] ], "normalized": [] }, { "id": "PMID-7670114_T5", "type": "Protein", "text": [ "PU.1" ], "offsets": [ [ 708, 712 ] ], "normalized": [] }, { "id": "PMID-7670114_T6", "type": "Protein", "text": [ "PU.1" ], "offsets": [ [ 874, 878 ] ], "normalized": [] }, { "id": "PMID-7670114_T7", "type": "Protein", "text": [ "PU.1" ], "offsets": [ [ 899, 903 ] ], "normalized": [] }, { "id": "PMID-7670114_T8", "type": "Protein", "text": [ "PU.1" ], "offsets": [ [ 1325, 1329 ] ], "normalized": [] }, { "id": "PMID-7670114_T9", "type": "Protein", "text": [ "PU.1" ], "offsets": [ [ 1710, 1714 ] ], "normalized": [] }, { "id": "PMID-7670114_T10", "type": "Protein", "text": [ "PU.1" ], "offsets": [ [ 1795, 1799 ] ], "normalized": [] }, { "id": "PMID-7670114_T11", "type": "Protein", "text": [ "PU.1" ], "offsets": [ [ 1898, 1902 ] ], "normalized": [] } ]

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[]

[]

[ { "id": "PMID-7673240__text", "type": "abstract", "text": [ "A regulatory element in the human interleukin 2 gene promoter is a binding site for the zinc finger proteins Sp1 and EGR-1. \nActivation of the interleukin 2 (IL-2) gene after antigen recognition is a critical event for T cell proliferation and effector function. Prior studies have identified several transcription factors that contribute to the activity of the IL-2 promoter in stimulated T lymphocytes. Here we describe a novel regulatory element within the IL-2 promoter located immediately upstream of the nuclear factor of activated T cell (NFAT) domain. This region (termed the zinc finger protein binding region (ZIP)) serves as binding site for two differently regulated zinc finger proteins: the constitutively expressed transcription factor Sp1 and the inducible early growth response protein EGR-1. In unstimulated cells which do not secrete IL-2, only Sp1 binds to this region, while in stimulated IL-2 secreting cells the inducible EGR-1 protein recognizes this element. In Jurkat T cells, the ZIP site serves as an activator for IL-2 gene expression, and a combination of ZIP and NFAT binding sites is required for maximal IL-2 promoter activity. These results suggest a critical role of the ZIP site for IL-2 promoter activity. " ], "offsets": [ [ 0, 1243 ] ] } ]

[ { "id": "PMID-7673240_T1", "type": "Protein", "text": [ "interleukin 2" ], "offsets": [ [ 34, 47 ] ], "normalized": [] }, { "id": "PMID-7673240_T2", "type": "Protein", "text": [ "Sp1" ], "offsets": [ [ 109, 112 ] ], "normalized": [] }, { "id": "PMID-7673240_T3", "type": "Protein", "text": [ "EGR-1" ], "offsets": [ [ 117, 122 ] ], "normalized": [] }, { "id": "PMID-7673240_T4", "type": "Protein", "text": [ "interleukin 2" ], "offsets": [ [ 143, 156 ] ], "normalized": [] }, { "id": "PMID-7673240_T5", "type": "Protein", "text": [ "IL-2" ], "offsets": [ [ 158, 162 ] ], "normalized": [] }, { "id": "PMID-7673240_T6", "type": "Protein", "text": [ "IL-2" ], "offsets": [ [ 362, 366 ] ], "normalized": [] }, { "id": "PMID-7673240_T7", "type": "Protein", "text": [ "IL-2" ], "offsets": [ [ 460, 464 ] ], "normalized": [] }, { "id": "PMID-7673240_T8", "type": "Protein", "text": [ "Sp1" ], "offsets": [ [ 751, 754 ] ], "normalized": [] }, { "id": "PMID-7673240_T9", "type": "Protein", "text": [ "EGR-1" ], "offsets": [ [ 803, 808 ] ], "normalized": [] }, { "id": "PMID-7673240_T10", "type": "Protein", "text": [ "IL-2" ], "offsets": [ [ 853, 857 ] ], "normalized": [] }, { "id": "PMID-7673240_T11", "type": "Protein", "text": [ "Sp1" ], "offsets": [ [ 864, 867 ] ], "normalized": [] }, { "id": "PMID-7673240_T12", "type": "Protein", "text": [ "IL-2" ], "offsets": [ [ 910, 914 ] ], "normalized": [] }, { "id": "PMID-7673240_T13", "type": "Protein", "text": [ "EGR-1" ], "offsets": [ [ 945, 950 ] ], "normalized": [] }, { "id": "PMID-7673240_T14", "type": "Protein", "text": [ "IL-2" ], "offsets": [ [ 1043, 1047 ] ], "normalized": [] }, { "id": "PMID-7673240_T15", "type": "Protein", "text": [ "IL-2" ], "offsets": [ [ 1137, 1141 ] ], "normalized": [] }, { "id": "PMID-7673240_T16", "type": "Protein", "text": [ "IL-2" ], "offsets": [ [ 1219, 1223 ] ], "normalized": [] }, { "id": "PMID-7673240_T17", "type": "Entity", "text": [ "regulatory element" ], "offsets": [ [ 2, 20 ] ], "normalized": [] }, { "id": "PMID-7673240_T21", "type": "Entity", "text": [ "promoter" ], "offsets": [ [ 367, 375 ] ], "normalized": [] }, { "id": "PMID-7673240_T33", "type": "Entity", "text": [ "promoter" ], "offsets": [ [ 1142, 1150 ] ], "normalized": [] }, { "id": "PMID-7673240_T35", "type": "Entity", "text": [ "promoter" ], "offsets": [ [ 1224, 1232 ] ], "normalized": [] } ]

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[ { "id": "PMID-7673240_1", "entity_ids": [ "PMID-7673240_T5", "PMID-7673240_T4" ] } ]

[]

[ { "id": "PMID-7682243__text", "type": "abstract", "text": [ "Functional antagonism between vitamin D3 and retinoic acid in the regulation of CD14 and CD23 expression during monocytic differentiation of U-937 cells. \n1,25 alpha-Dihydroxicholecalciferol (VitD3) and retinoic acid (RA) are important regulators of the proliferation and differentiation of several cell types. This paper describes how the expression of the monocyte-macrophage Ag, CD14, and the low affinity Fc receptor for IgE, CD23, were inversely regulated during VitD3- and RA-induced monocytic differentiation of human U-937 monoblasts. PMA induced the expression of both CD14 and CD23 mRNA and protein. Exposure to VitD3 rapidly induced the de novo expression of CD14 mRNA and protein. The addition of cycloheximide completely blocked the VitD3 induction of CD14 mRNA expression, indicating that the induction was dependent on ongoing protein synthesis. While inducing CD14 expression, VitD3 concomitantly suppressed the basal, PMA-, and RA-inducible CD23 expression in a dose-dependent manner. In contrast, U-937 cells induced by RA strongly increased their expression of CD23 mRNA and protein, whereas they completely lacked detectable CD14 cell surface or mRNA expression. Furthermore, the VitD3- and the PMA-induced CD14 expression was inhibited as a temporal consequence of the RA-induced differentiation. The results suggest that there exists a functional antagonism between VitD3 and RA that may have important implications for the regulation of certain immune and inflammatory responses through their inverse effects on CD14 and CD23 gene expression. " ], "offsets": [ [ 0, 1566 ] ] } ]

[ { "id": "PMID-7682243_T1", "type": "Protein", "text": [ "CD14" ], "offsets": [ [ 80, 84 ] ], "normalized": [] }, { "id": "PMID-7682243_T2", "type": "Protein", "text": [ "CD23" ], "offsets": [ [ 89, 93 ] ], "normalized": [] }, { "id": "PMID-7682243_T3", "type": "Protein", "text": [ "CD14" ], "offsets": [ [ 382, 386 ] ], "normalized": [] }, { "id": "PMID-7682243_T4", "type": "Protein", "text": [ "CD23" ], "offsets": [ [ 430, 434 ] ], "normalized": [] }, { "id": "PMID-7682243_T5", "type": "Protein", "text": [ "CD14" ], "offsets": [ [ 578, 582 ] ], "normalized": [] }, { "id": "PMID-7682243_T6", "type": "Protein", "text": [ "CD23" ], "offsets": [ [ 587, 591 ] ], "normalized": [] }, { "id": "PMID-7682243_T7", "type": "Protein", "text": [ "CD14" ], "offsets": [ [ 670, 674 ] ], "normalized": [] }, { "id": "PMID-7682243_T8", "type": "Protein", "text": [ "CD14" ], "offsets": [ [ 765, 769 ] ], "normalized": [] }, { "id": "PMID-7682243_T9", "type": "Protein", "text": [ "CD14" ], "offsets": [ [ 876, 880 ] ], "normalized": [] }, { "id": "PMID-7682243_T10", "type": "Protein", "text": [ "CD23" ], "offsets": [ [ 958, 962 ] ], "normalized": [] }, { "id": "PMID-7682243_T11", "type": "Protein", "text": [ "CD23" ], "offsets": [ [ 1080, 1084 ] ], "normalized": [] }, { "id": "PMID-7682243_T12", "type": "Protein", "text": [ "CD14" ], "offsets": [ [ 1145, 1149 ] ], "normalized": [] }, { "id": "PMID-7682243_T13", "type": "Protein", "text": [ "CD14" ], "offsets": [ [ 1227, 1231 ] ], "normalized": [] }, { "id": "PMID-7682243_T14", "type": "Protein", "text": [ "CD14" ], "offsets": [ [ 1535, 1539 ] ], "normalized": [] }, { "id": "PMID-7682243_T15", "type": "Protein", "text": [ "CD23" ], "offsets": [ [ 1544, 1548 ] ], "normalized": [] } ]

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"offsets": [ [ 559, 569 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "PMID-7682243_T6" } ] }, { "id": "PMID-7682243_E17", "type": "Positive_regulation", "trigger": { "text": [ "induced" ], "offsets": [ [ 636, 643 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "PMID-7682243_E20" } ] }, { "id": "PMID-7682243_E18", "type": "Positive_regulation", "trigger": { "text": [ "induced" ], "offsets": [ [ 636, 643 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "PMID-7682243_E19" } ] }, { "id": "PMID-7682243_E19", "type": "Gene_expression", "trigger": { "text": [ "expression" ], "offsets": [ [ 656, 666 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "PMID-7682243_T7" } ] }, { "id": "PMID-7682243_E20", "type": "Transcription", "trigger": { "text": [ "expression" ], "offsets": [ [ 656, 666 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "PMID-7682243_T7" } ] }, { "id": "PMID-7682243_E21", "type": "Negative_regulation", "trigger": { "text": [ "blocked" ], "offsets": [ [ 734, 741 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "PMID-7682243_E22" } ] }, { "id": "PMID-7682243_E22", "type": "Positive_regulation", "trigger": { "text": [ "induction" ], "offsets": [ [ 752, 761 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "PMID-7682243_E23" } ] }, { "id": "PMID-7682243_E23", "type": "Transcription", "trigger": { "text": [ "expression" ], "offsets": [ [ 775, 785 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "PMID-7682243_T8" } ] }, { "id": "PMID-7682243_E24", "type": "Regulation", "trigger": { "text": [ "dependent" ], "offsets": [ [ 821, 830 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "PMID-7682243_E22" } ] }, { "id": "PMID-7682243_E25", "type": "Positive_regulation", "trigger": { "text": [ "inducing" ], "offsets": [ [ 867, 875 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "PMID-7682243_E26" } ] }, { "id": "PMID-7682243_E26", "type": "Gene_expression", "trigger": { "text": [ "expression" ], "offsets": [ [ 881, 891 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "PMID-7682243_T9" } ] }, { "id": "PMID-7682243_E27", "type": "Negative_regulation", "trigger": { "text": [ "suppressed" ], "offsets": [ [ 913, 923 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "PMID-7682243_E30" } ] }, { "id": "PMID-7682243_E28", "type": "Negative_regulation", "trigger": { "text": [ "suppressed" ], "offsets": [ [ 913, 923 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "PMID-7682243_E29" } ] }, { "id": "PMID-7682243_E29", "type": "Positive_regulation", "trigger": { "text": [ "inducible" ], "offsets": [ [ 948, 957 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "PMID-7682243_E30" } ] }, { "id": "PMID-7682243_E30", "type": "Gene_expression", "trigger": { "text": [ "expression" ], "offsets": [ [ 963, 973 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "PMID-7682243_T10" } ] }, { "id": "PMID-7682243_E31", "type": "Positive_regulation", "trigger": { "text": [ "increased" ], "offsets": [ [ 1050, 1059 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "PMID-7682243_E34" } ] }, { "id": "PMID-7682243_E32", "type": "Positive_regulation", "trigger": { "text": [ "increased" ], "offsets": [ [ 1050, 1059 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "PMID-7682243_E33" } ] }, { "id": "PMID-7682243_E33", "type": "Transcription", "trigger": { "text": [ "expression" ], "offsets": [ [ 1066, 1076 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "PMID-7682243_T11" } ] }, { "id": "PMID-7682243_E34", "type": "Gene_expression", "trigger": { "text": [ "expression" ], "offsets": [ [ 1066, 1076 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "PMID-7682243_T11" } ] }, { "id": "PMID-7682243_E35", "type": "Gene_expression", "trigger": { "text": [ "expression" ], "offsets": [ [ 1171, 1181 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "PMID-7682243_T12" } ] }, { "id": "PMID-7682243_E36", "type": "Transcription", "trigger": { "text": [ "expression" ], "offsets": [ [ 1171, 1181 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "PMID-7682243_T12" } ] }, { "id": "PMID-7682243_E37", "type": "Positive_regulation", "trigger": { "text": [ "induced" ], "offsets": [ [ 1219, 1226 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "PMID-7682243_E38" } ] }, { "id": "PMID-7682243_E38", "type": "Gene_expression", "trigger": { "text": [ "expression" ], "offsets": [ [ 1232, 1242 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "PMID-7682243_T13" } ] }, { "id": "PMID-7682243_E39", "type": "Negative_regulation", "trigger": { "text": [ "inhibited" ], "offsets": [ [ 1247, 1256 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "PMID-7682243_E37" } ] }, { "id": "PMID-7682243_E40", "type": "Positive_regulation", "trigger": { "text": [ "as a temporal consequence of" ], "offsets": [ [ 1257, 1285 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "PMID-7682243_E39" } ] }, { "id": "PMID-7682243_E41", "type": "Regulation", "trigger": { "text": [ "effects" ], "offsets": [ [ 1524, 1531 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "PMID-7682243_E44" } ] }, { "id": "PMID-7682243_E42", "type": "Regulation", "trigger": { "text": [ "effects" ], "offsets": [ [ 1524, 1531 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "PMID-7682243_E43" } ] }, { "id": "PMID-7682243_E43", "type": "Gene_expression", "trigger": { "text": [ "gene expression" ], "offsets": [ [ 1549, 1564 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "PMID-7682243_T15" } ] }, { "id": "PMID-7682243_E44", "type": "Gene_expression", "trigger": { "text": [ "gene expression" ], "offsets": [ [ 1549, 1564 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "PMID-7682243_T14" } ] } ]

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[ { "id": "PMID-7688596__text", "type": "abstract", "text": [ "Cytokine modulation of HIV expression. \nCytokines, the peptide hormones which control the homeostasis of the immune system and also play a fundamental role in inflammatory and immune mediated reactions, have been involved at multiple levels in the pathogenesis of the acquired immune deficiency syndrome (AIDS). Infection with the human immunodeficiency virus (HIV) has been shown to induce production of several cytokines both in vitro and in vivo. Conversely, several cytokines modulate the levels of HIV expression in infected cells of both T lymphocytic and mononuclear phagocytic lineage. Activated mononuclear cells, particularly B cells which are in a state of chronic activation in HIV infected individuals, release HIV-inductive cytokines and thus play a potentially important role in the pathogenesis of HIV infection. " ], "offsets": [ [ 0, 829 ] ] } ]

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[ { "id": "PMID-7692906__text", "type": "abstract", "text": [ "Inhibition of HIV-1 latency reactivation by dehydroepiandrosterone (DHEA) and an analog of DHEA. \nThe initial infection with human immunodeficiency virus type 1 (HIV-1) in most individuals usually results in the establishment of a latent or chronic infection before eventual progression toward acquired immunodeficiency syndrome. HIV-1 can also establish a latent or persistent infection in some T cell lines that show minimal constitutive virus expression. However, activation of the T cell lines leading to enhanced HIV-1 replication can be induced by antigens, mitogens, and cytokines (tumor necrosis factor alpha [TNF-alpha], interleukin 1, and interleukin-2). Various gene products from other viruses (HTLV-1, HSV, EBV, CMV, HBV, and HHV-6) can also enhance HIV-1 long terminal repeat (LTR)-driven reporter gene activity. On the basis of these observations, it has been proposed that reactivation of latent HIV-1 harbored in chronically infected T lymphocytes, monocytes, or macrophages plays an important role in the pathogenesis of AIDS. So far, there are no drugs or therapy available that can provide protection against HIV-1 latency reactivation. ACH-2, derived from a human T cell line (CEM), is chronically infected with HIV-1, with low levels of constitutive virus expression. ACH-2 can be converted to productive infection by stimulation of the cells with 12-O-tetradecanoylphorbol-13-acetate (TPA), mitogen or cytokines (TNF-alpha), or infection with HSV. Therefore the ACH-2 cell line is a good candidate for studying the effects of drugs on HIV-1 activation. Previously, we have reported that DHEA and synthetic analogs of DHEA can be modest inhibitors of HIV-1 IIIB replication in phytohemagglutinin-stimulated peripheral blood lymphocyte cultures. (ABSTRACT TRUNCATED AT 250 WORDS) " ], "offsets": [ [ 0, 1801 ] ] } ]

[ { "id": "PMID-7692906_T1", "type": "Protein", "text": [ "tumor necrosis factor alpha" ], "offsets": [ [ 589, 616 ] ], "normalized": [] }, { "id": "PMID-7692906_T2", "type": "Protein", "text": [ "TNF-alpha" ], "offsets": [ [ 618, 627 ] ], "normalized": [] }, { "id": "PMID-7692906_T3", "type": "Protein", "text": [ "interleukin-2" ], "offsets": [ [ 649, 662 ] ], "normalized": [] }, { "id": "PMID-7692906_T4", "type": "Protein", "text": [ "TNF-alpha" ], "offsets": [ [ 1436, 1445 ] ], "normalized": [] }, { "id": "PMID-7692906_T5", "type": "Protein", "text": [ "phytohemagglutinin" ], "offsets": [ [ 1699, 1717 ] ], "normalized": [] } ]

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[ { "id": "PMID-7706235__text", "type": "abstract", "text": [ "Nitric oxide-stimulated guanine nucleotide exchange on p21ras. \nThe protooncogene p21ras, a monomeric G protein family member, plays a critical role in converting extracellular signals into intracellular biochemical events. Here, we report that nitric oxide (NO) activates p21ras in human T cells as evidenced by an increase in GTP-bound p21ras. In vitro studies using pure recombinant p21ras demonstrate that the activation is direct and reversible. Circular dichroism analysis reveals that NO induces a profound conformational change in p21ras in association with GDP/GTP exchange. The mechanism of activation is due to S-nitrosylation of a critical cysteine residue which stimulates guanine nucleotide exchange. Furthermore, we demonstrate that p21ras is essential for NO-induced downstream signaling, such as NF-kappa B activation, and that endogenous NO can activate p21ras in the same cell. These studies identify p21ras as a target of the same cell. These studies identify p21ras as a target of NO in T cells and suggest that NO activates p21ras by an action which mimics that of guanine nucleotide exchange factors. " ], "offsets": [ [ 0, 1124 ] ] } ]

[ { "id": "PMID-7706235_T1", "type": "Protein", "text": [ "p21ras" ], "offsets": [ [ 55, 61 ] ], "normalized": [] }, { "id": "PMID-7706235_T2", "type": "Protein", "text": [ "p21ras" ], "offsets": [ [ 82, 88 ] ], "normalized": [] }, { "id": "PMID-7706235_T3", "type": "Protein", "text": [ "p21ras" ], "offsets": [ [ 273, 279 ] ], "normalized": [] }, { "id": "PMID-7706235_T4", "type": "Protein", "text": [ "p21ras" ], "offsets": [ [ 338, 344 ] ], "normalized": [] }, { "id": "PMID-7706235_T5", "type": "Protein", "text": [ "p21ras" ], "offsets": [ [ 386, 392 ] ], "normalized": [] }, { "id": "PMID-7706235_T6", "type": "Protein", "text": [ "p21ras" ], "offsets": [ [ 539, 545 ] ], "normalized": [] }, { "id": "PMID-7706235_T7", "type": "Protein", "text": [ "p21ras" ], "offsets": [ [ 748, 754 ] ], "normalized": [] }, { "id": "PMID-7706235_T8", "type": "Protein", "text": [ "p21ras" ], "offsets": [ [ 872, 878 ] ], "normalized": [] }, { "id": "PMID-7706235_T9", "type": "Protein", "text": [ "p21ras" ], "offsets": [ [ 920, 926 ] ], "normalized": [] }, { "id": "PMID-7706235_T10", "type": "Protein", "text": [ "p21ras" ], "offsets": [ [ 980, 986 ] ], "normalized": [] }, { "id": "PMID-7706235_T11", "type": "Protein", "text": [ "p21ras" ], "offsets": [ [ 1046, 1052 ] ], "normalized": [] } ]

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[ { "id": "PMID-7706273__text", "type": "abstract", "text": [ "Transcriptional regulation of the vacuolar H(+)-ATPase B2 subunit gene in differentiating THP-1 cells. \nMonocyte-macrophage differentiation was used as a model system for studying gene regulation of the human vacuolar H(+)-ATPase (V-ATPase). We examined mRNA levels of various V-ATPase subunits during differentiation of both native monocytes and the cell line THP-1, and found that transcriptional and post-transcriptional mechanisms could account for increases in cell V-ATPase content. From nuclear runoff experiments, we found that one subunit in particular, the B2 isoform (Mr = 56,000), was amplified primarily by transcriptional means. We have begun to examine the structure of the B2 subunit promoter region. Isolation and sequencing of the first exon and 5'-flanking region of this gene reveal a TATA-less promoter with a high G + C content. Primer extension and ribonuclease protection analyses indicate a single major transcriptional start site. We transfected promoter-luciferase reporter plasmids into THP-1 cells to define sequences that mediate transcriptional control during monocyte differentiation. We found that sequences downstream from the transcriptional start site were sufficient to confer increased expression during THP-1 differentiation. DNase I footprinting and sequence analysis revealed the existence of multiple AP2 and Sp1 binding sites in the 5'-untranslated and proximal coding regions. " ], "offsets": [ [ 0, 1421 ] ] } ]

[ { "id": "PMID-7706273_T1", "type": "Protein", "text": [ "B2" ], "offsets": [ [ 55, 57 ] ], "normalized": [] }, { "id": "PMID-7706273_T2", "type": "Protein", "text": [ "B2" ], "offsets": [ [ 567, 569 ] ], "normalized": [] }, { "id": "PMID-7706273_T3", "type": "Protein", "text": [ "B2" ], "offsets": [ [ 689, 691 ] ], "normalized": [] }, { "id": "PMID-7706273_T4", "type": "Protein", "text": [ "DNase I" ], "offsets": [ [ 1265, 1272 ] ], "normalized": [] }, { "id": "PMID-7706273_T5", "type": "Protein", "text": [ "Sp1" ], "offsets": [ [ 1351, 1354 ] ], "normalized": [] } ]

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[ { "id": "PMID-7706710__text", "type": "abstract", "text": [ "Functional characterization of novel IL-2 transcriptional inhibitors. \nIL-2-mediated T cell proliferation is a critical early event in the inflammatory process. Formation of the NFAT-1 transcriptional complex on the IL-2 promoter is essential for IL-2 transcription. Using a cell line that is stably transfected with a trimer of the NFAT-1 regulatory element linked to a lac-Z reporter gene, we screened for inhibitors of NFAT-1-mediated beta-galactosidase activity. WIN 61058 and WIN 53071 were identified as microM inhibitors. These compounds also inhibited beta-galactosidase mRNA levels. Similar inhibition of NFAT-1-mediated gene expression was observed in a second cell line, which is stably transfected with NFAT-1 regulatory elements linked to the reporter gene for sCD8. At 10 microM, both compounds inhibited IL-2 mRNA and protein levels in the NFAT-1-linked lac-Z transfectants, and in human lymphocytes. Both compounds inhibited the mixed lymphocyte reaction, and this inhibition was reversed by exogenous IL-2. WIN 53071 inhibited IL-2 production induced in the calcium-dependent PMA and ionomycin pathway. Conversely, calcium-independent anti-CD28 Ab and PMA-induced IL-2 production was resistant. Both compounds altered the NFAT-1 transcriptional complex, causing its retarded mobility on gels. By these functional criteria, we believe we have identified two structurally distinct, novel inhibitors of NFAT-1-mediated transcription. " ], "offsets": [ [ 0, 1448 ] ] } ]

[ { "id": "PMID-7706710_T1", "type": "Protein", "text": [ "IL-2" ], "offsets": [ [ 37, 41 ] ], "normalized": [] }, { "id": "PMID-7706710_T2", "type": "Protein", "text": [ "IL-2" ], "offsets": [ [ 71, 75 ] ], "normalized": [] }, { "id": "PMID-7706710_T3", "type": "Protein", "text": [ "NFAT-1" ], "offsets": [ [ 178, 184 ] ], "normalized": [] }, { "id": "PMID-7706710_T4", "type": "Protein", "text": [ "IL-2" ], "offsets": [ [ 216, 220 ] ], "normalized": [] }, { "id": "PMID-7706710_T5", "type": "Protein", "text": [ "IL-2" ], "offsets": [ [ 247, 251 ] ], "normalized": [] }, { "id": "PMID-7706710_T6", "type": "Protein", "text": [ "NFAT-1" ], "offsets": [ [ 333, 339 ] ], "normalized": [] }, { "id": "PMID-7706710_T7", "type": "Protein", "text": [ "lac-Z" ], "offsets": [ [ 371, 376 ] ], "normalized": [] }, { "id": "PMID-7706710_T8", "type": "Protein", "text": [ "NFAT-1" ], "offsets": [ [ 422, 428 ] ], "normalized": [] }, { "id": "PMID-7706710_T9", "type": "Protein", "text": [ "beta-galactosidase" ], "offsets": [ [ 438, 456 ] ], "normalized": [] }, { "id": "PMID-7706710_T10", "type": "Protein", "text": [ "beta-galactosidase" ], "offsets": [ [ 560, 578 ] ], "normalized": [] }, { "id": "PMID-7706710_T11", "type": "Protein", "text": [ "NFAT-1" ], "offsets": [ [ 614, 620 ] ], "normalized": [] }, { "id": "PMID-7706710_T12", "type": "Protein", "text": [ "NFAT-1" ], "offsets": [ [ 715, 721 ] ], "normalized": [] }, { "id": "PMID-7706710_T13", "type": "Protein", "text": [ "IL-2" ], "offsets": [ [ 819, 823 ] ], "normalized": [] }, { "id": "PMID-7706710_T14", "type": "Protein", "text": [ "NFAT-1" ], "offsets": [ [ 855, 861 ] ], "normalized": [] }, { "id": "PMID-7706710_T15", "type": "Protein", "text": [ "lac-Z" ], "offsets": [ [ 869, 874 ] ], "normalized": [] }, { "id": "PMID-7706710_T16", "type": "Protein", "text": [ "IL-2" ], "offsets": [ [ 1018, 1022 ] ], "normalized": [] }, { "id": "PMID-7706710_T17", "type": "Protein", "text": [ "IL-2" ], "offsets": [ [ 1044, 1048 ] ], "normalized": [] }, { "id": "PMID-7706710_T18", "type": "Protein", "text": [ "IL-2" ], "offsets": [ [ 1181, 1185 ] ], "normalized": [] }, { "id": "PMID-7706710_T19", "type": "Protein", "text": [ "NFAT-1" ], "offsets": [ [ 1239, 1245 ] ], "normalized": [] }, { "id": "PMID-7706710_T20", "type": "Protein", "text": [ "NFAT-1" ], "offsets": [ [ 1417, 1423 ] ], "normalized": [] }, { "id": "PMID-7706710_T23", "type": "Entity", "text": [ "promoter" ], "offsets": [ [ 221, 229 ] ], "normalized": [] } ]

[ { "id": "PMID-7706710_E1", "type": "Negative_regulation", "trigger": { "text": [ "transcriptional inhibitors" ], "offsets": [ [ 42, 68 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "PMID-7706710_T1" } ] }, { "id": "PMID-7706710_E2", "type": "Binding", "trigger": { "text": [ "complex" ], "offsets": [ [ 201, 208 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "PMID-7706710_T3" }, { "role": "Theme", "ref_id": "PMID-7706710_T4" }, { "role": "Site", "ref_id": "PMID-7706710_T23" } ] }, { "id": "PMID-7706710_E3", "type": "Positive_regulation", "trigger": { "text": [ "essential" ], "offsets": [ [ 233, 242 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "PMID-7706710_E4" }, { "role": "Cause", "ref_id": "PMID-7706710_E2" } ] }, { "id": "PMID-7706710_E4", "type": "Transcription", "trigger": { "text": [ "transcription" ], "offsets": [ [ 252, 265 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "PMID-7706710_T5" } ] }, { "id": "PMID-7706710_E5", "type": "Positive_regulation", "trigger": { "text": [ "screened" ], "offsets": [ [ 395, 403 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "PMID-7706710_E6" } ] }, { "id": "PMID-7706710_E6", "type": "Negative_regulation", "trigger": { "text": [ "inhibitors" ], "offsets": [ [ 408, 418 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "PMID-7706710_T9" } ] }, { "id": "PMID-7706710_E7", "type": "Positive_regulation", "trigger": { "text": [ "mediated" ], "offsets": [ [ 429, 437 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "PMID-7706710_T9" }, { "role": "Cause", "ref_id": "PMID-7706710_T8" } ] }, { "id": "PMID-7706710_E8", "type": "Negative_regulation", "trigger": { "text": [ "inhibitors" ], "offsets": [ [ 517, 527 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "PMID-7706710_T9" } ] }, { "id": "PMID-7706710_E9", "type": "Negative_regulation", "trigger": { "text": [ "inhibited" ], "offsets": [ [ 550, 559 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "PMID-7706710_E10" } ] }, { "id": "PMID-7706710_E10", "type": "Transcription", "trigger": { "text": [ "levels" ], "offsets": [ [ 584, 590 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "PMID-7706710_T10" } ] }, { "id": "PMID-7706710_E11", "type": "Gene_expression", "trigger": { "text": [ "transfected" ], "offsets": [ [ 698, 709 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "PMID-7706710_T12" } ] }, { "id": "PMID-7706710_E12", "type": "Positive_regulation", "trigger": { "text": [ "transfected" ], "offsets": [ [ 698, 709 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "PMID-7706710_E11" } ] }, { "id": "PMID-7706710_E13", "type": "Negative_regulation", "trigger": { "text": [ "inhibited" ], "offsets": [ [ 809, 818 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "PMID-7706710_E16" } ] }, { "id": "PMID-7706710_E14", "type": "Negative_regulation", "trigger": { "text": [ "inhibited" ], "offsets": [ [ 809, 818 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "PMID-7706710_E15" } ] }, { "id": "PMID-7706710_E15", "type": "Transcription", "trigger": { "text": [ "levels" ], "offsets": [ [ 841, 847 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "PMID-7706710_T13" } ] }, { "id": "PMID-7706710_E16", "type": "Gene_expression", "trigger": { "text": [ "levels" ], "offsets": [ [ 841, 847 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "PMID-7706710_T13" } ] }, { "id": "PMID-7706710_E17", "type": "Negative_regulation", "trigger": { "text": [ "inhibited" ], "offsets": [ [ 1034, 1043 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "PMID-7706710_E18" } ] }, { "id": "PMID-7706710_E18", "type": "Gene_expression", "trigger": { "text": [ "production" ], "offsets": [ [ 1049, 1059 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "PMID-7706710_T17" } ] }, { "id": "PMID-7706710_E19", "type": "Positive_regulation", "trigger": { "text": [ "induced" ], "offsets": [ [ 1060, 1067 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "PMID-7706710_E18" } ] }, { "id": "PMID-7706710_E20", "type": "Positive_regulation", "trigger": { "text": [ "induced" ], "offsets": [ [ 1173, 1180 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "PMID-7706710_E21" } ] }, { "id": "PMID-7706710_E21", "type": "Gene_expression", "trigger": { "text": [ "production" ], "offsets": [ [ 1186, 1196 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "PMID-7706710_T18" } ] }, { "id": "PMID-7706710_E22", "type": "Regulation", "trigger": { "text": [ "altered" ], "offsets": [ [ 1227, 1234 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "PMID-7706710_E23" } ] }, { "id": "PMID-7706710_E23", "type": "Binding", "trigger": { "text": [ "transcriptional complex" ], "offsets": [ [ 1246, 1269 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "PMID-7706710_T19" } ] } ]

[]

[]

[ { "id": "PMID-7706727__text", "type": "abstract", "text": [ "cDNA cloning of a NGFI-B/nur77-related transcription factor from an apoptotic human T cell line. \nA human T lymphoid cell line, PEER, dies by apoptosis in the presence of PMA and calcium ionophore. A new gene, TINUR, was cloned from apoptotic PEER cells. The expression of the TINUR gene is induced within 1 h after the cross-linking of the T cell Ag receptor complex. TINUR belongs to the NGFI-B/nur77 family of the steroid receptor superfamily and is an orphan receptor. TINUR binds to the same DNA sequence as NGFI-B/nur77. We also propose that the NGFI-B/nur77 family can be classified into two subtypes. " ], "offsets": [ [ 0, 609 ] ] } ]

[ { "id": "PMID-7706727_T1", "type": "Protein", "text": [ "NGFI-B" ], "offsets": [ [ 18, 24 ] ], "normalized": [] }, { "id": "PMID-7706727_T2", "type": "Protein", "text": [ "nur77" ], "offsets": [ [ 25, 30 ] ], "normalized": [] }, { "id": "PMID-7706727_T3", "type": "Protein", "text": [ "TINUR" ], "offsets": [ [ 210, 215 ] ], "normalized": [] }, { "id": "PMID-7706727_T4", "type": "Protein", "text": [ "TINUR" ], "offsets": [ [ 277, 282 ] ], "normalized": [] }, { "id": "PMID-7706727_T5", "type": "Protein", "text": [ "TINUR" ], "offsets": [ [ 369, 374 ] ], "normalized": [] }, { "id": "PMID-7706727_T6", "type": "Protein", "text": [ "NGFI-B" ], "offsets": [ [ 390, 396 ] ], "normalized": [] }, { "id": "PMID-7706727_T7", "type": "Protein", "text": [ "nur77" ], "offsets": [ [ 397, 402 ] ], "normalized": [] }, { "id": "PMID-7706727_T8", "type": "Protein", "text": [ "TINUR" ], "offsets": [ [ 473, 478 ] ], "normalized": [] }, { "id": "PMID-7706727_T9", "type": "Protein", "text": [ "NGFI-B" ], "offsets": [ [ 513, 519 ] ], "normalized": [] }, { "id": "PMID-7706727_T10", "type": "Protein", "text": [ "nur77" ], "offsets": [ [ 520, 525 ] ], "normalized": [] }, { "id": "PMID-7706727_T11", "type": "Protein", "text": [ "NGFI-B" ], "offsets": [ [ 552, 558 ] ], "normalized": [] }, { "id": "PMID-7706727_T12", "type": "Protein", "text": [ "nur77" ], "offsets": [ [ 559, 564 ] ], "normalized": [] } ]

[ { "id": "PMID-7706727_E1", "type": "Gene_expression", "trigger": { "text": [ "expression" ], "offsets": [ [ 259, 269 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "PMID-7706727_T4" } ] }, { "id": "PMID-7706727_E2", "type": "Positive_regulation", "trigger": { "text": [ "induced" ], "offsets": [ [ 291, 298 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "PMID-7706727_E1" } ] }, { "id": "PMID-7706727_E3", "type": "Binding", "trigger": { "text": [ "binds" ], "offsets": [ [ 479, 484 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "PMID-7706727_T9" } ] }, { "id": "PMID-7706727_E4", "type": "Binding", "trigger": { "text": [ "binds" ], "offsets": [ [ 479, 484 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "PMID-7706727_T8" } ] } ]

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[]

[ { "id": "PMID-7713868__text", "type": "abstract", "text": [ "Platelet-activating factor stimulates transcription of the heparin-binding epidermal growth factor-like growth factor in monocytes. Correlation with an increased kappa B binding activity. \nHuman peripheral blood monocytes responded to stimulation of platelet-activating factor (PAF) with up-regulation of the transcript for heparin-binding epidermal growth factor-like growth factor (HB-EGF), a potent mitogen for vascular smooth muscle cells. This function of PAF was observed at nanomolar concentrations of the ligand, starting at 30 min after stimulation. The PAF-induced up-regulation of HB-EGF mRNA was accompanied by an increase in kappa B binding activity. These functions of PAF appeared to be mediated through the cell surface PAF receptors, as two PAF receptor antagonists, WEB 2086 and L-659,989, blocked both the up-regulation of HB-EGF mRNA and kappa B binding activity induced by PAF. The antagonists, however, had no effect on phorbol ester-induced up-regulation of HB-EGF mRNA and kappa B binding activity. Pretreatment of monocytes with pertussis toxin inhibited these functions of PAF, whereas cholera toxin had no inhibitory effect. Pyrrolidine dithiocarbamate, an inhibitor for NF-kappa B activation, markedly reduced PAF-stimulated kappa B binding activity as well as up-regulation of HB-EGF mRNA. These results suggest a potential role of PAF in HB-EGF expression and provide evidence that this stimulation may occur through increased kappa B binding activity. " ], "offsets": [ [ 0, 1483 ] ] } ]

[ { "id": "PMID-7713868_T1", "type": "Protein", "text": [ "heparin-binding epidermal growth factor-like growth factor" ], "offsets": [ [ 59, 117 ] ], "normalized": [] }, { "id": "PMID-7713868_T2", "type": "Protein", "text": [ "heparin-binding epidermal growth factor-like growth factor" ], "offsets": [ [ 324, 382 ] ], "normalized": [] }, { "id": "PMID-7713868_T3", "type": "Protein", "text": [ "HB-EGF" ], "offsets": [ [ 384, 390 ] ], "normalized": [] }, { "id": "PMID-7713868_T4", "type": "Protein", "text": [ "HB-EGF" ], "offsets": [ [ 592, 598 ] ], "normalized": [] }, { "id": "PMID-7713868_T5", "type": "Protein", "text": [ "HB-EGF" ], "offsets": [ [ 842, 848 ] ], "normalized": [] }, { "id": "PMID-7713868_T6", "type": "Protein", "text": [ "HB-EGF" ], "offsets": [ [ 981, 987 ] ], "normalized": [] }, { "id": "PMID-7713868_T7", "type": "Protein", "text": [ "HB-EGF" ], "offsets": [ [ 1306, 1312 ] ], "normalized": [] }, { "id": "PMID-7713868_T8", "type": "Protein", "text": [ "HB-EGF" ], "offsets": [ [ 1368, 1374 ] ], "normalized": [] } ]

[ { "id": "PMID-7713868_E1", "type": "Positive_regulation", "trigger": { "text": [ "stimulates" ], "offsets": [ [ 27, 37 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "PMID-7713868_E2" } ] }, { "id": "PMID-7713868_E2", "type": "Transcription", "trigger": { "text": [ "transcription" ], "offsets": [ [ 38, 51 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "PMID-7713868_T1" } ] }, { "id": "PMID-7713868_E3", "type": "Positive_regulation", "trigger": { "text": [ "up-regulation" ], "offsets": [ [ 288, 301 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "PMID-7713868_T2" } ] }, { "id": "PMID-7713868_E4", "type": "Positive_regulation", "trigger": { "text": [ "up-regulation" ], "offsets": [ [ 575, 588 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "PMID-7713868_T4" } ] }, { "id": "PMID-7713868_E5", "type": "Positive_regulation", "trigger": { "text": [ "mediated" ], "offsets": [ [ 702, 710 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "PMID-7713868_E4" } ] }, { "id": "PMID-7713868_E6", "type": "Negative_regulation", "trigger": { "text": [ "blocked" ], "offsets": [ [ 808, 815 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "PMID-7713868_E7" } ] }, { "id": "PMID-7713868_E7", "type": "Positive_regulation", "trigger": { "text": [ "up-regulation" ], "offsets": [ [ 825, 838 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "PMID-7713868_T5" } ] }, { "id": "PMID-7713868_E8", "type": "Regulation", "trigger": { "text": [ "effect" ], "offsets": [ [ 932, 938 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "PMID-7713868_E9" } ] }, { "id": "PMID-7713868_E9", "type": "Positive_regulation", "trigger": { "text": [ "up-regulation" ], "offsets": [ [ 964, 977 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "PMID-7713868_T6" } ] }, { "id": "PMID-7713868_E10", "type": "Negative_regulation", "trigger": { "text": [ "inhibited" ], "offsets": [ [ 1070, 1079 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "PMID-7713868_E4" } ] }, { "id": "PMID-7713868_E11", "type": "Negative_regulation", "trigger": { "text": [ "inhibitory effect" ], "offsets": [ [ 1133, 1150 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "PMID-7713868_E4" } ] }, { "id": "PMID-7713868_E12", "type": "Negative_regulation", "trigger": { "text": [ "reduced" ], "offsets": [ [ 1230, 1237 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "PMID-7713868_E13" } ] }, { "id": "PMID-7713868_E13", "type": "Positive_regulation", "trigger": { "text": [ "up-regulation" ], "offsets": [ [ 1289, 1302 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "PMID-7713868_T7" } ] }, { "id": "PMID-7713868_E14", "type": "Positive_regulation", "trigger": { "text": [ "potential role" ], "offsets": [ [ 1343, 1357 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "PMID-7713868_E15" } ] }, { "id": "PMID-7713868_E15", "type": "Gene_expression", "trigger": { "text": [ "expression" ], "offsets": [ [ 1375, 1385 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "PMID-7713868_T8" } ] }, { "id": "PMID-7713868_E16", "type": "Positive_regulation", "trigger": { "text": [ "occur" ], "offsets": [ [ 1433, 1438 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "PMID-7713868_E14" } ] } ]

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[]

[ { "id": "PMID-7718519__text", "type": "abstract", "text": [ "IL-1 receptor and TCR signals synergize to activate NF-kappa B-mediated gene transcription. \nPrevious studies have demonstrated that IL-1 receptor (IL-1R)- and TCR-initiated signals can interact synergistically to increase the rate of transcription of several lymphokine and lymphokine receptor genes during the competence phase of the activation program in T helper lymphocytes. In this report we describe how signals initiated through the type I IL-1R interact with signals from the antigen receptor to synergistically augment the transactivating properties of NF-kappa B. The synergistic antigen receptor initiated signals are mediated through protein kinase C because they can be mimicked by the phorbol ester, 12-O-tetradecanoylphorbol-13-acetate, but not with calcium ionophores; and are staurosporine sensitive but cyclosporine resistant. Gel shift analyses demonstrate that NF-kappa B nuclear translocation is stimulated primarily by IL-1 rather than by antigen receptor signals. Western blot and phosphorylation analyses demonstrate that the synergistic effect on NF-kappa B functional activity is independent of I kappa B alpha (MAD3)-NF-kappa B dissociation in the cytosol and is not associated with I kappa B nuclear translocation. The IL-1-induced NF-kappa B DNA nuclear localization is transient and can be prolonged either by an antigen receptor-initiated signal or by inhibiting protein synthesis. These results suggest that IL-1 induces both NF-kappa B nuclear translocation and the synthesis of a protein(s) responsible for terminating NF-kappa B-DNA interaction in the nucleus. Antigen receptor signals prolong NF-kappa B-DNA interaction, probably by functionally antagonizing the IL-1-induced synthesis of a protein(s) responsible for the transient NF-kappa B-DNA interaction and consequently synergistically enhance IL-1-induced NF-kappa B-dependent gene transcription. " ], "offsets": [ [ 0, 1891 ] ] } ]

[ { "id": "PMID-7718519_T1", "type": "Protein", "text": [ "type I IL-1R" ], "offsets": [ [ 441, 453 ] ], "normalized": [] }, { "id": "PMID-7718519_T2", "type": "Protein", "text": [ "I kappa B alpha" ], "offsets": [ [ 1122, 1137 ] ], "normalized": [] }, { "id": "PMID-7718519_T3", "type": "Protein", "text": [ "MAD3" ], "offsets": [ [ 1139, 1143 ] ], "normalized": [] } ]

[]

[ { "id": "PMID-7718519_1", "entity_ids": [ "PMID-7718519_T2", "PMID-7718519_T3" ] } ]

[]

[ { "id": "PMID-7720085__text", "type": "abstract", "text": [ "Induction of transcription factors in human T lymphocytes by aspirin-like drugs. \nAspirin-like drugs (ALD) induce calcium mobilization, an essential component of T cell activation, but do not induce the biosynthesis of IL-2. To understand the extent to which ALD may mimic mitogenic stimulation, we studied cytoplasmic and nuclear signaling steps in ALD-treated T cells. We found that ALD induce a transient activation of protein kinase (PKC) but have no effect (in comparison to anti-CD3 antibodies) on protein tyrosine phosphorylation nor on PCL gamma 1 tyrosine phosphorylation. ALD-induced calcium mobilization and PKC activation are independent of tyrosine protein kinase activity as shown by the lack of effect of herbimycin, a tyrosine-protein kinase-specific inhibitor. Although we detected no IL-2 mRNA in ALD-treated cells, the nuclei of these cells contain proteins capable of binding to three regulatory sequences in the IL-2 promoter region: NFAT, NF kappa B, and AP-1. These binding activities are expressed only in activated T cells. The expression of AP-1 depended on calcium mobilization and PKC activation. These data suggest that ALD cause transient but significant changes in T cell transmembrane signaling, although some events induced by stimulation with anti-CD3 antibodies are not induced by ALD. The signal is transmitted to the nucleus and induces DNA-binding activity by several transcription factors. However, the ALD stimulus is not capable of causing complete T cell activation. " ], "offsets": [ [ 0, 1509 ] ] } ]

[ { "id": "PMID-7720085_T1", "type": "Protein", "text": [ "IL-2" ], "offsets": [ [ 219, 223 ] ], "normalized": [] }, { "id": "PMID-7720085_T2", "type": "Protein", "text": [ "PCL gamma 1" ], "offsets": [ [ 544, 555 ] ], "normalized": [] }, { "id": "PMID-7720085_T3", "type": "Protein", "text": [ "IL-2" ], "offsets": [ [ 802, 806 ] ], "normalized": [] }, { "id": "PMID-7720085_T4", "type": "Protein", "text": [ "IL-2" ], "offsets": [ [ 933, 937 ] ], "normalized": [] }, { "id": "PMID-7720085_T8", "type": "Entity", "text": [ "tyrosine" ], "offsets": [ [ 556, 564 ] ], "normalized": [] }, { "id": "PMID-7720085_T12", "type": "Entity", "text": [ "promoter region" ], "offsets": [ [ 938, 953 ] ], "normalized": [] } ]

[ { "id": "PMID-7720085_E1", "type": "Positive_regulation", "trigger": { "text": [ "induce" ], "offsets": [ [ 192, 198 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "PMID-7720085_E2" } ] }, { "id": "PMID-7720085_E2", "type": "Gene_expression", "trigger": { "text": [ "biosynthesis" ], "offsets": [ [ 203, 215 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "PMID-7720085_T1" } ] }, { "id": "PMID-7720085_E3", "type": "Regulation", "trigger": { "text": [ "effect" ], "offsets": [ [ 455, 461 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "PMID-7720085_E4" } ] }, { "id": "PMID-7720085_E4", "type": "Phosphorylation", "trigger": { "text": [ "phosphorylation" ], "offsets": [ [ 565, 580 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "PMID-7720085_T2" }, { "role": "Site", "ref_id": "PMID-7720085_T8" } ] }, { "id": "PMID-7720085_E5", "type": "Transcription", "trigger": { "text": [ "detected" ], "offsets": [ [ 790, 798 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "PMID-7720085_T3" } ] }, { "id": "PMID-7720085_E6", "type": "Binding", "trigger": { "text": [ "binding" ], "offsets": [ [ 888, 895 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "PMID-7720085_T4" }, { "role": "Site", "ref_id": "PMID-7720085_T12" } ] }, { "id": "PMID-7720085_E7", "type": "Positive_regulation", "trigger": { "text": [ "expressed" ], "offsets": [ [ 1012, 1021 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "PMID-7720085_E6" } ] } ]

[]

[]

[ { "id": "PMID-7721885__text", "type": "abstract", "text": [ "Interleukin (IL)-10 inhibits nuclear factor kappa B (NF kappa B) activation in human monocytes. IL-10 and IL-4 suppress cytokine synthesis by different mechanisms. \nOur previous studies in human monocytes have demonstrated that interleukin (IL)-10 inhibits lipopolysaccharide (LPS)-stimulated production of inflammatory cytokines, IL-1 beta, IL-6, IL-8, and tumor necrosis factor (TNF)-alpha by blocking gene transcription. Using electrophoretic mobility shift assays (EMSA), we now show that, in monocytes stimulated with LPS or TNF alpha, IL-10 inhibits nuclear stimulation of nuclear factor kappa B (NF kappa B), a transcription factor involved in the expression of inflammatory cytokine genes. Several other transcription factors including NF-IL-6, AP-1, AP-2, GR, CREB, Oct-1, and Sp-1 are not affected by IL-10. This selective inhibition by IL-10 of NF kappa B activation occurs rapidly and in a dose-dependent manner and correlates well with IL-10's cytokine synthesis inhibitory activity in terms of both kinetics and dose responsiveness. Furthermore, compounds such as tosylphenylalanyl chloromethyl ketone and pyrrolidinedithiocarbamate that are known to selectively inhibit NF kappa B activation block cytokine gene transcription in LPS-stimulated monocytes. Taken together, these results suggest that inhibition of NF kappa B activation may be an important mechanism for IL-10 suppression of cytokine gene transcription in human monocytes. IL-4, another cytokine that inhibits cytokine mRNA accumulation in monocytes, shows little inhibitory effect on LPS-induced NF kappa B activation. Further examination reveals that, unlike IL-10, IL-4 enhances mRNA degradation and does not suppress cytokine gene transcription. These data indicate that IL-10 and IL-4 inhibit cytokine production by different mechanisms. " ], "offsets": [ [ 0, 1822 ] ] } ]

[ { "id": "PMID-7721885_T1", "type": "Protein", "text": [ "Interleukin (IL)-10" ], "offsets": [ [ 0, 19 ] ], "normalized": [] }, { "id": "PMID-7721885_T2", "type": "Protein", "text": [ "IL-10" ], "offsets": [ [ 96, 101 ] ], "normalized": [] }, { "id": "PMID-7721885_T3", "type": "Protein", "text": [ "IL-4" ], "offsets": [ [ 106, 110 ] ], "normalized": [] }, { "id": "PMID-7721885_T4", "type": "Protein", "text": [ "interleukin (IL)-10" ], "offsets": [ [ 228, 247 ] ], "normalized": [] }, { "id": "PMID-7721885_T5", "type": "Protein", "text": [ "IL-1 beta" ], "offsets": [ [ 331, 340 ] ], "normalized": [] }, { "id": "PMID-7721885_T6", "type": "Protein", "text": [ "IL-6" ], "offsets": [ [ 342, 346 ] ], "normalized": [] }, { "id": "PMID-7721885_T7", "type": "Protein", "text": [ "IL-8" ], "offsets": [ [ 348, 352 ] ], "normalized": [] }, { "id": "PMID-7721885_T8", "type": "Protein", "text": [ "tumor necrosis factor (TNF)-alpha" ], "offsets": [ [ 358, 391 ] ], "normalized": [] }, { "id": "PMID-7721885_T9", "type": "Protein", "text": [ "TNF alpha" ], "offsets": [ [ 530, 539 ] ], "normalized": [] }, { "id": "PMID-7721885_T10", "type": "Protein", "text": [ "IL-10" ], "offsets": [ [ 541, 546 ] ], "normalized": [] }, { "id": "PMID-7721885_T11", "type": "Protein", "text": [ "NF-IL-6" ], "offsets": [ [ 744, 751 ] ], "normalized": [] }, { "id": "PMID-7721885_T12", "type": "Protein", "text": [ "AP-1" ], "offsets": [ [ 753, 757 ] ], "normalized": [] }, { "id": "PMID-7721885_T13", "type": "Protein", "text": [ "AP-2" ], "offsets": [ [ 759, 763 ] ], "normalized": [] }, { "id": "PMID-7721885_T14", "type": "Protein", "text": [ "GR" ], "offsets": [ [ 765, 767 ] ], "normalized": [] }, { "id": "PMID-7721885_T15", "type": "Protein", "text": [ "CREB" ], "offsets": [ [ 769, 773 ] ], "normalized": [] }, { "id": "PMID-7721885_T16", "type": "Protein", "text": [ "Oct-1" ], "offsets": [ [ 775, 780 ] ], "normalized": [] }, { "id": "PMID-7721885_T17", "type": "Protein", "text": [ "Sp-1" ], "offsets": [ [ 786, 790 ] ], "normalized": [] }, { "id": "PMID-7721885_T18", "type": "Protein", "text": [ "IL-10" ], "offsets": [ [ 811, 816 ] ], "normalized": [] }, { "id": "PMID-7721885_T19", "type": "Protein", "text": [ "IL-10" ], "offsets": [ [ 847, 852 ] ], "normalized": [] }, { "id": "PMID-7721885_T20", "type": "Protein", "text": [ "IL-10" ], "offsets": [ [ 949, 954 ] ], "normalized": [] }, { "id": "PMID-7721885_T21", "type": "Protein", "text": [ "IL-10" ], "offsets": [ [ 1383, 1388 ] ], "normalized": [] }, { "id": "PMID-7721885_T22", "type": "Protein", "text": [ "IL-4" ], "offsets": [ [ 1452, 1456 ] ], "normalized": [] }, { "id": "PMID-7721885_T23", "type": "Protein", "text": [ "IL-10" ], "offsets": [ [ 1640, 1645 ] ], "normalized": [] }, { "id": "PMID-7721885_T24", "type": "Protein", "text": [ "IL-4" ], "offsets": [ [ 1647, 1651 ] ], "normalized": [] }, { "id": "PMID-7721885_T25", "type": "Protein", "text": [ "IL-10" ], "offsets": [ [ 1754, 1759 ] ], "normalized": [] }, { "id": "PMID-7721885_T26", "type": "Protein", "text": [ "IL-4" ], "offsets": [ [ 1764, 1768 ] ], "normalized": [] } ]

[ { "id": "PMID-7721885_E1", "type": "Negative_regulation", "trigger": { "text": [ "inhibits" ], "offsets": [ [ 248, 256 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "PMID-7721885_E5" } ] }, { "id": "PMID-7721885_E2", "type": "Negative_regulation", "trigger": { "text": [ "inhibits" ], "offsets": [ [ 248, 256 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "PMID-7721885_E8" } ] }, { "id": "PMID-7721885_E3", "type": "Negative_regulation", "trigger": { "text": [ "inhibits" ], "offsets": [ [ 248, 256 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "PMID-7721885_E6" } ] }, { "id": "PMID-7721885_E4", "type": "Negative_regulation", "trigger": { "text": [ "inhibits" ], "offsets": [ [ 248, 256 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "PMID-7721885_E7" } ] }, { "id": "PMID-7721885_E5", "type": "Positive_regulation", "trigger": { "text": [ "stimulated" ], "offsets": [ [ 282, 292 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "PMID-7721885_E12" } ] }, { "id": "PMID-7721885_E6", "type": "Positive_regulation", "trigger": { "text": [ "stimulated" ], "offsets": [ [ 282, 292 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "PMID-7721885_E9" } ] }, { "id": "PMID-7721885_E7", "type": "Positive_regulation", "trigger": { "text": [ "stimulated" ], "offsets": [ [ 282, 292 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "PMID-7721885_E10" } ] }, { "id": "PMID-7721885_E8", "type": "Positive_regulation", "trigger": { "text": [ "stimulated" ], "offsets": [ [ 282, 292 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "PMID-7721885_E11" } ] }, { "id": "PMID-7721885_E9", "type": "Gene_expression", "trigger": { "text": [ "production" ], "offsets": [ [ 293, 303 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "PMID-7721885_T6" } ] }, { "id": "PMID-7721885_E10", "type": "Gene_expression", "trigger": { "text": [ "production" ], "offsets": [ [ 293, 303 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "PMID-7721885_T7" } ] }, { "id": "PMID-7721885_E11", "type": "Gene_expression", "trigger": { "text": [ "production" ], "offsets": [ [ 293, 303 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "PMID-7721885_T5" } ] }, { "id": "PMID-7721885_E12", "type": "Gene_expression", "trigger": { "text": [ "production" ], "offsets": [ [ 293, 303 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "PMID-7721885_T8" } ] }, { "id": "PMID-7721885_E13", "type": "Regulation", "trigger": { "text": [ "affected" ], "offsets": [ [ 799, 807 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "PMID-7721885_T13" }, { "role": "Cause", "ref_id": "PMID-7721885_T18" } ] }, { "id": "PMID-7721885_E14", "type": "Regulation", "trigger": { "text": [ "affected" ], "offsets": [ [ 799, 807 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "PMID-7721885_T12" }, { "role": "Cause", "ref_id": "PMID-7721885_T18" } ] }, { "id": "PMID-7721885_E15", "type": "Regulation", "trigger": { "text": [ "affected" ], "offsets": [ [ 799, 807 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "PMID-7721885_T15" }, { "role": "Cause", "ref_id": "PMID-7721885_T18" } ] }, { "id": "PMID-7721885_E16", "type": "Regulation", "trigger": { "text": [ "affected" ], "offsets": [ [ 799, 807 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "PMID-7721885_T16" }, { "role": "Cause", "ref_id": "PMID-7721885_T18" } ] }, { "id": "PMID-7721885_E17", "type": "Regulation", "trigger": { "text": [ "affected" ], "offsets": [ [ 799, 807 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "PMID-7721885_T14" }, { "role": "Cause", "ref_id": "PMID-7721885_T18" } ] }, { "id": "PMID-7721885_E18", "type": "Regulation", "trigger": { "text": [ "affected" ], "offsets": [ [ 799, 807 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "PMID-7721885_T11" }, { "role": "Cause", "ref_id": "PMID-7721885_T18" } ] }, { "id": "PMID-7721885_E19", "type": "Regulation", "trigger": { "text": [ "affected" ], "offsets": [ [ 799, 807 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "PMID-7721885_T17" }, { "role": "Cause", "ref_id": "PMID-7721885_T18" } ] } ]

[]

[]

[ { "id": "PMID-7730624__text", "type": "abstract", "text": [ "Activation of transcription by binding of NF-E1 (YY1) to a newly identified element in the first exon of the human DR alpha gene. \nA previously unrecognized element, located downstream of the start site of transcription in the first exon of the DR alpha gene, has been defined that enhances promoter activity up to eightfold in a position-dependent manner. Mutations in this DNA-binding site abolished binding of a nuclear factor in human B cell nuclear extract and decreased the activity of the DR alpha promoter to a basal level. Significant sequence homology of this element was found in the DNA of the DR beta, DP alpha and -beta, and DQ alpha genes, always located downstream of the transcriptional start site. The nuclear factor binds to the DR alpha and DP alpha element but not to the element in the DQ alpha gene. It was identified as NF-E1 (YY1). This protein, previously identified by its binding to the Ig kappa 3' enhancer and the Ig heavy chain mu E1 site, thus also appears to be quite important in the regulation of MHC class II gene expression. " ], "offsets": [ [ 0, 1062 ] ] } ]

[ { "id": "PMID-7730624_T1", "type": "Protein", "text": [ "NF-E1" ], "offsets": [ [ 42, 47 ] ], "normalized": [] }, { "id": "PMID-7730624_T2", "type": "Protein", "text": [ "YY1" ], "offsets": [ [ 49, 52 ] ], "normalized": [] }, { "id": "PMID-7730624_T3", "type": "Protein", "text": [ "DR alpha" ], "offsets": [ [ 115, 123 ] ], "normalized": [] }, { "id": "PMID-7730624_T4", "type": "Protein", "text": [ "DR alpha" ], "offsets": [ [ 245, 253 ] ], "normalized": [] }, { "id": "PMID-7730624_T5", "type": "Protein", "text": [ "DR alpha" ], "offsets": [ [ 496, 504 ] ], "normalized": [] }, { "id": "PMID-7730624_T6", "type": "Protein", "text": [ "DR beta" ], "offsets": [ [ 606, 613 ] ], "normalized": [] }, { "id": "PMID-7730624_T7", "type": "Protein", "text": [ "DQ alpha" ], "offsets": [ [ 639, 647 ] ], "normalized": [] }, { "id": "PMID-7730624_T8", "type": "Protein", "text": [ "DR alpha" ], "offsets": [ [ 748, 756 ] ], "normalized": [] }, { "id": "PMID-7730624_T9", "type": "Protein", "text": [ "DP alpha" ], "offsets": [ [ 761, 769 ] ], "normalized": [] }, { "id": "PMID-7730624_T10", "type": "Protein", "text": [ "DQ alpha" ], "offsets": [ [ 808, 816 ] ], "normalized": [] }, { "id": "PMID-7730624_T11", "type": "Protein", "text": [ "NF-E1" ], "offsets": [ [ 844, 849 ] ], "normalized": [] }, { "id": "PMID-7730624_T12", "type": "Protein", "text": [ "YY1" ], "offsets": [ [ 851, 854 ] ], "normalized": [] }, { "id": "PMID-7730624_T15", "type": "Entity", "text": [ "promoter" ], "offsets": [ [ 505, 513 ] ], "normalized": [] }, { "id": "PMID-7730624_T17", "type": "Entity", "text": [ "element" ], "offsets": [ [ 793, 800 ] ], "normalized": [] } ]

[ { "id": "PMID-7730624_E1", "type": "Binding", "trigger": { "text": [ "binding" ], "offsets": [ [ 31, 38 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "PMID-7730624_T1" }, { "role": "Theme", "ref_id": "PMID-7730624_T3" } ] }, { "id": "PMID-7730624_E2", "type": "Negative_regulation", "trigger": { "text": [ "decreased" ], "offsets": [ [ 466, 475 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "PMID-7730624_T5" }, { "role": "Site", "ref_id": "PMID-7730624_T15" } ] }, { "id": "PMID-7730624_E3", "type": "Binding", "trigger": { "text": [ "binds" ], "offsets": [ [ 735, 740 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "PMID-7730624_T10" }, { "role": "Site", "ref_id": "PMID-7730624_T17" } ] }, { "id": "PMID-7730624_E4", "type": "Binding", "trigger": { "text": [ "binding" ], "offsets": [ [ 900, 907 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "PMID-7730624_T11" } ] } ]

[ { "id": "PMID-7730624_1", "entity_ids": [ "PMID-7730624_T1", "PMID-7730624_T2" ] }, { "id": "PMID-7730624_2", "entity_ids": [ "PMID-7730624_T11", "PMID-7730624_T12" ] } ]

[]

[ { "id": "PMID-7739562__text", "type": "abstract", "text": [ "Coupling of a signal response domain in I kappa B alpha to multiple pathways for NF-kappa B activation. \nThe eukaryotic transcription factor NF-kappa B plays a central role in the induced expression of human immunodeficiency virus type 1 and in many aspects of the genetic program mediating normal T-cell activation and growth. The nuclear activity of NF-kappa B is tightly regulated from the cytoplasmic compartment by an inhibitory subunit called I kappa B alpha. This cytoplasmic inhibitor is rapidly phosphorylated and degraded in response to a diverse set of NF-kappa B-inducing agents, including T-cell mitogens, proinflammatory cytokines, and viral transactivators such as the Tax protein of human T-cell leukemia virus type 1. To explore these I kappa B alpha-dependent mechanisms for NF-kappa B induction, we identified novel mutants of I kappa B alpha that uncouple its inhibitory and signal-transducing functions in human T lymphocytes. Specifically, removal of the N-terminal 36 amino acids of I kappa B alpha failed to disrupt its ability to form latent complexes with NF-kappa B in the cytoplasm. However, this deletion mutation prevented the induced phosphorylation, degradative loss, and functional release of I kappa B alpha from NF-kappa B in Tax-expressing cells. Alanine substitutions introduced at two serine residues positioned within this N-terminal regulatory region of I kappa B alpha also yielded constitutive repressors that escaped from Tax-induced turnover and that potently inhibited immune activation pathways for NF-kappa B induction, including those initiated from antigen and cytokine receptors. In contrast, introduction of a phosphoserine mimetic at these sites rectified this functional defect, a finding consistent with a causal linkage between the phosphorylation status and proteolytic stability of this cytoplasmic inhibitor. Together, these in vivo studies define a critical signal response domain in I kappa B alpha that coordinately controls the biologic activities of I kappa B alpha and NF-kappa B in response to viral and immune stimuli. " ], "offsets": [ [ 0, 2085 ] ] } ]

[ { "id": "PMID-7739562_T1", "type": "Protein", "text": [ "I kappa B alpha" ], "offsets": [ [ 40, 55 ] ], "normalized": [] }, { "id": "PMID-7739562_T2", "type": "Protein", "text": [ "I kappa B alpha" ], "offsets": [ [ 449, 464 ] ], "normalized": [] }, { "id": "PMID-7739562_T3", "type": "Protein", "text": [ "Tax" ], "offsets": [ [ 684, 687 ] ], "normalized": [] }, { "id": "PMID-7739562_T4", "type": "Protein", "text": [ "I kappa B alpha" ], "offsets": [ [ 752, 767 ] ], "normalized": [] }, { "id": "PMID-7739562_T5", "type": "Protein", "text": [ "I kappa B alpha" ], "offsets": [ [ 846, 861 ] ], "normalized": [] }, { "id": "PMID-7739562_T6", "type": "Protein", "text": [ "I kappa B alpha" ], "offsets": [ [ 1006, 1021 ] ], "normalized": [] }, { "id": "PMID-7739562_T7", "type": "Protein", "text": [ "I kappa B alpha" ], "offsets": [ [ 1226, 1241 ] ], "normalized": [] }, { "id": "PMID-7739562_T8", "type": "Protein", "text": [ "Tax" ], "offsets": [ [ 1261, 1264 ] ], "normalized": [] }, { "id": "PMID-7739562_T9", "type": "Protein", "text": [ "I kappa B alpha" ], "offsets": [ [ 1394, 1409 ] ], "normalized": [] }, { "id": "PMID-7739562_T10", "type": "Protein", "text": [ "Tax" ], "offsets": [ [ 1465, 1468 ] ], "normalized": [] }, { "id": "PMID-7739562_T11", "type": "Protein", "text": [ "I kappa B alpha" ], "offsets": [ [ 1943, 1958 ] ], "normalized": [] }, { "id": "PMID-7739562_T12", "type": "Protein", "text": [ "I kappa B alpha" ], "offsets": [ [ 2013, 2028 ] ], "normalized": [] } ]

[ { "id": "PMID-7739562_E1", "type": "Phosphorylation", "trigger": { "text": [ "phosphorylated" ], "offsets": [ [ 504, 518 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "PMID-7739562_T2" } ] }, { "id": "PMID-7739562_E2", "type": "Protein_catabolism", "trigger": { "text": [ "degraded" ], "offsets": [ [ 523, 531 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "PMID-7739562_T2" } ] }, { "id": "PMID-7739562_E3", "type": "Positive_regulation", "trigger": { "text": [ "in response to" ], "offsets": [ [ 532, 546 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "PMID-7739562_E2" }, { "role": "Cause", "ref_id": "PMID-7739562_T3" } ] }, { "id": "PMID-7739562_E4", "type": "Positive_regulation", "trigger": { "text": [ "in response to" ], "offsets": [ [ 532, 546 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "PMID-7739562_E1" }, { "role": "Cause", "ref_id": "PMID-7739562_T3" } ] }, { "id": "PMID-7739562_E5", "type": "Positive_regulation", "trigger": { "text": [ "in response to" ], "offsets": [ [ 532, 546 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "PMID-7739562_E2" } ] }, { "id": "PMID-7739562_E6", "type": "Positive_regulation", "trigger": { "text": [ "in response to" ], "offsets": [ [ 532, 546 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "PMID-7739562_E1" } ] }, { "id": "PMID-7739562_E7", "type": "Negative_regulation", "trigger": { "text": [ "prevented" ], "offsets": [ [ 1143, 1152 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "PMID-7739562_E10" }, { "role": "Cause", "ref_id": "PMID-7739562_T5" } ] }, { "id": "PMID-7739562_E8", "type": "Negative_regulation", "trigger": { "text": [ "prevented" ], "offsets": [ [ 1143, 1152 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "PMID-7739562_E9" }, { "role": "Cause", "ref_id": "PMID-7739562_T5" } ] }, { "id": "PMID-7739562_E9", "type": "Positive_regulation", "trigger": { "text": [ "induced" ], "offsets": [ [ 1157, 1164 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "PMID-7739562_E11" } ] }, { "id": "PMID-7739562_E10", "type": "Positive_regulation", "trigger": { "text": [ "induced" ], "offsets": [ [ 1157, 1164 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "PMID-7739562_E12" } ] }, { "id": "PMID-7739562_E11", "type": "Phosphorylation", "trigger": { "text": [ "phosphorylation" ], "offsets": [ [ 1165, 1180 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "PMID-7739562_T7" } ] }, { "id": "PMID-7739562_E12", "type": "Protein_catabolism", "trigger": { "text": [ "degradative loss" ], "offsets": [ [ 1182, 1198 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "PMID-7739562_T7" } ] }, { "id": "PMID-7739562_E13", "type": "Phosphorylation", "trigger": { "text": [ "phosphorylation" ], "offsets": [ [ 1787, 1802 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "PMID-7739562_T7" } ] }, { "id": "PMID-7739562_E14", "type": "Protein_catabolism", "trigger": { "text": [ "proteolytic" ], "offsets": [ [ 1814, 1825 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "PMID-7739562_T7" } ] }, { "id": "PMID-7739562_E15", "type": "Regulation", "trigger": { "text": [ "controls" ], "offsets": [ [ 1977, 1985 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "PMID-7739562_T12" } ] }, { "id": "PMID-7739562_E16", "type": "Positive_regulation", "trigger": { "text": [ "in response to" ], "offsets": [ [ 2044, 2058 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "PMID-7739562_E15" } ] } ]

[]

[]

[ { "id": "PMID-7742037__text", "type": "abstract", "text": [ "HIV type 1 protease activation of NF-kappa B within T lymphoid cells. \nNF-kappa B is a nuclear protein of the rel oncogene family capable of enhancing transcription of several cellular genes, including IL-2 and the IL-2 receptor, and viral genes transcribed from the HIV-1 LTR. It has been reported that HIV-1 protease may cleave the NF-kappa B precursor to its active form in vitro. In this study the effects of HIV protease on NF-kappa B precursor activation were examined in Jurkat T cells by introducing a protease expression vector into the cells. Increased NF-kappa B activity was observed and this increased activity was blocked by a specific inhibitor of the viral protease. Viral transcription, as measured using LTR-CAT assays, was only slightly enhanced in the HIV-protease expressing cells, while secretion of IL-2 and expression of the IL-2 receptor were not affected. The limited activation of NF-kappa B by HIV protease appears unlikely to have a significant effect on virus expression or T cell function. " ], "offsets": [ [ 0, 1021 ] ] } ]

[ { "id": "PMID-7742037_T1", "type": "Protein", "text": [ "HIV type 1 protease" ], "offsets": [ [ 0, 19 ] ], "normalized": [] }, { "id": "PMID-7742037_T2", "type": "Protein", "text": [ "IL-2" ], "offsets": [ [ 202, 206 ] ], "normalized": [] }, { "id": "PMID-7742037_T3", "type": "Protein", "text": [ "HIV-1 protease" ], "offsets": [ [ 304, 318 ] ], "normalized": [] }, { "id": "PMID-7742037_T4", "type": "Protein", "text": [ "HIV protease" ], "offsets": [ [ 413, 425 ] ], "normalized": [] }, { "id": "PMID-7742037_T5", "type": "Protein", "text": [ "CAT" ], "offsets": [ [ 726, 729 ] ], "normalized": [] }, { "id": "PMID-7742037_T6", "type": "Protein", "text": [ "HIV-protease" ], "offsets": [ [ 772, 784 ] ], "normalized": [] }, { "id": "PMID-7742037_T7", "type": "Protein", "text": [ "IL-2" ], "offsets": [ [ 822, 826 ] ], "normalized": [] }, { "id": "PMID-7742037_T8", "type": "Protein", "text": [ "HIV protease" ], "offsets": [ [ 922, 934 ] ], "normalized": [] } ]

[ { "id": "PMID-7742037_E1", "type": "Positive_regulation", "trigger": { "text": [ "enhancing" ], "offsets": [ [ 141, 150 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "PMID-7742037_E2" } ] }, { "id": "PMID-7742037_E2", "type": "Transcription", "trigger": { "text": [ "transcription" ], "offsets": [ [ 151, 164 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "PMID-7742037_T2" } ] }, { "id": "PMID-7742037_E3", "type": "Positive_regulation", "trigger": { "text": [ "introducing" ], "offsets": [ [ 496, 507 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "PMID-7742037_E4" } ] }, { "id": "PMID-7742037_E4", "type": "Gene_expression", "trigger": { "text": [ "expression" ], "offsets": [ [ 519, 529 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "PMID-7742037_T4" } ] }, { "id": "PMID-7742037_E5", "type": "Negative_regulation", "trigger": { "text": [ "inhibitor" ], "offsets": [ [ 650, 659 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "PMID-7742037_T4" } ] }, { "id": "PMID-7742037_E6", "type": "Gene_expression", "trigger": { "text": [ "expressing" ], "offsets": [ [ 785, 795 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "PMID-7742037_T6" } ] }, { "id": "PMID-7742037_E7", "type": "Localization", "trigger": { "text": [ "secretion" ], "offsets": [ [ 809, 818 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "PMID-7742037_T7" } ] }, { "id": "PMID-7742037_E8", "type": "Regulation", "trigger": { "text": [ "affected" ], "offsets": [ [ 872, 880 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "PMID-7742037_E7" } ] } ]

[]

[]

[ { "id": "PMID-7788861__text", "type": "abstract", "text": [ "Expression of Ah receptor (TCDD receptor) during human monocytic differentiation. \nWe have previously found a high expression of human Ah receptor (TCDD receptor) mRNA in peripheral blood cells of individuals. In this paper, the expression of this gene in blood cells was first investigated in fractions of nucleated cells, revealing predominant expression of the Ah receptor gene in the monocyte fraction. Then the expression levels of AhR mRNA in various hematopoietic cell lines were examined together with those of Arnt and P450IA1. AhR was expressed at high levels in monocytoid U937, THP1, and HEL/S cells, and at moderate levels in promyelocytic HL60 cells and erythroblastic HEL cells. However, it was not detected in lymphoid cells MOLT4 (T cell) and BALL1 (B cell), nor in K562 erythroblasts. Furthermore, a specific induction of AhR during monocytic differentiation was investigated in HL60 and HEL cells. HL60 cells were induced to differentiate toward monocytes-macrophages by incubation with phorbol ester, showing a 5- to 2-fold increase of AhR mRNA. The incubation with transforming growth factor beta 1 and 1 alpha,25-dihydroxyvitamin D3 resulted in a 5- to 7-fold increase of AhR mRNA. The HEL cells also exhibited a similar elevation of AhR mRNA level, when they had differentiated toward monocyte-macrophage cells by these combined inducers, but little change in the mRNA level was observed when the cells were induced to differentiate into other cell types. Treatment of the differentiated HL60 cells with 3-methylcholanthrene, a ligand of AhR, induced the expression of the P450IA1 gene. These results indicated that expression of AhR mRNA was significantly induced during monocytic differentiation and that the differentiated cells were responsive to xenobiotics. Our results suggest that AhR may play an important role in the function of monocytes and also in the eventual activation of environmental carcinogens. " ], "offsets": [ [ 0, 1938 ] ] } ]

[ { "id": "PMID-7788861_T1", "type": "Protein", "text": [ "Ah receptor" ], "offsets": [ [ 14, 25 ] ], "normalized": [] }, { "id": "PMID-7788861_T2", "type": "Protein", "text": [ "TCDD receptor" ], "offsets": [ [ 27, 40 ] ], "normalized": [] }, { "id": "PMID-7788861_T3", "type": "Protein", "text": [ "Ah receptor" ], "offsets": [ [ 135, 146 ] ], "normalized": [] }, { "id": "PMID-7788861_T4", "type": "Protein", "text": [ "TCDD receptor" ], "offsets": [ [ 148, 161 ] ], "normalized": [] }, { "id": "PMID-7788861_T5", "type": "Protein", "text": [ "Ah receptor" ], "offsets": [ [ 364, 375 ] ], "normalized": [] }, { "id": "PMID-7788861_T6", "type": "Protein", "text": [ "AhR" ], "offsets": [ [ 437, 440 ] ], "normalized": [] }, { "id": "PMID-7788861_T7", "type": "Protein", "text": [ "P450IA1" ], "offsets": [ [ 528, 535 ] ], "normalized": [] }, { "id": "PMID-7788861_T8", "type": "Protein", "text": [ "AhR" ], "offsets": [ [ 537, 540 ] ], "normalized": [] }, { "id": "PMID-7788861_T9", "type": "Protein", "text": [ "AhR" ], "offsets": [ [ 840, 843 ] ], "normalized": [] }, { "id": "PMID-7788861_T10", "type": "Protein", "text": [ "AhR" ], "offsets": [ [ 1056, 1059 ] ], "normalized": [] }, { "id": "PMID-7788861_T11", "type": "Protein", "text": [ "transforming growth factor beta 1" ], "offsets": [ [ 1086, 1119 ] ], "normalized": [] }, { "id": "PMID-7788861_T12", "type": "Protein", "text": [ "AhR" ], "offsets": [ [ 1194, 1197 ] ], "normalized": [] }, { "id": "PMID-7788861_T13", "type": "Protein", "text": [ "AhR" ], "offsets": [ [ 1256, 1259 ] ], "normalized": [] }, { "id": "PMID-7788861_T14", "type": "Protein", "text": [ "AhR" ], "offsets": [ [ 1561, 1564 ] ], "normalized": [] }, { "id": "PMID-7788861_T15", "type": "Protein", "text": [ "P450IA1" ], "offsets": [ [ 1596, 1603 ] ], "normalized": [] }, { "id": "PMID-7788861_T16", "type": "Protein", "text": [ "AhR" ], "offsets": [ [ 1653, 1656 ] ], "normalized": [] }, { "id": "PMID-7788861_T17", "type": "Protein", "text": [ "AhR" ], "offsets": [ [ 1812, 1815 ] ], "normalized": [] } ]

[ { "id": "PMID-7788861_E1", "type": "Gene_expression", "trigger": { "text": [ "Expression" ], "offsets": [ [ 0, 10 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "PMID-7788861_T1" } ] }, { "id": "PMID-7788861_E2", "type": "Transcription", "trigger": { "text": [ "expression" ], "offsets": [ [ 115, 125 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "PMID-7788861_T4" } ] }, { "id": "PMID-7788861_E3", "type": "Gene_expression", "trigger": { "text": [ "expression" ], "offsets": [ [ 229, 239 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "PMID-7788861_T4" } ] }, { "id": "PMID-7788861_E4", "type": "Gene_expression", "trigger": { "text": [ "expression" ], "offsets": [ [ 346, 356 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "PMID-7788861_T5" } ] }, { "id": "PMID-7788861_E5", "type": "Gene_expression", "trigger": { "text": [ "expression" ], "offsets": [ [ 416, 426 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "PMID-7788861_T7" } ] }, { "id": "PMID-7788861_E6", "type": "Transcription", "trigger": { "text": [ "expression" ], "offsets": [ [ 416, 426 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "PMID-7788861_T6" } ] }, { "id": "PMID-7788861_E7", "type": "Gene_expression", "trigger": { "text": [ "expressed" ], "offsets": [ [ 545, 554 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "PMID-7788861_T8" } ] }, { "id": "PMID-7788861_E8", "type": "Gene_expression", "trigger": { "text": [ "detected" ], "offsets": [ [ 714, 722 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "PMID-7788861_T8" } ] }, { "id": "PMID-7788861_E9", "type": "Positive_regulation", "trigger": { "text": [ "induction" ], "offsets": [ [ 827, 836 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "PMID-7788861_T9" } ] }, { "id": "PMID-7788861_E10", "type": "Positive_regulation", "trigger": { "text": [ "increase" ], "offsets": [ [ 1044, 1052 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "PMID-7788861_T10" } ] }, { "id": "PMID-7788861_E11", "type": "Positive_regulation", "trigger": { "text": [ "increase" ], "offsets": [ [ 1182, 1190 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "PMID-7788861_T12" } ] }, { "id": "PMID-7788861_E12", "type": "Positive_regulation", "trigger": { "text": [ "elevation" ], "offsets": [ [ 1243, 1252 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "PMID-7788861_T13" } ] }, { "id": "PMID-7788861_E13", "type": "Regulation", "trigger": { "text": [ "change" ], "offsets": [ [ 1373, 1379 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "PMID-7788861_T13" } ] }, { "id": "PMID-7788861_E14", "type": "Binding", "trigger": { "text": [ "ligand" ], "offsets": [ [ 1551, 1557 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "PMID-7788861_T14" } ] }, { "id": "PMID-7788861_E15", "type": "Positive_regulation", "trigger": { "text": [ "induced" ], "offsets": [ [ 1566, 1573 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "PMID-7788861_E16" } ] }, { "id": "PMID-7788861_E16", "type": "Gene_expression", "trigger": { "text": [ "expression" ], "offsets": [ [ 1578, 1588 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "PMID-7788861_T15" } ] }, { "id": "PMID-7788861_E17", "type": "Transcription", "trigger": { "text": [ "expression" ], "offsets": [ [ 1639, 1649 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "PMID-7788861_T16" } ] }, { "id": "PMID-7788861_E18", "type": "Positive_regulation", "trigger": { "text": [ "induced" ], "offsets": [ [ 1680, 1687 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "PMID-7788861_E17" } ] } ]

[ { "id": "PMID-7788861_1", "entity_ids": [ "PMID-7788861_T1", "PMID-7788861_T2" ] }, { "id": "PMID-7788861_2", "entity_ids": [ "PMID-7788861_T4", "PMID-7788861_T3" ] } ]

[]

[ { "id": "PMID-7802642__text", "type": "abstract", "text": [ "Platelet-activating factor (PAF) positively auto-regulates the expression of human PAF receptor transcript 1 (leukocyte-type) through NF-kappa B. \nThe human platelet-activating factor receptor (PAFR) gene is transcribed by two distinct promoters (promoter 1 and promoter 2) to generate two transcripts (designated as PAFR transcript 1 and PAFR transcript 2), though their open reading frames are identical. By primer extension analysis to discriminate two transcripts, we found that the levels of PAFR transcript 1 (leukocyte-type), but not PAFR transcript 2 (tissue-type), are upregulated by PAF as well as by 12-O-tetradecanoylphorbol-13-acetate (TPA) in the human stomach cancer cell line (JR-St cells) which expresses both functional PAFR transcript 1 and PAFR transcript 2 endogenously. Functional analysis of the promoter 1 with a transient expression assay using chloramphenicol acetyltransferase (CAT) gene as a reporter showed that both PAF and TPA activated the promoter 1 but not the deleted promoter lacking the three consensus binding sites for NF-kappa B located from -571 bp to -459 bp. These findings suggest a molecular mechanism of positive regulation of PAFR gene expression by PAF through NF-kappa B, possibly by a phosphorylation reaction involving protein kinase C by PAF. " ], "offsets": [ [ 0, 1295 ] ] } ]

[ { "id": "PMID-7802642_T1", "type": "Protein", "text": [ "PAF receptor" ], "offsets": [ [ 83, 95 ] ], "normalized": [] }, { "id": "PMID-7802642_T2", "type": "Protein", "text": [ "platelet-activating factor receptor" ], "offsets": [ [ 157, 192 ] ], "normalized": [] }, { "id": "PMID-7802642_T3", "type": "Protein", "text": [ "PAFR" ], "offsets": [ [ 194, 198 ] ], "normalized": [] }, { "id": "PMID-7802642_T4", "type": "Protein", "text": [ "PAFR" ], "offsets": [ [ 317, 321 ] ], "normalized": [] }, { "id": "PMID-7802642_T5", "type": "Protein", "text": [ "PAFR" ], "offsets": [ [ 339, 343 ] ], "normalized": [] }, { "id": "PMID-7802642_T6", "type": "Protein", "text": [ "PAFR" ], "offsets": [ [ 497, 501 ] ], "normalized": [] }, { "id": "PMID-7802642_T7", "type": "Protein", "text": [ "PAFR" ], "offsets": [ [ 541, 545 ] ], "normalized": [] }, { "id": "PMID-7802642_T8", "type": "Protein", "text": [ "PAFR" ], "offsets": [ [ 738, 742 ] ], "normalized": [] }, { "id": "PMID-7802642_T9", "type": "Protein", "text": [ "PAFR" ], "offsets": [ [ 760, 764 ] ], "normalized": [] }, { "id": "PMID-7802642_T10", "type": "Protein", "text": [ "chloramphenicol acetyltransferase" ], "offsets": [ [ 870, 903 ] ], "normalized": [] }, { "id": "PMID-7802642_T11", "type": "Protein", "text": [ "CAT" ], "offsets": [ [ 905, 908 ] ], "normalized": [] }, { "id": "PMID-7802642_T12", "type": "Protein", "text": [ "PAFR" ], "offsets": [ [ 1173, 1177 ] ], "normalized": [] } ]

[ { "id": "PMID-7802642_E1", "type": "Positive_regulation", "trigger": { "text": [ "expression" ], "offsets": [ [ 63, 73 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "PMID-7802642_T1" } ] }, { "id": "PMID-7802642_E2", "type": "Transcription", "trigger": { "text": [ "transcribed" ], "offsets": [ [ 208, 219 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "PMID-7802642_T3" } ] }, { "id": "PMID-7802642_E3", "type": "Positive_regulation", "trigger": { "text": [ "by" ], "offsets": [ [ 220, 222 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "PMID-7802642_E2" } ] }, { "id": "PMID-7802642_E4", "type": "Positive_regulation", "trigger": { "text": [ "upregulated" ], "offsets": [ [ 578, 589 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "PMID-7802642_T7" } ] }, { "id": "PMID-7802642_E5", "type": "Gene_expression", "trigger": { "text": [ "expresses" ], "offsets": [ [ 712, 721 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "PMID-7802642_T8" } ] }, { "id": "PMID-7802642_E6", "type": "Gene_expression", "trigger": { "text": [ "expresses" ], "offsets": [ [ 712, 721 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "PMID-7802642_T9" } ] }, { "id": "PMID-7802642_E7", "type": "Positive_regulation", "trigger": { "text": [ "positive regulation" ], "offsets": [ [ 1150, 1169 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "PMID-7802642_E8" } ] }, { "id": "PMID-7802642_E8", "type": "Gene_expression", "trigger": { "text": [ "expression" ], "offsets": [ [ 1183, 1193 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "PMID-7802642_T12" } ] } ]

[ { "id": "PMID-7802642_1", "entity_ids": [ "PMID-7802642_T3", "PMID-7802642_T2" ] }, { "id": "PMID-7802642_2", "entity_ids": [ "PMID-7802642_T10", "PMID-7802642_T11" ] } ]

[]

[ { "id": "PMID-7823943__text", "type": "abstract", "text": [ "Distinct roles of the molecular chaperone hsp90 in modulating dioxin receptor function via the basic helix-loop-helix and PAS domains. \nThe intracellular dioxin receptor mediates signal transduction by dioxin and functions as a ligand-activated transcription factor. It contains a basic helix-loop-helix (bHLH) motif contiguous with a Per-Arnt-Sim (PAS) homology region. In extracts from nonstimulated cells the receptor is recovered in an inducible cytoplasmic form associated with the 90-kDa heat shock protein (hsp90), a molecular chaperone. We have reconstituted ligand-dependent activation of the receptor to a DNA-binding form by using the dioxin receptor and its bHLH-PAS partner factor Arnt expressed by in vitro translation in reticulocyte lysate. Deletion of the PAS domain of the receptor resulted in constitutive dimerization with Arnt. In contrast, this receptor mutant showed low levels of xenobiotic response element-binding activity, indicating that the PAS domain may be important for DNA-binding affinity and/or specificity of the receptor. It was not possible to reconstitute dioxin receptor function with proteins expressed in wheat germ lysate. In line with these observations, reticulocyte lysate but not wheat germ lysate promoted the association of de novo synthesized dioxin receptor with hsp90. At least two distinct domains of the receptor mediated interaction with hsp90: the ligand-binding domain located within the PAS region and, surprisingly, the bHLH domain. Whereas ligand-binding activity correlated with association with hsp90, bHLH-hsp90 interaction appeared to be important for DNA-binding activity but not for dimerization of the receptor. Several distinct roles for hsp90 in modulating dioxin receptor function are therefore likely: correct folding of the ligand-binding domain, interference with Arnt heterodimerization, and folding of a DNA-binding conformation of the bHLH domain. Thus, the dioxin receptor system provides a complex and interesting model of the regulation of transcription factors by hsp90. " ], "offsets": [ [ 0, 2051 ] ] } ]

[]

[]

[]

[]

[ { "id": "PMID-7826623__text", "type": "abstract", "text": [ "T-cell functional regions of the human IL-3 proximal promoter. \nThe human interleukin-3 (IL-3) gene is expressed almost exclusively in activated T cells. Its expression is regulated at both the transcriptional and post-transcriptional level. We have previously shown that treatment of Jurkat T cells with phytohemaglutinin (PHA) and the phorbol ester, PMA, activated transcription initiation from the IL-3 gene. To define the regions of the gene required for transcription activation, we generated a series of reporter constructs containing different regions of the IL-3 gene 5' and 3' flanking sequences. Both positive and negative regulatory elements were identified in the proximal 5' flanking region of the IL-3 gene. The promoter region between -173 and -60 contained the strongest activating elements. The transcription factor AP-1 could bind to this positive activator region of the promoter. We also examined the function of the IL-3 CK-1/CK-2 elements that are present in many cytokine genes and found that they acted as a repressor of basal level expression when cloned upstream of a heterologous promoter but were also inducible by PMA/PHA. " ], "offsets": [ [ 0, 1152 ] ] } ]

[ { "id": "PMID-7826623_T1", "type": "Protein", "text": [ "IL-3" ], "offsets": [ [ 39, 43 ] ], "normalized": [] }, { "id": "PMID-7826623_T2", "type": "Protein", "text": [ "interleukin-3" ], "offsets": [ [ 74, 87 ] ], "normalized": [] }, { "id": "PMID-7826623_T3", "type": "Protein", "text": [ "IL-3" ], "offsets": [ [ 89, 93 ] ], "normalized": [] }, { "id": "PMID-7826623_T4", "type": "Protein", "text": [ "phytohemaglutinin" ], "offsets": [ [ 305, 322 ] ], "normalized": [] }, { "id": "PMID-7826623_T5", "type": "Protein", "text": [ "PHA" ], "offsets": [ [ 324, 327 ] ], "normalized": [] }, { "id": "PMID-7826623_T6", "type": "Protein", "text": [ "IL-3" ], "offsets": [ [ 401, 405 ] ], "normalized": [] }, { "id": "PMID-7826623_T7", "type": "Protein", "text": [ "IL-3" ], "offsets": [ [ 566, 570 ] ], "normalized": [] }, { "id": "PMID-7826623_T8", "type": "Protein", "text": [ "IL-3" ], "offsets": [ [ 711, 715 ] ], "normalized": [] }, { "id": "PMID-7826623_T9", "type": "Protein", "text": [ "IL-3" ], "offsets": [ [ 937, 941 ] ], "normalized": [] }, { "id": "PMID-7826623_T10", "type": "Protein", "text": [ "CK-1" ], "offsets": [ [ 942, 946 ] ], "normalized": [] }, { "id": "PMID-7826623_T11", "type": "Protein", "text": [ "CK-2" ], "offsets": [ [ 947, 951 ] ], "normalized": [] }, { "id": "PMID-7826623_T12", "type": "Protein", "text": [ "PHA" ], "offsets": [ [ 1147, 1150 ] ], "normalized": [] } ]

[ { "id": "PMID-7826623_E1", "type": "Gene_expression", "trigger": { "text": [ "expressed" ], "offsets": [ [ 103, 112 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "PMID-7826623_T3" } ] }, { "id": "PMID-7826623_E2", "type": "Gene_expression", "trigger": { "text": [ "expression" ], "offsets": [ [ 158, 168 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "PMID-7826623_T3" } ] }, { "id": "PMID-7826623_E3", "type": "Regulation", "trigger": { "text": [ "regulated" ], "offsets": [ [ 172, 181 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "PMID-7826623_E2" } ] }, { "id": "PMID-7826623_E4", "type": "Regulation", "trigger": { "text": [ "regulated" ], "offsets": [ [ 172, 181 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "PMID-7826623_E5" } ] }, { "id": "PMID-7826623_E5", "type": "Transcription", "trigger": { "text": [ "transcriptional" ], "offsets": [ [ 194, 209 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "PMID-7826623_T3" } ] }, { "id": "PMID-7826623_E6", "type": "Positive_regulation", "trigger": { "text": [ "activated" ], "offsets": [ [ 357, 366 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "PMID-7826623_E7" } ] }, { "id": "PMID-7826623_E7", "type": "Transcription", "trigger": { "text": [ "transcription initiation" ], "offsets": [ [ 367, 391 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "PMID-7826623_T6" } ] }, { "id": "PMID-7826623_E8", "type": "Positive_regulation", "trigger": { "text": [ "required" ], "offsets": [ [ 446, 454 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "PMID-7826623_E6" }, { "role": "Cause", "ref_id": "PMID-7826623_T7" } ] } ]

[ { "id": "PMID-7826623_1", "entity_ids": [ "PMID-7826623_T3", "PMID-7826623_T2" ] }, { "id": "PMID-7826623_2", "entity_ids": [ "PMID-7826623_T4", "PMID-7826623_T5" ] } ]

[]

[ { "id": "PMID-7836389__text", "type": "abstract", "text": [ "Two distinct signalling pathways are involved in the control of the biphasic junB transcription induced by interleukin-6 in the B cell hybridoma 7TD1. \nWe have measured the level of junB mRNA in the B hybridoma cell line 7TD1, under interleukin-6 (IL-6) stimulation. IL-6 increases junB mRNA in a biphasic fashion. The first early-induced peak was transient and likely corresponds to the well documented typical junB mRNA, stimulated in response to numerous growth factors, including IL-6. At variance, the second peak which has never been reported previously, lasted several hours. As a consequence of its effect on junB mRNA, IL-6 stimulated, in a biphasic fashion, the nuclear accumulation of the JunB protein. In this study, we demonstrated that IL-6 regulation occurred exclusively at the transcriptional level and that the bimodal increase of junB mRNA and JunB protein can be accounted for by a biphasic stimulation of junB transcription. Furthermore, our data point to two major differences between the mechanism of control of the early and the late IL-6-induced junB transcription waves. First, cycloheximide strongly potentiated the transcription of the second wave, whereas it failed to affect the early-induced burst. Second, tyrphostin, a tyrosine kinase inhibitor, impaired the expression of the first but not the second junB mRNA peak. Conversely, genistein, another tyrosine kinase inhibitor, totally abolished the expression of the second peak of junB mRNA whereas it did not affect the expression of the first peak. Altogether these data indicate that, in 7TD1 cells, IL-6 controls junB transcription in a biphasic fashion by means of two separate transduction pathways. " ], "offsets": [ [ 0, 1689 ] ] } ]

[ { "id": "PMID-7836389_T1", "type": "Protein", "text": [ "junB" ], "offsets": [ [ 77, 81 ] ], "normalized": [] }, { "id": "PMID-7836389_T2", "type": "Protein", "text": [ "interleukin-6" ], "offsets": [ [ 107, 120 ] ], "normalized": [] }, { "id": "PMID-7836389_T3", "type": "Protein", "text": [ "junB" ], "offsets": [ [ 182, 186 ] ], "normalized": [] }, { "id": "PMID-7836389_T4", "type": "Protein", "text": [ "interleukin-6" ], "offsets": [ [ 233, 246 ] ], "normalized": [] }, { "id": "PMID-7836389_T5", "type": "Protein", "text": [ "IL-6" ], "offsets": [ [ 248, 252 ] ], "normalized": [] }, { "id": "PMID-7836389_T6", "type": "Protein", "text": [ "IL-6" ], "offsets": [ [ 267, 271 ] ], "normalized": [] }, { "id": "PMID-7836389_T7", "type": "Protein", "text": [ "junB" ], "offsets": [ [ 282, 286 ] ], "normalized": [] }, { "id": "PMID-7836389_T8", "type": "Protein", "text": [ "junB" ], "offsets": [ [ 412, 416 ] ], "normalized": [] }, { "id": "PMID-7836389_T9", "type": "Protein", "text": [ "IL-6" ], "offsets": [ [ 484, 488 ] ], "normalized": [] }, { "id": "PMID-7836389_T10", "type": "Protein", "text": [ "junB" ], "offsets": [ [ 617, 621 ] ], "normalized": [] }, { "id": "PMID-7836389_T11", "type": "Protein", "text": [ "IL-6" ], "offsets": [ [ 628, 632 ] ], "normalized": [] }, { "id": "PMID-7836389_T12", "type": "Protein", "text": [ "JunB" ], "offsets": [ [ 700, 704 ] ], "normalized": [] }, { "id": "PMID-7836389_T13", "type": "Protein", "text": [ "IL-6" ], "offsets": [ [ 750, 754 ] ], "normalized": [] }, { "id": "PMID-7836389_T14", "type": "Protein", "text": [ "junB" ], "offsets": [ [ 849, 853 ] ], "normalized": [] }, { "id": "PMID-7836389_T15", "type": "Protein", "text": [ "JunB" ], "offsets": [ [ 863, 867 ] ], "normalized": [] }, { "id": "PMID-7836389_T16", "type": "Protein", "text": [ "junB" ], "offsets": [ [ 926, 930 ] ], "normalized": [] }, { "id": "PMID-7836389_T17", "type": "Protein", "text": [ "IL-6" ], "offsets": [ [ 1058, 1062 ] ], "normalized": [] }, { "id": "PMID-7836389_T18", "type": "Protein", "text": [ "junB" ], "offsets": [ [ 1071, 1075 ] ], "normalized": [] }, { "id": "PMID-7836389_T19", "type": "Protein", "text": [ "junB" ], "offsets": [ [ 1335, 1339 ] ], "normalized": [] }, { "id": "PMID-7836389_T20", "type": "Protein", "text": [ "junB" ], "offsets": [ [ 1464, 1468 ] ], "normalized": [] }, { "id": "PMID-7836389_T21", "type": "Protein", "text": [ "IL-6" ], "offsets": [ [ 1586, 1590 ] ], "normalized": [] }, { "id": "PMID-7836389_T22", "type": "Protein", "text": [ "junB" ], "offsets": [ [ 1600, 1604 ] ], "normalized": [] }, { "id": "PMID-7836389_T32", "type": "Entity", "text": [ "nuclear" ], "offsets": [ [ 672, 679 ] ], "normalized": [] } ]

[ { "id": "PMID-7836389_E1", "type": "Regulation", "trigger": { "text": [ "control" ], "offsets": [ [ 53, 60 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "PMID-7836389_E2" } ] }, { "id": "PMID-7836389_E2", "type": "Transcription", "trigger": { "text": [ "transcription" ], "offsets": [ [ 82, 95 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "PMID-7836389_T1" } ] }, { "id": "PMID-7836389_E3", "type": "Positive_regulation", "trigger": { "text": [ "induced" ], "offsets": [ [ 96, 103 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "PMID-7836389_E2" }, { "role": "Cause", "ref_id": "PMID-7836389_T2" } ] }, { "id": "PMID-7836389_E4", "type": "Transcription", "trigger": { "text": [ "level" ], "offsets": [ [ 173, 178 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "PMID-7836389_T3" } ] }, { "id": "PMID-7836389_E5", "type": "Regulation", "trigger": { "text": [ "under" ], "offsets": [ [ 227, 232 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "PMID-7836389_E4" } ] }, { "id": "PMID-7836389_E6", "type": "Positive_regulation", "trigger": { "text": [ "increases" ], "offsets": [ [ 272, 281 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "PMID-7836389_T7" }, { "role": "Cause", "ref_id": "PMID-7836389_T6" } ] }, { "id": "PMID-7836389_E7", "type": "Positive_regulation", "trigger": { "text": [ "stimulated" ], "offsets": [ [ 423, 433 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "PMID-7836389_T8" }, { "role": "Cause", "ref_id": "PMID-7836389_T9" } ] }, { "id": "PMID-7836389_E8", "type": "Regulation", "trigger": { "text": [ "effect" ], "offsets": [ [ 607, 613 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "PMID-7836389_T10" }, { "role": "Cause", "ref_id": "PMID-7836389_T11" } ] }, { "id": "PMID-7836389_E9", "type": "Positive_regulation", "trigger": { "text": [ "stimulated" ], "offsets": [ [ 633, 643 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "PMID-7836389_E10" }, { "role": "Cause", "ref_id": "PMID-7836389_E8" } ] }, { "id": "PMID-7836389_E10", "type": "Localization", "trigger": { "text": [ "accumulation" ], "offsets": [ [ 680, 692 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "PMID-7836389_T12" }, { "role": "AtLoc", "ref_id": "PMID-7836389_T32" } ] }, { "id": "PMID-7836389_E11", "type": "Positive_regulation", "trigger": { "text": [ "increase" ], "offsets": [ [ 837, 845 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "PMID-7836389_T14" }, { "role": "Cause", "ref_id": "PMID-7836389_E13" } ] }, { "id": "PMID-7836389_E12", "type": "Positive_regulation", "trigger": { "text": [ "increase" ], "offsets": [ [ 837, 845 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "PMID-7836389_T15" }, { "role": "Cause", "ref_id": "PMID-7836389_E13" } ] }, { "id": "PMID-7836389_E13", "type": "Positive_regulation", "trigger": { "text": [ "stimulation" ], "offsets": [ [ 911, 922 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "PMID-7836389_E14" }, { "role": "Cause", "ref_id": "PMID-7836389_T13" } ] }, { "id": "PMID-7836389_E14", "type": "Transcription", "trigger": { "text": [ "transcription" ], "offsets": [ [ 931, 944 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "PMID-7836389_T16" } ] }, { "id": "PMID-7836389_E15", "type": "Regulation", "trigger": { "text": [ "control" ], "offsets": [ [ 1024, 1031 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "PMID-7836389_E16" } ] }, { "id": "PMID-7836389_E16", "type": "Positive_regulation", "trigger": { "text": [ "induced" ], "offsets": [ [ 1063, 1070 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "PMID-7836389_E17" }, { "role": "Cause", "ref_id": "PMID-7836389_T17" } ] }, { "id": "PMID-7836389_E17", "type": "Transcription", "trigger": { "text": [ "transcription" ], "offsets": [ [ 1076, 1089 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "PMID-7836389_T18" } ] }, { "id": "PMID-7836389_E18", "type": "Negative_regulation", "trigger": { "text": [ "impaired" ], "offsets": [ [ 1279, 1287 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "PMID-7836389_E19" } ] }, { "id": "PMID-7836389_E19", "type": "Transcription", "trigger": { "text": [ "expression" ], "offsets": [ [ 1292, 1302 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "PMID-7836389_T19" } ] }, { "id": "PMID-7836389_E20", "type": "Negative_regulation", "trigger": { "text": [ "abolished" ], "offsets": [ [ 1417, 1426 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "PMID-7836389_E21" } ] }, { "id": "PMID-7836389_E21", "type": "Transcription", "trigger": { "text": [ "expression" ], "offsets": [ [ 1431, 1441 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "PMID-7836389_T20" } ] }, { "id": "PMID-7836389_E22", "type": "Regulation", "trigger": { "text": [ "affect" ], "offsets": [ [ 1493, 1499 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "PMID-7836389_E21" } ] }, { "id": "PMID-7836389_E23", "type": "Regulation", "trigger": { "text": [ "controls" ], "offsets": [ [ 1591, 1599 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "PMID-7836389_E24" }, { "role": "Cause", "ref_id": "PMID-7836389_T21" } ] }, { "id": "PMID-7836389_E24", "type": "Transcription", "trigger": { "text": [ "transcription" ], "offsets": [ [ 1605, 1618 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "PMID-7836389_T22" } ] }, { "id": "PMID-7836389_E25", "type": "Positive_regulation", "trigger": { "text": [ "by means of" ], "offsets": [ [ 1641, 1652 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "PMID-7836389_E23" } ] } ]

[ { "id": "PMID-7836389_1", "entity_ids": [ "PMID-7836389_T4", "PMID-7836389_T5" ] } ]

[]

[ { "id": "PMID-7843230__text", "type": "abstract", "text": [ "Biphasic control of nuclear factor-kappa B activation by the T cell receptor complex: role of tumor necrosis factor alpha. \nThe regulation of nuclear factor (NF)-kappa B activation by the T cell receptor (TcR)/CD3 complex in primary human T cells has been studied at various times after activation. Only p50 NF-kappa B protein bound the kappa B element of interleukin-2 receptor (IL-2R) alpha chain promoter on resting T cells. However, immediately after TcR/CD3 cross-linking (after approximately 1 h; immediate) binding of p50.p65 heterodimers was observed. p50.c-rel heterodimers were also detected bound to this sequence at early time points (7-16 h; early), and both remained active at later time points (40 h; late) after activation. This regulation takes place mainly at the level of nuclear translocation of p65 and c-rel, at immediate and early time points. Activation also induced c-rel and p105/p50 mRNA synthesis, but not p65 mRNA whose expression was constitutive. Interestingly, all those early and late events, but not the immediate ones, were inhibited by a neutralizing anti-tumor necrosis factor alpha (TNF-alpha) monoclonal antibody. Similarly, cycloheximide prevented the p65 and c-rel translocation and consequent formation of active binding heterodimers, at early and late times. Cyclosporin A impaired not only early and late, but also immediate events; however, addition of TNF-alpha prevented all inhibition. These results indicate that the regulation of NF-kappa B activation during T cell activation by TcR/CD3 signals is biphasic: TcR/CD3 triggers its immediate translocation, which is transient if no TNF-alpha is present. TNF-alpha, therefore, emerges as the main factor responsible for a second phase of NF-kappa B regulation, controlling both translocation of p65 and c-rel, and new mRNA synthesis for c-rel and p105/p50. " ], "offsets": [ [ 0, 1854 ] ] } ]

[ { "id": "PMID-7843230_T1", "type": "Protein", "text": [ "tumor necrosis factor alpha" ], "offsets": [ [ 94, 121 ] ], "normalized": [] }, { "id": "PMID-7843230_T2", "type": "Protein", "text": [ "p50" ], "offsets": [ [ 304, 307 ] ], "normalized": [] }, { "id": "PMID-7843230_T3", "type": "Protein", "text": [ "interleukin-2 receptor (IL-2R) alpha chain" ], "offsets": [ [ 356, 398 ] ], "normalized": [] }, { "id": "PMID-7843230_T4", "type": "Protein", "text": [ "p50" ], "offsets": [ [ 525, 528 ] ], "normalized": [] }, { "id": "PMID-7843230_T5", "type": "Protein", "text": [ "p65" ], "offsets": [ [ 529, 532 ] ], "normalized": [] }, { "id": "PMID-7843230_T6", "type": "Protein", "text": [ "p50" ], "offsets": [ [ 560, 563 ] ], "normalized": [] }, { "id": "PMID-7843230_T7", "type": "Protein", "text": [ "c-rel" ], "offsets": [ [ 564, 569 ] ], "normalized": [] }, { "id": "PMID-7843230_T8", "type": "Protein", "text": [ "p65" ], "offsets": [ [ 816, 819 ] ], "normalized": [] }, { "id": "PMID-7843230_T9", "type": "Protein", "text": [ "c-rel" ], "offsets": [ [ 824, 829 ] ], "normalized": [] }, { "id": "PMID-7843230_T10", "type": "Protein", "text": [ "c-rel" ], "offsets": [ [ 891, 896 ] ], "normalized": [] }, { "id": "PMID-7843230_T11", "type": "Protein", "text": [ "p105" ], "offsets": [ [ 901, 905 ] ], "normalized": [] }, { "id": "PMID-7843230_T12", "type": "Protein", "text": [ "p50" ], "offsets": [ [ 906, 909 ] ], "normalized": [] }, { "id": "PMID-7843230_T13", "type": "Protein", "text": [ "p65" ], "offsets": [ [ 934, 937 ] ], "normalized": [] }, { "id": "PMID-7843230_T14", "type": "Protein", "text": [ "tumor necrosis factor alpha" ], "offsets": [ [ 1092, 1119 ] ], "normalized": [] }, { "id": "PMID-7843230_T15", "type": "Protein", "text": [ "TNF-alpha" ], "offsets": [ [ 1121, 1130 ] ], "normalized": [] }, { "id": "PMID-7843230_T16", "type": "Protein", "text": [ "p65" ], "offsets": [ [ 1192, 1195 ] ], "normalized": [] }, { "id": "PMID-7843230_T17", "type": "Protein", "text": [ "c-rel" ], "offsets": [ [ 1200, 1205 ] ], "normalized": [] }, { "id": "PMID-7843230_T18", "type": "Protein", "text": [ "TNF-alpha" ], "offsets": [ [ 1398, 1407 ] ], "normalized": [] }, { "id": "PMID-7843230_T19", "type": "Protein", "text": [ "TNF-alpha" ], "offsets": [ [ 1630, 1639 ] ], "normalized": [] }, { "id": "PMID-7843230_T20", "type": "Protein", "text": [ "TNF-alpha" ], "offsets": [ [ 1652, 1661 ] ], "normalized": [] }, { "id": "PMID-7843230_T21", "type": "Protein", "text": [ "p65" ], "offsets": [ [ 1792, 1795 ] ], "normalized": [] }, { "id": "PMID-7843230_T22", "type": "Protein", "text": [ "c-rel" ], "offsets": [ [ 1800, 1805 ] ], "normalized": [] }, { "id": "PMID-7843230_T23", "type": "Protein", "text": [ "c-rel" ], "offsets": [ [ 1834, 1839 ] ], "normalized": [] }, { "id": "PMID-7843230_T24", "type": "Protein", "text": [ "p105" ], "offsets": [ [ 1844, 1848 ] ], "normalized": [] }, { "id": "PMID-7843230_T25", "type": "Protein", "text": [ "p50" ], "offsets": [ [ 1849, 1852 ] ], "normalized": [] }, { "id": "PMID-7843230_T32", "type": "Entity", "text": [ "nuclear" ], "offsets": [ [ 791, 798 ] ], "normalized": [] } ]

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[]

[ { "id": "PMID-7843251__text", "type": "abstract", "text": [ "Protein kinase C is not a downstream effector of p21ras in activated T cells. \nThe aim of this present study was to investigate the role of protein kinase C (PKC), downstream of p21ras, in activating interleukin-2 (IL-2) gene expression. It has been reported that PKC is an effector of p21ras in T cells. Data is presented, using the potent and selective PKC inhibitor Ro 31-8425 and transient expression of a constitutively active ras mutant, which clearly shows that PKC is not downstream of p21ras in the induction of NF-AT and AP-1 transcriptional activity and in the expression of IL-2 in human Jurkat T cells. Reporter gene experiments demonstrated that NF-kappa B transcriptional activity is not affected by expression of activated p21ras. The signaling pathways involving PKC activation, calcium mobilization and ras activation combine to provide the necessary components for production of IL-2 during T cell activation. " ], "offsets": [ [ 0, 929 ] ] } ]

[ { "id": "PMID-7843251_T1", "type": "Protein", "text": [ "p21ras" ], "offsets": [ [ 49, 55 ] ], "normalized": [] }, { "id": "PMID-7843251_T2", "type": "Protein", "text": [ "p21ras" ], "offsets": [ [ 178, 184 ] ], "normalized": [] }, { "id": "PMID-7843251_T3", "type": "Protein", "text": [ "interleukin-2" ], "offsets": [ [ 200, 213 ] ], "normalized": [] }, { "id": "PMID-7843251_T4", "type": "Protein", "text": [ "IL-2" ], "offsets": [ [ 215, 219 ] ], "normalized": [] }, { "id": "PMID-7843251_T5", "type": "Protein", "text": [ "p21ras" ], "offsets": [ [ 286, 292 ] ], "normalized": [] }, { "id": "PMID-7843251_T6", "type": "Protein", "text": [ "IL-2" ], "offsets": [ [ 586, 590 ] ], "normalized": [] }, { "id": "PMID-7843251_T7", "type": "Protein", "text": [ "p21ras" ], "offsets": [ [ 739, 745 ] ], "normalized": [] }, { "id": "PMID-7843251_T8", "type": "Protein", "text": [ "IL-2" ], "offsets": [ [ 898, 902 ] ], "normalized": [] } ]

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[]

[ { "id": "PMID-7848679__text", "type": "abstract", "text": [ "Association of alterations in NF-kappa B moieties with HIV type 1 proviral latency in certain monocytic cells. \nHuman immunodeficiency virus type 1 (HIV-1) replication is controlled by a complex array of virally encoded and cellular proteins. A wide spectrum of levels of HIV-1 expression have been demonstrated in various cells, both in cell culture and in vivo. Molecular mechanisms leading to restricted HIV-1 replication may differ between certain cell types. It is now demonstrated that HIV-1 proviral latency in the monocytic cell line U1, in which only extremely low levels of HIV-1 expression are detected in the baseline unstimulated state, is associated with alterations in nuclear factor-kappa B (NF-kappa B) moieties demonstrated in these cells by electrophoretic mobility shift assays (EMSAs) and in situ UV cross-linking studies. A predominance of p50 NF-kappa B moieties and possibly p50 homodimers or closely related species, rather than the p50-p56 heterodimer of NF-kappa B that is the predominant NF-kappa B species in most T lymphocytic and monocytic cells, is demonstrated in the nuclei of U1 cells. This pattern of NF-kappa B-related moieties differs from the latently infected T lymphocytic cell line ACH-2, and from the U937 monocytic line, the parental cell line of the U1 cellular clone. As such, these data suggest that different proximal mechanisms may lead to restricted HIV-1 replication in various cell types. " ], "offsets": [ [ 0, 1441 ] ] } ]

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[]

[]

[ { "id": "PMID-7848921__text", "type": "abstract", "text": [ "Overexpression of protein kinase C-zeta stimulates leukemic cell differentiation. \nA function for protein kinase C-zeta (PKC-zeta), a member of the phorbol ester nonresponsive atypical protein kinase C subfamily, in modulating differentiation was examined in the leukemic U937 cell. Transfected U937 cells stably overexpressing PKC-zeta displayed a longer doubling time, lower saturation density at confluency, and an increase in adherence to plastic as compared to control cells. PKC-zeta cells expressed a more differentiated phenotype as assessed by changes in morphology, surface antigen expression, and lysosomal enzyme activities and were distinct from parental U937 cells stimulated to differentiate by exposure to phorbol esters. In contrast to parental U937 cells, PKC-zeta cells constitutively expressed mRNA transcripts for c-jun and a low mobility AP-1 binding activity. Thus, PKC-zeta overexpression stimulates a type of phenotypic differentiation that differs significantly from maturation occurring upon activation of other PKC subfamilies induced by phorbol ester treatment. Increased expression of the c-jun protooncogene and an increase in AP-1 binding activity in PKC-zeta cells provides a potential mechanism for explaining the altered differentiation status of this cell. " ], "offsets": [ [ 0, 1293 ] ] } ]

[ { "id": "PMID-7848921_T1", "type": "Protein", "text": [ "protein kinase C-zeta" ], "offsets": [ [ 18, 39 ] ], "normalized": [] }, { "id": "PMID-7848921_T2", "type": "Protein", "text": [ "protein kinase C-zeta" ], "offsets": [ [ 98, 119 ] ], "normalized": [] }, { "id": "PMID-7848921_T3", "type": "Protein", "text": [ "PKC-zeta" ], "offsets": [ [ 121, 129 ] ], "normalized": [] }, { "id": "PMID-7848921_T4", "type": "Protein", "text": [ "PKC-zeta" ], "offsets": [ [ 328, 336 ] ], "normalized": [] }, { "id": "PMID-7848921_T5", "type": "Protein", "text": [ "PKC-zeta" ], "offsets": [ [ 481, 489 ] ], "normalized": [] }, { "id": "PMID-7848921_T6", "type": "Protein", "text": [ "PKC-zeta" ], "offsets": [ [ 774, 782 ] ], "normalized": [] }, { "id": "PMID-7848921_T7", "type": "Protein", "text": [ "c-jun" ], "offsets": [ [ 835, 840 ] ], "normalized": [] }, { "id": "PMID-7848921_T8", "type": "Protein", "text": [ "PKC-zeta" ], "offsets": [ [ 889, 897 ] ], "normalized": [] }, { "id": "PMID-7848921_T9", "type": "Protein", "text": [ "c-jun" ], "offsets": [ [ 1119, 1124 ] ], "normalized": [] }, { "id": "PMID-7848921_T10", "type": "Protein", "text": [ "PKC-zeta" ], "offsets": [ [ 1183, 1191 ] ], "normalized": [] } ]

[ { "id": "PMID-7848921_E1", "type": "Positive_regulation", "trigger": { "text": [ "Overexpression" ], "offsets": [ [ 0, 14 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "PMID-7848921_E2" } ] }, { "id": "PMID-7848921_E2", "type": "Gene_expression", "trigger": { "text": [ "Overexpression" ], "offsets": [ [ 0, 14 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "PMID-7848921_T1" } ] }, { "id": "PMID-7848921_E3", "type": "Regulation", "trigger": { "text": [ "nonresponsive" ], "offsets": [ [ 162, 175 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "PMID-7848921_T3" } ] }, { "id": "PMID-7848921_E4", "type": "Gene_expression", "trigger": { "text": [ "overexpressing" ], "offsets": [ [ 313, 327 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "PMID-7848921_T4" } ] }, { "id": "PMID-7848921_E5", "type": "Positive_regulation", "trigger": { "text": [ "overexpressing" ], "offsets": [ [ 313, 327 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "PMID-7848921_E4" } ] }, { "id": "PMID-7848921_E6", "type": "Transcription", "trigger": { "text": [ "expressed" ], "offsets": [ [ 804, 813 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "PMID-7848921_T7" } ] }, { "id": "PMID-7848921_E7", "type": "Gene_expression", "trigger": { "text": [ "overexpression" ], "offsets": [ [ 898, 912 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "PMID-7848921_T8" } ] }, { "id": "PMID-7848921_E8", "type": "Positive_regulation", "trigger": { "text": [ "overexpression" ], "offsets": [ [ 898, 912 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "PMID-7848921_E7" } ] }, { "id": "PMID-7848921_E9", "type": "Positive_regulation", "trigger": { "text": [ "Increased" ], "offsets": [ [ 1091, 1100 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "PMID-7848921_E10" } ] }, { "id": "PMID-7848921_E10", "type": "Gene_expression", "trigger": { "text": [ "expression" ], "offsets": [ [ 1101, 1111 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "PMID-7848921_T9" } ] } ]

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[]

[ { "id": "PMID-7849291__text", "type": "abstract", "text": [ "Posttranscriptional regulation of macrophage tissue factor expression by antioxidants. \nTissue factor (TF) expression by cells of monocyte/macrophage lineage represents an important mechanism underlying the initiation of fibrin deposition at sites of extravascular inflammation. Recent evidence suggests a role for oxidant stress in the signalling pathway of various cell types by virtue of its ability to induce DNA binding of various transcription factors, including nuclear factor kappa B and AP-1. The effect of antioxidant treatment on lipopolysaccharide (LPS)-induced TF expression was examined in murine peritoneal macrophages and human monocytes. Both pyrrolidine dithiocarbamate, an oxidant scavenger, and N-acetyl-cysteine, a precursor of the endogenous antioxidant glutathione, inhibited stimulation of macrophage procoagulant activity by LPS. Northern blot analysis showed that neither of these agents reduced LPS-stimulated TF mRNA accumulation, thereby suggesting a posttranscriptional mechanism for the effect. Immunofluorescence studies of human monocytes using polyclonal anti-TF antibody showed that N-acetyl-cysteine treatment prevented the characteristic plasmalemmal localization of TF antigen that occurs in response to LPS. Western blot analysis showed that N-acetyl-cysteine reduced the accumulation of the 47-kD mature glycoprotein in LPS-treated cells, a finding consistent with the results of the immunofluorescence studies. Furthermore, these conditions did not result in an accumulation of the less mature forms of TF. When considered together, these data suggest that antioxidants exert their effects by impairing translation and/or by causing degradation of newly translated protein. The effect of antioxidants on tumor necrosis factor appeared to be species specific, with no effect on LPS-induced tumor necrosis factor in murine cells, but with inhibition in human monocytes. The posttranscriptional effect of antioxidants on TF expression data suggests a novel mechanism whereby these agents might modulate monocyte/macrophage activation. " ], "offsets": [ [ 0, 2073 ] ] } ]

[ { "id": "PMID-7849291_T1", "type": "Protein", "text": [ "tissue factor" ], "offsets": [ [ 45, 58 ] ], "normalized": [] }, { "id": "PMID-7849291_T2", "type": "Protein", "text": [ "Tissue factor" ], "offsets": [ [ 88, 101 ] ], "normalized": [] }, { "id": "PMID-7849291_T3", "type": "Protein", "text": [ "TF" ], "offsets": [ [ 103, 105 ] ], "normalized": [] }, { "id": "PMID-7849291_T4", "type": "Protein", "text": [ "TF" ], "offsets": [ [ 574, 576 ] ], "normalized": [] }, { "id": "PMID-7849291_T5", "type": "Protein", "text": [ "TF" ], "offsets": [ [ 937, 939 ] ], "normalized": [] }, { "id": "PMID-7849291_T6", "type": "Protein", "text": [ "TF" ], "offsets": [ [ 1094, 1096 ] ], "normalized": [] }, { "id": "PMID-7849291_T7", "type": "Protein", "text": [ "TF" ], "offsets": [ [ 1204, 1206 ] ], "normalized": [] }, { "id": "PMID-7849291_T8", "type": "Protein", "text": [ "TF" ], "offsets": [ [ 1544, 1546 ] ], "normalized": [] }, { "id": "PMID-7849291_T9", "type": "Protein", "text": [ "TF" ], "offsets": [ [ 1959, 1961 ] ], "normalized": [] }, { "id": "PMID-7849291_T20", "type": "Entity", "text": [ "plasmalemmal" ], "offsets": [ [ 1175, 1187 ] ], "normalized": [] } ]

[ { "id": "PMID-7849291_E1", "type": "Regulation", "trigger": { "text": [ "Posttranscriptional regulation" ], "offsets": [ [ 0, 30 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "PMID-7849291_E2" } ] }, { "id": "PMID-7849291_E2", "type": "Gene_expression", "trigger": { "text": [ "expression" ], "offsets": [ [ 59, 69 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "PMID-7849291_T1" } ] }, { "id": "PMID-7849291_E3", "type": "Gene_expression", "trigger": { "text": [ "expression" ], "offsets": [ [ 107, 117 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "PMID-7849291_T3" } ] }, { "id": "PMID-7849291_E4", "type": "Regulation", "trigger": { "text": [ "effect" ], "offsets": [ [ 506, 512 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "PMID-7849291_E5" } ] }, { "id": "PMID-7849291_E5", "type": "Positive_regulation", "trigger": { "text": [ "induced" ], "offsets": [ [ 566, 573 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "PMID-7849291_E6" } ] }, { "id": "PMID-7849291_E6", "type": "Gene_expression", "trigger": { "text": [ "expression" ], "offsets": [ [ 577, 587 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "PMID-7849291_T4" } ] }, { "id": "PMID-7849291_E7", "type": "Negative_regulation", "trigger": { "text": [ "reduced" ], "offsets": [ [ 914, 921 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "PMID-7849291_E8" } ] }, { "id": "PMID-7849291_E8", "type": "Positive_regulation", "trigger": { "text": [ "stimulated" ], "offsets": [ [ 926, 936 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "PMID-7849291_E9" } ] }, { "id": "PMID-7849291_E9", "type": "Positive_regulation", "trigger": { "text": [ "accumulation" ], "offsets": [ [ 945, 957 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "PMID-7849291_T5" } ] }, { "id": "PMID-7849291_E10", "type": "Negative_regulation", "trigger": { "text": [ "prevented" ], "offsets": [ [ 1146, 1155 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "PMID-7849291_E12" } ] }, { "id": "PMID-7849291_E11", "type": "Localization", "trigger": { "text": [ "localization" ], "offsets": [ [ 1188, 1200 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "PMID-7849291_T7" }, { "role": "ToLoc", "ref_id": "PMID-7849291_T20" } ] }, { "id": "PMID-7849291_E12", "type": "Positive_regulation", "trigger": { "text": [ "occurs" ], "offsets": [ [ 1220, 1226 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "PMID-7849291_E11" } ] }, { "id": "PMID-7849291_E13", "type": "Positive_regulation", "trigger": { "text": [ "result" ], "offsets": [ [ 1490, 1496 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "PMID-7849291_E14" } ] }, { "id": "PMID-7849291_E14", "type": "Positive_regulation", "trigger": { "text": [ "accumulation" ], "offsets": [ [ 1503, 1515 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "PMID-7849291_T8" } ] }, { "id": "PMID-7849291_E15", "type": "Regulation", "trigger": { "text": [ "posttranscriptional effect" ], "offsets": [ [ 1913, 1939 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "PMID-7849291_E16" } ] }, { "id": "PMID-7849291_E16", "type": "Gene_expression", "trigger": { "text": [ "expression" ], "offsets": [ [ 1962, 1972 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "PMID-7849291_T9" } ] } ]

[ { "id": "PMID-7849291_1", "entity_ids": [ "PMID-7849291_T3", "PMID-7849291_T2" ] } ]

[]

[ { "id": "PMID-7853483__text", "type": "abstract", "text": [ "Regulation of I kappa B alpha and p105 in monocytes and macrophages persistently infected with human immunodeficiency virus. \nThe mechanisms regulating human immunodeficiency virus (HIV) persistence in human monocytes/macrophages are partially understood. Persistent HIV infection of U937 monocytic cells results in NF-kappa B activation. Whether virus-induced NF-kappa B activation is a mechanism that favors continuous viral replication in macrophages remains unknown. To further delineate the molecular mechanisms involved in the activation of NF-kappa B in HIV-infected monocytes and macrophages, we have focused on the regulation of the I kappa B molecules. First, we show that persistent HIV infection results in the activation of NF-kappa B not only in monocytic cells but also in macrophages. In HIV-infected cells, I kappa B alpha protein levels are decreased secondary to enhanced protein degradation. This parallels the increased I kappa B alpha synthesis secondary to increased I kappa B alpha gene transcription, i.e., increased RNA and transcriptional activity of its promoter-enhancer. Another protein with I kappa B function, p105, is also modified in HIV-infected cells: p105 and p50 steady-state protein levels are increased as a result of increased synthesis and proteolytic processing of p105. Transcriptional activity of p105 is also increased in infected cells and is also mediated by NF-kappa B through a specific kappa B motif. These results demonstrate the existence of a triple autoregulatory loop in monocytes and macrophages involving HIV, p105 and p50, and MAD3, with the end result of persistent NF-kappa B activation and viral persistence. Furthermore, persistent HIV infection of monocytes and macrophages provides a useful model with which to study concomitant modifications of different I kappa B molecules. " ], "offsets": [ [ 0, 1842 ] ] } ]

[ { "id": "PMID-7853483_T1", "type": "Protein", "text": [ "I kappa B alpha" ], "offsets": [ [ 14, 29 ] ], "normalized": [] }, { "id": "PMID-7853483_T2", "type": "Protein", "text": [ "p105" ], "offsets": [ [ 34, 38 ] ], "normalized": [] }, { "id": "PMID-7853483_T3", "type": "Protein", "text": [ "I kappa B alpha" ], "offsets": [ [ 824, 839 ] ], "normalized": [] }, { "id": "PMID-7853483_T4", "type": "Protein", "text": [ "I kappa B alpha" ], "offsets": [ [ 941, 956 ] ], "normalized": [] }, { "id": "PMID-7853483_T5", "type": "Protein", "text": [ "I kappa B alpha" ], "offsets": [ [ 990, 1005 ] ], "normalized": [] }, { "id": "PMID-7853483_T6", "type": "Protein", "text": [ "p105" ], "offsets": [ [ 1142, 1146 ] ], "normalized": [] }, { "id": "PMID-7853483_T7", "type": "Protein", "text": [ "p105" ], "offsets": [ [ 1188, 1192 ] ], "normalized": [] }, { "id": "PMID-7853483_T8", "type": "Protein", "text": [ "p50" ], "offsets": [ [ 1197, 1200 ] ], "normalized": [] }, { "id": "PMID-7853483_T9", "type": "Protein", "text": [ "p105" ], "offsets": [ [ 1308, 1312 ] ], "normalized": [] }, { "id": "PMID-7853483_T10", "type": "Protein", "text": [ "p105" ], "offsets": [ [ 1342, 1346 ] ], "normalized": [] }, { "id": "PMID-7853483_T11", "type": "Protein", "text": [ "p105" ], "offsets": [ [ 1568, 1572 ] ], "normalized": [] }, { "id": "PMID-7853483_T12", "type": "Protein", "text": [ "p50" ], "offsets": [ [ 1577, 1580 ] ], "normalized": [] }, { "id": "PMID-7853483_T13", "type": "Protein", "text": [ "MAD3" ], "offsets": [ [ 1586, 1590 ] ], "normalized": [] } ]

[ { "id": "PMID-7853483_E1", "type": "Regulation", "trigger": { "text": [ "Regulation" ], "offsets": [ [ 0, 10 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "PMID-7853483_T1" } ] }, { "id": "PMID-7853483_E2", "type": "Regulation", "trigger": { "text": [ "Regulation" ], "offsets": [ [ 0, 10 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "PMID-7853483_T2" } ] }, { "id": "PMID-7853483_E3", "type": "Negative_regulation", "trigger": { "text": [ "decreased" ], "offsets": [ [ 859, 868 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "PMID-7853483_T3" } ] }, { "id": "PMID-7853483_E4", "type": "Positive_regulation", "trigger": { "text": [ "increased" ], "offsets": [ [ 980, 989 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "PMID-7853483_E5" } ] }, { "id": "PMID-7853483_E5", "type": "Transcription", "trigger": { "text": [ "transcription" ], "offsets": [ [ 1011, 1024 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "PMID-7853483_T5" } ] }, { "id": "PMID-7853483_E6", "type": "Positive_regulation", "trigger": { "text": [ "increased" ], "offsets": [ [ 1032, 1041 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "PMID-7853483_T5" } ] }, { "id": "PMID-7853483_E7", "type": "Positive_regulation", "trigger": { "text": [ "increased" ], "offsets": [ [ 1032, 1041 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "PMID-7853483_E8" } ] }, { "id": "PMID-7853483_E8", "type": "Transcription", "trigger": { "text": [ "transcriptional activity" ], "offsets": [ [ 1050, 1074 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "PMID-7853483_T5" } ] }, { "id": "PMID-7853483_E9", "type": "Regulation", "trigger": { "text": [ "modified" ], "offsets": [ [ 1156, 1164 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "PMID-7853483_T6" } ] }, { "id": "PMID-7853483_E10", "type": "Positive_regulation", "trigger": { "text": [ "increased" ], "offsets": [ [ 1233, 1242 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "PMID-7853483_T7" } ] }, { "id": "PMID-7853483_E11", "type": "Positive_regulation", "trigger": { "text": [ "increased" ], "offsets": [ [ 1233, 1242 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "PMID-7853483_T8" } ] }, { "id": "PMID-7853483_E12", "type": "Transcription", "trigger": { "text": [ "Transcriptional activity" ], "offsets": [ [ 1314, 1338 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "PMID-7853483_T10" } ] }, { "id": "PMID-7853483_E13", "type": "Positive_regulation", "trigger": { "text": [ "increased" ], "offsets": [ [ 1355, 1364 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "PMID-7853483_E12" } ] }, { "id": "PMID-7853483_E14", "type": "Positive_regulation", "trigger": { "text": [ "mediated" ], "offsets": [ [ 1395, 1403 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "PMID-7853483_E12" } ] }, { "id": "PMID-7853483_E15", "type": "Regulation", "trigger": { "text": [ "triple autoregulatory loop" ], "offsets": [ [ 1497, 1523 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "PMID-7853483_T13" } ] }, { "id": "PMID-7853483_E16", "type": "Regulation", "trigger": { "text": [ "triple autoregulatory loop" ], "offsets": [ [ 1497, 1523 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "PMID-7853483_T11" } ] }, { "id": "PMID-7853483_E17", "type": "Regulation", "trigger": { "text": [ "triple autoregulatory loop" ], "offsets": [ [ 1497, 1523 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "PMID-7853483_T12" } ] } ]

[]

[]

[ { "id": "PMID-7858491__text", "type": "abstract", "text": [ "Expression and genomic configuration of GM-CSF, IL-3, M-CSF receptor (C-FMS), early growth response gene-1 (EGR-1) and M-CSF genes in primary myelodysplastic syndromes. \nPeripheral blood mononuclear cells from seventeen patients with primary myelodysplastic syndromes (MDS) in advanced stage were enriched for blasts and tested for (1) karyotype, (2) genomic configuration and (3) expression of IL-3, GM-CSF, FMS and EGR-1 genes which are all located on the long arm of chromosome 5. The expression of the M-CSF gene, that has been recently reassigned to the short arm of chromosome 1 (lp), was also investigated. Aims of the study were to (1) assess the potential role of the expression of these genes in the maintenance and expansion of the neoplastic clones and (2) search for constitutional losses or rearrangements of one allele followed by a deletion of the second allele of the same genes in the leukemic cells. The latter issue was investigated by comparing, in 8 cases, constitutive DNA from skin fibroblasts with leukemic DNA. Eleven of the 17 patients had abnormal karyotypes. The M-CSF gene was expressed in 6 cases and the FMS and the EGR-1 genes were expressed in 2 of the latter cases. An autocrine mechanism of growth could be hypothesized only for the 2 patients whose cells expressed both the M-CSF and FMS genes. No germline changes or rearrangements were observed in any of the genes studied. Thus, deregulation of genes encoding for certain hemopoietic growth factors or receptors does not seem to represent a major mechanism of MDS progression. " ], "offsets": [ [ 0, 1567 ] ] } ]

[ { "id": "PMID-7858491_T1", "type": "Protein", "text": [ "GM-CSF" ], "offsets": [ [ 40, 46 ] ], "normalized": [] }, { "id": "PMID-7858491_T2", "type": "Protein", "text": [ "IL-3" ], "offsets": [ [ 48, 52 ] ], "normalized": [] }, { "id": "PMID-7858491_T3", "type": "Protein", "text": [ "M-CSF receptor" ], "offsets": [ [ 54, 68 ] ], "normalized": [] }, { "id": "PMID-7858491_T4", "type": "Protein", "text": [ "C-FMS" ], "offsets": [ [ 70, 75 ] ], "normalized": [] }, { "id": "PMID-7858491_T5", "type": "Protein", "text": [ "early growth response gene-1" ], "offsets": [ [ 78, 106 ] ], "normalized": [] }, { "id": "PMID-7858491_T6", "type": "Protein", "text": [ "EGR-1" ], "offsets": [ [ 108, 113 ] ], "normalized": [] }, { "id": "PMID-7858491_T7", "type": "Protein", "text": [ "M-CSF" ], "offsets": [ [ 119, 124 ] ], "normalized": [] }, { "id": "PMID-7858491_T8", "type": "Protein", "text": [ "IL-3" ], "offsets": [ [ 395, 399 ] ], "normalized": [] }, { "id": "PMID-7858491_T9", "type": "Protein", "text": [ "GM-CSF" ], "offsets": [ [ 401, 407 ] ], "normalized": [] }, { "id": "PMID-7858491_T10", "type": "Protein", "text": [ "FMS" ], "offsets": [ [ 409, 412 ] ], "normalized": [] }, { "id": "PMID-7858491_T11", "type": "Protein", "text": [ "EGR-1" ], "offsets": [ [ 417, 422 ] ], "normalized": [] }, { "id": "PMID-7858491_T12", "type": "Protein", "text": [ "M-CSF" ], "offsets": [ [ 506, 511 ] ], "normalized": [] }, { "id": "PMID-7858491_T13", "type": "Protein", "text": [ "M-CSF" ], "offsets": [ [ 1092, 1097 ] ], "normalized": [] }, { "id": "PMID-7858491_T14", "type": "Protein", "text": [ "FMS" ], "offsets": [ [ 1136, 1139 ] ], "normalized": [] }, { "id": "PMID-7858491_T15", "type": "Protein", "text": [ "EGR-1" ], "offsets": [ [ 1148, 1153 ] ], "normalized": [] }, { "id": "PMID-7858491_T16", "type": "Protein", "text": [ "M-CSF" ], "offsets": [ [ 1311, 1316 ] ], "normalized": [] }, { "id": "PMID-7858491_T17", "type": "Protein", "text": [ "FMS" ], "offsets": [ [ 1321, 1324 ] ], "normalized": [] } ]

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[]

[ { "id": "PMID-7859290__text", "type": "abstract", "text": [ "OBF-1, a novel B cell-specific coactivator that stimulates immunoglobulin promoter activity through association with octamer-binding proteins. \nRecent biochemical and genetic studies indicate that in addition to the octamer-binding proteins Oct-1 and Oct-2, other B cell components are required for lymphoid-restricted, octamer site-mediated immunoglobulin gene promoter activity. Using a genetic screen in yeast, we have isolated B cell-derived cDNAs encoding Oct-binding factor 1 (OBF-1), a novel protein that specifically associates with Oct-1 and Oct-2. Biochemical studies demonstrate that OBF-1 has no intrinsic DNA-binding activity and recognizes the POU domains of Oct-1 and Oct-2, but not those of Oct-4 and Oct-6. The OBF-1 mRNA is expressed in a highly cell-specific manner, being most abundant in B cells and essentially absent in most of the other cells or tissues tested. Furthermore, expression of OBF-1 in HeLa cells selectively stimulates the activity of a natural immunoglobulin promoter in an octamer site-dependent manner. Thus, OBF-1 has all the properties expected for a B cell-specific transcriptional coactivator protein. " ], "offsets": [ [ 0, 1146 ] ] } ]

[ { "id": "PMID-7859290_T1", "type": "Protein", "text": [ "OBF-1" ], "offsets": [ [ 0, 5 ] ], "normalized": [] }, { "id": "PMID-7859290_T2", "type": "Protein", "text": [ "Oct-1" ], "offsets": [ [ 241, 246 ] ], "normalized": [] }, { "id": "PMID-7859290_T3", "type": "Protein", "text": [ "Oct-2" ], "offsets": [ [ 251, 256 ] ], "normalized": [] }, { "id": "PMID-7859290_T4", "type": "Protein", "text": [ "Oct-binding factor 1" ], "offsets": [ [ 461, 481 ] ], "normalized": [] }, { "id": "PMID-7859290_T5", "type": "Protein", "text": [ "OBF-1" ], "offsets": [ [ 483, 488 ] ], "normalized": [] }, { "id": "PMID-7859290_T6", "type": "Protein", "text": [ "Oct-1" ], "offsets": [ [ 541, 546 ] ], "normalized": [] }, { "id": "PMID-7859290_T7", "type": "Protein", "text": [ "Oct-2" ], "offsets": [ [ 551, 556 ] ], "normalized": [] }, { "id": "PMID-7859290_T8", "type": "Protein", "text": [ "OBF-1" ], "offsets": [ [ 595, 600 ] ], "normalized": [] }, { "id": "PMID-7859290_T9", "type": "Protein", "text": [ "Oct-1" ], "offsets": [ [ 673, 678 ] ], "normalized": [] }, { "id": "PMID-7859290_T10", "type": "Protein", "text": [ "Oct-2" ], "offsets": [ [ 683, 688 ] ], "normalized": [] }, { "id": "PMID-7859290_T11", "type": "Protein", "text": [ "Oct-4" ], "offsets": [ [ 707, 712 ] ], "normalized": [] }, { "id": "PMID-7859290_T12", "type": "Protein", "text": [ "Oct-6" ], "offsets": [ [ 717, 722 ] ], "normalized": [] }, { "id": "PMID-7859290_T13", "type": "Protein", "text": [ "OBF-1" ], "offsets": [ [ 728, 733 ] ], "normalized": [] }, { "id": "PMID-7859290_T14", "type": "Protein", "text": [ "OBF-1" ], "offsets": [ [ 913, 918 ] ], "normalized": [] }, { "id": "PMID-7859290_T15", "type": "Protein", "text": [ "OBF-1" ], "offsets": [ [ 1049, 1054 ] ], "normalized": [] }, { "id": "PMID-7859290_T20", "type": "Entity", "text": [ "POU domains" ], "offsets": [ [ 658, 669 ] ], "normalized": [] } ]

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[ { "id": "PMID-7859290_1", "entity_ids": [ "PMID-7859290_T5", "PMID-7859290_T4" ] } ]

[]

[ { "id": "PMID-7859735__text", "type": "abstract", "text": [ "Glucocorticoid-induced apoptosis of human leukemic cells is caused by the repressive function of the glucocorticoid receptor. \nInduction of apoptosis in lymphocytes, which may account for the therapeutic effects of glucocorticoids in various diseases including leukemia, depends on the glucocorticoid receptor. However, the events leading from the activated receptor to cell lysis are not understood. A prevailing hypothesis postulates induction of so-called 'lysis genes' by the activated receptor. In this study, we show that an activation-deficient glucocorticoid receptor mutant is as effective as the wild-type receptor in repression of AP-1 activity, inhibition of interleukin-2 production, inhibition of c-myc expression and induction of apoptosis. Furthermore, we show that retinoic acid can also induce apoptosis in these cells through the retinoic acid receptor, whose repressive functions but not target site specificity, are similar to those of the glucocorticoid receptor. Therefore, the primary effect of the receptor in glucocorticoid-mediated apoptosis correlates with transcriptional repression rather than activation and could be mediated by interference with other transcription factors required for cell survival. " ], "offsets": [ [ 0, 1234 ] ] } ]

[ { "id": "PMID-7859735_T1", "type": "Protein", "text": [ "glucocorticoid receptor" ], "offsets": [ [ 101, 124 ] ], "normalized": [] }, { "id": "PMID-7859735_T2", "type": "Protein", "text": [ "glucocorticoid receptor" ], "offsets": [ [ 286, 309 ] ], "normalized": [] }, { "id": "PMID-7859735_T3", "type": "Protein", "text": [ "glucocorticoid receptor" ], "offsets": [ [ 552, 575 ] ], "normalized": [] }, { "id": "PMID-7859735_T4", "type": "Protein", "text": [ "interleukin-2" ], "offsets": [ [ 671, 684 ] ], "normalized": [] }, { "id": "PMID-7859735_T5", "type": "Protein", "text": [ "c-myc" ], "offsets": [ [ 711, 716 ] ], "normalized": [] }, { "id": "PMID-7859735_T6", "type": "Protein", "text": [ "glucocorticoid receptor" ], "offsets": [ [ 961, 984 ] ], "normalized": [] } ]

[ { "id": "PMID-7859735_E1", "type": "Positive_regulation", "trigger": { "text": [ "activated" ], "offsets": [ [ 348, 357 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "PMID-7859735_T2" } ] }, { "id": "PMID-7859735_E2", "type": "Positive_regulation", "trigger": { "text": [ "activated" ], "offsets": [ [ 480, 489 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "PMID-7859735_T2" } ] }, { "id": "PMID-7859735_E3", "type": "Negative_regulation", "trigger": { "text": [ "inhibition" ], "offsets": [ [ 657, 667 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "PMID-7859735_E4" }, { "role": "Cause", "ref_id": "PMID-7859735_T3" } ] }, { "id": "PMID-7859735_E4", "type": "Gene_expression", "trigger": { "text": [ "production" ], "offsets": [ [ 685, 695 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "PMID-7859735_T4" } ] }, { "id": "PMID-7859735_E5", "type": "Negative_regulation", "trigger": { "text": [ "inhibition" ], "offsets": [ [ 697, 707 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "PMID-7859735_E6" }, { "role": "Cause", "ref_id": "PMID-7859735_T3" } ] }, { "id": "PMID-7859735_E6", "type": "Gene_expression", "trigger": { "text": [ "expression" ], "offsets": [ [ 717, 727 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "PMID-7859735_T5" } ] } ]

[]

[]

[ { "id": "PMID-7859743__text", "type": "abstract", "text": [ "HIV-1 Tat potentiates TNF-induced NF-kappa B activation and cytotoxicity by altering the cellular redox state. \nThis study demonstrates that human immunodeficiency virus type 1 (HIV-1) Tat protein amplifies the activity of tumor necrosis factor (TNF), a cytokine that stimulates HIV-1 replication through activation of NF-kappa B. In HeLa cells stably transfected with the HIV-1 tat gene (HeLa-tat cells), expression of the Tat protein enhanced both TNF-induced activation of NF-kappa B and TNF-mediated cytotoxicity. A similar potentiation of TNF effects was observed in Jurkat T cells and HeLa cells treated with soluble Tat protein. TNF-mediated activation of NF-kappa B and cytotoxicity involves the intracellular formation of reactive oxygen intermediates. Therefore, Tat-mediated effects on the cellular redox state were analyzed. In both T cells and HeLa cells HIV-1 Tat suppressed the expression of Mn-dependent superoxide dismutase (Mn-SOD), a mitochondrial enzyme that is part of the cellular defense system against oxidative stress. Thus, Mn-SOD RNA protein levels and activity were markedly reduced in the presence of Tat. Decreased Mn-SOD expression was associated with decreased levels of glutathione and a lower ratio of reduced:oxidized glutathione. A truncated Tat protein (Tat1-72), known to transactivate the HIV-1 long terminal repeat (LTR), no longer affected Mn-SOD expression, the cellular redox state or TNF-mediated cytotoxicity. Thus, our experiments demonstrate that the C-terminal region of HIV-1 Tat is required to suppress Mn-SOD expression and to induce pro-oxidative conditions reflected by a drop in reduced glutathione (GSH) and the GSH:oxidized GSH (GSSG) ratio. (ABSTRACT TRUNCATED AT 250 WORDS) " ], "offsets": [ [ 0, 1732 ] ] } ]

[ { "id": "PMID-7859743_T1", "type": "Protein", "text": [ "Tat" ], "offsets": [ [ 6, 9 ] ], "normalized": [] }, { "id": "PMID-7859743_T2", "type": "Protein", "text": [ "Tat" ], "offsets": [ [ 185, 188 ] ], "normalized": [] }, { "id": "PMID-7859743_T3", "type": "Protein", "text": [ "Tat" ], "offsets": [ [ 424, 427 ] ], "normalized": [] }, { "id": "PMID-7859743_T4", "type": "Protein", "text": [ "Tat" ], "offsets": [ [ 623, 626 ] ], "normalized": [] }, { "id": "PMID-7859743_T5", "type": "Protein", "text": [ "Tat" ], "offsets": [ [ 773, 776 ] ], "normalized": [] }, { "id": "PMID-7859743_T6", "type": "Protein", "text": [ "Tat" ], "offsets": [ [ 874, 877 ] ], "normalized": [] }, { "id": "PMID-7859743_T7", "type": "Protein", "text": [ "Mn-dependent superoxide dismutase" ], "offsets": [ [ 907, 940 ] ], "normalized": [] }, { "id": "PMID-7859743_T8", "type": "Protein", "text": [ "Mn-SOD" ], "offsets": [ [ 942, 948 ] ], "normalized": [] }, { "id": "PMID-7859743_T9", "type": "Protein", "text": [ "Mn-SOD" ], "offsets": [ [ 1050, 1056 ] ], "normalized": [] }, { "id": "PMID-7859743_T10", "type": "Protein", "text": [ "Tat" ], "offsets": [ [ 1130, 1133 ] ], "normalized": [] }, { "id": "PMID-7859743_T11", "type": "Protein", "text": [ "Mn-SOD" ], "offsets": [ [ 1145, 1151 ] ], "normalized": [] }, { "id": "PMID-7859743_T12", "type": "Protein", "text": [ "Tat" ], "offsets": [ [ 1278, 1281 ] ], "normalized": [] }, { "id": "PMID-7859743_T13", "type": "Protein", "text": [ "Mn-SOD" ], "offsets": [ [ 1381, 1387 ] ], "normalized": [] }, { "id": "PMID-7859743_T14", "type": "Protein", "text": [ "Tat" ], "offsets": [ [ 1525, 1528 ] ], "normalized": [] }, { "id": "PMID-7859743_T15", "type": "Protein", "text": [ "Mn-SOD" ], "offsets": [ [ 1553, 1559 ] ], "normalized": [] } ]

[ { "id": "PMID-7859743_E1", "type": "Gene_expression", "trigger": { "text": [ "expression" ], "offsets": [ [ 406, 416 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "PMID-7859743_T3" } ] }, { "id": "PMID-7859743_E2", "type": "Negative_regulation", "trigger": { "text": [ "suppressed" ], "offsets": [ [ 878, 888 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "PMID-7859743_E3" }, { "role": "Cause", "ref_id": "PMID-7859743_T6" } ] }, { "id": "PMID-7859743_E3", "type": "Gene_expression", "trigger": { "text": [ "expression" ], "offsets": [ [ 893, 903 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "PMID-7859743_T8" } ] }, { "id": "PMID-7859743_E4", "type": "Transcription", "trigger": { "text": [ "RNA" ], "offsets": [ [ 1057, 1060 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "PMID-7859743_T9" } ] }, { "id": "PMID-7859743_E5", "type": "Gene_expression", "trigger": { "text": [ "protein levels" ], "offsets": [ [ 1061, 1075 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "PMID-7859743_T9" } ] }, { "id": "PMID-7859743_E6", "type": "Negative_regulation", "trigger": { "text": [ "reduced" ], "offsets": [ [ 1103, 1110 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "PMID-7859743_E5" }, { "role": "Cause", "ref_id": "PMID-7859743_T10" } ] }, { "id": "PMID-7859743_E7", "type": "Negative_regulation", "trigger": { "text": [ "reduced" ], "offsets": [ [ 1103, 1110 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "PMID-7859743_T9" }, { "role": "Cause", "ref_id": "PMID-7859743_T10" } ] }, { "id": "PMID-7859743_E8", "type": "Negative_regulation", "trigger": { "text": [ "reduced" ], "offsets": [ [ 1103, 1110 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "PMID-7859743_E4" }, { "role": "Cause", "ref_id": "PMID-7859743_T10" } ] }, { "id": "PMID-7859743_E9", "type": "Negative_regulation", "trigger": { "text": [ "Decreased" ], "offsets": [ [ 1135, 1144 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "PMID-7859743_E10" } ] }, { "id": "PMID-7859743_E10", "type": "Gene_expression", "trigger": { "text": [ "expression" ], "offsets": [ [ 1152, 1162 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "PMID-7859743_T11" } ] }, { "id": "PMID-7859743_E11", "type": "Regulation", "trigger": { "text": [ "affected" ], "offsets": [ [ 1372, 1380 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "PMID-7859743_E12" }, { "role": "Cause", "ref_id": "PMID-7859743_T12" } ] }, { "id": "PMID-7859743_E12", "type": "Gene_expression", "trigger": { "text": [ "expression" ], "offsets": [ [ 1388, 1398 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "PMID-7859743_T13" } ] }, { "id": "PMID-7859743_E13", "type": "Negative_regulation", "trigger": { "text": [ "suppress" ], "offsets": [ [ 1544, 1552 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "PMID-7859743_E14" } ] }, { "id": "PMID-7859743_E14", "type": "Gene_expression", "trigger": { "text": [ "expression" ], "offsets": [ [ 1560, 1570 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "PMID-7859743_T15" } ] } ]

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[]

[ { "id": "PMID-7862157__text", "type": "abstract", "text": [ "Expression of the Runt domain-encoding PEBP2 alpha genes in T cells during thymic development. \nThe PEBP2 alpha A and PEBP2 alpha B genes encode the DNA-binding subunit of a murine transcription factor, PEBP2, which is implicated as a T-cell-specific transcriptional regulator. These two related genes share the evolutionarily conserved region encoding the Runt domain. PEBP2 alpha B is the murine counterpart of human AML1, which is located at the breakpoints of the 8;21 and 3;21 chromosome translocations associated with acute myeloid leukemia. Northern (RNA) blots of various adult mouse tissues revealed that the levels of expression of both genes were most prominent in the thymus. Furthermore, transcripts of PEBP2 alpha A and mouse AML1/PEBP2 alpha B were detected in T lymphocytes in the thymuses from day 16 embryos and newborns, as well as 4-week-old adult mice, by in situ hybridization. The expression of the genes persisted in peripheral lymph nodes of adult mice. The transcripts were detected in all the CD4- CD8-, CD4+ CD8+, CD4+ CD8-, and CD4- CD8+ cell populations. The results indicated that both genes are expressed in T cells throughout their development, supporting the notion that PEBP2 is a T-cell-specific transcription factor. Transcripts of mouse AML1/PEBP2 alpha B were also detected in day 12 fetal hematopoietic liver and in the bone marrow cells of newborn mice. The implication of mouse AML1/PEBP2 alpha B expression in hematopoietic cells other than those of T-cell lineage is discussed in relation to myeloid leukemogenesis. " ], "offsets": [ [ 0, 1560 ] ] } ]

[ { "id": "PMID-7862157_T1", "type": "Protein", "text": [ "PEBP2 alpha A" ], "offsets": [ [ 100, 113 ] ], "normalized": [] }, { "id": "PMID-7862157_T2", "type": "Protein", "text": [ "PEBP2 alpha B" ], "offsets": [ [ 118, 131 ] ], "normalized": [] }, { "id": "PMID-7862157_T3", "type": "Protein", "text": [ "PEBP2 alpha B" ], "offsets": [ [ 370, 383 ] ], "normalized": [] }, { "id": "PMID-7862157_T4", "type": "Protein", "text": [ "AML1" ], "offsets": [ [ 419, 423 ] ], "normalized": [] }, { "id": "PMID-7862157_T5", "type": "Protein", "text": [ "PEBP2 alpha A" ], "offsets": [ [ 716, 729 ] ], "normalized": [] }, { "id": "PMID-7862157_T6", "type": "Protein", "text": [ "AML1/PEBP2 alpha B" ], "offsets": [ [ 740, 758 ] ], "normalized": [] }, { "id": "PMID-7862157_T7", "type": "Protein", "text": [ "CD4" ], "offsets": [ [ 1020, 1023 ] ], "normalized": [] }, { "id": "PMID-7862157_T8", "type": "Protein", "text": [ "CD4" ], "offsets": [ [ 1031, 1034 ] ], "normalized": [] }, { "id": "PMID-7862157_T9", "type": "Protein", "text": [ "CD4" ], "offsets": [ [ 1042, 1045 ] ], "normalized": [] }, { "id": "PMID-7862157_T10", "type": "Protein", "text": [ "CD4" ], "offsets": [ [ 1057, 1060 ] ], "normalized": [] }, { "id": "PMID-7862157_T11", "type": "Protein", "text": [ "AML1/PEBP2 alpha B" ], "offsets": [ [ 1275, 1293 ] ], "normalized": [] }, { "id": "PMID-7862157_T12", "type": "Protein", "text": [ "AML1/PEBP2 alpha B" ], "offsets": [ [ 1420, 1438 ] ], "normalized": [] } ]

[ { "id": "PMID-7862157_E1", "type": "Gene_expression", "trigger": { "text": [ "expression" ], "offsets": [ [ 628, 638 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "PMID-7862157_T2" } ] }, { "id": "PMID-7862157_E2", "type": "Gene_expression", "trigger": { "text": [ "expression" ], "offsets": [ [ 628, 638 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "PMID-7862157_T1" } ] }, { "id": "PMID-7862157_E3", "type": "Positive_regulation", "trigger": { "text": [ "prominent" ], "offsets": [ [ 663, 672 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "PMID-7862157_E2" } ] }, { "id": "PMID-7862157_E4", "type": "Positive_regulation", "trigger": { "text": [ "prominent" ], "offsets": [ [ 663, 672 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "PMID-7862157_E1" } ] }, { "id": "PMID-7862157_E5", "type": "Transcription", "trigger": { "text": [ "detected" ], "offsets": [ [ 764, 772 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "PMID-7862157_T6" } ] }, { "id": "PMID-7862157_E6", "type": "Transcription", "trigger": { "text": [ "detected" ], "offsets": [ [ 764, 772 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "PMID-7862157_T5" } ] }, { "id": "PMID-7862157_E7", "type": "Gene_expression", "trigger": { "text": [ "expression" ], "offsets": [ [ 904, 914 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "PMID-7862157_T6" } ] }, { "id": "PMID-7862157_E8", "type": "Gene_expression", "trigger": { "text": [ "expression" ], "offsets": [ [ 904, 914 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "PMID-7862157_T5" } ] }, { "id": "PMID-7862157_E9", "type": "Positive_regulation", "trigger": { "text": [ "persisted" ], "offsets": [ [ 928, 937 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "PMID-7862157_E7" } ] }, { "id": "PMID-7862157_E10", "type": "Positive_regulation", "trigger": { "text": [ "persisted" ], "offsets": [ [ 928, 937 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "PMID-7862157_E8" } ] }, { "id": "PMID-7862157_E11", "type": "Transcription", "trigger": { "text": [ "detected" ], "offsets": [ [ 1000, 1008 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "PMID-7862157_T6" } ] }, { "id": "PMID-7862157_E12", "type": "Transcription", "trigger": { "text": [ "detected" ], "offsets": [ [ 1000, 1008 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "PMID-7862157_T5" } ] }, { "id": "PMID-7862157_E13", "type": "Gene_expression", "trigger": { "text": [ "expressed" ], "offsets": [ [ 1127, 1136 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "PMID-7862157_T5" } ] }, { "id": "PMID-7862157_E14", "type": "Gene_expression", "trigger": { "text": [ "expressed" ], "offsets": [ [ 1127, 1136 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "PMID-7862157_T6" } ] }, { "id": "PMID-7862157_E15", "type": "Transcription", "trigger": { "text": [ "detected" ], "offsets": [ [ 1304, 1312 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "PMID-7862157_T11" } ] }, { "id": "PMID-7862157_E16", "type": "Gene_expression", "trigger": { "text": [ "expression" ], "offsets": [ [ 1439, 1449 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "PMID-7862157_T12" } ] } ]

[]

[]

[ { "id": "PMID-7862168__text", "type": "abstract", "text": [ "Regulation of cell-type-specific interleukin-2 receptor alpha-chain gene expression: potential role of physical interactions between Elf-1, HMG-I(Y), and NF-kappa B family proteins. \nThe interleukin 2 receptor alpha-chain (IL-2R alpha) gene is rapidly and potently induced in T cells in response to mitogenic stimuli. Previously, an inducible enhancer between nucleotides -299 and -228 that contains NF-kappa B and CArG motifs was identified. We now report the characterization of a second essential positive regulatory element located between nucleotides -137 and -64 that binds Elf-1 and HMG-I(Y). This element had maximal activity in lymphoid cells, paralleling the cell type specificity of Elf-1 expression. Transcription from the IL-2R alpha promoter was inhibited when either the Elf-1 or the HMG-I(Y) binding site was mutated. Coexpression of both proteins activated transcription of the -137 to -64 element in COS-7 cells. Elf-1 physically associated with HMG-I and with NF-kappa B p50 and c-Rel in vitro, suggesting that protein-protein interactions might functionally coordinate the actions of the upstream and downstream positive regulatory elements. This is the first report of a physical interaction between an Ets family member and NF-kappa B family proteins. These findings provide significant new insights into the protein-protein and protein-DNA interactions that regulate cell-type-specific and inducible IL-2R alpha gene expression and also have implications for other genes regulated by Elf-1 and NF-kappa B family proteins. " ], "offsets": [ [ 0, 1545 ] ] } ]

[ { "id": "PMID-7862168_T1", "type": "Protein", "text": [ "interleukin-2 receptor alpha-chain" ], "offsets": [ [ 33, 67 ] ], "normalized": [] }, { "id": "PMID-7862168_T2", "type": "Protein", "text": [ "Elf-1" ], "offsets": [ [ 133, 138 ] ], "normalized": [] }, { "id": "PMID-7862168_T3", "type": "Protein", "text": [ "HMG-I(Y)" ], "offsets": [ [ 140, 148 ] ], "normalized": [] }, { "id": "PMID-7862168_T4", "type": "Protein", "text": [ "interleukin 2 receptor alpha-chain" ], "offsets": [ [ 187, 221 ] ], "normalized": [] }, { "id": "PMID-7862168_T5", "type": "Protein", "text": [ "IL-2R alpha" ], "offsets": [ [ 223, 234 ] ], "normalized": [] }, { "id": "PMID-7862168_T6", "type": "Protein", "text": [ "Elf-1" ], "offsets": [ [ 580, 585 ] ], "normalized": [] }, { "id": "PMID-7862168_T7", "type": "Protein", "text": [ "HMG-I(Y)" ], "offsets": [ [ 590, 598 ] ], "normalized": [] }, { "id": "PMID-7862168_T8", "type": "Protein", "text": [ "Elf-1" ], "offsets": [ [ 694, 699 ] ], "normalized": [] }, { "id": "PMID-7862168_T9", "type": "Protein", "text": [ "IL-2R alpha" ], "offsets": [ [ 735, 746 ] ], "normalized": [] }, { "id": "PMID-7862168_T10", "type": "Protein", "text": [ "Elf-1" ], "offsets": [ [ 786, 791 ] ], "normalized": [] }, { "id": "PMID-7862168_T11", "type": "Protein", "text": [ "HMG-I(Y)" ], "offsets": [ [ 799, 807 ] ], "normalized": [] }, { "id": "PMID-7862168_T12", "type": "Protein", "text": [ "Elf-1" ], "offsets": [ [ 931, 936 ] ], "normalized": [] }, { "id": "PMID-7862168_T13", "type": "Protein", "text": [ "HMG-I" ], "offsets": [ [ 964, 969 ] ], "normalized": [] }, { "id": "PMID-7862168_T14", "type": "Protein", "text": [ "p50" ], "offsets": [ [ 990, 993 ] ], "normalized": [] }, { "id": "PMID-7862168_T15", "type": "Protein", "text": [ "c-Rel" ], "offsets": [ [ 998, 1003 ] ], "normalized": [] }, { "id": "PMID-7862168_T16", "type": "Protein", "text": [ "IL-2R alpha" ], "offsets": [ [ 1423, 1434 ] ], "normalized": [] }, { "id": "PMID-7862168_T17", "type": "Protein", "text": [ "Elf-1" ], "offsets": [ [ 1507, 1512 ] ], "normalized": [] }, { "id": "PMID-7862168_T27", "type": "Entity", "text": [ "promoter" ], "offsets": [ [ 747, 755 ] ], "normalized": [] } ]

[ { "id": "PMID-7862168_E1", "type": "Regulation", "trigger": { "text": [ "Regulation" ], "offsets": [ [ 0, 10 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "PMID-7862168_E2" } ] }, { "id": "PMID-7862168_E2", "type": "Gene_expression", "trigger": { "text": [ "expression" ], "offsets": [ [ 73, 83 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "PMID-7862168_T1" } ] }, { "id": "PMID-7862168_E3", "type": "Binding", "trigger": { "text": [ "interactions" ], "offsets": [ [ 112, 124 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "PMID-7862168_T2" } ] }, { "id": "PMID-7862168_E4", "type": "Binding", "trigger": { "text": [ "interactions" ], "offsets": [ [ 112, 124 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "PMID-7862168_T3" } ] }, { "id": "PMID-7862168_E5", "type": "Gene_expression", "trigger": { "text": [ "induced" ], "offsets": [ [ 265, 272 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "PMID-7862168_T5" } ] }, { "id": "PMID-7862168_E6", "type": "Positive_regulation", "trigger": { "text": [ "response" ], "offsets": [ [ 287, 295 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "PMID-7862168_E5" } ] }, { "id": "PMID-7862168_E7", "type": "Binding", "trigger": { "text": [ "binds" ], "offsets": [ [ 574, 579 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "PMID-7862168_T7" } ] }, { "id": "PMID-7862168_E8", "type": "Binding", "trigger": { "text": [ "binds" ], "offsets": [ [ 574, 579 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "PMID-7862168_T6" } ] }, { "id": "PMID-7862168_E9", "type": "Gene_expression", "trigger": { "text": [ "expression" ], "offsets": [ [ 700, 710 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "PMID-7862168_T8" } ] }, { "id": "PMID-7862168_E10", "type": "Transcription", "trigger": { "text": [ "Transcription" ], "offsets": [ [ 712, 725 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "PMID-7862168_T9" } ] }, { "id": "PMID-7862168_E11", "type": "Positive_regulation", "trigger": { "text": [ "from" ], "offsets": [ [ 726, 730 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "PMID-7862168_E10" }, { "role": "Cause", "ref_id": "PMID-7862168_T9" }, { "role": "CSite", "ref_id": "PMID-7862168_T27" } ] }, { "id": "PMID-7862168_E12", "type": "Negative_regulation", "trigger": { "text": [ "inhibited" ], "offsets": [ [ 760, 769 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "PMID-7862168_E11" } ] }, { "id": "PMID-7862168_E13", "type": "Gene_expression", "trigger": { "text": [ "Coexpression" ], "offsets": [ [ 834, 846 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "PMID-7862168_T10" } ] }, { "id": "PMID-7862168_E14", "type": "Gene_expression", "trigger": { "text": [ "Coexpression" ], "offsets": [ [ 834, 846 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "PMID-7862168_T11" } ] }, { "id": "PMID-7862168_E15", "type": "Binding", "trigger": { "text": [ "associated" ], "offsets": [ [ 948, 958 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "PMID-7862168_T12" }, { "role": "Theme", "ref_id": "PMID-7862168_T15" } ] }, { "id": "PMID-7862168_E16", "type": "Binding", "trigger": { "text": [ "associated" ], "offsets": [ [ 948, 958 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "PMID-7862168_T12" }, { "role": "Theme", "ref_id": "PMID-7862168_T14" } ] }, { "id": "PMID-7862168_E17", "type": "Binding", "trigger": { "text": [ "associated" ], "offsets": [ [ 948, 958 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "PMID-7862168_T12" }, { "role": "Theme", "ref_id": "PMID-7862168_T13" } ] }, { "id": "PMID-7862168_E18", "type": "Regulation", "trigger": { "text": [ "regulate" ], "offsets": [ [ 1381, 1389 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "PMID-7862168_E19" } ] }, { "id": "PMID-7862168_E19", "type": "Gene_expression", "trigger": { "text": [ "expression" ], "offsets": [ [ 1440, 1450 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "PMID-7862168_T16" } ] } ]

[ { "id": "PMID-7862168_1", "entity_ids": [ "PMID-7862168_T5", "PMID-7862168_T4" ] } ]

[]

[ { "id": "PMID-7864072__text", "type": "abstract", "text": [ "Effects of glucocorticoids on transcription factor activation in human peripheral blood mononuclear cells. \nGlucocorticoids have an inhibitory effect on inflammatory and immune responses, and this may be through the modulation of transcription factor binding to DNA. The interaction of the transcription factors, activator protein-1 (AP-1), nuclear factor kappa B (NF kappa B), and cAMP-responsive element binding protein (CREB) with DNA and glucocorticoid receptors (GR) was analyzed in human peripheral blood mononuclear cells by gel mobility shift assays. TNF-alpha, IL-1 beta and phorbol myristate acetate (PMA) treatment increased AP-1 and NF kappa B DNA binding by up to 200% but decreased CREB binding (38%) over a 60-min time course. Dexamethasone produced a rapid and sustained increase in glucocorticoid response element binding and a concomitant 40-50% decrease in AP-1, NF kappa B, and CREB DNA binding that was blocked by combined dexamethasone and cytokine or PMA treatment. These latter effects were due to increases in the nuclear localization of GR, not to reduced amounts of the other transcription factors. This suggests that in these cells GR within the nucleus interacts with cytokine-stimulated transcription factors by the process of cross coupling. This may be an important molecular site of steroid action. " ], "offsets": [ [ 0, 1332 ] ] } ]

[ { "id": "PMID-7864072_T1", "type": "Protein", "text": [ "glucocorticoid receptors" ], "offsets": [ [ 442, 466 ] ], "normalized": [] }, { "id": "PMID-7864072_T2", "type": "Protein", "text": [ "GR" ], "offsets": [ [ 468, 470 ] ], "normalized": [] }, { "id": "PMID-7864072_T3", "type": "Protein", "text": [ "TNF-alpha" ], "offsets": [ [ 559, 568 ] ], "normalized": [] }, { "id": "PMID-7864072_T4", "type": "Protein", "text": [ "IL-1 beta" ], "offsets": [ [ 570, 579 ] ], "normalized": [] }, { "id": "PMID-7864072_T5", "type": "Protein", "text": [ "GR" ], "offsets": [ [ 1063, 1065 ] ], "normalized": [] }, { "id": "PMID-7864072_T6", "type": "Protein", "text": [ "GR" ], "offsets": [ [ 1160, 1162 ] ], "normalized": [] }, { "id": "PMID-7864072_T8", "type": "Entity", "text": [ "nuclear" ], "offsets": [ [ 1039, 1046 ] ], "normalized": [] } ]

[ { "id": "PMID-7864072_E1", "type": "Binding", "trigger": { "text": [ "interaction" ], "offsets": [ [ 271, 282 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "PMID-7864072_T2" } ] }, { "id": "PMID-7864072_E2", "type": "Localization", "trigger": { "text": [ "localization" ], "offsets": [ [ 1047, 1059 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "PMID-7864072_T5" }, { "role": "AtLoc", "ref_id": "PMID-7864072_T8" } ] }, { "id": "PMID-7864072_E3", "type": "Binding", "trigger": { "text": [ "interacts" ], "offsets": [ [ 1182, 1191 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "PMID-7864072_T6" } ] } ]

[ { "id": "PMID-7864072_1", "entity_ids": [ "PMID-7864072_T2", "PMID-7864072_T1" ] } ]

[]

[ { "id": "PMID-7865130__text", "type": "abstract", "text": [ "Isolation of cDNA clones for 42 different Kruppel-related zinc finger proteins expressed in the human monoblast cell line U-937. \nTo study the complexity and structural characteristics of zinc finger proteins expressed during human hematopoiesis and to isolate novel regulators of blood cell development, a degenerate oligonucleotide probe specific for a consensus zinc finger peptide domain was used to isolate 63 cDNA clones for Kruppel-related zinc finger genes from the human monoblast cell line U-937. By extensive nucleotide sequence and Northern blot analysis, these cDNA clones were found to originate from approximately 42 different genes (HZF 1-42) of which only 8 have previously been described. Northern blot analysis showed that a majority of these genes were expressed at comparable levels in U-937 and HeLa cells. The large number of individual genes represented among the 63 clones and their apparent non-cell-type-specific expression suggest that the majority of the Kruppel-related zinc finger genes are likely to be expressed in most human tissues. In contrast, some of the genes displayed a restricted expression pattern, indicating that they represent potential regulators of monocyte differentiation or proliferation. Detailed structural analysis of the first 12 cDNAs (HZF 1-10) and a partial characterization of HZF 11-42 revealed that a common feature of human Kruppel-related zinc finger proteins is the presence of tandem arrays of zinc fingers ranging in number from 3 to over 20 that are preferentially located in the carboxy-terminal regions of the proteins. In addition, several novel KRAB-containing zinc finger genes and a novel conserved sequence element were identified. " ], "offsets": [ [ 0, 1706 ] ] } ]

[ { "id": "PMID-7865130_T1", "type": "Protein", "text": [ "HZF 1" ], "offsets": [ [ 649, 654 ] ], "normalized": [] }, { "id": "PMID-7865130_T2", "type": "Protein", "text": [ "42" ], "offsets": [ [ 655, 657 ] ], "normalized": [] }, { "id": "PMID-7865130_T3", "type": "Protein", "text": [ "HZF 1" ], "offsets": [ [ 1292, 1297 ] ], "normalized": [] }, { "id": "PMID-7865130_T4", "type": "Protein", "text": [ "10" ], "offsets": [ [ 1298, 1300 ] ], "normalized": [] }, { "id": "PMID-7865130_T5", "type": "Protein", "text": [ "HZF 11" ], "offsets": [ [ 1336, 1342 ] ], "normalized": [] }, { "id": "PMID-7865130_T6", "type": "Protein", "text": [ "42" ], "offsets": [ [ 1343, 1345 ] ], "normalized": [] } ]

[ { "id": "PMID-7865130_E1", "type": "Gene_expression", "trigger": { "text": [ "expressed" ], "offsets": [ [ 773, 782 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "PMID-7865130_T2" } ] }, { "id": "PMID-7865130_E2", "type": "Gene_expression", "trigger": { "text": [ "expressed" ], "offsets": [ [ 773, 782 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "PMID-7865130_T1" } ] }, { "id": "PMID-7865130_E3", "type": "Gene_expression", "trigger": { "text": [ "expression" ], "offsets": [ [ 940, 950 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "PMID-7865130_T1" } ] }, { "id": "PMID-7865130_E4", "type": "Gene_expression", "trigger": { "text": [ "expression" ], "offsets": [ [ 940, 950 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "PMID-7865130_T2" } ] }, { "id": "PMID-7865130_E5", "type": "Gene_expression", "trigger": { "text": [ "expression" ], "offsets": [ [ 1122, 1132 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "PMID-7865130_T1" } ] } ]

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[ { "id": "PMID-7869038__text", "type": "abstract", "text": [ "Calcium/calmodulin-dependent protein kinase II downregulates both calcineurin and protein kinase C-mediated pathways for cytokine gene transcription in human T cells. \nEngagement of the T cell receptor for antigen activates phospholipase C resulting in an increase in intracellular free calcium concentration ([Ca2+]i) and activation of protein kinase C (PKC). Increased [Ca2+]i activates Ca2+/calmodulin-dependent kinases including the multifunctional Ca2+/calmodulin-dependent protein kinase II (CaM-K II), as well as calcineurin, a type 2B protein phosphatase. Recent studies have identified calcineurin as a key enzyme for interleukin (IL)-2 and IL-4 promoter activation. However, the role of CaM-K II remains unknown. We have used mutants of these kinases and phosphatases (gamma B*CaM-K and delta CaM-AI, respectively) to explore their relative role in cytokine gene transcription and their interactions with PKC-dependent signaling systems. gamma B*CaM-K and delta CaM-AI, known to exhibit constitutive Ca(2+)-independent activity, were cotransfected (alone or in combination) in Jurkat T cells with a plasmid containing the intact IL-2 promoter driving the expression of the chloramphenicol acetyltransferase reporter gene. Cotransfection of gamma B*CaM-K with the IL-2 promoter construct downregulated its transcription in response to stimulation with ionomycin and phorbol myristate acetate (PMA). The inhibitory effect of CaM-K II on IL-2 promoter was associated with decreased transcription of its AP-1 and NF-AT transactivating pathways. Under the same conditions, delta CaM-AI superinduced IL-2 promoter activity (approximately twofold increase). When both mutants were used in combination, gamma B*CaM-K inhibited the induction of the IL-2 promoter by delta CaM-AI. Similar results were obtained when a construct containing the IL-4 promoter also was used. gamma B*CaM-K also downregulated the activation of AP-1 in response to transfection with a constitutively active mutant of PKC or stimulation with PMA. These results suggest that CaM-K II may exert negative influences on cytokine gene transcription in human T cells, and provide preliminary evidence for negative cross-talk with the calcineurin- and PKC- dependent signaling systems. " ], "offsets": [ [ 0, 2256 ] ] } ]

[ { "id": "PMID-7869038_T1", "type": "Protein", "text": [ "calmodulin" ], "offsets": [ [ 394, 404 ] ], "normalized": [] }, { "id": "PMID-7869038_T2", "type": "Protein", "text": [ "interleukin (IL)-2" ], "offsets": [ [ 627, 645 ] ], "normalized": [] }, { "id": "PMID-7869038_T3", "type": "Protein", "text": [ "IL-4" ], "offsets": [ [ 650, 654 ] ], "normalized": [] }, { "id": "PMID-7869038_T4", "type": "Protein", "text": [ "IL-2" ], "offsets": [ [ 1139, 1143 ] ], "normalized": [] }, { "id": "PMID-7869038_T5", "type": "Protein", "text": [ "chloramphenicol acetyltransferase" ], "offsets": [ [ 1183, 1216 ] ], "normalized": [] }, { "id": "PMID-7869038_T6", "type": "Protein", "text": [ "IL-2" ], "offsets": [ [ 1273, 1277 ] ], "normalized": [] }, { "id": "PMID-7869038_T7", "type": "Protein", "text": [ "IL-2" ], "offsets": [ [ 1445, 1449 ] ], "normalized": [] }, { "id": "PMID-7869038_T8", "type": "Protein", "text": [ "IL-2" ], "offsets": [ [ 1604, 1608 ] ], "normalized": [] }, { "id": "PMID-7869038_T9", "type": "Protein", "text": [ "IL-2" ], "offsets": [ [ 1750, 1754 ] ], "normalized": [] }, { "id": "PMID-7869038_T10", "type": "Protein", "text": [ "IL-4" ], "offsets": [ [ 1843, 1847 ] ], "normalized": [] }, { "id": "PMID-7869038_T12", "type": "Entity", "text": [ "promoter" ], "offsets": [ [ 655, 663 ] ], "normalized": [] }, { "id": "PMID-7869038_T15", "type": "Entity", "text": [ "promoter" ], "offsets": [ [ 1450, 1458 ] ], "normalized": [] }, { "id": "PMID-7869038_T20", "type": "Entity", "text": [ "promoter" ], "offsets": [ [ 1609, 1617 ] ], "normalized": [] }, { "id": "PMID-7869038_T23", "type": "Entity", "text": [ "promoter" ], "offsets": [ [ 1755, 1763 ] ], "normalized": [] } ]

[ { "id": "PMID-7869038_E1", "type": "Positive_regulation", "trigger": { "text": [ "key enzyme" ], "offsets": [ [ 612, 622 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "PMID-7869038_E3" } ] }, { "id": "PMID-7869038_E2", "type": "Positive_regulation", "trigger": { "text": [ "key enzyme" ], "offsets": [ [ 612, 622 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "PMID-7869038_E4" } ] }, { "id": "PMID-7869038_E3", "type": "Positive_regulation", "trigger": { "text": [ "activation" ], "offsets": [ [ 664, 674 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "PMID-7869038_T3" }, { "role": "Site", "ref_id": "PMID-7869038_T12" } ] }, { "id": "PMID-7869038_E4", "type": "Positive_regulation", "trigger": { "text": [ "activation" ], "offsets": [ [ 664, 674 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "PMID-7869038_T2" }, { "role": "Site", "ref_id": "PMID-7869038_T12" } ] }, { "id": "PMID-7869038_E5", "type": "Negative_regulation", "trigger": { "text": [ "inhibitory effect" ], "offsets": [ [ 1412, 1429 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "PMID-7869038_T7" }, { "role": "Site", "ref_id": "PMID-7869038_T15" } ] }, { "id": "PMID-7869038_E6", "type": "Negative_regulation", "trigger": { "text": [ "decreased" ], "offsets": [ [ 1479, 1488 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "PMID-7869038_E8" } ] }, { "id": "PMID-7869038_E7", "type": "Transcription", "trigger": { "text": [ "transcription" ], "offsets": [ [ 1489, 1502 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "PMID-7869038_T7" } ] }, { "id": "PMID-7869038_E8", "type": "Positive_regulation", "trigger": { "text": [ "transactivating pathways" ], "offsets": [ [ 1525, 1549 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "PMID-7869038_E7" } ] }, { "id": "PMID-7869038_E9", "type": "Positive_regulation", "trigger": { "text": [ "superinduced" ], "offsets": [ [ 1591, 1603 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "PMID-7869038_T8" }, { "role": "Site", "ref_id": "PMID-7869038_T20" } ] }, { "id": "PMID-7869038_E10", "type": "Negative_regulation", "trigger": { "text": [ "inhibited" ], "offsets": [ [ 1719, 1728 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "PMID-7869038_E11" } ] }, { "id": "PMID-7869038_E11", "type": "Positive_regulation", "trigger": { "text": [ "induction" ], "offsets": [ [ 1733, 1742 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "PMID-7869038_T9" }, { "role": "Site", "ref_id": "PMID-7869038_T23" } ] } ]

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[ { "id": "PMID-7878466__text", "type": "abstract", "text": [ "Control of I kappa B-alpha proteolysis by site-specific, signal-induced phosphorylation. \nI kappa B-alpha inhibits transcription factor NF-kappa B by retaining it in the cytoplasm. Various stimuli, typically those associated with stress or pathogens, rapidly inactivate I kappa B-alpha. This liberates NF-kappa B to translocate to the nucleus and initiate transcription of genes important for the defense of the organism. Activation of NF-kappa B correlates with phosphorylation of I kappa B-alpha and requires the proteolysis of this inhibitor. When either serine-32 or serine-36 of I kappa B-alpha was mutated, the protein did not undergo signal-induced phosphorylation or degradation, and NF-kappa B could not be activated. These results suggest that phosphorylation at one or both of these residues is critical for activation of NF-kappa B. " ], "offsets": [ [ 0, 845 ] ] } ]

[ { "id": "PMID-7878466_T1", "type": "Protein", "text": [ "I kappa B-alpha" ], "offsets": [ [ 11, 26 ] ], "normalized": [] }, { "id": "PMID-7878466_T2", "type": "Protein", "text": [ "I kappa B-alpha" ], "offsets": [ [ 90, 105 ] ], "normalized": [] }, { "id": "PMID-7878466_T3", "type": "Protein", "text": [ "I kappa B-alpha" ], "offsets": [ [ 270, 285 ] ], "normalized": [] }, { "id": "PMID-7878466_T4", "type": "Protein", "text": [ "I kappa B-alpha" ], "offsets": [ [ 482, 497 ] ], "normalized": [] }, { "id": "PMID-7878466_T5", "type": "Protein", "text": [ "I kappa B-alpha" ], "offsets": [ [ 584, 599 ] ], "normalized": [] }, { "id": "PMID-7878466_T13", "type": "Entity", "text": [ "serine-32" ], "offsets": [ [ 558, 567 ] ], "normalized": [] }, { "id": "PMID-7878466_T14", "type": "Entity", "text": [ "serine-36" ], "offsets": [ [ 571, 580 ] ], "normalized": [] } ]

[ { "id": "PMID-7878466_E1", "type": "Regulation", "trigger": { "text": [ "Control" ], "offsets": [ [ 0, 7 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "PMID-7878466_E2" }, { "role": "Cause", "ref_id": "PMID-7878466_E3" } ] }, { "id": "PMID-7878466_E2", "type": "Protein_catabolism", "trigger": { "text": [ "proteolysis" ], "offsets": [ [ 27, 38 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "PMID-7878466_T1" } ] }, { "id": "PMID-7878466_E3", "type": "Phosphorylation", "trigger": { "text": [ "phosphorylation" ], "offsets": [ [ 72, 87 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "PMID-7878466_T1" } ] }, { "id": "PMID-7878466_E4", "type": "Negative_regulation", "trigger": { "text": [ "inactivate" ], "offsets": [ [ 259, 269 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "PMID-7878466_T3" } ] }, { "id": "PMID-7878466_E5", "type": "Phosphorylation", "trigger": { "text": [ "phosphorylation" ], "offsets": [ [ 463, 478 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "PMID-7878466_T4" } ] }, { "id": "PMID-7878466_E6", "type": "Regulation", "trigger": { "text": [ "requires" ], "offsets": [ [ 502, 510 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "PMID-7878466_E7" } ] }, { "id": "PMID-7878466_E7", "type": "Protein_catabolism", "trigger": { "text": [ "proteolysis" ], "offsets": [ [ 515, 526 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "PMID-7878466_T4" } ] }, { "id": "PMID-7878466_E8", "type": "Phosphorylation", "trigger": { "text": [ "phosphorylation" ], "offsets": [ [ 656, 671 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "PMID-7878466_T5" }, { "role": "Site", "ref_id": "PMID-7878466_T14" } ] }, { "id": "PMID-7878466_E9", "type": "Phosphorylation", "trigger": { "text": [ "phosphorylation" ], "offsets": [ [ 656, 671 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "PMID-7878466_T5" }, { "role": "Site", "ref_id": "PMID-7878466_T13" } ] }, { "id": "PMID-7878466_E10", "type": "Protein_catabolism", "trigger": { "text": [ "degradation" ], "offsets": [ [ 675, 686 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "PMID-7878466_T5" } ] }, { "id": "PMID-7878466_E11", "type": "Phosphorylation", "trigger": { "text": [ "phosphorylation" ], "offsets": [ [ 754, 769 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "PMID-7878466_T5" }, { "role": "Site", "ref_id": "PMID-7878466_T14" } ] }, { "id": "PMID-7878466_E12", "type": "Phosphorylation", "trigger": { "text": [ "phosphorylation" ], "offsets": [ [ 754, 769 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "PMID-7878466_T5" }, { "role": "Site", "ref_id": "PMID-7878466_T13" } ] } ]

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[ { "id": "PMID-7882168__text", "type": "abstract", "text": [ "HIV-1 Nef leads to inhibition or activation of T cells depending on its intracellular localization. \nNef of primate lentiviruses is required for viremia and progression to AIDS in monkeys. Negative, positive, and no effects of Nef have also been reported on viral replication in cells. To reconcile these observations, we expressed a hybrid CD8-Nef protein in Jurkat cells. Two opposite phenotypes were found, which depended on the intracellular localization of Nef. Expressed in the cytoplasm or on the cell surface, the chimera inhibited or activated early signaling events from the T cell antigen receptor. Activated Jurkat cells died by apoptosis, and only cells with mutated nef genes expressing truncated Nefs survived, which rendered Nef nonfunctional. These mutations paralleled those in other viral strains passaged in vitro. Not only do these positional effects of Nef reconcile diverse phenotypes of Nef and suggest a role for its N-terminal myristylation, but they also explain effects of Nef in HIV infection and progression to AIDS. " ], "offsets": [ [ 0, 1047 ] ] } ]

[ { "id": "PMID-7882168_T1", "type": "Protein", "text": [ "Nef" ], "offsets": [ [ 6, 9 ] ], "normalized": [] }, { "id": "PMID-7882168_T2", "type": "Protein", "text": [ "Nef" ], "offsets": [ [ 101, 104 ] ], "normalized": [] }, { "id": "PMID-7882168_T3", "type": "Protein", "text": [ "Nef" ], "offsets": [ [ 227, 230 ] ], "normalized": [] }, { "id": "PMID-7882168_T4", "type": "Protein", "text": [ "Nef" ], "offsets": [ [ 345, 348 ] ], "normalized": [] }, { "id": "PMID-7882168_T5", "type": "Protein", "text": [ "Nef" ], "offsets": [ [ 462, 465 ] ], "normalized": [] }, { "id": "PMID-7882168_T6", "type": "Protein", "text": [ "nef" ], "offsets": [ [ 680, 683 ] ], "normalized": [] }, { "id": "PMID-7882168_T7", "type": "Protein", "text": [ "Nef" ], "offsets": [ [ 711, 714 ] ], "normalized": [] }, { "id": "PMID-7882168_T8", "type": "Protein", "text": [ "Nef" ], "offsets": [ [ 741, 744 ] ], "normalized": [] }, { "id": "PMID-7882168_T9", "type": "Protein", "text": [ "Nef" ], "offsets": [ [ 875, 878 ] ], "normalized": [] }, { "id": "PMID-7882168_T10", "type": "Protein", "text": [ "Nef" ], "offsets": [ [ 911, 914 ] ], "normalized": [] }, { "id": "PMID-7882168_T11", "type": "Protein", "text": [ "Nef" ], "offsets": [ [ 1001, 1004 ] ], "normalized": [] }, { "id": "PMID-7882168_T12", "type": "Entity", "text": [ "intracellular" ], "offsets": [ [ 72, 85 ] ], "normalized": [] }, { "id": "PMID-7882168_T14", "type": "Entity", "text": [ "intracellular" ], "offsets": [ [ 432, 445 ] ], "normalized": [] } ]

[ { "id": "PMID-7882168_E1", "type": "Localization", "trigger": { "text": [ "localization" ], "offsets": [ [ 86, 98 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "PMID-7882168_T1" }, { "role": "AtLoc", "ref_id": "PMID-7882168_T12" } ] }, { "id": "PMID-7882168_E2", "type": "Localization", "trigger": { "text": [ "localization" ], "offsets": [ [ 446, 458 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "PMID-7882168_T5" }, { "role": "AtLoc", "ref_id": "PMID-7882168_T14" } ] }, { "id": "PMID-7882168_E3", "type": "Gene_expression", "trigger": { "text": [ "expressing" ], "offsets": [ [ 690, 700 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "PMID-7882168_T7" } ] } ]

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[]

[ { "id": "PMID-7884865__text", "type": "abstract", "text": [ "LMP-1 activates NF-kappa B by targeting the inhibitory molecule I kappa B alpha. \nLMP-1, an Epstein-Barr virus membrane protein expressed during latent infection, has oncogenic properties, as judged from its ability to transform B lymphocytes and rodent fibroblasts. LMP-1 induces the expression of bcl2, an oncogene which protects cells from apoptosis, as well as of genes encoding other proteins involved in cell regulation and growth control. The mechanisms by which LMP-1 upregulates these proteins is unknown, but it is plausible that LMP-1 modifies signal transduction pathways that result in the activation of one or more transcription factors that ultimately regulate transcription of oncogenic genes. NF-kappa B, a transcription factor controlling the expression of genes involved in cell activation and growth control, has been shown to be activated by LMP-1. The mechanism(s) regulating this activation remains unknown. Our data indicate that increased NF-kappa B DNA binding and functional activity are present in B-lymphoid cells stably or transiently expressing LMP-1. I kappa B alpha is selectively modified in LMP-1-expressing B cells. A phosphorylated form of I kappa B alpha and increased protein turnover-degradation correlate with increased NF-kappa B nuclear translocation. This results in increased transcription of NF-kappa B-dependent-genes, including those encoding p105 and I kappa B alpha (MAD3). These results indicate that LMP-1 activates NF-kappa B in B-cell lines by targeting I kappa B alpha. Identification of the pathways activated by LMP-1 to result in posttranslational modifications of I kappa B alpha will aid in determining the role of this virus-host cell protein interaction in Epstein-Barr virus-mediated oncogenesis. " ], "offsets": [ [ 0, 1760 ] ] } ]

[ { "id": "PMID-7884865_T1", "type": "Protein", "text": [ "LMP-1" ], "offsets": [ [ 0, 5 ] ], "normalized": [] }, { "id": "PMID-7884865_T2", "type": "Protein", "text": [ "I kappa B alpha" ], "offsets": [ [ 64, 79 ] ], "normalized": [] }, { "id": "PMID-7884865_T3", "type": "Protein", "text": [ "LMP-1" ], "offsets": [ [ 82, 87 ] ], "normalized": [] }, { "id": "PMID-7884865_T4", "type": "Protein", "text": [ "LMP-1" ], "offsets": [ [ 267, 272 ] ], "normalized": [] }, { "id": "PMID-7884865_T5", "type": "Protein", "text": [ "bcl2" ], "offsets": [ [ 299, 303 ] ], "normalized": [] }, { "id": "PMID-7884865_T6", "type": "Protein", "text": [ "LMP-1" ], "offsets": [ [ 470, 475 ] ], "normalized": [] }, { "id": "PMID-7884865_T7", "type": "Protein", "text": [ "LMP-1" ], "offsets": [ [ 540, 545 ] ], "normalized": [] }, { "id": "PMID-7884865_T8", "type": "Protein", "text": [ "LMP-1" ], "offsets": [ [ 863, 868 ] ], "normalized": [] }, { "id": "PMID-7884865_T9", "type": "Protein", "text": [ "LMP-1" ], "offsets": [ [ 1076, 1081 ] ], "normalized": [] }, { "id": "PMID-7884865_T10", "type": "Protein", "text": [ "I kappa B alpha" ], "offsets": [ [ 1083, 1098 ] ], "normalized": [] }, { "id": "PMID-7884865_T11", "type": "Protein", "text": [ "LMP-1" ], "offsets": [ [ 1126, 1131 ] ], "normalized": [] }, { "id": "PMID-7884865_T12", "type": "Protein", "text": [ "I kappa B alpha" ], "offsets": [ [ 1177, 1192 ] ], "normalized": [] }, { "id": "PMID-7884865_T13", "type": "Protein", "text": [ "p105" ], "offsets": [ [ 1391, 1395 ] ], "normalized": [] }, { "id": "PMID-7884865_T14", "type": "Protein", "text": [ "I kappa B alpha" ], "offsets": [ [ 1400, 1415 ] ], "normalized": [] }, { "id": "PMID-7884865_T15", "type": "Protein", "text": [ "MAD3" ], "offsets": [ [ 1417, 1421 ] ], "normalized": [] }, { "id": "PMID-7884865_T16", "type": "Protein", "text": [ "LMP-1" ], "offsets": [ [ 1452, 1457 ] ], "normalized": [] }, { "id": "PMID-7884865_T17", "type": "Protein", "text": [ "I kappa B alpha" ], "offsets": [ [ 1508, 1523 ] ], "normalized": [] }, { "id": "PMID-7884865_T18", "type": "Protein", "text": [ "LMP-1" ], "offsets": [ [ 1569, 1574 ] ], "normalized": [] }, { "id": "PMID-7884865_T19", "type": "Protein", "text": [ "I kappa B alpha" ], "offsets": [ [ 1623, 1638 ] ], "normalized": [] } ]

[ { "id": "PMID-7884865_E1", "type": "Regulation", "trigger": { "text": [ "targeting" ], "offsets": [ [ 30, 39 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "PMID-7884865_T2" }, { "role": "Cause", "ref_id": "PMID-7884865_T1" } ] }, { "id": "PMID-7884865_E2", "type": "Gene_expression", "trigger": { "text": [ "expressed" ], "offsets": [ [ 128, 137 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "PMID-7884865_T3" } ] }, { "id": "PMID-7884865_E3", "type": "Positive_regulation", "trigger": { "text": [ "induces" ], "offsets": [ [ 273, 280 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "PMID-7884865_E4" }, { "role": "Cause", "ref_id": "PMID-7884865_T4" } ] }, { "id": "PMID-7884865_E4", "type": "Gene_expression", "trigger": { "text": [ "expression" ], "offsets": [ [ 285, 295 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "PMID-7884865_T5" } ] }, { "id": "PMID-7884865_E5", "type": "Positive_regulation", "trigger": { "text": [ "upregulates" ], "offsets": [ [ 476, 487 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "PMID-7884865_T5" }, { "role": "Cause", "ref_id": "PMID-7884865_T6" } ] }, { "id": "PMID-7884865_E6", "type": "Gene_expression", "trigger": { "text": [ "expressing" ], "offsets": [ [ 1065, 1075 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "PMID-7884865_T9" } ] }, { "id": "PMID-7884865_E7", "type": "Gene_expression", "trigger": { "text": [ "expressing" ], "offsets": [ [ 1132, 1142 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "PMID-7884865_T11" } ] }, { "id": "PMID-7884865_E8", "type": "Phosphorylation", "trigger": { "text": [ "phosphorylated form" ], "offsets": [ [ 1154, 1173 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "PMID-7884865_T12" } ] }, { "id": "PMID-7884865_E9", "type": "Positive_regulation", "trigger": { "text": [ "increased" ], "offsets": [ [ 1311, 1320 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "PMID-7884865_E12" } ] }, { "id": "PMID-7884865_E10", "type": "Positive_regulation", "trigger": { "text": [ "increased" ], "offsets": [ [ 1311, 1320 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "PMID-7884865_E11" } ] }, { "id": "PMID-7884865_E11", "type": "Transcription", "trigger": { "text": [ "transcription" ], "offsets": [ [ 1321, 1334 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "PMID-7884865_T15" } ] }, { "id": "PMID-7884865_E12", "type": "Transcription", "trigger": { "text": [ "transcription" ], "offsets": [ [ 1321, 1334 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "PMID-7884865_T13" } ] }, { "id": "PMID-7884865_E13", "type": "Regulation", "trigger": { "text": [ "targeting" ], "offsets": [ [ 1498, 1507 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "PMID-7884865_T17" }, { "role": "Cause", "ref_id": "PMID-7884865_T16" } ] } ]

[ { "id": "PMID-7884865_1", "entity_ids": [ "PMID-7884865_T15", "PMID-7884865_T14" ] } ]

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[ { "id": "PMID-7888116__text", "type": "abstract", "text": [ "The regulation of HIV by retinoic acid correlates with cellular expression of the retinoic acid receptors. \nOBJECTIVES: To analyze the effect of retinoic acids (RA) on HIV-1 expression and correlate this effect with expression levels of RA receptors (RARs) in T-lymphoid and monocytoid cell lines. DESIGN AND METHODS: The effect of all-trans and 9-cis RA on HIV-1 production in T-lymphoid (H9, CEM) and monocytoid (U937,THP-1) cell lines was measured during acute and chronic infection. The expression levels of human RAR alpha (hRAR alpha, receptor for all-trans RA) and the human retinoid-X receptor alpha (hRXR alpha receptor for 9-cis RA) were determined by Northern blot analysis. RESULTS: Both all-trans and 9-cis RA inhibited virus replication in HIV-1 IIIB-infected monocytoid cells, in the presence and absence of the co-stimulatory agent phorbol myristate acetate (PMA). The retinoids had weak or no stimulatory effects on HIV production by T-cell lines. HIV production by PMA-stimulated T-cell lines was inhibited by these retinoids. The 9-cis RA was generally more effective than all-trans RA in inhibiting HIV production and in combination generally more effective than the single agents alone. Human RAR alpha was expressed in H9, U937 and THP-1 cells, but almost undetectable in CEM cells. Human RXR alpha was significantly expressed in U937 and THP-1 cells, weakly expressed in H9 cells and not detectable in CEM cells. After stimulation by PMA, RXR alpha expression increased in H9 and U937 cells but not in CEM cells. Human RAR alpha expression was unchanged in H9 and CEM cells, and elevated in U937 cells, after PMA stimulation. CONCLUSION: The effect of RA on HIV-1 expression was cell-type-dependent and partially correlated with cellular expression of RARs. Endogenous or exogenously administered RA may have a significant role in HIV regulation. " ], "offsets": [ [ 0, 1870 ] ] } ]

[ { "id": "PMID-7888116_T1", "type": "Protein", "text": [ "RAR alpha" ], "offsets": [ [ 518, 527 ] ], "normalized": [] }, { "id": "PMID-7888116_T2", "type": "Protein", "text": [ "hRAR alpha" ], "offsets": [ [ 529, 539 ] ], "normalized": [] }, { "id": "PMID-7888116_T3", "type": "Protein", "text": [ "retinoid-X receptor alpha" ], "offsets": [ [ 582, 607 ] ], "normalized": [] }, { "id": "PMID-7888116_T4", "type": "Protein", "text": [ "hRXR alpha" ], "offsets": [ [ 609, 619 ] ], "normalized": [] }, { "id": "PMID-7888116_T5", "type": "Protein", "text": [ "RXR alpha" ], "offsets": [ [ 1311, 1320 ] ], "normalized": [] }, { "id": "PMID-7888116_T6", "type": "Protein", "text": [ "RXR alpha" ], "offsets": [ [ 1462, 1471 ] ], "normalized": [] }, { "id": "PMID-7888116_T7", "type": "Protein", "text": [ "RAR alpha" ], "offsets": [ [ 1542, 1551 ] ], "normalized": [] } ]

[ { "id": "PMID-7888116_E1", "type": "Gene_expression", "trigger": { "text": [ "expression" ], "offsets": [ [ 491, 501 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "PMID-7888116_T1" } ] }, { "id": "PMID-7888116_E2", "type": "Gene_expression", "trigger": { "text": [ "expression" ], "offsets": [ [ 491, 501 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "PMID-7888116_T4" } ] }, { "id": "PMID-7888116_E3", "type": "Binding", "trigger": { "text": [ "receptor" ], "offsets": [ [ 541, 549 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "PMID-7888116_T1" } ] }, { "id": "PMID-7888116_E4", "type": "Binding", "trigger": { "text": [ "receptor" ], "offsets": [ [ 620, 628 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "PMID-7888116_T4" } ] }, { "id": "PMID-7888116_E5", "type": "Gene_expression", "trigger": { "text": [ "expressed" ], "offsets": [ [ 1339, 1348 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "PMID-7888116_T5" } ] }, { "id": "PMID-7888116_E6", "type": "Gene_expression", "trigger": { "text": [ "expressed" ], "offsets": [ [ 1381, 1390 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "PMID-7888116_T5" } ] }, { "id": "PMID-7888116_E7", "type": "Gene_expression", "trigger": { "text": [ "detectable" ], "offsets": [ [ 1411, 1421 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "PMID-7888116_T5" } ] }, { "id": "PMID-7888116_E8", "type": "Gene_expression", "trigger": { "text": [ "expression" ], "offsets": [ [ 1472, 1482 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "PMID-7888116_T6" } ] }, { "id": "PMID-7888116_E9", "type": "Positive_regulation", "trigger": { "text": [ "increased" ], "offsets": [ [ 1483, 1492 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "PMID-7888116_E8" } ] }, { "id": "PMID-7888116_E10", "type": "Gene_expression", "trigger": { "text": [ "expression" ], "offsets": [ [ 1552, 1562 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "PMID-7888116_T7" } ] }, { "id": "PMID-7888116_E11", "type": "Regulation", "trigger": { "text": [ "unchanged" ], "offsets": [ [ 1567, 1576 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "PMID-7888116_E10" } ] }, { "id": "PMID-7888116_E12", "type": "Positive_regulation", "trigger": { "text": [ "elevated" ], "offsets": [ [ 1602, 1610 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "PMID-7888116_E10" } ] } ]

[ { "id": "PMID-7888116_1", "entity_ids": [ "PMID-7888116_T1", "PMID-7888116_T2" ] } ]

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[ { "id": "PMID-7890658__text", "type": "abstract", "text": [ "Identification of human TR2 orphan receptor response element in the transcriptional initiation site of the simian virus 40 major late promoter [published erratum appears in J Biol Chem 1995 Nov 3;270(44):26721] \nA DNA response element (TR2RE-SV40) for the TR2 orphan receptor, a member of the steroid-thyroid hormone receptor superfamily, has been identified in the simian virus 40 (SV40) +55 region (nucleotide numbers 368-389, 5'-GTTAAGGTTCGTAGGTCATGGA-3'). Electrophoretic mobility shift assay, using in vitro translated TR2 orphan receptor with a molecular mass of 67 kilodaltons, showed a specific binding with high affinity (dissociation constant = 9 nM) for this DNA sequence. DNA-swap experiments using chloramphenicol acetyl-transferase assay demonstrated that androgen can suppress the transcriptional activities of SV40 early promoter via the interaction between this TR2RE-SV40 and the chimeric receptor AR/TR2/AR with the DNA-binding domain of the TR2 orphan receptor flanked by the N-terminal and androgen-binding domains of the androgen receptor. In addition, this TR2RE-SV40 can function as a repressor to suppress the transcriptional activities of both SV40 early and late promoters. Together, these data suggest the TR2RE-SV40 may represent the first identified natural DNA response element for the TR2 orphan receptor that may function as a repressor for the SV40 gene expression. " ], "offsets": [ [ 0, 1400 ] ] } ]

[ { "id": "PMID-7890658_T1", "type": "Protein", "text": [ "chloramphenicol acetyl-transferase" ], "offsets": [ [ 711, 745 ] ], "normalized": [] } ]

[]

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[]

[ { "id": "PMID-7890777__text", "type": "abstract", "text": [ "Mapping of the interaction site of the defective transcription factor in the class II major histocompatibility complex mutant cell line clone-13 to the divergent X2-box. \nWe have previously described a mutant B lymphoblastoid cell line, Clone-13, that expresses HLA-DQ in the absence of HLA-DR and -DP. Several criteria indicated that the defect in this cell line influences the activity of an isotype-specific transcription factor. Indeed, transient transfection of HLA-DRA and DQB reporter constructs indicated that the affected factor operates via cis-elements located between -141 base pairs and the transcription initiation site. A series of hybrid DRA/DQB reporter constructs was generated to further map the relevant cis-elements in this system. Insertion of oligonucleotides spanning the DQB X-box (but not the DQB-W region or the DQB Y-box) upstream of -141 in a DRA reporter plasmid rescued expression to nearly wild-type levels. Substitution promoters were then generated where the entire X-box, or only the X1- or X2-boxes of HLA-DRA were replaced with the analogous regions of HLA-DQB. The DQB X2-box was able to restore expression to the silent DRA reporter construct. Moreover, replacement of the DQB X2-box with the DRA X2-box markedly diminished the activity of the DQB promoter in the mutant cell. None of the hybrid reporter constructs were defective when transfected into the wild-type, HLA-DR/-DQ positive parental cell line, Jijoye. These studies suggest that the divergent X2-box of the class II major histocompatibility complex promoters plays an important role in influencing differential expression of the human class II isotypes. " ], "offsets": [ [ 0, 1657 ] ] } ]

[ { "id": "PMID-7890777_T1", "type": "Protein", "text": [ "HLA-DRA" ], "offsets": [ [ 1038, 1045 ] ], "normalized": [] } ]

[]

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[ { "id": "PMID-7892566__text", "type": "abstract", "text": [ "[Regulation of transcription of the interleukin-2 gene in B-lymphocytes] \nSince most B cell clones immortalized with EBV virus can be induced to produce interleukin-2, a typical T cell cytokine, we studied the role of different elements of the IL-2 promoter in such clones by transfection. It was found, in particular, that the element TCEd, which binds the transcription factor NF-kB, is very active in all three B clones tested. This element has no activity in T cells of the Jurkat line. The NFATd element, which binds the transcription factor NFAT-1 and is very active in T cells, is only weakly active in one B clone and not at all in another. Different elements thus contribute to IL-2 promoter activity in different cells. " ], "offsets": [ [ 0, 730 ] ] } ]

[ { "id": "PMID-7892566_T1", "type": "Protein", "text": [ "interleukin-2" ], "offsets": [ [ 36, 49 ] ], "normalized": [] }, { "id": "PMID-7892566_T2", "type": "Protein", "text": [ "interleukin-2" ], "offsets": [ [ 153, 166 ] ], "normalized": [] }, { "id": "PMID-7892566_T3", "type": "Protein", "text": [ "IL-2" ], "offsets": [ [ 244, 248 ] ], "normalized": [] }, { "id": "PMID-7892566_T4", "type": "Protein", "text": [ "NFAT-1" ], "offsets": [ [ 547, 553 ] ], "normalized": [] }, { "id": "PMID-7892566_T5", "type": "Protein", "text": [ "IL-2" ], "offsets": [ [ 687, 691 ] ], "normalized": [] } ]

[ { "id": "PMID-7892566_E1", "type": "Regulation", "trigger": { "text": [ "Regulation" ], "offsets": [ [ 1, 11 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "PMID-7892566_E2" } ] }, { "id": "PMID-7892566_E2", "type": "Transcription", "trigger": { "text": [ "transcription" ], "offsets": [ [ 15, 28 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "PMID-7892566_T1" } ] }, { "id": "PMID-7892566_E3", "type": "Positive_regulation", "trigger": { "text": [ "induced" ], "offsets": [ [ 134, 141 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "PMID-7892566_E4" } ] }, { "id": "PMID-7892566_E4", "type": "Gene_expression", "trigger": { "text": [ "produce" ], "offsets": [ [ 145, 152 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "PMID-7892566_T2" } ] }, { "id": "PMID-7892566_E5", "type": "Binding", "trigger": { "text": [ "binds" ], "offsets": [ [ 516, 521 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "PMID-7892566_T4" } ] } ]

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[ { "id": "PMID-7905504__text", "type": "abstract", "text": [ "Effects of CD45 on NF-kappa B. Implications for replication of HIV-1. \nIncreased levels of replication of the HIV type 1 are observed after the activation of infected T cells through the TCR. However, anti-CD45 antibodies inhibit these effects in cells from infected individuals. In this study, we examined interrelationships between CD45 and HIV-1 further. We measured effects on the HIV-1 LTR in T cell lines that were stimulated with antibodies against CD45 and in those that lacked the expression of CD45 on their surfaces. First, anti-CD45 antibodies did not affect basal but decreased activated levels of expression from the HIV-1 LTR. Second, T cells, which lack CD45 and cannot signal via the TCR, supported higher levels of viral replication and gene expression. This was due to the presence of active NF-kappa B complexes in the nucleus of CD45- T cells. Additionally, infected T cells displayed lower levels of CD45 on their surfaces. Thus, CD45 plays an active role in the physiology of T cells and in the replication of HIV-1. " ], "offsets": [ [ 0, 1040 ] ] } ]

[ { "id": "PMID-7905504_T1", "type": "Protein", "text": [ "CD45" ], "offsets": [ [ 11, 15 ] ], "normalized": [] }, { "id": "PMID-7905504_T2", "type": "Protein", "text": [ "CD45" ], "offsets": [ [ 206, 210 ] ], "normalized": [] }, { "id": "PMID-7905504_T3", "type": "Protein", "text": [ "CD45" ], "offsets": [ [ 334, 338 ] ], "normalized": [] }, { "id": "PMID-7905504_T4", "type": "Protein", "text": [ "CD45" ], "offsets": [ [ 456, 460 ] ], "normalized": [] }, { "id": "PMID-7905504_T5", "type": "Protein", "text": [ "CD45" ], "offsets": [ [ 504, 508 ] ], "normalized": [] }, { "id": "PMID-7905504_T6", "type": "Protein", "text": [ "CD45" ], "offsets": [ [ 540, 544 ] ], "normalized": [] }, { "id": "PMID-7905504_T7", "type": "Protein", "text": [ "CD45" ], "offsets": [ [ 670, 674 ] ], "normalized": [] }, { "id": "PMID-7905504_T8", "type": "Protein", "text": [ "CD45" ], "offsets": [ [ 850, 854 ] ], "normalized": [] }, { "id": "PMID-7905504_T9", "type": "Protein", "text": [ "CD45" ], "offsets": [ [ 922, 926 ] ], "normalized": [] }, { "id": "PMID-7905504_T10", "type": "Protein", "text": [ "CD45" ], "offsets": [ [ 952, 956 ] ], "normalized": [] } ]

[ { "id": "PMID-7905504_E1", "type": "Gene_expression", "trigger": { "text": [ "expression" ], "offsets": [ [ 490, 500 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "PMID-7905504_T5" } ] }, { "id": "PMID-7905504_E2", "type": "Negative_regulation", "trigger": { "text": [ "lack" ], "offsets": [ [ 665, 669 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "PMID-7905504_T7" } ] }, { "id": "PMID-7905504_E3", "type": "Negative_regulation", "trigger": { "text": [ "displayed lower levels" ], "offsets": [ [ 896, 918 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "PMID-7905504_T9" } ] } ]

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[ { "id": "PMID-7909357__text", "type": "abstract", "text": [ "ERP, a new member of the ets transcription factor/oncoprotein family: cloning, characterization, and differential expression during B-lymphocyte development. \nThe ets gene family encodes a group of proteins which function as transcription factors under physiological conditions and, if aberrantly expressed, can cause cellular transformation. We have recently identified two regulatory elements in the murine immunoglobulin heavy-chain (IgH) enhancer, pi and microB, which exhibit striking similarity to binding sites for ets-related proteins. To identify ets-related transcriptional regulators expressed in pre-B lymphocytes that may interact with either the pi or the microB site, we have used a PCR approach with degenerate oligonucleotides encoding conserved sequences in all members of the ets family. We have cloned the gene for a new ets-related transcription factor, ERP (ets-related protein), from the murine pre-B cell line BASC 6C2 and from mouse lung tissue. The ERP protein contains a region of high homology with the ETS DNA-binding domain common to all members of the ets transcription factor/oncoprotein family. Three additional smaller regions show homology to the ELK-1 and SAP-1 genes, a subgroup of the ets gene family that interacts with the serum response factor. Full-length ERP expresses only negligible DNA-binding activity by itself. Removal of the carboxy terminus enables ERP to interact with a variety of ets-binding sites including the E74 site, the IgH enhancer pi site, and the lck promoter ets site, suggesting a carboxy-terminal negative regulatory domain. At least three ERP-related transcripts are expressed in a variety of tissues. However, within the B-cell lineage, ERP is highly expressed primarily at early stages of B-lymphocyte development, and expression declines drastically upon B-cell maturation, correlating with the enhancer activity of the IgH pi site. These data suggest that ERP might play a role in B-cell development and in IgH gene regulation. " ], "offsets": [ [ 0, 1999 ] ] } ]

[ { "id": "PMID-7909357_T1", "type": "Protein", "text": [ "ERP" ], "offsets": [ [ 0, 3 ] ], "normalized": [] }, { "id": "PMID-7909357_T2", "type": "Protein", "text": [ "ERP" ], "offsets": [ [ 875, 878 ] ], "normalized": [] }, { "id": "PMID-7909357_T3", "type": "Protein", "text": [ "ets-related protein" ], "offsets": [ [ 880, 899 ] ], "normalized": [] }, { "id": "PMID-7909357_T4", "type": "Protein", "text": [ "ERP" ], "offsets": [ [ 975, 978 ] ], "normalized": [] }, { "id": "PMID-7909357_T5", "type": "Protein", "text": [ "ELK-1" ], "offsets": [ [ 1182, 1187 ] ], "normalized": [] }, { "id": "PMID-7909357_T6", "type": "Protein", "text": [ "SAP-1" ], "offsets": [ [ 1192, 1197 ] ], "normalized": [] }, { "id": "PMID-7909357_T7", "type": "Protein", "text": [ "serum response factor" ], "offsets": [ [ 1263, 1284 ] ], "normalized": [] }, { "id": "PMID-7909357_T8", "type": "Protein", "text": [ "ERP" ], "offsets": [ [ 1298, 1301 ] ], "normalized": [] }, { "id": "PMID-7909357_T9", "type": "Protein", "text": [ "ERP" ], "offsets": [ [ 1400, 1403 ] ], "normalized": [] }, { "id": "PMID-7909357_T10", "type": "Protein", "text": [ "lck" ], "offsets": [ [ 1510, 1513 ] ], "normalized": [] }, { "id": "PMID-7909357_T11", "type": "Protein", "text": [ "ERP" ], "offsets": [ [ 1606, 1609 ] ], "normalized": [] }, { "id": "PMID-7909357_T12", "type": "Protein", "text": [ "ERP" ], "offsets": [ [ 1705, 1708 ] ], "normalized": [] }, { "id": "PMID-7909357_T13", "type": "Protein", "text": [ "ERP" ], "offsets": [ [ 1927, 1930 ] ], "normalized": [] }, { "id": "PMID-7909357_T19", "type": "Entity", "text": [ "promoter ets site" ], "offsets": [ [ 1514, 1531 ] ], "normalized": [] } ]

[ { "id": "PMID-7909357_E1", "type": "Gene_expression", "trigger": { "text": [ "expression" ], "offsets": [ [ 114, 124 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "PMID-7909357_T1" } ] }, { "id": "PMID-7909357_E2", "type": "Binding", "trigger": { "text": [ "interacts" ], "offsets": [ [ 1244, 1253 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "PMID-7909357_T5" }, { "role": "Theme", "ref_id": "PMID-7909357_T7" } ] }, { "id": "PMID-7909357_E3", "type": "Binding", "trigger": { "text": [ "interacts" ], "offsets": [ [ 1244, 1253 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "PMID-7909357_T6" }, { "role": "Theme", "ref_id": "PMID-7909357_T7" } ] }, { "id": "PMID-7909357_E4", "type": "Binding", "trigger": { "text": [ "binding activity" ], "offsets": [ [ 1332, 1348 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "PMID-7909357_T8" } ] }, { "id": "PMID-7909357_E5", "type": "Positive_regulation", "trigger": { "text": [ "enables" ], "offsets": [ [ 1392, 1399 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "PMID-7909357_E7" } ] }, { "id": "PMID-7909357_E6", "type": "Positive_regulation", "trigger": { "text": [ "enables" ], "offsets": [ [ 1392, 1399 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "PMID-7909357_E8" } ] }, { "id": "PMID-7909357_E7", "type": "Binding", "trigger": { "text": [ "interact" ], "offsets": [ [ 1407, 1415 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "PMID-7909357_T9" } ] }, { "id": "PMID-7909357_E8", "type": "Binding", "trigger": { "text": [ "interact" ], "offsets": [ [ 1407, 1415 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "PMID-7909357_T9" }, { "role": "Theme", "ref_id": "PMID-7909357_T10" }, { "role": "Site", "ref_id": "PMID-7909357_T19" } ] }, { "id": "PMID-7909357_E9", "type": "Gene_expression", "trigger": { "text": [ "expressed" ], "offsets": [ [ 1719, 1728 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "PMID-7909357_T12" } ] }, { "id": "PMID-7909357_E10", "type": "Negative_regulation", "trigger": { "text": [ "declines" ], "offsets": [ [ 1799, 1807 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "PMID-7909357_E9" } ] } ]

[ { "id": "PMID-7909357_1", "entity_ids": [ "PMID-7909357_T2", "PMID-7909357_T3" ] } ]

[]

[ { "id": "PMID-7912114__text", "type": "abstract", "text": [ "Pentoxifylline for the treatment of infection with human immunodeficiency virus. \nCytokine dysregulation in human immunodeficiency virus type 1 (HIV-1) infection has been documented in numerous studies and has been cited as an important component in the pathogenesis of this retroviral infection. Pharmacological modification of cytokine dysregulation, therefore, has been suggested as a therapeutic modality for HIV-1 infection. Dr. Dezube of Beth Israel Hospital (Boston) concisely reviews the state of our knowledge regarding the effects of pentoxifylline on expression of tumor necrosis factor-alpha, a cytokine known to influence HIV-1 replication and to play a possible role in the clinical manifestations of advanced infection with this virus. Pentoxifylline, a trisubstituted xanthine derivative, has been used to decrease blood viscosity and is reasonably well tolerated by most recipients of the drug. Results of preliminary studies, many of which were conducted by Dr. Dezube, suggest that use of this agent in combination with antiretroviral compounds may prove useful in the treatment of patients with HIV-1 infection. " ], "offsets": [ [ 0, 1132 ] ] } ]

[ { "id": "PMID-7912114_T1", "type": "Protein", "text": [ "tumor necrosis factor-alpha" ], "offsets": [ [ 576, 603 ] ], "normalized": [] } ]

[ { "id": "PMID-7912114_E1", "type": "Regulation", "trigger": { "text": [ "effects" ], "offsets": [ [ 533, 540 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "PMID-7912114_E2" } ] }, { "id": "PMID-7912114_E2", "type": "Gene_expression", "trigger": { "text": [ "expression" ], "offsets": [ [ 562, 572 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "PMID-7912114_T1" } ] } ]

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[ { "id": "PMID-7915519__text", "type": "abstract", "text": [ "Signals transduced through the CD4 molecule on T lymphocytes activate NF-kappa B. \nWe have demonstrated that native envelope glycoproteins of HIV-1, gp160 can induce activation of the transcription factor, NF-kappa B. The stimulatory effects of gp160 are mediated through the CD4 molecule, since pretreatment with soluble CD4 abrogates its activity. The gp160-induced NF-kappa B complex consists of p65, p50 and c-rel proteins. The stimulatory effect of gp160 on NF-kappa B activation is protein synthesis independent, is dependent upon protein tyrosine phosphorylation, and abrogated by inhibitors of protein kinase C. The gp160-mediated activation of NF-kappa B in CD4 positive T cells may be involved in biological effects, e.g., enhanced HIV replication, hypergammaglobulinemia, increased cytokine secretion, hypercellularity in bone marrow and apoptosis. " ], "offsets": [ [ 0, 860 ] ] } ]

[ { "id": "PMID-7915519_T1", "type": "Protein", "text": [ "CD4" ], "offsets": [ [ 31, 34 ] ], "normalized": [] }, { "id": "PMID-7915519_T2", "type": "Protein", "text": [ "gp160" ], "offsets": [ [ 149, 154 ] ], "normalized": [] }, { "id": "PMID-7915519_T3", "type": "Protein", "text": [ "gp160" ], "offsets": [ [ 245, 250 ] ], "normalized": [] }, { "id": "PMID-7915519_T4", "type": "Protein", "text": [ "CD4" ], "offsets": [ [ 276, 279 ] ], "normalized": [] }, { "id": "PMID-7915519_T5", "type": "Protein", "text": [ "CD4" ], "offsets": [ [ 322, 325 ] ], "normalized": [] }, { "id": "PMID-7915519_T6", "type": "Protein", "text": [ "gp160" ], "offsets": [ [ 354, 359 ] ], "normalized": [] }, { "id": "PMID-7915519_T7", "type": "Protein", "text": [ "p65" ], "offsets": [ [ 399, 402 ] ], "normalized": [] }, { "id": "PMID-7915519_T8", "type": "Protein", "text": [ "p50" ], "offsets": [ [ 404, 407 ] ], "normalized": [] }, { "id": "PMID-7915519_T9", "type": "Protein", "text": [ "c-rel" ], "offsets": [ [ 412, 417 ] ], "normalized": [] }, { "id": "PMID-7915519_T10", "type": "Protein", "text": [ "gp160" ], "offsets": [ [ 454, 459 ] ], "normalized": [] }, { "id": "PMID-7915519_T11", "type": "Protein", "text": [ "gp160" ], "offsets": [ [ 624, 629 ] ], "normalized": [] }, { "id": "PMID-7915519_T12", "type": "Protein", "text": [ "CD4" ], "offsets": [ [ 667, 670 ] ], "normalized": [] } ]

[ { "id": "PMID-7915519_E1", "type": "Positive_regulation", "trigger": { "text": [ "induced" ], "offsets": [ [ 360, 367 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "PMID-7915519_E2" }, { "role": "Cause", "ref_id": "PMID-7915519_T6" } ] }, { "id": "PMID-7915519_E2", "type": "Binding", "trigger": { "text": [ "complex" ], "offsets": [ [ 379, 386 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "PMID-7915519_T7" }, { "role": "Theme", "ref_id": "PMID-7915519_T8" }, { "role": "Theme", "ref_id": "PMID-7915519_T9" } ] } ]

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[ { "id": "PMID-7917514__text", "type": "abstract", "text": [ "Role of HIV-1 Nef expression in activation pathways in CD4+ T cells. \nThe role of the human immunodeficiency virus (HIV-1) Nef protein in T cell activation pathways was investigated using a Jurkat CD4+ cell line stably transfected with a Nef expression vector. Secretion of IL-2 and TNF-alpha, surface expression of IL-2R, and DNA-binding activity of NF-kappa B and AP-1 (Fos/Jun) complex in response to phorbol myristate acetate, TNF-alpha, or immobilized antibodies to CD3 were monitored. These parameters were not modified by Nef expression in Jurkat cells, whereas stimulation with the same stimuli resulted in partial inhibition of LTR activation in Nef+ Jurkat cells. This inhibition was not mediated through Nef phosphorylation on Thr-15 or GTP-binding activity because mutations in critical sites did not alter this inhibition. Analysis of truncated LTRs confirmed that inhibition of LTR activation was not mediated through NF-kappa B-binding activity but through the region containing the negative responding elements (NREs). These results suggest that Nef downmodulates LTR activation without significantly inhibiting the capacity of T cells to respond to immunological activations. " ], "offsets": [ [ 0, 1193 ] ] } ]

[ { "id": "PMID-7917514_T1", "type": "Protein", "text": [ "Nef" ], "offsets": [ [ 14, 17 ] ], "normalized": [] }, { "id": "PMID-7917514_T2", "type": "Protein", "text": [ "CD4" ], "offsets": [ [ 55, 58 ] ], "normalized": [] }, { "id": "PMID-7917514_T3", "type": "Protein", "text": [ "Nef" ], "offsets": [ [ 123, 126 ] ], "normalized": [] }, { "id": "PMID-7917514_T4", "type": "Protein", "text": [ "CD4" ], "offsets": [ [ 197, 200 ] ], "normalized": [] }, { "id": "PMID-7917514_T5", "type": "Protein", "text": [ "Nef" ], "offsets": [ [ 238, 241 ] ], "normalized": [] }, { "id": "PMID-7917514_T6", "type": "Protein", "text": [ "IL-2" ], "offsets": [ [ 274, 278 ] ], "normalized": [] }, { "id": "PMID-7917514_T7", "type": "Protein", "text": [ "TNF-alpha" ], "offsets": [ [ 283, 292 ] ], "normalized": [] }, { "id": "PMID-7917514_T8", "type": "Protein", "text": [ "Fos" ], "offsets": [ [ 372, 375 ] ], "normalized": [] }, { "id": "PMID-7917514_T9", "type": "Protein", "text": [ "Jun" ], "offsets": [ [ 376, 379 ] ], "normalized": [] }, { "id": "PMID-7917514_T10", "type": "Protein", "text": [ "TNF-alpha" ], "offsets": [ [ 431, 440 ] ], "normalized": [] }, { "id": "PMID-7917514_T11", "type": "Protein", "text": [ "Nef" ], "offsets": [ [ 529, 532 ] ], "normalized": [] }, { "id": "PMID-7917514_T12", "type": "Protein", "text": [ "Nef" ], "offsets": [ [ 655, 658 ] ], "normalized": [] }, { "id": "PMID-7917514_T13", "type": "Protein", "text": [ "Nef" ], "offsets": [ [ 715, 718 ] ], "normalized": [] }, { "id": "PMID-7917514_T14", "type": "Protein", "text": [ "Nef" ], "offsets": [ [ 1062, 1065 ] ], "normalized": [] }, { "id": "PMID-7917514_T24", "type": "Entity", "text": [ "Thr-15" ], "offsets": [ [ 738, 744 ] ], "normalized": [] } ]

[ { "id": "PMID-7917514_E1", "type": "Gene_expression", "trigger": { "text": [ "expression" ], "offsets": [ [ 18, 28 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "PMID-7917514_T1" } ] }, { "id": "PMID-7917514_E2", "type": "Positive_regulation", "trigger": { "text": [ "transfected" ], "offsets": [ [ 219, 230 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "PMID-7917514_E3" } ] }, { "id": "PMID-7917514_E3", "type": "Gene_expression", "trigger": { "text": [ "expression" ], "offsets": [ [ 242, 252 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "PMID-7917514_T5" } ] }, { "id": "PMID-7917514_E4", "type": "Localization", "trigger": { "text": [ "Secretion" ], "offsets": [ [ 261, 270 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "PMID-7917514_T6" } ] }, { "id": "PMID-7917514_E5", "type": "Localization", "trigger": { "text": [ "Secretion" ], "offsets": [ [ 261, 270 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "PMID-7917514_T7" } ] }, { "id": "PMID-7917514_E6", "type": "Binding", "trigger": { "text": [ "binding activity" ], "offsets": [ [ 331, 347 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "PMID-7917514_T9" } ] }, { "id": "PMID-7917514_E7", "type": "Binding", "trigger": { "text": [ "binding activity" ], "offsets": [ [ 331, 347 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "PMID-7917514_T8" } ] }, { "id": "PMID-7917514_E8", "type": "Positive_regulation", "trigger": { "text": [ "response" ], "offsets": [ [ 392, 400 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "PMID-7917514_E5" } ] }, { "id": "PMID-7917514_E9", "type": "Positive_regulation", "trigger": { "text": [ "response" ], "offsets": [ [ 392, 400 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "PMID-7917514_E7" } ] }, { "id": "PMID-7917514_E10", "type": "Positive_regulation", "trigger": { "text": [ "response" ], "offsets": [ [ 392, 400 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "PMID-7917514_E4" }, { "role": "Cause", "ref_id": "PMID-7917514_T10" } ] }, { "id": "PMID-7917514_E11", "type": "Positive_regulation", "trigger": { "text": [ "response" ], "offsets": [ [ 392, 400 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "PMID-7917514_E6" }, { "role": "Cause", "ref_id": "PMID-7917514_T10" } ] }, { "id": "PMID-7917514_E12", "type": "Positive_regulation", "trigger": { "text": [ "response" ], "offsets": [ [ 392, 400 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "PMID-7917514_E7" }, { "role": "Cause", "ref_id": "PMID-7917514_T10" } ] }, { "id": "PMID-7917514_E13", "type": "Positive_regulation", "trigger": { "text": [ "response" ], "offsets": [ [ 392, 400 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "PMID-7917514_E6" } ] }, { "id": "PMID-7917514_E14", "type": "Positive_regulation", "trigger": { "text": [ "response" ], "offsets": [ [ 392, 400 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "PMID-7917514_E5" }, { "role": "Cause", "ref_id": "PMID-7917514_T10" } ] }, { "id": "PMID-7917514_E15", "type": "Positive_regulation", "trigger": { "text": [ "response" ], "offsets": [ [ 392, 400 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "PMID-7917514_E4" } ] }, { "id": "PMID-7917514_E16", "type": "Regulation", "trigger": { "text": [ "modified" ], "offsets": [ [ 517, 525 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "PMID-7917514_E4" }, { "role": "Cause", "ref_id": "PMID-7917514_E20" } ] }, { "id": "PMID-7917514_E17", "type": "Regulation", "trigger": { "text": [ "modified" ], "offsets": [ [ 517, 525 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "PMID-7917514_E6" }, { "role": "Cause", "ref_id": "PMID-7917514_E20" } ] }, { "id": "PMID-7917514_E18", "type": "Regulation", "trigger": { "text": [ "modified" ], "offsets": [ [ 517, 525 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "PMID-7917514_E5" }, { "role": "Cause", "ref_id": "PMID-7917514_E20" } ] }, { "id": "PMID-7917514_E19", "type": "Regulation", "trigger": { "text": [ "modified" ], "offsets": [ [ 517, 525 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "PMID-7917514_E7" }, { "role": "Cause", "ref_id": "PMID-7917514_E20" } ] }, { "id": "PMID-7917514_E20", "type": "Gene_expression", "trigger": { "text": [ "expression" ], "offsets": [ [ 533, 543 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "PMID-7917514_T11" } ] }, { "id": "PMID-7917514_E21", "type": "Phosphorylation", "trigger": { "text": [ "phosphorylation" ], "offsets": [ [ 719, 734 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "PMID-7917514_T13" }, { "role": "Site", "ref_id": "PMID-7917514_T24" } ] }, { "id": "PMID-7917514_E22", "type": "Binding", "trigger": { "text": [ "binding activity" ], "offsets": [ [ 752, 768 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "PMID-7917514_T13" } ] } ]

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[ { "id": "PMID-7919963__text", "type": "abstract", "text": [ "A low NM23.H1 gene expression identifying high malignancy human melanomas. \nThe NM23 gene has been proposed as a metastasis-suppressor gene, and its use has been suggested as prognostic factor. NM23 was identified in a system of murine melanoma cell lines, in which an inverse relationship was found between NM23 expression and metastatic ability. In a human malignant melanoma study NM23 expression was found to be significantly lower in metastases that developed less than 24 months after diagnosis of the primary tumours. The present paper studies the expression of the NM23.H1 gene in cell lines which derive from primary or metastatic human malignant melanomas in relation to staging, infiltration degree, lymphocytic infiltration, cell morphology, cell pigmentation, karyotype, and disease-free survival. The level of mRNA expression of the NM23 gene is significantly lower in cell lines that derive from more infiltrating primary melanomas than in cell lines obtained from less infiltrating tumours. Moreover, cell lines derived from tumours of patients with a disease-free survival of more than 24 months (24-58 months) express the NM23 gene at higher levels than cell lines obtained from melanomas of patients with a disease-free survival of less than 24 months (6-15 months). " ], "offsets": [ [ 0, 1286 ] ] } ]

[ { "id": "PMID-7919963_T1", "type": "Protein", "text": [ "NM23.H1" ], "offsets": [ [ 6, 13 ] ], "normalized": [] }, { "id": "PMID-7919963_T2", "type": "Protein", "text": [ "NM23.H1" ], "offsets": [ [ 573, 580 ] ], "normalized": [] } ]

[ { "id": "PMID-7919963_E1", "type": "Gene_expression", "trigger": { "text": [ "expression" ], "offsets": [ [ 19, 29 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "PMID-7919963_T1" } ] }, { "id": "PMID-7919963_E2", "type": "Gene_expression", "trigger": { "text": [ "expression" ], "offsets": [ [ 555, 565 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "PMID-7919963_T2" } ] } ]

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[ { "id": "PMID-7923175__text", "type": "abstract", "text": [ "T cells from renal cell carcinoma patients exhibit an abnormal pattern of kappa B-specific DNA-binding activity: a preliminary report. \nRecent data suggest that the poor induction of a T-cell response to human renal cell carcinoma (RCC) may be related to alterations in signal transduction pathways. We report that T cells from RCC patients have two alterations in kappa B motif-specific DNA-binding activity. The first alteration involves the constitutive expression of substantial kappa B-binding activity in nuclear extracts, which was observed in the electrophoretic mobility shift assay. The magnitude of kappa B activity in unstimulated patient T cells was similar to that observed in T cells from normal individuals that had been activated in vitro. On the basis of Western blotting experiments using antibodies to kappa B/Rel family proteins, the kappa B-binding activity constitutively expressed in T cells from RCC patients is composed mostly of the NF-kappa B1 (p50) subunit. The second abnormality in kappa B-binding activity in T cells from these patients is that RelA, a member of the Rel homology family which is part of the normal NF-kappa B complex, was not induced in the nucleus following activation. Western blotting analysis did not detect any RelA in nuclear extracts either before or after stimulation of T cells. The altered kappa B-binding activity in T cells from RCC patients may impair their capacity to respond normally to various stimuli. " ], "offsets": [ [ 0, 1469 ] ] } ]

[ { "id": "PMID-7923175_T1", "type": "Protein", "text": [ "NF-kappa B1" ], "offsets": [ [ 960, 971 ] ], "normalized": [] }, { "id": "PMID-7923175_T2", "type": "Protein", "text": [ "p50" ], "offsets": [ [ 973, 976 ] ], "normalized": [] }, { "id": "PMID-7923175_T3", "type": "Protein", "text": [ "RelA" ], "offsets": [ [ 1077, 1081 ] ], "normalized": [] }, { "id": "PMID-7923175_T4", "type": "Protein", "text": [ "RelA" ], "offsets": [ [ 1265, 1269 ] ], "normalized": [] }, { "id": "PMID-7923175_T8", "type": "Entity", "text": [ "nuclear extracts" ], "offsets": [ [ 1273, 1289 ] ], "normalized": [] } ]

[ { "id": "PMID-7923175_E1", "type": "Binding", "trigger": { "text": [ "binding activity" ], "offsets": [ [ 863, 879 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "PMID-7923175_T1" } ] }, { "id": "PMID-7923175_E2", "type": "Positive_regulation", "trigger": { "text": [ "induced" ], "offsets": [ [ 1175, 1182 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "PMID-7923175_T3" } ] }, { "id": "PMID-7923175_E3", "type": "Localization", "trigger": { "text": [ "detect" ], "offsets": [ [ 1254, 1260 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "PMID-7923175_T4" }, { "role": "AtLoc", "ref_id": "PMID-7923175_T8" } ] } ]

[ { "id": "PMID-7923175_1", "entity_ids": [ "PMID-7923175_T1", "PMID-7923175_T2" ] } ]

[]

[ { "id": "PMID-7925300__text", "type": "abstract", "text": [ "Activation of NF-kappa B in vivo is regulated by multiple phosphorylations. \nThe activation of nuclear factor kappa B (NF-kappa B) in intact cells is mechanistically not well understood. Therefore we investigated the modifications imposed on NF-kappa B/I kappa B components following stimulation and show that the final step of NF-kappa B induction in vivo involves phosphorylation of several members of the NF-kappa B/I kappa B protein families. In HeLa cells as well as in B cells, TNF-alpha rapidly induced nuclear translocation primarily of p50-p65, but not of c-rel. Both NF-kappa B precursors and I kappa B alpha became strongly phosphorylated with the same kinetics. In addition to the inducible phosphorylation after stimulation, B lymphocytes containing constitutive nuclear NF-kappa B revealed constitutively phosphorylated p65 and I kappa B alpha. Phosphorylation was accompanied by induced processing of the precursors p100 and p105 and by degradation of I kappa B alpha. As an in vitro model we show that phosphorylation of p105 impedes its ability to interact with NF-kappa B, as has been shown before for I kappa B alpha. Surprisingly, even p65, but not c-rel, was phosphorylated after induction in vivo, suggesting that TNF-alpha selectively activates only specific NF-kappa B heteromers and that modifications regulate not only I kappa B molecules but also NF-kappa B molecules. In fact, cellular NF-kappa B activity was phosphorylation-dependent and the DNA binding activity of p65-containing NF-kappa B was enhanced by phosphorylation in vitro. Furthermore, we found that the induction by hydrogen peroxide of NF-kappa B translocation to the nucleus, which is assumed to be triggered by reactive oxygen intermediates, also coincided with incorporation of phosphate into the same subunits that were modified after stimulation by TNF-alpha. Thus, phosphorylation appears to be a general mechanism for activation of NF-kappa B in vivo. " ], "offsets": [ [ 0, 1952 ] ] } ]

[ { "id": "PMID-7925300_T1", "type": "Protein", "text": [ "TNF-alpha" ], "offsets": [ [ 484, 493 ] ], "normalized": [] }, { "id": "PMID-7925300_T2", "type": "Protein", "text": [ "p50" ], "offsets": [ [ 545, 548 ] ], "normalized": [] }, { "id": "PMID-7925300_T3", "type": "Protein", "text": [ "p65" ], "offsets": [ [ 549, 552 ] ], "normalized": [] }, { "id": "PMID-7925300_T4", "type": "Protein", "text": [ "c-rel" ], "offsets": [ [ 565, 570 ] ], "normalized": [] }, { "id": "PMID-7925300_T5", "type": "Protein", "text": [ "I kappa B alpha" ], "offsets": [ [ 603, 618 ] ], "normalized": [] }, { "id": "PMID-7925300_T6", "type": "Protein", "text": [ "p65" ], "offsets": [ [ 834, 837 ] ], "normalized": [] }, { "id": "PMID-7925300_T7", "type": "Protein", "text": [ "I kappa B alpha" ], "offsets": [ [ 842, 857 ] ], "normalized": [] }, { "id": "PMID-7925300_T8", "type": "Protein", "text": [ "p100" ], "offsets": [ [ 931, 935 ] ], "normalized": [] }, { "id": "PMID-7925300_T9", "type": "Protein", "text": [ "p105" ], "offsets": [ [ 940, 944 ] ], "normalized": [] }, { "id": "PMID-7925300_T10", "type": "Protein", "text": [ "I kappa B alpha" ], "offsets": [ [ 967, 982 ] ], "normalized": [] }, { "id": "PMID-7925300_T11", "type": "Protein", "text": [ "p105" ], "offsets": [ [ 1037, 1041 ] ], "normalized": [] }, { "id": "PMID-7925300_T12", "type": "Protein", "text": [ "I kappa B alpha" ], "offsets": [ [ 1120, 1135 ] ], "normalized": [] }, { "id": "PMID-7925300_T13", "type": "Protein", "text": [ "p65" ], "offsets": [ [ 1156, 1159 ] ], "normalized": [] }, { "id": "PMID-7925300_T14", "type": "Protein", "text": [ "c-rel" ], "offsets": [ [ 1169, 1174 ] ], "normalized": [] }, { "id": "PMID-7925300_T15", "type": "Protein", "text": [ "TNF-alpha" ], "offsets": [ [ 1236, 1245 ] ], "normalized": [] }, { "id": "PMID-7925300_T16", "type": "Protein", "text": [ "p65" ], "offsets": [ [ 1496, 1499 ] ], "normalized": [] }, { "id": "PMID-7925300_T17", "type": "Protein", "text": [ "TNF-alpha" ], "offsets": [ [ 1847, 1856 ] ], "normalized": [] }, { "id": "PMID-7925300_T19", "type": "Entity", "text": [ "nuclear" ], "offsets": [ [ 510, 517 ] ], "normalized": [] } ]

[ { "id": "PMID-7925300_E1", "type": "Positive_regulation", "trigger": { "text": [ "induced" ], "offsets": [ [ 502, 509 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "PMID-7925300_E4" }, { "role": "Cause", "ref_id": "PMID-7925300_T1" } ] }, { "id": "PMID-7925300_E2", "type": "Positive_regulation", "trigger": { "text": [ "induced" ], "offsets": [ [ 502, 509 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "PMID-7925300_E6" }, { "role": "Cause", "ref_id": "PMID-7925300_T1" } ] }, { "id": "PMID-7925300_E3", "type": "Positive_regulation", "trigger": { "text": [ "induced" ], "offsets": [ [ 502, 509 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "PMID-7925300_E5" }, { "role": "Cause", "ref_id": "PMID-7925300_T1" } ] }, { "id": "PMID-7925300_E4", "type": "Localization", "trigger": { "text": [ "translocation" ], "offsets": [ [ 518, 531 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "PMID-7925300_T2" }, { "role": "ToLoc", "ref_id": "PMID-7925300_T19" } ] }, { "id": "PMID-7925300_E5", "type": "Localization", "trigger": { "text": [ "translocation" ], "offsets": [ [ 518, 531 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "PMID-7925300_T4" }, { "role": "ToLoc", "ref_id": "PMID-7925300_T19" } ] }, { "id": "PMID-7925300_E6", "type": "Localization", "trigger": { "text": [ "translocation" ], "offsets": [ [ 518, 531 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "PMID-7925300_T3" }, { "role": "ToLoc", "ref_id": "PMID-7925300_T19" } ] }, { "id": "PMID-7925300_E7", "type": "Phosphorylation", "trigger": { "text": [ "phosphorylated" ], "offsets": [ [ 635, 649 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "PMID-7925300_T5" } ] }, { "id": "PMID-7925300_E8", "type": "Phosphorylation", "trigger": { "text": [ "phosphorylated" ], "offsets": [ [ 819, 833 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "PMID-7925300_T7" } ] }, { "id": "PMID-7925300_E9", "type": "Phosphorylation", "trigger": { "text": [ "phosphorylated" ], "offsets": [ [ 819, 833 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "PMID-7925300_T6" } ] }, { "id": "PMID-7925300_E10", "type": "Protein_catabolism", "trigger": { "text": [ "degradation" ], "offsets": [ [ 952, 963 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "PMID-7925300_T10" } ] }, { "id": "PMID-7925300_E11", "type": "Phosphorylation", "trigger": { "text": [ "phosphorylation" ], "offsets": [ [ 1018, 1033 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "PMID-7925300_T12" } ] }, { "id": "PMID-7925300_E12", "type": "Phosphorylation", "trigger": { "text": [ "phosphorylation" ], "offsets": [ [ 1018, 1033 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "PMID-7925300_T11" } ] }, { "id": "PMID-7925300_E13", "type": "Negative_regulation", "trigger": { "text": [ "impedes" ], "offsets": [ [ 1042, 1049 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "PMID-7925300_E16" }, { "role": "Cause", "ref_id": "PMID-7925300_E12" } ] }, { "id": "PMID-7925300_E14", "type": "Negative_regulation", "trigger": { "text": [ "impedes" ], "offsets": [ [ 1042, 1049 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "PMID-7925300_E15" }, { "role": "Cause", "ref_id": "PMID-7925300_E11" } ] }, { "id": "PMID-7925300_E15", "type": "Binding", "trigger": { "text": [ "interact" ], "offsets": [ [ 1065, 1073 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "PMID-7925300_T12" } ] }, { "id": "PMID-7925300_E16", "type": "Binding", "trigger": { "text": [ "interact" ], "offsets": [ [ 1065, 1073 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "PMID-7925300_T11" } ] }, { "id": "PMID-7925300_E17", "type": "Phosphorylation", "trigger": { "text": [ "phosphorylated" ], "offsets": [ [ 1180, 1194 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "PMID-7925300_T13" } ] }, { "id": "PMID-7925300_E18", "type": "Phosphorylation", "trigger": { "text": [ "phosphorylated" ], "offsets": [ [ 1180, 1194 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "PMID-7925300_T14" } ] }, { "id": "PMID-7925300_E19", "type": "Positive_regulation", "trigger": { "text": [ "induction" ], "offsets": [ [ 1201, 1210 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "PMID-7925300_T14" } ] }, { "id": "PMID-7925300_E20", "type": "Positive_regulation", "trigger": { "text": [ "induction" ], "offsets": [ [ 1201, 1210 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "PMID-7925300_T13" } ] }, { "id": "PMID-7925300_E21", "type": "Binding", "trigger": { "text": [ "binding activity" ], "offsets": [ [ 1476, 1492 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "PMID-7925300_T16" } ] }, { "id": "PMID-7925300_E22", "type": "Positive_regulation", "trigger": { "text": [ "enhanced" ], "offsets": [ [ 1526, 1534 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "PMID-7925300_E21" } ] } ]

[]

[]

[ { "id": "PMID-7926759__text", "type": "abstract", "text": [ "An active v-abl protein tyrosine kinase blocks immunoglobulin light-chain gene rearrangement. \nLymphoid cells transformed by Abelson murine leukemia virus have provided one of the classic models for study of early B-cell development and immunoglobulin rearrangement. Most of these cells have rearranged their heavy-chain locus but not their light chain genes, suggesting that an active v-abl protein interferes with this differentiation step. To test this hypothesis, light-chain gene structure was examined in pre-B cells transformed by temperature-sensitive mutants of the Abelson virus and in derivatives that survive at the nonpermissive temperature because they express a human BCL-2 gene. Our studies reveal that inactivation of the v-abl protein tyrosine kinase triggers high-frequency rearrangement of kappa and lambda light-chain genes. These events are accompanied by marked increases in the expression of RAG-1 and RAG-2 RNAs. These increases occur in the absence of protein synthesis but are dependent on inactivation of the v-abl protein tyrosine kinase. As documented in the accompanying paper (Klug et al., this issue), an active v-abl protein also suppresses the activity of NF-kappa B/rel and expression controlled by the kappa intron enhancer. Together these data demonstrate that the v-abl protein specifically interferes with light-chain gene rearrangement by suppressing at least two pathways essential for this stage of B-cell differentiation and suggest that tyrosine phosphorylation is important in regulating RAG gene expression. " ], "offsets": [ [ 0, 1555 ] ] } ]

[ { "id": "PMID-7926759_T1", "type": "Protein", "text": [ "v-abl" ], "offsets": [ [ 10, 15 ] ], "normalized": [] }, { "id": "PMID-7926759_T2", "type": "Protein", "text": [ "v-abl" ], "offsets": [ [ 386, 391 ] ], "normalized": [] }, { "id": "PMID-7926759_T3", "type": "Protein", "text": [ "BCL-2" ], "offsets": [ [ 683, 688 ] ], "normalized": [] }, { "id": "PMID-7926759_T4", "type": "Protein", "text": [ "v-abl" ], "offsets": [ [ 739, 744 ] ], "normalized": [] }, { "id": "PMID-7926759_T5", "type": "Protein", "text": [ "kappa" ], "offsets": [ [ 810, 815 ] ], "normalized": [] }, { "id": "PMID-7926759_T6", "type": "Protein", "text": [ "lambda light-chain" ], "offsets": [ [ 820, 838 ] ], "normalized": [] }, { "id": "PMID-7926759_T7", "type": "Protein", "text": [ "RAG-1" ], "offsets": [ [ 916, 921 ] ], "normalized": [] }, { "id": "PMID-7926759_T8", "type": "Protein", "text": [ "RAG-2" ], "offsets": [ [ 926, 931 ] ], "normalized": [] }, { "id": "PMID-7926759_T9", "type": "Protein", "text": [ "v-abl" ], "offsets": [ [ 1037, 1042 ] ], "normalized": [] }, { "id": "PMID-7926759_T10", "type": "Protein", "text": [ "v-abl" ], "offsets": [ [ 1145, 1150 ] ], "normalized": [] }, { "id": "PMID-7926759_T11", "type": "Protein", "text": [ "v-abl" ], "offsets": [ [ 1303, 1308 ] ], "normalized": [] } ]

[ { "id": "PMID-7926759_E1", "type": "Gene_expression", "trigger": { "text": [ "express" ], "offsets": [ [ 667, 674 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "PMID-7926759_T3" } ] }, { "id": "PMID-7926759_E2", "type": "Negative_regulation", "trigger": { "text": [ "inactivation" ], "offsets": [ [ 719, 731 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "PMID-7926759_T4" } ] }, { "id": "PMID-7926759_E3", "type": "Positive_regulation", "trigger": { "text": [ "increases" ], "offsets": [ [ 885, 894 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "PMID-7926759_E6" } ] }, { "id": "PMID-7926759_E4", "type": "Positive_regulation", "trigger": { "text": [ "increases" ], "offsets": [ [ 885, 894 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "PMID-7926759_E5" } ] }, { "id": "PMID-7926759_E5", "type": "Transcription", "trigger": { "text": [ "expression" ], "offsets": [ [ 902, 912 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "PMID-7926759_T7" } ] }, { "id": "PMID-7926759_E6", "type": "Transcription", "trigger": { "text": [ "expression" ], "offsets": [ [ 902, 912 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "PMID-7926759_T8" } ] }, { "id": "PMID-7926759_E7", "type": "Positive_regulation", "trigger": { "text": [ "dependent" ], "offsets": [ [ 1004, 1013 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "PMID-7926759_E3" }, { "role": "Cause", "ref_id": "PMID-7926759_E9" } ] }, { "id": "PMID-7926759_E8", "type": "Positive_regulation", "trigger": { "text": [ "dependent" ], "offsets": [ [ 1004, 1013 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "PMID-7926759_E4" }, { "role": "Cause", "ref_id": "PMID-7926759_E9" } ] }, { "id": "PMID-7926759_E9", "type": "Negative_regulation", "trigger": { "text": [ "inactivation" ], "offsets": [ [ 1017, 1029 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "PMID-7926759_T9" } ] } ]

[]

[]

[ { "id": "PMID-7927175__text", "type": "abstract", "text": [ "[An overexpression of retinoic acid receptor alpha blocks myeloid cell differentiation at the promyelocyte stage] \nRetinoic acid (RA), a vitamin A derivative, exerts a wide range of biological effects related to cell proliferation and differentiation. The pleiotropic effects of RA are thought to be mediated through specific nuclear RA receptors (RARs). RARs are members of the steroid/thyroid hormone receptor superfamily and exhibit a molecular structure that possess discrete DNA-binding and RA (ligand)-binding domains. In hematopoietic system, RA and RARs, predominantly RAR alpha may play key roles for the proliferation and differentiation of hematopoietic progenitors. However, it is currently unknown how RA and RARs are involved in regulating normal hematopoietic differentiation. To make clear the roles of RA and RAR alpha in the normal hematopoiesis, I have introduced the construct of human RAR alpha (hRAR alpha) into murine bone marrow cells with retroviral vector, and selected infected cells with drug resistant marker (Neo(r)) cultured on the stroma cell line (PA6-neo), and analyzed the behavior of infected cells. All of procedure were done in vitro. Most cells infected with hRAR alpha exhibited promyelocytic morphology and were thought to be blocked at the promyelocytic stage in their myeloid differentiation. Furthermore, these immature cells differentiated terminally into mature granulocytes by adding with RA (10(-6) M). RAR alpha infected cells were also able to differentiate into mature macrophages in the both of long term culture and IL3 colony. These observations suggest that an overexpression of RAR alpha alone is effective to suppress myeloid cell differentiation and RAR alpha plays a crucial role in the terminal differentiation of myeloid precursors. The system described here may serve as a model for studying the the essential genes for differentiation of normal bone marrow cells. " ], "offsets": [ [ 0, 1927 ] ] } ]

[ { "id": "PMID-7927175_T1", "type": "Protein", "text": [ "retinoic acid receptor alpha" ], "offsets": [ [ 22, 50 ] ], "normalized": [] }, { "id": "PMID-7927175_T2", "type": "Protein", "text": [ "RAR alpha" ], "offsets": [ [ 577, 586 ] ], "normalized": [] }, { "id": "PMID-7927175_T3", "type": "Protein", "text": [ "RAR alpha" ], "offsets": [ [ 826, 835 ] ], "normalized": [] }, { "id": "PMID-7927175_T4", "type": "Protein", "text": [ "RAR alpha" ], "offsets": [ [ 906, 915 ] ], "normalized": [] }, { "id": "PMID-7927175_T5", "type": "Protein", "text": [ "hRAR alpha" ], "offsets": [ [ 917, 927 ] ], "normalized": [] }, { "id": "PMID-7927175_T6", "type": "Protein", "text": [ "hRAR alpha" ], "offsets": [ [ 1198, 1208 ] ], "normalized": [] }, { "id": "PMID-7927175_T7", "type": "Protein", "text": [ "RAR alpha" ], "offsets": [ [ 1451, 1460 ] ], "normalized": [] }, { "id": "PMID-7927175_T8", "type": "Protein", "text": [ "RAR alpha" ], "offsets": [ [ 1634, 1643 ] ], "normalized": [] }, { "id": "PMID-7927175_T9", "type": "Protein", "text": [ "RAR alpha" ], "offsets": [ [ 1708, 1717 ] ], "normalized": [] } ]

[ { "id": "PMID-7927175_E1", "type": "Positive_regulation", "trigger": { "text": [ "overexpression" ], "offsets": [ [ 4, 18 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "PMID-7927175_E2" } ] }, { "id": "PMID-7927175_E2", "type": "Gene_expression", "trigger": { "text": [ "overexpression" ], "offsets": [ [ 4, 18 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "PMID-7927175_T1" } ] }, { "id": "PMID-7927175_E3", "type": "Gene_expression", "trigger": { "text": [ "overexpression" ], "offsets": [ [ 1616, 1630 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "PMID-7927175_T8" } ] }, { "id": "PMID-7927175_E4", "type": "Positive_regulation", "trigger": { "text": [ "overexpression" ], "offsets": [ [ 1616, 1630 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "PMID-7927175_E3" } ] } ]

[ { "id": "PMID-7927175_1", "entity_ids": [ "PMID-7927175_T4", "PMID-7927175_T5" ] } ]

[]

[ { "id": "PMID-7929104__text", "type": "abstract", "text": [ "Regulation of interleukin-2 receptor alpha chain expression and nuclear factor.kappa B activation by protein kinase C in T lymphocytes. Autocrine role of tumor necrosis factor alpha. \nThe regulation of interleukin-2 receptor alpha chain (IL-2R alpha) expression and nuclear factor (NF) activation by protein kinase C (PKC) in resting T cells, has been studied. Treatment of human resting T cells with phorbol esters strongly induced the expression of IL-2R alpha and the activation of NF.kappa B. This activation was due to the translocation of p65 and c-Rel NF.kappa B proteins from cytoplasmic stores to the nucleus, where they bound the kappa B sequence of the IL-2R alpha promoter either as p50.p65 or as p50.c-Rel heterodimers. Interestingly, all of those events were largely indirect and mediated by endogenously secreted tumor necrosis factor alpha (TNF alpha), as they were strongly inhibited by a neutralizing anti-TNF alpha monoclonal antibody. Furthermore, cyclosporin A, which blocked TNF alpha production induced by PKC, strongly inhibited IL-2R alpha and NF.kappa B activation. The addition of either TNF alpha or IL-2 partially recovered cyclosporin A-induced IL-2R alpha inhibition, but only TNF alpha completely recovered NF.kappa B activation. Those results indicate that, in resting T cells, PKC activation has only a triggering role, whereas the endogenously secreted TNF alpha plays an essential role in the quantitative control of the expression of IL-2R alpha chain or NF.kappa B activation. " ], "offsets": [ [ 0, 1515 ] ] } ]

[ { "id": "PMID-7929104_T1", "type": "Protein", "text": [ "interleukin-2 receptor alpha chain" ], "offsets": [ [ 14, 48 ] ], "normalized": [] }, { "id": "PMID-7929104_T2", "type": "Protein", "text": [ "tumor necrosis factor alpha" ], "offsets": [ [ 154, 181 ] ], "normalized": [] }, { "id": "PMID-7929104_T3", "type": "Protein", "text": [ "interleukin-2 receptor alpha chain" ], "offsets": [ [ 202, 236 ] ], "normalized": [] }, { "id": "PMID-7929104_T4", "type": "Protein", "text": [ "IL-2R alpha" ], "offsets": [ [ 238, 249 ] ], "normalized": [] }, { "id": "PMID-7929104_T5", "type": "Protein", "text": [ "IL-2R alpha" ], "offsets": [ [ 451, 462 ] ], "normalized": [] }, { "id": "PMID-7929104_T6", "type": "Protein", "text": [ "p65" ], "offsets": [ [ 545, 548 ] ], "normalized": [] }, { "id": "PMID-7929104_T7", "type": "Protein", "text": [ "c-Rel" ], "offsets": [ [ 553, 558 ] ], "normalized": [] }, { "id": "PMID-7929104_T8", "type": "Protein", "text": [ "IL-2R alpha" ], "offsets": [ [ 664, 675 ] ], "normalized": [] }, { "id": "PMID-7929104_T9", "type": "Protein", "text": [ "p50" ], "offsets": [ [ 695, 698 ] ], "normalized": [] }, { "id": "PMID-7929104_T10", "type": "Protein", "text": [ "p65" ], "offsets": [ [ 699, 702 ] ], "normalized": [] }, { "id": "PMID-7929104_T11", "type": "Protein", "text": [ "p50" ], "offsets": [ [ 709, 712 ] ], "normalized": [] }, { "id": "PMID-7929104_T12", "type": "Protein", "text": [ "c-Rel" ], "offsets": [ [ 713, 718 ] ], "normalized": [] }, { "id": "PMID-7929104_T13", "type": "Protein", "text": [ "tumor necrosis factor alpha" ], "offsets": [ [ 828, 855 ] ], "normalized": [] }, { "id": "PMID-7929104_T14", "type": "Protein", "text": [ "TNF alpha" ], "offsets": [ [ 857, 866 ] ], "normalized": [] }, { "id": "PMID-7929104_T15", "type": "Protein", "text": [ "TNF alpha" ], "offsets": [ [ 924, 933 ] ], "normalized": [] }, { "id": "PMID-7929104_T16", "type": "Protein", "text": [ "TNF alpha" ], "offsets": [ [ 997, 1006 ] ], "normalized": [] }, { "id": "PMID-7929104_T17", "type": "Protein", "text": [ "IL-2R alpha" ], "offsets": [ [ 1053, 1064 ] ], "normalized": [] }, { "id": "PMID-7929104_T18", "type": "Protein", "text": [ "TNF alpha" ], "offsets": [ [ 1115, 1124 ] ], "normalized": [] }, { "id": "PMID-7929104_T19", "type": "Protein", "text": [ "IL-2" ], "offsets": [ [ 1128, 1132 ] ], "normalized": [] }, { "id": "PMID-7929104_T20", "type": "Protein", "text": [ "IL-2R alpha" ], "offsets": [ [ 1175, 1186 ] ], "normalized": [] }, { "id": "PMID-7929104_T21", "type": "Protein", "text": [ "TNF alpha" ], "offsets": [ [ 1208, 1217 ] ], "normalized": [] }, { "id": "PMID-7929104_T22", "type": "Protein", "text": [ "TNF alpha" ], "offsets": [ [ 1388, 1397 ] ], "normalized": [] }, { "id": "PMID-7929104_T23", "type": "Protein", "text": [ "IL-2R alpha chain" ], "offsets": [ [ 1471, 1488 ] ], "normalized": [] }, { "id": "PMID-7929104_T31", "type": "Entity", "text": [ "nucleus" ], "offsets": [ [ 610, 617 ] ], "normalized": [] } ]

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[]

[ { "id": "PMID-7929355__text", "type": "abstract", "text": [ "Protease inhibitors block lipopolysaccharide induction of tissue factor gene expression in human monocytic cells by preventing activation of c-Rel/p65 heterodimers. \nTissue factor (TF) is expressed rapidly by human monocytes exposed to bacterial endotoxin (lipopolysaccharide, or LPS). Transcriptional regulation is mediated by binding of c-Rel/p65 heterodimers to a kappa B-like site in the TF promoter. Nuclear translocation of cytosolic c-Rel/p65 heterodimers and other members of the NF-kappa B/Rel family requires dissociation and proteolytic degradation of the inhibitor protein, I kappa B alpha. The protease inhibitors N alpha-tosylphenylalanyl chloromethyl ketone (TPCK) and N alpha-tosyl-L-lysine chloromethyl ketone (TLCK) block activation of NF-kappa B/Rel proteins by preventing degradation of I kappa B alpha. To determine if TPCK and TLCK inhibited LPS induction of TF expression, freshly isolated human monocytes and monocytic THP-1 cells were pretreated with these inhibitors for 30 min before LPS stimulation. Both TPCK and TLCK inhibited LPS induction of TF protein, TF mRNA and TF promoter activity in a dose-dependent manner. These inhibitors specifically prevented degradation of I kappa B alpha and nuclear translocation of c-Rel/p65 heterodimers. In contrast, TPCK and TLCK did not block induction of an immediate-early gene encoding the transcription factor, Egr-1. Taken together, these data indicated that inhibiting nuclear translocation of c-Rel/p65 heterodimers prevented LPS induction of TF gene transcription in monocytic cells. " ], "offsets": [ [ 0, 1561 ] ] } ]

[ { "id": "PMID-7929355_T1", "type": "Protein", "text": [ "c-Rel" ], "offsets": [ [ 141, 146 ] ], "normalized": [] }, { "id": "PMID-7929355_T2", "type": "Protein", "text": [ "p65" ], "offsets": [ [ 147, 150 ] ], "normalized": [] }, { "id": "PMID-7929355_T3", "type": "Protein", "text": [ "Tissue factor" ], "offsets": [ [ 166, 179 ] ], "normalized": [] }, { "id": "PMID-7929355_T4", "type": "Protein", "text": [ "TF" ], "offsets": [ [ 181, 183 ] ], "normalized": [] }, { "id": "PMID-7929355_T5", "type": "Protein", "text": [ "c-Rel" ], "offsets": [ [ 339, 344 ] ], "normalized": [] }, { "id": "PMID-7929355_T6", "type": "Protein", "text": [ "p65" ], "offsets": [ [ 345, 348 ] ], "normalized": [] }, { "id": "PMID-7929355_T7", "type": "Protein", "text": [ "TF" ], "offsets": [ [ 392, 394 ] ], "normalized": [] }, { "id": "PMID-7929355_T8", "type": "Protein", "text": [ "c-Rel" ], "offsets": [ [ 440, 445 ] ], "normalized": [] }, { "id": "PMID-7929355_T9", "type": "Protein", "text": [ "p65" ], "offsets": [ [ 446, 449 ] ], "normalized": [] }, { "id": "PMID-7929355_T10", "type": "Protein", "text": [ "I kappa B alpha" ], "offsets": [ [ 586, 601 ] ], "normalized": [] }, { "id": "PMID-7929355_T11", "type": "Protein", "text": [ "I kappa B alpha" ], "offsets": [ [ 807, 822 ] ], "normalized": [] }, { "id": "PMID-7929355_T12", "type": "Protein", "text": [ "TF" ], "offsets": [ [ 881, 883 ] ], "normalized": [] }, { "id": "PMID-7929355_T13", "type": "Protein", "text": [ "TF" ], "offsets": [ [ 1074, 1076 ] ], "normalized": [] }, { "id": "PMID-7929355_T14", "type": "Protein", "text": [ "TF" ], "offsets": [ [ 1086, 1088 ] ], "normalized": [] }, { "id": "PMID-7929355_T15", "type": "Protein", "text": [ "TF" ], "offsets": [ [ 1098, 1100 ] ], "normalized": [] }, { "id": "PMID-7929355_T16", "type": "Protein", "text": [ "I kappa B alpha" ], "offsets": [ [ 1202, 1217 ] ], "normalized": [] }, { "id": "PMID-7929355_T17", "type": "Protein", "text": [ "c-Rel" ], "offsets": [ [ 1247, 1252 ] ], "normalized": [] }, { "id": "PMID-7929355_T18", "type": "Protein", "text": [ "p65" ], "offsets": [ [ 1253, 1256 ] ], "normalized": [] }, { "id": "PMID-7929355_T19", "type": "Protein", "text": [ "Egr-1" ], "offsets": [ [ 1384, 1389 ] ], "normalized": [] }, { "id": "PMID-7929355_T20", "type": "Protein", "text": [ "c-Rel" ], "offsets": [ [ 1469, 1474 ] ], "normalized": [] }, { "id": "PMID-7929355_T21", "type": "Protein", "text": [ "p65" ], "offsets": [ [ 1475, 1478 ] ], "normalized": [] }, { "id": "PMID-7929355_T22", "type": "Protein", "text": [ "TF" ], "offsets": [ [ 1519, 1521 ] ], "normalized": [] }, { "id": "PMID-7929355_T28", "type": "Entity", "text": [ "kappa B-like site" ], "offsets": [ [ 367, 384 ] ], "normalized": [] }, { "id": "PMID-7929355_T29", "type": "Entity", "text": [ "Nuclear" ], "offsets": [ [ 405, 412 ] ], "normalized": [] }, { "id": "PMID-7929355_T40", "type": "Entity", "text": [ "promoter" ], "offsets": [ [ 1101, 1109 ] ], "normalized": [] }, { "id": "PMID-7929355_T43", "type": "Entity", "text": [ "nuclear" ], "offsets": [ [ 1222, 1229 ] ], "normalized": [] }, { "id": "PMID-7929355_T48", "type": "Entity", "text": [ "nuclear" ], "offsets": [ [ 1444, 1451 ] ], "normalized": [] } ]

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"Positive_regulation", "trigger": { "text": [ "induction" ], "offsets": [ [ 1061, 1070 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "PMID-7929355_T14" } ] }, { "id": "PMID-7929355_E25", "type": "Positive_regulation", "trigger": { "text": [ "induction" ], "offsets": [ [ 1061, 1070 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "PMID-7929355_T15" }, { "role": "Site", "ref_id": "PMID-7929355_T40" } ] }, { "id": "PMID-7929355_E26", "type": "Positive_regulation", "trigger": { "text": [ "induction" ], "offsets": [ [ 1061, 1070 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "PMID-7929355_T13" } ] }, { "id": "PMID-7929355_E27", "type": "Negative_regulation", "trigger": { "text": [ "prevented" ], "offsets": [ [ 1177, 1186 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "PMID-7929355_E32" } ] }, { "id": "PMID-7929355_E28", "type": "Negative_regulation", "trigger": { "text": [ "prevented" ], "offsets": [ [ 1177, 1186 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "PMID-7929355_E30" } ] }, { "id": "PMID-7929355_E29", "type": "Negative_regulation", "trigger": { "text": [ "prevented" ], "offsets": [ [ 1177, 1186 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "PMID-7929355_E31" } ] }, { "id": "PMID-7929355_E30", "type": "Protein_catabolism", "trigger": { "text": [ "degradation" ], "offsets": [ [ 1187, 1198 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "PMID-7929355_T16" } ] }, { "id": "PMID-7929355_E31", "type": "Localization", "trigger": { "text": [ "translocation" ], "offsets": [ [ 1230, 1243 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "PMID-7929355_T17" }, { "role": "ToLoc", "ref_id": "PMID-7929355_T43" } ] }, { "id": "PMID-7929355_E32", "type": "Localization", "trigger": { "text": [ "translocation" ], "offsets": [ [ 1230, 1243 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "PMID-7929355_T18" }, { "role": "ToLoc", "ref_id": "PMID-7929355_T43" } ] }, { "id": "PMID-7929355_E33", "type": "Negative_regulation", "trigger": { "text": [ "block" ], "offsets": [ [ 1306, 1311 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "PMID-7929355_E34" } ] }, { "id": "PMID-7929355_E34", "type": "Positive_regulation", "trigger": { "text": [ "induction" ], "offsets": [ [ 1312, 1321 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "PMID-7929355_T19" } ] }, { "id": "PMID-7929355_E35", "type": "Negative_regulation", "trigger": { "text": [ "inhibiting" ], "offsets": [ [ 1433, 1443 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "PMID-7929355_E37" } ] }, { "id": "PMID-7929355_E36", "type": "Negative_regulation", "trigger": { "text": [ "inhibiting" ], "offsets": [ [ 1433, 1443 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "PMID-7929355_E38" } ] }, { "id": "PMID-7929355_E37", "type": "Localization", "trigger": { "text": [ "translocation" ], "offsets": [ [ 1452, 1465 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "PMID-7929355_T21" }, { "role": "ToLoc", "ref_id": "PMID-7929355_T48" } ] }, { "id": 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[]

[ { "id": "PMID-7931077__text", "type": "abstract", "text": [ "A family of serine proteases expressed exclusively in myelo-monocytic cells specifically processes the nuclear factor-kappa B subunit p65 in vitro and may impair human immunodeficiency virus replication in these cells. \nTwo groups of U937 promonocytic cells were obtained by limiting dilution cloning which differed strikingly in their ability to support human immunodeficiency virus 1 (HIV-1) replication. \"Plus\" clones replicated the virus efficiently, whereas \"minus\" clones did not. We examined these clones for differences in nuclear factor (NF)-kappa B activity which might account for the observed phenomenon. Stimulation of plus clones liberated the classical p50-p65 complex from cytoplasmic pools, whereas minus clones produced an apparently novel, faster-migrating complex, as judged by electrophoretic mobility shift assays. It is surprising that the faster-migrating complex was composed also of p50 and p65. However, the p65 subunit was COOH-terminally truncated, as shown by immunoprecipitation. The truncation resulted from limited proteolysis of p65 during cellular extraction which released particular lysosomal serine proteases, such as elastase, cathepsin G, and proteinase 3. These specific proteases are coordinately expressed and were present exclusively in the minus U937 clones, but not in the plus clones, as demonstrated in the case of cathepsin G. In addition, these proteases were detected in certain subclones of THP-1 and HL-60 cells and in primary monocytes, in each case correlating with the truncated from of p65. We demonstrate in vitro cleavage of p65 by purified elastase and cathepsin G. It is possible that particular serine proteases may have inhibiting effects on the replication of HIV-1 in myelo-monocytic cells. The data also demonstrate that special precautions must be taken when making extracts from myelo-monocytic cells. " ], "offsets": [ [ 0, 1870 ] ] } ]

[ { "id": "PMID-7931077_T1", "type": "Protein", "text": [ "p65" ], "offsets": [ [ 134, 137 ] ], "normalized": [] }, { "id": "PMID-7931077_T2", "type": "Protein", "text": [ "p50" ], "offsets": [ [ 668, 671 ] ], "normalized": [] }, { "id": "PMID-7931077_T3", "type": "Protein", "text": [ "p65" ], "offsets": [ [ 672, 675 ] ], "normalized": [] }, { "id": "PMID-7931077_T4", "type": "Protein", "text": [ "p50" ], "offsets": [ [ 909, 912 ] ], "normalized": [] }, { "id": "PMID-7931077_T5", "type": "Protein", "text": [ "p65" ], "offsets": [ [ 917, 920 ] ], "normalized": [] }, { "id": "PMID-7931077_T6", "type": "Protein", "text": [ "p65" ], "offsets": [ [ 935, 938 ] ], "normalized": [] }, { "id": "PMID-7931077_T7", "type": "Protein", "text": [ "p65" ], "offsets": [ [ 1063, 1066 ] ], "normalized": [] }, { "id": "PMID-7931077_T8", "type": "Protein", "text": [ "cathepsin G" ], "offsets": [ [ 1166, 1177 ] ], "normalized": [] }, { "id": "PMID-7931077_T9", "type": "Protein", "text": [ "proteinase 3" ], "offsets": [ [ 1183, 1195 ] ], "normalized": [] }, { "id": "PMID-7931077_T10", "type": "Protein", "text": [ "cathepsin G" ], "offsets": [ [ 1363, 1374 ] ], "normalized": [] }, { "id": "PMID-7931077_T11", "type": "Protein", "text": [ "p65" ], "offsets": [ [ 1543, 1546 ] ], "normalized": [] }, { "id": "PMID-7931077_T12", "type": "Protein", "text": [ "p65" ], "offsets": [ [ 1584, 1587 ] ], "normalized": [] }, { "id": "PMID-7931077_T13", "type": "Protein", "text": [ "cathepsin G" ], "offsets": [ [ 1613, 1624 ] ], "normalized": [] } ]

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[]

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[ { "id": "PMID-7935451__text", "type": "abstract", "text": [ "Human T-cell leukemia virus type I Tax activation of NF-kappa B/Rel involves phosphorylation and degradation of I kappa B alpha and RelA (p65)-mediated induction of the c-rel gene. \nThe tax gene product of human T-cell leukemia virus type I (HTLV-I) is a potent transcriptional activator that both stimulates viral gene expression and activates an array of cellular genes involved in T-cell growth. Tax acts indirectly by inducing or modifying the action of various host transcription factors, including members of the NF-kappa B/Rel family of enhancer-binding proteins. In resting T cells, many of these NF-kappa B/Rel factors are sequestered in the cytoplasm by various ankyrin-rich inhibitory proteins, including I kappa B alpha. HTLV-I Tax expression leads to the constitutive nuclear expression of biologically active NF-kappa B and c-Rel complexes; however, the biochemical mechanism(s) underlying this response remains poorly understood. In this study, we demonstrate that Tax-stimulated nuclear expression of NF-kappa B in both HTLV-I-infected and Tax-transfected human T cells is associated with the phosphorylation and rapid proteolytic degradation of I kappa B alpha. In contrast to prior in vitro studies, at least a fraction of the phosphorylated form of I kappa B alpha remains physically associated with the NF-kappa B complex in vivo but is subject to rapid degradation, thereby promoting the nuclear translocation of the active NF-kappa B complex. We further demonstrate that Tax induction of nuclear c-Rel expression is activated by the RelA (p65) subunit of NF-kappa B, which activates transcription of the c-rel gene through an intrinsic kappa B enhancer element. In normal cells, the subsequent accumulation of nuclear c-Rel acts to inhibit its own continued production, indicating the presence of an autoregulatory loop. (ABSTRACT TRUNCATED AT 250 WORDS) " ], "offsets": [ [ 0, 1877 ] ] } ]

[ { "id": "PMID-7935451_T1", "type": "Protein", "text": [ "Tax" ], "offsets": [ [ 35, 38 ] ], "normalized": [] }, { "id": "PMID-7935451_T2", "type": "Protein", "text": [ "I kappa B alpha" ], "offsets": [ [ 112, 127 ] ], "normalized": [] }, { "id": "PMID-7935451_T3", "type": "Protein", "text": [ "RelA" ], "offsets": [ [ 132, 136 ] ], "normalized": [] }, { "id": "PMID-7935451_T4", "type": "Protein", "text": [ "p65" ], "offsets": [ [ 138, 141 ] ], "normalized": [] }, { "id": "PMID-7935451_T5", "type": "Protein", "text": [ "tax" ], "offsets": [ [ 186, 189 ] ], "normalized": [] }, { "id": "PMID-7935451_T6", "type": "Protein", "text": [ "Tax" ], "offsets": [ [ 399, 402 ] ], "normalized": [] }, { "id": "PMID-7935451_T7", "type": "Protein", "text": [ "I kappa B alpha" ], "offsets": [ [ 716, 731 ] ], "normalized": [] }, { "id": "PMID-7935451_T8", "type": "Protein", "text": [ "Tax" ], "offsets": [ [ 740, 743 ] ], "normalized": [] }, { "id": "PMID-7935451_T9", "type": "Protein", "text": [ "c-Rel" ], "offsets": [ [ 838, 843 ] ], "normalized": [] }, { "id": "PMID-7935451_T10", "type": "Protein", "text": [ "Tax" ], "offsets": [ [ 980, 983 ] ], "normalized": [] }, { "id": "PMID-7935451_T11", "type": "Protein", "text": [ "Tax" ], "offsets": [ [ 1056, 1059 ] ], "normalized": [] }, { "id": "PMID-7935451_T12", "type": "Protein", "text": [ "I kappa B alpha" ], "offsets": [ [ 1162, 1177 ] ], "normalized": [] }, { "id": "PMID-7935451_T13", "type": "Protein", "text": [ "I kappa B alpha" ], "offsets": [ [ 1268, 1283 ] ], "normalized": [] }, { "id": "PMID-7935451_T14", "type": "Protein", "text": [ "Tax" ], "offsets": [ [ 1493, 1496 ] ], "normalized": [] }, { "id": "PMID-7935451_T15", "type": "Protein", "text": [ "c-Rel" ], "offsets": [ [ 1518, 1523 ] ], "normalized": [] }, { "id": "PMID-7935451_T16", "type": "Protein", "text": [ "RelA" ], "offsets": [ [ 1555, 1559 ] ], "normalized": [] }, { "id": "PMID-7935451_T17", "type": "Protein", "text": [ "p65" ], "offsets": [ [ 1561, 1564 ] ], "normalized": [] }, { "id": "PMID-7935451_T18", "type": "Protein", "text": [ "c-rel" ], "offsets": [ [ 1626, 1631 ] ], "normalized": [] }, { "id": "PMID-7935451_T19", "type": "Protein", "text": [ "c-Rel" ], "offsets": [ [ 1740, 1745 ] ], "normalized": [] } ]

[ { "id": "PMID-7935451_E1", "type": "Phosphorylation", "trigger": { "text": [ "phosphorylation" ], "offsets": [ [ 77, 92 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "PMID-7935451_T2" } ] }, { "id": "PMID-7935451_E2", "type": "Protein_catabolism", "trigger": { "text": [ "degradation" ], "offsets": [ [ 97, 108 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "PMID-7935451_T2" } ] }, { "id": "PMID-7935451_E3", "type": "Gene_expression", "trigger": { "text": [ "expression" ], "offsets": [ [ 744, 754 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "PMID-7935451_T8" } ] }, { "id": "PMID-7935451_E4", "type": "Positive_regulation", "trigger": { "text": [ "leads" ], "offsets": [ [ 755, 760 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "PMID-7935451_E5" }, { "role": "Cause", "ref_id": "PMID-7935451_E3" } ] }, { "id": "PMID-7935451_E5", "type": "Gene_expression", "trigger": { "text": [ "expression" ], "offsets": [ [ 789, 799 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "PMID-7935451_T9" } ] }, { "id": "PMID-7935451_E6", "type": "Phosphorylation", "trigger": { "text": [ "phosphorylation" ], "offsets": [ [ 1109, 1124 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "PMID-7935451_T12" } ] }, { "id": "PMID-7935451_E7", "type": "Protein_catabolism", "trigger": { "text": [ "degradation" ], "offsets": [ [ 1147, 1158 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "PMID-7935451_T12" } ] }, { "id": "PMID-7935451_E8", "type": "Binding", "trigger": { "text": [ "associated" ], "offsets": [ [ 1303, 1313 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "PMID-7935451_T13" } ] }, { "id": "PMID-7935451_E9", "type": "Protein_catabolism", "trigger": { "text": [ "degradation" ], "offsets": [ [ 1374, 1385 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "PMID-7935451_T13" } ] }, { "id": "PMID-7935451_E10", "type": "Positive_regulation", "trigger": { "text": [ "induction" ], "offsets": [ [ 1497, 1506 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "PMID-7935451_E11" }, { "role": "Cause", "ref_id": "PMID-7935451_T14" } ] }, { "id": "PMID-7935451_E11", "type": "Gene_expression", "trigger": { "text": [ "expression" ], "offsets": [ [ 1524, 1534 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "PMID-7935451_T15" } ] }, { "id": "PMID-7935451_E12", "type": "Positive_regulation", "trigger": { "text": [ "activated" ], "offsets": [ [ 1538, 1547 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "PMID-7935451_E10" }, { "role": "Cause", "ref_id": "PMID-7935451_T17" } ] }, { "id": "PMID-7935451_E13", "type": "Positive_regulation", "trigger": { "text": [ "activates" ], "offsets": [ [ 1595, 1604 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "PMID-7935451_E14" }, { "role": "Cause", "ref_id": "PMID-7935451_T18" } ] }, { "id": "PMID-7935451_E14", "type": "Transcription", "trigger": { "text": [ "transcription" ], "offsets": [ [ 1605, 1618 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "PMID-7935451_T18" } ] }, { "id": "PMID-7935451_E15", "type": "Positive_regulation", "trigger": { "text": [ "accumulation" ], "offsets": [ [ 1716, 1728 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "PMID-7935451_T19" } ] }, { "id": "PMID-7935451_E16", "type": "Negative_regulation", "trigger": { "text": [ "inhibit" ], "offsets": [ [ 1754, 1761 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "PMID-7935451_E17" }, { "role": "Cause", "ref_id": "PMID-7935451_E15" } ] }, { "id": "PMID-7935451_E17", "type": "Gene_expression", "trigger": { "text": [ "production" ], "offsets": [ [ 1780, 1790 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "PMID-7935451_T19" } ] } ]

[ { "id": "PMID-7935451_1", "entity_ids": [ "PMID-7935451_T3", "PMID-7935451_T4" ] }, { "id": "PMID-7935451_2", "entity_ids": [ "PMID-7935451_T17", "PMID-7935451_T16" ] } ]

[]

[ { "id": "PMID-7945272__text", "type": "abstract", "text": [ "Arrested development: understanding v-abl. \nThe protein tyrosine kinase activity of the v-abl oncogene has been demonstrated to subvert the normal second messenger systems used by lymphoid cells for growth and differentiation. Transformation of bone marrow with the Abelson murine leukemia virus results in the appearance of B cell lineage cells arrested at the pre-B cell stage. Recent reports have characterized these cells expressing high v-abl kinase activity as deficient in detectable NF-kappaB DNA binding activity and low level RAG gene expression. These observations suggest that v-abl may be inhibiting the differentiation of B cells by blocking these two crucial elements in the maturation pathway. " ], "offsets": [ [ 0, 710 ] ] } ]

[ { "id": "PMID-7945272_T1", "type": "Protein", "text": [ "v-abl" ], "offsets": [ [ 36, 41 ] ], "normalized": [] }, { "id": "PMID-7945272_T2", "type": "Protein", "text": [ "v-abl" ], "offsets": [ [ 88, 93 ] ], "normalized": [] }, { "id": "PMID-7945272_T3", "type": "Protein", "text": [ "v-abl" ], "offsets": [ [ 442, 447 ] ], "normalized": [] }, { "id": "PMID-7945272_T4", "type": "Protein", "text": [ "v-abl" ], "offsets": [ [ 589, 594 ] ], "normalized": [] } ]

[]

[]

[]

[ { "id": "PMID-7949138__text", "type": "abstract", "text": [ "Distinct DNase-I hypersensitive sites are associated with TAL-1 transcription in erythroid and T-cell lines. \nThe tal-1 gene, frequently activated in human T-cell acute lymphoblastic leukemia (T-ALL), is expressed in the erythroid, megakaryocytic, and mast cell lineages during normal hematopoiesis. To gain further insight into the molecular mechanisms that control tal-1 expression, we investigated tal-1 chromatin structure in erythroid/megakaryocytic cell lines and in T-cell lines either with or without tal-1 rearrangements. Tal-1 transcription was shown to be monoallelic in Jurkat, a T-cell line that expresses tal-1 in the absence of apparent genomic alteration of the locus. Methylation studies indicated that the tal-15' GC-rich region behaves like a CpG island, hypomethylated in normal cells, and methylated de novo on transcriptionally inactive alleles in established cell lines. Five major DNase-I hypersensitive sites (HS) were mapped in the tal-1 locus. HS I, IV, and V were exclusively observed in the erythroid/megakaryocytic cell lines that express tal-1 from the promoters 1a and 1b. HS II was weak in hematopoietic cell lines, absent in Hela, and greatly enhanced in Jurkat, suggesting that this region might be implicated in the cis-activation of tal-1 promoter 1b in this cell line. HS III was weak in HEL and Jurkat, and greatly enhanced in DU528, a T-cell line that bears a t (1;14) and initiates tal-1 transcription within exon 4. These results suggest that distinct regulatory elements are associated with the use of the different tal-1 promoters. " ], "offsets": [ [ 0, 1576 ] ] } ]

[ { "id": "PMID-7949138_T1", "type": "Protein", "text": [ "DNase-I" ], "offsets": [ [ 9, 16 ] ], "normalized": [] }, { "id": "PMID-7949138_T2", "type": "Protein", "text": [ "TAL-1" ], "offsets": [ [ 58, 63 ] ], "normalized": [] }, { "id": "PMID-7949138_T3", "type": "Protein", "text": [ "tal-1" ], "offsets": [ [ 114, 119 ] ], "normalized": [] }, { "id": "PMID-7949138_T4", "type": "Protein", "text": [ "tal-1" ], "offsets": [ [ 367, 372 ] ], "normalized": [] }, { "id": "PMID-7949138_T5", "type": "Protein", "text": [ "tal-1" ], "offsets": [ [ 401, 406 ] ], "normalized": [] }, { "id": "PMID-7949138_T6", "type": "Protein", "text": [ "tal-1" ], "offsets": [ [ 509, 514 ] ], "normalized": [] }, { "id": "PMID-7949138_T7", "type": "Protein", "text": [ "Tal-1" ], "offsets": [ [ 531, 536 ] ], "normalized": [] }, { "id": "PMID-7949138_T8", "type": "Protein", "text": [ "tal-1" ], "offsets": [ [ 619, 624 ] ], "normalized": [] }, { "id": "PMID-7949138_T9", "type": "Protein", "text": [ "tal-1" ], "offsets": [ [ 724, 729 ] ], "normalized": [] }, { "id": "PMID-7949138_T10", "type": "Protein", "text": [ "DNase-I" ], "offsets": [ [ 905, 912 ] ], "normalized": [] }, { "id": "PMID-7949138_T11", "type": "Protein", "text": [ "tal-1" ], "offsets": [ [ 958, 963 ] ], "normalized": [] }, { "id": "PMID-7949138_T12", "type": "Protein", "text": [ "tal-1" ], "offsets": [ [ 1069, 1074 ] ], "normalized": [] }, { "id": "PMID-7949138_T13", "type": "Protein", "text": [ "tal-1" ], "offsets": [ [ 1270, 1275 ] ], "normalized": [] }, { "id": "PMID-7949138_T14", "type": "Protein", "text": [ "tal-1" ], "offsets": [ [ 1423, 1428 ] ], "normalized": [] }, { "id": "PMID-7949138_T15", "type": "Protein", "text": [ "tal-1" ], "offsets": [ [ 1559, 1564 ] ], "normalized": [] }, { "id": "PMID-7949138_T26", "type": "Entity", "text": [ "promoter 1b" ], "offsets": [ [ 1276, 1287 ] ], "normalized": [] } ]

[ { "id": "PMID-7949138_E1", "type": "Transcription", "trigger": { "text": [ "transcription" ], "offsets": [ [ 64, 77 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "PMID-7949138_T2" } ] }, { "id": "PMID-7949138_E2", "type": "Positive_regulation", "trigger": { "text": [ "activated" ], "offsets": [ [ 137, 146 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "PMID-7949138_T3" } ] }, { "id": "PMID-7949138_E3", "type": "Gene_expression", "trigger": { "text": [ "expressed" ], "offsets": [ [ 204, 213 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "PMID-7949138_T3" } ] }, { "id": "PMID-7949138_E4", "type": "Regulation", "trigger": { "text": [ "control" ], "offsets": [ [ 359, 366 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "PMID-7949138_E5" } ] }, { "id": "PMID-7949138_E5", "type": "Gene_expression", "trigger": { "text": [ "expression" ], "offsets": [ [ 373, 383 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "PMID-7949138_T4" } ] }, { "id": "PMID-7949138_E6", "type": "Transcription", "trigger": { "text": [ "transcription" ], "offsets": [ [ 537, 550 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "PMID-7949138_T7" } ] }, { "id": "PMID-7949138_E7", "type": "Gene_expression", "trigger": { "text": [ "expresses" ], "offsets": [ [ 609, 618 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "PMID-7949138_T8" } ] }, { "id": "PMID-7949138_E8", "type": "Gene_expression", "trigger": { "text": [ "express" ], "offsets": [ [ 1061, 1068 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "PMID-7949138_T12" } ] }, { "id": "PMID-7949138_E9", "type": "Positive_regulation", "trigger": { "text": [ "from" ], "offsets": [ [ 1075, 1079 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "PMID-7949138_E8" } ] }, { "id": "PMID-7949138_E10", "type": "Positive_regulation", "trigger": { "text": [ "cis-activation" ], "offsets": [ [ 1252, 1266 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "PMID-7949138_T13" }, { "role": "Site", "ref_id": "PMID-7949138_T26" } ] }, { "id": "PMID-7949138_E11", "type": "Transcription", "trigger": { "text": [ "transcription" ], "offsets": [ [ 1429, 1442 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "PMID-7949138_T14" } ] } ]

[]

[]

[ { "id": "PMID-7958618__text", "type": "abstract", "text": [ "Functions of glutathione and glutathione disulfide in immunology and immunopathology. \nEven a moderate increase in the cellular cysteine supply elevates the intracellular glutathione (GSH) and glutathione disulfide (GSSG) levels and potentiates immunological functions of lymphocytes in vitro. At low GSSG levels, T cells cannot optimally activate the immunologically important transcription factor NF kappa B, whereas high GSSG levels inhibit the DNA binding activity of NF kappa B. The effects of GSSG are antagonized by reduced thioredoxin (TRX). As the protein tyrosine kinase activities p56lck and p59fyn are activated in intact cells by hydrogen peroxide, they are likely targets for GSSG action. These redox-regulated enzymes trigger signal cascades for NF kappa B activation and transduce signals from the T cell antigen receptor, from CD4 and CD8 molecules, and from the IL-2 receptor beta-chain. The effector phase of cytotoxic T cell responses and IL-2-dependent functions are inhibited even by a partial depletion of the intracellular GSH pool. As signal transduction is facilitated by prooxidant conditions, we propose that the well-known immunological consequences of GSH depletion ultimately may be results of the accompanying GSSG deficiency. As HIV-infected patients and SIV-infected rhesus macaques have, on the average, significantly decreased plasma cyst(e)ine and intracellular GSH levels, we also hypothesize that AIDS may be the consequence of a GSSG deficiency as well. " ], "offsets": [ [ 0, 1494 ] ] } ]

[ { "id": "PMID-7958618_T1", "type": "Protein", "text": [ "thioredoxin" ], "offsets": [ [ 531, 542 ] ], "normalized": [] }, { "id": "PMID-7958618_T2", "type": "Protein", "text": [ "TRX" ], "offsets": [ [ 544, 547 ] ], "normalized": [] }, { "id": "PMID-7958618_T3", "type": "Protein", "text": [ "p56lck" ], "offsets": [ [ 592, 598 ] ], "normalized": [] }, { "id": "PMID-7958618_T4", "type": "Protein", "text": [ "p59fyn" ], "offsets": [ [ 603, 609 ] ], "normalized": [] }, { "id": "PMID-7958618_T5", "type": "Protein", "text": [ "CD4" ], "offsets": [ [ 844, 847 ] ], "normalized": [] }, { "id": "PMID-7958618_T6", "type": "Protein", "text": [ "IL-2 receptor beta-chain" ], "offsets": [ [ 880, 904 ] ], "normalized": [] }, { "id": "PMID-7958618_T7", "type": "Protein", "text": [ "IL-2" ], "offsets": [ [ 959, 963 ] ], "normalized": [] } ]

[ { "id": "PMID-7958618_E1", "type": "Positive_regulation", "trigger": { "text": [ "activated" ], "offsets": [ [ 614, 623 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "PMID-7958618_T3" } ] }, { "id": "PMID-7958618_E2", "type": "Positive_regulation", "trigger": { "text": [ "activated" ], "offsets": [ [ 614, 623 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "PMID-7958618_T4" } ] }, { "id": "PMID-7958618_E3", "type": "Regulation", "trigger": { "text": [ "targets" ], "offsets": [ [ 678, 685 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "PMID-7958618_T3" } ] }, { "id": "PMID-7958618_E4", "type": "Regulation", "trigger": { "text": [ "targets" ], "offsets": [ [ 678, 685 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "PMID-7958618_T4" } ] }, { "id": "PMID-7958618_E5", "type": "Positive_regulation", "trigger": { "text": [ "trigger signal cascades" ], "offsets": [ [ 733, 756 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "PMID-7958618_T3" } ] }, { "id": "PMID-7958618_E6", "type": "Positive_regulation", "trigger": { "text": [ "trigger signal cascades" ], "offsets": [ [ 733, 756 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "PMID-7958618_T4" } ] } ]

[ { "id": "PMID-7958618_1", "entity_ids": [ "PMID-7958618_T1", "PMID-7958618_T2" ] } ]

[]

[ { "id": "PMID-7961690__text", "type": "abstract", "text": [ "Erythropoietin-dependent induction of hemoglobin synthesis in a cytokine-dependent cell line M-TAT. \nM-TAT is a cytokine-dependent cell line with the potential to differentiate along the erythroid and megakaryocytic lineages. We cultured M-TAT cells long term (> 1 year) in the continuous presence of erythropoietin (EPO), granulocyte-macrophage colony-stimulating factor (GM-CSF), or stem cell factor (SCF). These long term cultures are referred to as M-TAT/EPO, M-TAT/GM-CSF, and M-TAT/SCF cells, respectively. Hemoglobin concentration and gamma-globin and erythroid delta-aminolevulinate synthase mRNA levels were significantly higher in M-TAT/EPO cells than in M-TAT/GM-CSF cells. When the supplemented cytokine was switched from GM-CSF to EPO, hemoglobin synthesis in M-TAT/GM-CSF cells increased rapidly (within 5 h), and the level of GATA-1 mRNA increased. In contrast, the addition of GM-CSF to the M-TAT/EPO cell culture decreased the amount of hemoglobin, even in the presence of EPO, indicating that the EPO signal for erythroid differentiation is suppressed by GM-CSF. Thus, erythroid development of M-TAT cells is promoted by EPO and suppressed by GM-CSF. These results support the hypothesis that EPO actively influences the programming of gene expression required for erythroid progenitor cell differentiation. " ], "offsets": [ [ 0, 1326 ] ] } ]

[ { "id": "PMID-7961690_T1", "type": "Protein", "text": [ "Erythropoietin" ], "offsets": [ [ 0, 14 ] ], "normalized": [] }, { "id": "PMID-7961690_T2", "type": "Protein", "text": [ "erythropoietin" ], "offsets": [ [ 301, 315 ] ], "normalized": [] }, { "id": "PMID-7961690_T3", "type": "Protein", "text": [ "EPO" ], "offsets": [ [ 317, 320 ] ], "normalized": [] }, { "id": "PMID-7961690_T4", "type": "Protein", "text": [ "granulocyte-macrophage colony-stimulating factor" ], "offsets": [ [ 323, 371 ] ], "normalized": [] }, { "id": "PMID-7961690_T5", "type": "Protein", "text": [ "GM-CSF" ], "offsets": [ [ 373, 379 ] ], "normalized": [] }, { "id": "PMID-7961690_T6", "type": "Protein", "text": [ "stem cell factor" ], "offsets": [ [ 385, 401 ] ], "normalized": [] }, { "id": "PMID-7961690_T7", "type": "Protein", "text": [ "SCF" ], "offsets": [ [ 403, 406 ] ], "normalized": [] }, { "id": "PMID-7961690_T8", "type": "Protein", "text": [ "erythroid delta-aminolevulinate synthase" ], "offsets": [ [ 559, 599 ] ], "normalized": [] }, { "id": "PMID-7961690_T9", "type": "Protein", "text": [ "EPO" ], "offsets": [ [ 647, 650 ] ], "normalized": [] }, { "id": "PMID-7961690_T10", "type": "Protein", "text": [ "GM-CSF" ], "offsets": [ [ 671, 677 ] ], "normalized": [] }, { "id": "PMID-7961690_T11", "type": "Protein", "text": [ "GM-CSF" ], "offsets": [ [ 734, 740 ] ], "normalized": [] }, { "id": "PMID-7961690_T12", "type": "Protein", "text": [ "EPO" ], "offsets": [ [ 744, 747 ] ], "normalized": [] }, { "id": "PMID-7961690_T13", "type": "Protein", "text": [ "GM-CSF" ], "offsets": [ [ 779, 785 ] ], "normalized": [] }, { "id": "PMID-7961690_T14", "type": "Protein", "text": [ "GATA-1" ], "offsets": [ [ 841, 847 ] ], "normalized": [] }, { "id": "PMID-7961690_T15", "type": "Protein", "text": [ "GM-CSF" ], "offsets": [ [ 893, 899 ] ], "normalized": [] }, { "id": "PMID-7961690_T16", "type": "Protein", "text": [ "EPO" ], "offsets": [ [ 913, 916 ] ], "normalized": [] }, { "id": "PMID-7961690_T17", "type": "Protein", "text": [ "EPO" ], "offsets": [ [ 990, 993 ] ], "normalized": [] }, { "id": "PMID-7961690_T18", "type": "Protein", "text": [ "EPO" ], "offsets": [ [ 1015, 1018 ] ], "normalized": [] }, { "id": "PMID-7961690_T19", "type": "Protein", "text": [ "GM-CSF" ], "offsets": [ [ 1073, 1079 ] ], "normalized": [] }, { "id": "PMID-7961690_T20", "type": "Protein", "text": [ "EPO" ], "offsets": [ [ 1139, 1142 ] ], "normalized": [] }, { "id": "PMID-7961690_T21", "type": "Protein", "text": [ "GM-CSF" ], "offsets": [ [ 1161, 1167 ] ], "normalized": [] }, { "id": "PMID-7961690_T22", "type": "Protein", "text": [ "EPO" ], "offsets": [ [ 1211, 1214 ] ], "normalized": [] } ]

[ { "id": "PMID-7961690_E1", "type": "Transcription", "trigger": { "text": [ "mRNA levels" ], "offsets": [ [ 600, 611 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "PMID-7961690_T8" } ] }, { "id": "PMID-7961690_E2", "type": "Transcription", "trigger": { "text": [ "levels" ], "offsets": [ [ 605, 611 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "PMID-7961690_T8" } ] }, { "id": "PMID-7961690_E3", "type": "Positive_regulation", "trigger": { "text": [ "increased" ], "offsets": [ [ 853, 862 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "PMID-7961690_T14" } ] } ]

[ { "id": "PMID-7961690_1", "entity_ids": [ "PMID-7961690_T2", "PMID-7961690_T3" ] }, { "id": "PMID-7961690_2", "entity_ids": [ "PMID-7961690_T4", "PMID-7961690_T5" ] }, { "id": "PMID-7961690_3", "entity_ids": [ "PMID-7961690_T6", "PMID-7961690_T7" ] } ]

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[ { "id": "PMID-7964483__text", "type": "abstract", "text": [ "One gene, two transcripts: isolation of an alternative transcript encoding for the autoantigen La/SS-B from a cDNA library of a patient with primary Sjogrens' syndrome. \nA cDNA library was prepared from peripheral blood lymphocytes of an autoimmune patient with primary Sjogrens' syndrome. The cDNA library was screened with the patients own autoimmune serum being monospecific for the nuclear autoantigen La/SS-B. Thereby an alternative type of La mRNA was identified that differed from the known La mRNA due to an exchange of the exon 1. Sequencing of the genomic region between the exons 1 and 2 showed that the alternative 5'-end is a part of the intron. In addition, the presence of an alternative promoter site, which exists within the intron downstream of the exon 1, became evident. In consequence, the alternative La mRNA is the result of a promoter switching combined with an alternative splicing mechanism. In the intron, further transcription factor binding sites, including a NF-kappa B element, were identified leading to the suggestion that the expression of the gene encoding for the nuclear autoantigen La/SS-B alters in dependence on disease conditions. " ], "offsets": [ [ 0, 1172 ] ] } ]

[ { "id": "PMID-7964483_T1", "type": "Protein", "text": [ "autoantigen La" ], "offsets": [ [ 83, 97 ] ], "normalized": [] }, { "id": "PMID-7964483_T2", "type": "Protein", "text": [ "SS-B" ], "offsets": [ [ 98, 102 ] ], "normalized": [] }, { "id": "PMID-7964483_T3", "type": "Protein", "text": [ "autoantigen La" ], "offsets": [ [ 394, 408 ] ], "normalized": [] }, { "id": "PMID-7964483_T4", "type": "Protein", "text": [ "SS-B" ], "offsets": [ [ 409, 413 ] ], "normalized": [] }, { "id": "PMID-7964483_T5", "type": "Protein", "text": [ "La" ], "offsets": [ [ 446, 448 ] ], "normalized": [] }, { "id": "PMID-7964483_T6", "type": "Protein", "text": [ "La" ], "offsets": [ [ 498, 500 ] ], "normalized": [] }, { "id": "PMID-7964483_T7", "type": "Protein", "text": [ "La" ], "offsets": [ [ 823, 825 ] ], "normalized": [] }, { "id": "PMID-7964483_T8", "type": "Protein", "text": [ "autoantigen La" ], "offsets": [ [ 1108, 1122 ] ], "normalized": [] }, { "id": "PMID-7964483_T9", "type": "Protein", "text": [ "SS-B" ], "offsets": [ [ 1123, 1127 ] ], "normalized": [] } ]

[ { "id": "PMID-7964483_E1", "type": "Positive_regulation", "trigger": { "text": [ "result" ], "offsets": [ [ 838, 844 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "PMID-7964483_T7" } ] }, { "id": "PMID-7964483_E2", "type": "Gene_expression", "trigger": { "text": [ "expression" ], "offsets": [ [ 1060, 1070 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "PMID-7964483_T8" } ] }, { "id": "PMID-7964483_E3", "type": "Regulation", "trigger": { "text": [ "alters" ], "offsets": [ [ 1128, 1134 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "PMID-7964483_E2" } ] } ]

[ { "id": "PMID-7964483_1", "entity_ids": [ "PMID-7964483_T1", "PMID-7964483_T2" ] }, { "id": "PMID-7964483_2", "entity_ids": [ "PMID-7964483_T8", "PMID-7964483_T9" ] }, { "id": "PMID-7964483_3", "entity_ids": [ "PMID-7964483_T3", "PMID-7964483_T4" ] } ]

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[ { "id": "PMID-7964516__text", "type": "abstract", "text": [ "Functional Myc-Max heterodimer is required for activation-induced apoptosis in T cell hybridomas. \nT cell hybridomas respond to activation signals by undergoing apoptotic cell death, and this is likely to represent comparable events related to tolerance induction in immature and mature T cells in vivo. Previous studies using antisense oligonucleotides implicated the c-Myc protein in the phenomenon of activation-induced apoptosis. This role for c-Myc in apoptosis is now confirmed in studies using a dominant negative form of its heterodimeric binding partner, Max, which we show here inhibits activation-induced apoptosis. Further, coexpression of a reciprocally mutant Myc protein capable of forming functional heterodimers with the mutant Max can compensate for the dominant negative activity and restore activation-induced apoptosis. These results imply that Myc promotes activation-induced apoptosis by obligatory heterodimerization with Max, and therefore, by regulating gene transcription. " ], "offsets": [ [ 0, 1000 ] ] } ]

[ { "id": "PMID-7964516_T1", "type": "Protein", "text": [ "Myc" ], "offsets": [ [ 11, 14 ] ], "normalized": [] }, { "id": "PMID-7964516_T2", "type": "Protein", "text": [ "Max" ], "offsets": [ [ 15, 18 ] ], "normalized": [] }, { "id": "PMID-7964516_T3", "type": "Protein", "text": [ "c-Myc" ], "offsets": [ [ 369, 374 ] ], "normalized": [] }, { "id": "PMID-7964516_T4", "type": "Protein", "text": [ "c-Myc" ], "offsets": [ [ 448, 453 ] ], "normalized": [] }, { "id": "PMID-7964516_T5", "type": "Protein", "text": [ "Max" ], "offsets": [ [ 564, 567 ] ], "normalized": [] }, { "id": "PMID-7964516_T6", "type": "Protein", "text": [ "Myc" ], "offsets": [ [ 674, 677 ] ], "normalized": [] }, { "id": "PMID-7964516_T7", "type": "Protein", "text": [ "Max" ], "offsets": [ [ 745, 748 ] ], "normalized": [] }, { "id": "PMID-7964516_T8", "type": "Protein", "text": [ "Myc" ], "offsets": [ [ 866, 869 ] ], "normalized": [] }, { "id": "PMID-7964516_T9", "type": "Protein", "text": [ "Max" ], "offsets": [ [ 946, 949 ] ], "normalized": [] } ]

[ { "id": "PMID-7964516_E1", "type": "Binding", "trigger": { "text": [ "binding partner" ], "offsets": [ [ 547, 562 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "PMID-7964516_T4" }, { "role": "Theme", "ref_id": "PMID-7964516_T5" } ] }, { "id": "PMID-7964516_E2", "type": "Gene_expression", "trigger": { "text": [ "coexpression" ], "offsets": [ [ 636, 648 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "PMID-7964516_T7" } ] }, { "id": "PMID-7964516_E3", "type": "Gene_expression", "trigger": { "text": [ "coexpression" ], "offsets": [ [ 636, 648 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "PMID-7964516_T6" } ] }, { "id": "PMID-7964516_E4", "type": "Binding", "trigger": { "text": [ "capable of forming functional heterodimers" ], "offsets": [ [ 686, 728 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "PMID-7964516_T6" }, { "role": "Theme", "ref_id": "PMID-7964516_T7" } ] }, { "id": "PMID-7964516_E5", "type": "Binding", "trigger": { "text": [ "heterodimerization" ], "offsets": [ [ 922, 940 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "PMID-7964516_T8" }, { "role": "Theme", "ref_id": "PMID-7964516_T9" } ] } ]

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[]

[ { "id": "PMID-7964616__text", "type": "abstract", "text": [ "DNA-binding studies of the Epstein-Barr virus nuclear antigen 2 (EBNA-2): evidence for complex formation by latent membrane protein gene promoter-binding proteins in EBNA-2-positive cell lines. \nThe Epstein-Barr virus (EBV) nuclear antigen 2 (EBNA-2) protein is essential for the immortalization of human primary B cells by EBV. EBNA-2 trans-activates cellular and viral genes like CD23, c-fgr, latent membrane protein 1 (LMP1) and terminal protein 1 (TP1). Trans-activation of the TP1 promoter and of the BamHI C promoter has already been investigated in detail and appears to be mediated via protein-protein interactions and not by direct binding of EBNA-2 type A (of EBV type 1) to the DNA. EBNA-2 is able to trans-activate the expression of the LMP gene in several cell lines. Various reports have delineated the cis-acting elements of the LMP promoter through which EBNA-2 mediates trans-activation. To determine whether EBNA-2 also trans-activates the LMP promoter by protein-protein interactions, we performed a series of gel retardation assays and competition experiments with LMP promoter fragments of different sizes. We determined that the protein-binding region on the LMP promoter was within a 42 bp fragment encompassing nucleotides -135 to -176 relative to the LMP transcriptional start site. None of the DNA fragments investigated indicated interaction of EBNA-2 with the DNA via protein-protein interactions. No significant differences between EBNA-2-positive and EBNA-2-negative nuclear extracts could be seen in the gel retardation assay under conditions that clearly showed binding of EBNA-2A to the TP1 promoter. However, analysis of sucrose gradient fractions in the gel retardation assay provided evidence that the LMP promoter-binding proteins form a complex of higher M(r) in EBNA-2-positive cell extracts. These complexes were destroyed by detergent. We deduce from these results that EBNA-2-positive cells might indeed contain specific complexes bound to the LMP promoter which are, however, too labile to be detected in a standard gel retardation assay. " ], "offsets": [ [ 0, 2082 ] ] } ]

[ { "id": "PMID-7964616_T1", "type": "Protein", "text": [ "Epstein-Barr virus nuclear antigen 2" ], "offsets": [ [ 27, 63 ] ], "normalized": [] }, { "id": "PMID-7964616_T2", "type": "Protein", "text": [ "EBNA-2" ], "offsets": [ [ 65, 71 ] ], "normalized": [] }, { "id": "PMID-7964616_T3", "type": "Protein", "text": [ "EBNA-2" ], "offsets": [ [ 166, 172 ] ], "normalized": [] }, { "id": "PMID-7964616_T4", "type": "Protein", "text": [ "Epstein-Barr virus (EBV) nuclear antigen 2" ], "offsets": [ [ 199, 241 ] ], "normalized": [] }, { "id": "PMID-7964616_T5", "type": "Protein", "text": [ "EBNA-2" ], "offsets": [ [ 243, 249 ] ], "normalized": [] }, { "id": "PMID-7964616_T6", "type": "Protein", "text": [ "EBNA-2" ], "offsets": [ [ 329, 335 ] ], "normalized": [] }, { "id": "PMID-7964616_T7", "type": "Protein", "text": [ "CD23" ], "offsets": [ [ 382, 386 ] ], "normalized": [] }, { "id": "PMID-7964616_T8", "type": "Protein", "text": [ "c-fgr" ], "offsets": [ [ 388, 393 ] ], "normalized": [] }, { "id": "PMID-7964616_T9", "type": "Protein", "text": [ "latent membrane protein 1" ], "offsets": [ [ 395, 420 ] ], "normalized": [] }, { "id": "PMID-7964616_T10", "type": "Protein", "text": [ "LMP1" ], "offsets": [ [ 422, 426 ] ], "normalized": [] }, { "id": "PMID-7964616_T11", "type": "Protein", "text": [ "terminal protein 1" ], "offsets": [ [ 432, 450 ] ], "normalized": [] }, { "id": "PMID-7964616_T12", "type": "Protein", "text": [ "TP1" ], "offsets": [ [ 452, 455 ] ], "normalized": [] }, { "id": "PMID-7964616_T13", "type": "Protein", "text": [ "TP1" ], "offsets": [ [ 482, 485 ] ], "normalized": [] }, { "id": "PMID-7964616_T14", "type": "Protein", "text": [ "BamHI C" ], "offsets": [ [ 506, 513 ] ], "normalized": [] }, { "id": "PMID-7964616_T15", "type": "Protein", "text": [ "EBNA-2" ], "offsets": [ [ 652, 658 ] ], "normalized": [] }, { "id": "PMID-7964616_T16", "type": "Protein", "text": [ "EBNA-2" ], "offsets": [ [ 694, 700 ] ], "normalized": [] }, { "id": "PMID-7964616_T17", "type": "Protein", "text": [ "LMP" ], "offsets": [ [ 749, 752 ] ], "normalized": [] }, { "id": "PMID-7964616_T18", "type": "Protein", "text": [ "LMP" ], "offsets": [ [ 844, 847 ] ], "normalized": [] }, { "id": "PMID-7964616_T19", "type": "Protein", "text": [ "EBNA-2" ], "offsets": [ [ 871, 877 ] ], "normalized": [] }, { "id": "PMID-7964616_T20", "type": "Protein", "text": [ "EBNA-2" ], "offsets": [ [ 926, 932 ] ], "normalized": [] }, { "id": "PMID-7964616_T21", "type": "Protein", "text": [ "LMP" ], "offsets": [ [ 958, 961 ] ], "normalized": [] }, { "id": "PMID-7964616_T22", "type": "Protein", "text": [ "LMP" ], "offsets": [ [ 1085, 1088 ] ], "normalized": [] }, { "id": "PMID-7964616_T23", "type": "Protein", "text": [ "LMP" ], "offsets": [ [ 1181, 1184 ] ], "normalized": [] }, { "id": "PMID-7964616_T24", "type": "Protein", "text": [ "EBNA-2" ], "offsets": [ [ 1372, 1378 ] ], "normalized": [] }, { "id": "PMID-7964616_T25", "type": "Protein", "text": [ "EBNA-2" ], "offsets": [ [ 1461, 1467 ] ], "normalized": [] }, { "id": "PMID-7964616_T26", "type": "Protein", "text": [ "EBNA-2" ], "offsets": [ [ 1481, 1487 ] ], "normalized": [] }, { "id": "PMID-7964616_T27", "type": "Protein", "text": [ "EBNA-2A" ], "offsets": [ [ 1605, 1612 ] ], "normalized": [] }, { "id": "PMID-7964616_T28", "type": "Protein", "text": [ "TP1" ], "offsets": [ [ 1620, 1623 ] ], "normalized": [] }, { "id": "PMID-7964616_T29", "type": "Protein", "text": [ "LMP" ], "offsets": [ [ 1738, 1741 ] ], "normalized": [] }, { "id": "PMID-7964616_T30", "type": "Protein", "text": [ "EBNA-2" ], "offsets": [ [ 1801, 1807 ] ], "normalized": [] }, { "id": "PMID-7964616_T31", "type": "Protein", "text": [ "EBNA-2" ], "offsets": [ [ 1911, 1917 ] ], "normalized": [] }, { "id": "PMID-7964616_T32", "type": "Protein", "text": [ "LMP" ], "offsets": [ [ 1986, 1989 ] ], "normalized": [] }, { "id": "PMID-7964616_T36", "type": "Entity", "text": [ "promoter" ], "offsets": [ [ 486, 494 ] ], "normalized": [] }, { "id": "PMID-7964616_T37", "type": "Entity", "text": [ "promoter" ], "offsets": [ [ 514, 522 ] ], "normalized": [] }, { "id": "PMID-7964616_T41", "type": "Entity", "text": [ "cis-acting elements" ], "offsets": [ [ 817, 836 ] ], "normalized": [] }, { "id": "PMID-7964616_T44", "type": "Entity", "text": [ "promoter" ], "offsets": [ [ 962, 970 ] ], "normalized": [] }, { "id": "PMID-7964616_T47", "type": "Entity", "text": [ "promoter" ], "offsets": [ [ 1185, 1193 ] ], "normalized": [] }, { "id": "PMID-7964616_T51", "type": "Entity", "text": [ "promoter" ], "offsets": [ [ 1624, 1632 ] ], "normalized": [] }, { "id": "PMID-7964616_T52", "type": "Entity", "text": [ "promoter" ], "offsets": [ [ 1742, 1750 ] ], "normalized": [] }, { "id": "PMID-7964616_T55", "type": "Entity", "text": [ "promoter" ], "offsets": [ [ 1990, 1998 ] ], "normalized": [] } ]

[ { "id": "PMID-7964616_E1", "type": "Binding", "trigger": { "text": [ "binding" ], "offsets": [ [ 4, 11 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "PMID-7964616_T2" } ] }, { "id": "PMID-7964616_E2", "type": "Positive_regulation", "trigger": { "text": [ "trans-activates" ], "offsets": [ [ 336, 351 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "PMID-7964616_T8" }, { "role": "Cause", "ref_id": "PMID-7964616_T6" } ] }, { "id": "PMID-7964616_E3", "type": "Positive_regulation", "trigger": { "text": [ "trans-activates" ], "offsets": [ [ 336, 351 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "PMID-7964616_T10" }, { "role": "Cause", "ref_id": "PMID-7964616_T6" } ] }, { "id": "PMID-7964616_E4", "type": "Positive_regulation", "trigger": { "text": [ "trans-activates" ], "offsets": [ [ 336, 351 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "PMID-7964616_T7" }, { "role": "Cause", "ref_id": "PMID-7964616_T6" } ] }, { "id": "PMID-7964616_E5", "type": "Positive_regulation", "trigger": { "text": [ "trans-activates" ], "offsets": [ [ 336, 351 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "PMID-7964616_T12" }, { "role": "Cause", "ref_id": "PMID-7964616_T6" } ] }, { "id": "PMID-7964616_E6", "type": "Positive_regulation", "trigger": { "text": [ "Trans-activation" ], "offsets": [ [ 458, 474 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "PMID-7964616_T13" }, { "role": "Site", "ref_id": "PMID-7964616_T36" } ] }, { "id": "PMID-7964616_E7", "type": "Positive_regulation", "trigger": { "text": [ "Trans-activation" ], "offsets": [ [ 458, 474 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "PMID-7964616_T14" }, { "role": "Site", "ref_id": "PMID-7964616_T37" } ] }, { "id": "PMID-7964616_E8", "type": "Positive_regulation", "trigger": { "text": [ "mediated" ], "offsets": [ [ 581, 589 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "PMID-7964616_E6" } ] }, { "id": "PMID-7964616_E9", "type": "Positive_regulation", "trigger": { "text": [ "mediated" ], "offsets": [ [ 581, 589 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "PMID-7964616_E7" } ] }, { "id": "PMID-7964616_E10", "type": "Positive_regulation", "trigger": { "text": [ "trans-activate" ], "offsets": [ [ 712, 726 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "PMID-7964616_E11" }, { "role": "Cause", "ref_id": "PMID-7964616_T16" } ] }, { "id": "PMID-7964616_E11", "type": "Gene_expression", "trigger": { "text": [ "expression" ], "offsets": [ [ 731, 741 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "PMID-7964616_T17" } ] }, { "id": "PMID-7964616_E12", "type": "Positive_regulation", "trigger": { "text": [ "mediates" ], "offsets": [ [ 878, 886 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "PMID-7964616_T18" }, { "role": "Cause", "ref_id": "PMID-7964616_T19" }, { "role": "Site", "ref_id": "PMID-7964616_T41" } ] }, { "id": "PMID-7964616_E13", "type": "Positive_regulation", "trigger": { "text": [ "trans-activates" ], "offsets": [ [ 938, 953 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "PMID-7964616_T21" }, { "role": "Cause", "ref_id": "PMID-7964616_E14" }, { "role": "Site", "ref_id": "PMID-7964616_T44" } ] }, { "id": "PMID-7964616_E14", "type": "Binding", "trigger": { "text": [ "interactions" ], "offsets": [ [ 990, 1002 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "PMID-7964616_T20" } ] }, { "id": "PMID-7964616_E15", "type": "Binding", "trigger": { "text": [ "binding" ], "offsets": [ [ 1159, 1166 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "PMID-7964616_T23" }, { "role": "Site", "ref_id": "PMID-7964616_T47" } ] }, { "id": "PMID-7964616_E16", "type": "Binding", "trigger": { "text": [ "interaction" ], "offsets": [ [ 1357, 1368 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "PMID-7964616_T24" } ] }, { "id": "PMID-7964616_E17", "type": "Binding", "trigger": { "text": [ "interactions" ], "offsets": [ [ 1412, 1424 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "PMID-7964616_T24" } ] }, { "id": "PMID-7964616_E18", "type": "Binding", "trigger": { "text": [ "binding" ], "offsets": [ [ 1594, 1601 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "PMID-7964616_T27" }, { "role": "Theme", "ref_id": "PMID-7964616_T28" }, { "role": "Site", "ref_id": "PMID-7964616_T51" } ] }, { "id": "PMID-7964616_E19", "type": "Binding", "trigger": { "text": [ "binding" ], "offsets": [ [ 1751, 1758 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "PMID-7964616_T29" }, { "role": "Site", "ref_id": "PMID-7964616_T52" } ] }, { "id": "PMID-7964616_E20", "type": "Binding", "trigger": { "text": [ "bound" ], "offsets": [ [ 1973, 1978 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "PMID-7964616_T32" }, { "role": "Site", "ref_id": "PMID-7964616_T55" } ] } ]

[ { "id": "PMID-7964616_1", "entity_ids": [ "PMID-7964616_T12", "PMID-7964616_T11" ] }, { "id": "PMID-7964616_2", "entity_ids": [ "PMID-7964616_T10", "PMID-7964616_T9" ] }, { "id": "PMID-7964616_3", "entity_ids": [ "PMID-7964616_T2", "PMID-7964616_T1" ] }, { "id": "PMID-7964616_4", "entity_ids": [ "PMID-7964616_T4", "PMID-7964616_T5" ] } ]

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[ { "id": "PMID-7966569__text", "type": "abstract", "text": [ "Enhanced responsiveness to nuclear factor kappa B contributes to the unique phenotype of simian immunodeficiency virus variant SIVsmmPBj14. \nInfection with a variant of simian immunodeficiency virus, SIVsmmPBj14, leads to severe acute disease in macaques. This study was designed to investigate the functional significance of previously described mutations in the viral long terminal repeat (LTR) and to elucidate their contribution to the unique phenotype of SIVsmmPBj14. LTR-directed transcription was measured by using luciferase reporter constructs that were transiently transfected into cultured cells. In a wide range of cell types, the basal transcriptional activity of the LTR from SIVsmmPBj14 was found to be 2- to 4.5-fold higher than that of an LTR from a non-acutely pathogenic strain. These LTRs differ by five point mutations and a 22-bp duplication in SIVsmmPBj14, which includes a nuclear factor kappa B (NF kappa B) site. Transcriptional differences between these LTRs were further enhanced by two- to threefold upon treatment of cells with phorbol ester or tumor necrosis factor alpha or by cotransfection with plasmids expressing NF kappa B subunits. Mutagenesis studies, and the use of a reporter construct containing an enhancerless promoter, indicate that these transcriptional effects are due principally to the 22-bp sequence duplication and the NF kappa B site contained within it. Finally, infectious virus stocks that were isogenic except for the LTR were generated. The LTR from SIVsmmPBj14 was found to confer an increase in the kinetics of virus replication in cultured cells. Inclusion of this LTR in recombinant SIVs also resulted in a two- to threefold rise in the extent of cellular proliferation that was induced in quiescent simian peripheral blood mononuclear cells. These studies are consistent with the hypothesis that LTR mutations assist SIVsmmPBj14 in responding efficiently to cellular stimulation and allow it to replicate to high titers during the acute phase of viral infection. " ], "offsets": [ [ 0, 2025 ] ] } ]

[ { "id": "PMID-7966569_T1", "type": "Protein", "text": [ "tumor necrosis factor alpha" ], "offsets": [ [ 1075, 1102 ] ], "normalized": [] } ]

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[ { "id": "PMID-7969146__text", "type": "abstract", "text": [ "Identification of a region which directs the monocytic activity of the colony-stimulating factor 1 (macrophage colony-stimulating factor) receptor promoter and binds PEBP2/CBF (AML1). \nThe receptor for the macrophage colony-stimulating factor (or colony-stimulating factor 1 [CSF-1]) is expressed from different promoters in monocytic cells and placental trophoblasts. We have demonstrated that the monocyte-specific expression of the CSF-1 receptor is regulated at the level of transcription by a tissue-specific promoter whose activity is stimulated by the monocyte/B-cell-specific transcription factor PU.1 (D.-E.Zhang, C.J.Hetherington, H.-M.Chen, and D.G.Tenen, Mol.Cell. Biol.14:373-381, 1994). Here we report that the tissue specificity of this promoter is also mediated by sequences in a region II (bp -88 to - 59), which lies 10 bp upstream from the PU.1-binding site. When analyzed by DNase footprinting, region II was protected preferentially in monocytic cells. Electrophoretic mobility shift assays confirmed that region II interacts specifically with nuclear proteins from monocytic cells. Two gel shift complexes (Mono A and Mono B) were formed with separate sequence elements within this region. Competition and supershift experiments indicate that Mono B contains a member of the polyomavirus enhancer-binding protein 2/core-binding factor (PEBP2/CBF) family, which includes the AML1 gene product, while Mono A is a distinct complex preferentially expressed in monocytic cells. Promoter constructs with mutations in these sequence elements were no longer expressed specifically in monocytes. Furthermore, multimerized region II sequence elements enhanced the activity of a heterologous thymidine kinase promoter in monocytic cells but not other cell types tested. These results indicate that the monocyte/B-cell-specific transcription factor PU.1 and the Mono A and Mono B protein complexes act in concert to regulate monocyte-specific transcription of the CSF-1 receptor. " ], "offsets": [ [ 0, 1990 ] ] } ]

[ { "id": "PMID-7969146_T1", "type": "Protein", "text": [ "colony-stimulating factor 1 (macrophage colony-stimulating factor) receptor" ], "offsets": [ [ 71, 146 ] ], "normalized": [] }, { "id": "PMID-7969146_T2", "type": "Protein", "text": [ "AML1" ], "offsets": [ [ 177, 181 ] ], "normalized": [] }, { "id": "PMID-7969146_T3", "type": "Protein", "text": [ "macrophage colony-stimulating factor" ], "offsets": [ [ 206, 242 ] ], "normalized": [] }, { "id": "PMID-7969146_T4", "type": "Protein", "text": [ "colony-stimulating factor 1" ], "offsets": [ [ 247, 274 ] ], "normalized": [] }, { "id": "PMID-7969146_T5", "type": "Protein", "text": [ "CSF-1" ], "offsets": [ [ 276, 281 ] ], "normalized": [] }, { "id": "PMID-7969146_T6", "type": "Protein", "text": [ "CSF-1 receptor" ], "offsets": [ [ 435, 449 ] ], "normalized": [] }, { "id": "PMID-7969146_T7", "type": "Protein", "text": [ "PU.1" ], "offsets": [ [ 605, 609 ] ], "normalized": [] }, { "id": "PMID-7969146_T8", "type": "Protein", "text": [ "PU.1" ], "offsets": [ [ 859, 863 ] ], "normalized": [] }, { "id": "PMID-7969146_T9", "type": "Protein", "text": [ "AML1" ], "offsets": [ [ 1396, 1400 ] ], "normalized": [] }, { "id": "PMID-7969146_T10", "type": "Protein", "text": [ "PU.1" ], "offsets": [ [ 1859, 1863 ] ], "normalized": [] }, { "id": "PMID-7969146_T11", "type": "Protein", "text": [ "CSF-1 receptor" ], "offsets": [ [ 1974, 1988 ] ], "normalized": [] }, { "id": "PMID-7969146_T13", "type": "Entity", "text": [ "promoter" ], "offsets": [ [ 147, 155 ] ], "normalized": [] } ]

[ { "id": "PMID-7969146_E1", "type": "Regulation", "trigger": { "text": [ "directs" ], "offsets": [ [ 33, 40 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "PMID-7969146_T1" }, { "role": "Site", "ref_id": "PMID-7969146_T13" } ] }, { "id": "PMID-7969146_E2", "type": "Binding", "trigger": { "text": [ "binds" ], "offsets": [ [ 160, 165 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "PMID-7969146_T2" } ] }, { "id": "PMID-7969146_E3", "type": "Gene_expression", "trigger": { "text": [ "expression" ], "offsets": [ [ 417, 427 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "PMID-7969146_T6" } ] }, { "id": "PMID-7969146_E4", "type": "Regulation", "trigger": { "text": [ "regulated" ], "offsets": [ [ 453, 462 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "PMID-7969146_E3" } ] }, { "id": "PMID-7969146_E5", "type": "Binding", "trigger": { "text": [ "contains" ], "offsets": [ [ 1272, 1280 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "PMID-7969146_T9" } ] }, { "id": "PMID-7969146_E6", "type": "Regulation", "trigger": { "text": [ "in concert to regulate" ], "offsets": [ [ 1912, 1934 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "PMID-7969146_E7" }, { "role": "Cause", "ref_id": "PMID-7969146_T10" } ] }, { "id": "PMID-7969146_E7", "type": "Transcription", "trigger": { "text": [ "transcription" ], "offsets": [ [ 1953, 1966 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "PMID-7969146_T11" } ] } ]

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[ { "id": "PMID-7969177__text", "type": "abstract", "text": [ "A factor that regulates the class II major histocompatibility complex gene DPA is a member of a subfamily of zinc finger proteins that includes a Drosophila developmental control protein. \nA novel DNA sequence element termed the J element involved in the regulated expression of class II major histocompatibility complex genes was recently described. To study this element and its role in class II gene regulation further, a cDNA library was screened with oligonucleotide probes containing both the S element and the nearby J element of the human DPA gene. Several DNA clones were obtained by this procedure, one of which, clone 18, is reported and characterized here. It encodes a protein predicted to contain 688 amino acid residues, including 11 zinc finger motifs of the C2H2 type in the C-terminal region, that are Kruppel-like in the conservation of the H/C link sequence connecting them. The 160 N-terminal amino acids in the nonfinger region of clone 18 are highly homologous with similar regions of several other human, mouse, and Drosophila sequences, defining a subfamily of Kruppel-like zinc finger proteins termed TAB (tramtrack [ttk]-associated box) here. One of the Drosophila sequences, ttk, is a developmental control gene, while a second does not contain a zinc finger region but encodes a structure important in oocyte development. An acidic activation domain is located between the N-terminal conserved region of clone 18 and its zinc fingers. This protein appears to require both the S and J elements, which are separated by 10 bp for optimal binding. Antisense cDNA to clone 18 inhibited the expression of a reporter construct containing the DPA promoter, indicating its functional importance in the expression of this class II gene. " ], "offsets": [ [ 0, 1756 ] ] } ]

[ { "id": "PMID-7969177_T1", "type": "Protein", "text": [ "DPA" ], "offsets": [ [ 75, 78 ] ], "normalized": [] }, { "id": "PMID-7969177_T2", "type": "Protein", "text": [ "DPA" ], "offsets": [ [ 547, 550 ] ], "normalized": [] }, { "id": "PMID-7969177_T3", "type": "Protein", "text": [ "DPA" ], "offsets": [ [ 1664, 1667 ] ], "normalized": [] } ]

[ { "id": "PMID-7969177_E1", "type": "Regulation", "trigger": { "text": [ "regulates" ], "offsets": [ [ 14, 23 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "PMID-7969177_T1" } ] }, { "id": "PMID-7969177_E2", "type": "Positive_regulation", "trigger": { "text": [ "importance" ], "offsets": [ [ 1704, 1714 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "PMID-7969177_E3" } ] }, { "id": "PMID-7969177_E3", "type": "Gene_expression", "trigger": { "text": [ "expression" ], "offsets": [ [ 1722, 1732 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "PMID-7969177_T1" } ] } ]

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[ { "id": "PMID-7981603__text", "type": "abstract", "text": [ "Glucocorticoid-induced apoptosis of lymphoid cells. \nThe induction of cell death in lymphoid cells by glucocorticoids is one of the earliest and most thoroughly studied models of apoptosis. Although the exact mechanism by which apoptosis occurs in lymphocytes is unknown many biochemical and molecular changes have been shown to occur in these cells in response to glucocorticoids. The role of chromatin degradation and endonucleases in the apoptotic process has been closely studied, as well as the involvement of several oncogenes in glucocorticoid-induced cell lysis. In addition, the clinical importance of glucocorticoid-induced apoptosis in the treatment of lymphoid neoplasms has recently received increased attention. " ], "offsets": [ [ 0, 726 ] ] } ]

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[ { "id": "PMID-7983701__text", "type": "abstract", "text": [ "Inhibition of human immunodeficiency virus type 1 replication by a Tat-activated, transduced interferon gene: targeted expression to human immunodeficiency virus type 1-infected cells. \nWe have examined the feasibility of using interferon (IFN) gene transfer as a novel approach to anti-human immunodeficiency virus type 1 (HIV-1) therapy in this study. To limit expression of a transduced HIV-1 long terminal repeat (LTR)-IFNA2 (the new approved nomenclature for IFN genes is used throughout this article) hybrid gene to the HIV-1-infected cells, HIV-1 LTR was modified. Deletion of the NF-kappa B elements of the HIV-1 LTR significantly inhibited Tat-mediated transactivation in T-cell lines, as well as in a monocyte line, U937. Replacement of the NF-kappa B elements in the HIV-1 LTR by a DNA fragment derived from the 5'-flanking region of IFN-stimulated gene 15 (ISG15), containing the IFN-stimulated response element, partially restored Tat-mediated activation of LTR in T cells as well as in monocytes. Insertion of this chimeric promoter (ISG15 LTR) upstream of the human IFNA2 gene directed high levels of IFN synthesis in Tat-expressing cells, while this promoter was not responsive to tumor necrosis factor alpha-mediated activation. ISG15-LTR-IFN hybrid gene inserted into the retrovirus vector was transduced into Jurkat and U937 cells. Selected transfected clones produced low levels of IFN A (IFNA) constitutively, and their abilities to express interleukin-2 and interleukin-2 receptor upon stimulation with phytohemagglutinin and phorbol myristate acetate were retained. Enhancement of IFNA synthesis observed upon HIV-1 infection resulted in significant inhibition of HIV-1 replication for a period of at least 30 days. Virus isolated from IFNA-producing cells was able to replicate in the U937 cells but did not replicate efficiently in U937 cells transduced with the IFNA gene. These results suggest that targeting IFN synthesis to HIV-1-infected cells is an attainable goal and that autocrine IFN synthesis results in a long-lasting and permanent suppression of HIV-1 replication. " ], "offsets": [ [ 0, 2103 ] ] } ]

[ { "id": "PMID-7983701_T1", "type": "Protein", "text": [ "Tat" ], "offsets": [ [ 67, 70 ] ], "normalized": [] }, { "id": "PMID-7983701_T2", "type": "Protein", "text": [ "Tat" ], "offsets": [ [ 649, 652 ] ], "normalized": [] }, { "id": "PMID-7983701_T3", "type": "Protein", "text": [ "Tat" ], "offsets": [ [ 944, 947 ] ], "normalized": [] }, { "id": "PMID-7983701_T4", "type": "Protein", "text": [ "IFNA2" ], "offsets": [ [ 1081, 1086 ] ], "normalized": [] }, { "id": "PMID-7983701_T5", "type": "Protein", "text": [ "Tat" ], "offsets": [ [ 1133, 1136 ] ], "normalized": [] }, { "id": "PMID-7983701_T6", "type": "Protein", "text": [ "tumor necrosis factor alpha" ], "offsets": [ [ 1197, 1224 ] ], "normalized": [] }, { "id": "PMID-7983701_T7", "type": "Protein", "text": [ "IFN A" ], "offsets": [ [ 1402, 1407 ] ], "normalized": [] }, { "id": "PMID-7983701_T8", "type": "Protein", "text": [ "IFNA" ], "offsets": [ [ 1409, 1413 ] ], "normalized": [] }, { "id": "PMID-7983701_T9", "type": "Protein", "text": [ "interleukin-2" ], "offsets": [ [ 1462, 1475 ] ], "normalized": [] }, { "id": "PMID-7983701_T10", "type": "Protein", "text": [ "phytohemagglutinin" ], "offsets": [ [ 1525, 1543 ] ], "normalized": [] }, { "id": "PMID-7983701_T11", "type": "Protein", "text": [ "IFNA" ], "offsets": [ [ 1604, 1608 ] ], "normalized": [] }, { "id": "PMID-7983701_T12", "type": "Protein", "text": [ "IFNA" ], "offsets": [ [ 1759, 1763 ] ], "normalized": [] }, { "id": "PMID-7983701_T13", "type": "Protein", "text": [ "IFNA" ], "offsets": [ [ 1888, 1892 ] ], "normalized": [] } ]

[ { "id": "PMID-7983701_E1", "type": "Gene_expression", "trigger": { "text": [ "expressing" ], "offsets": [ [ 1137, 1147 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "PMID-7983701_T5" } ] }, { "id": "PMID-7983701_E2", "type": "Gene_expression", "trigger": { "text": [ "produced" ], "offsets": [ [ 1379, 1387 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "PMID-7983701_T8" } ] }, { "id": "PMID-7983701_E3", "type": "Gene_expression", "trigger": { "text": [ "express" ], "offsets": [ [ 1454, 1461 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "PMID-7983701_T9" } ] }, { "id": "PMID-7983701_E4", "type": "Positive_regulation", "trigger": { "text": [ "stimulation" ], "offsets": [ [ 1508, 1519 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "PMID-7983701_E3" }, { "role": "Cause", "ref_id": "PMID-7983701_T10" } ] }, { "id": "PMID-7983701_E5", "type": "Positive_regulation", "trigger": { "text": [ "stimulation" ], "offsets": [ [ 1508, 1519 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "PMID-7983701_E3" } ] }, { "id": "PMID-7983701_E6", "type": "Positive_regulation", "trigger": { "text": [ "Enhancement" ], "offsets": [ [ 1589, 1600 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "PMID-7983701_E7" } ] }, { "id": "PMID-7983701_E7", "type": "Gene_expression", "trigger": { "text": [ "synthesis" ], "offsets": [ [ 1609, 1618 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "PMID-7983701_T11" } ] }, { "id": "PMID-7983701_E8", "type": "Gene_expression", "trigger": { "text": [ "producing" ], "offsets": [ [ 1764, 1773 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "PMID-7983701_T12" } ] } ]

[ { "id": "PMID-7983701_1", "entity_ids": [ "PMID-7983701_T8", "PMID-7983701_T7" ] } ]

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[ { "id": "PMID-7986199__text", "type": "abstract", "text": [ "Pyrrolidine dithiocarbamate, a potent inhibitor of nuclear factor kappa B (NF-kappa B) activation, prevents apoptosis in human promyelocytic leukemia HL-60 cells and thymocytes. \nWe examined the effect of pyrrolidine dithiocarbamate (PDTC), which potently blocks the activation of nuclear factor kappa B (NF-kappa B), on the induction of apoptosis by a variety of agents. Treatment of a human promyelocytic leukemia cell line, HL-60, with 10 micrograms/mL etoposide or 2 microM 1-beta-D-arabinofuranosylcytosine induced NF-kappa B activation within 1 hr and subsequently caused apoptosis within 3-4 hr. The simultaneous addition of 50-500 microM PDTC with these agents blocked NF-kappa B activation and completely abrogated both morphologically apoptotic changes and internucleosomal DNA fragmentation for up to 6 hr. However, PDTC failed to inhibit the endonuclease activity contained in the whole cell lysates. The inhibitory effect of PDTC was also observed in etoposide- and dexamethasone-induced apoptosis in human thymocytes at a concentration of 1-10 microM. Since PDTC has both antioxidant and metal-ion chelating activities, we tested the effects of N-acetyl-L-cysteine (NAC) (antioxidant) or o-phenanthroline (OP) (metal-ion chelator) on the induction of apoptosis. Pretreatment of HL-60 cells or thymocytes with 100-500 microM OP for 2 hr, but not 10-60 mM NAC, suppressed subsequent occurrence of apoptosis induced by etoposide. These results suggest that the activation of NF-kappa B plays an important role in the apoptotic process of human hematopoietic cells. " ], "offsets": [ [ 0, 1576 ] ] } ]

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[ { "id": "PMID-7989745__text", "type": "abstract", "text": [ "Differential regulation of proto-oncogenes c-jun and c-fos in T lymphocytes activated through CD28. \nThe T cell surface molecule CD28 binds to ligands on accessory cells and APCs, playing an important costimulatory role in the response of T cells to Ags. Our knowledge of the intracellular signaling pathways coupled to this receptor is incomplete. In addition to activation of phospholipase C gamma 1, ligation of this receptor also seems to activate a calcium-independent, CD28-specific pathway. In this paper, we report that cross-linking of CD28 (but not CD2, CD5, LFA-1, or CD7) leads to an elevation of c-jun mRNA, with only minimal activation of c-fos expression. CD28-dependent induction of c-jun expression requires protein tyrosine kinase activity, but does not depend on activation of a phorbol ester-responsive protein kinase C or elevation of cytosolic calcium. Furthermore, CD28-dependent elevation of c-jun mRNA does not appear to be mediated at the level of mRNA stability. A mechanism is suggested whereby expression of c-jun and junB, in the absence of members of the fos family, can prevent inappropriate activation of T cells caused by ligation of CD28 in the absence of a specific antigenic stimulus. " ], "offsets": [ [ 0, 1222 ] ] } ]

[ { "id": "PMID-7989745_T1", "type": "Protein", "text": [ "c-jun" ], "offsets": [ [ 43, 48 ] ], "normalized": [] }, { "id": "PMID-7989745_T2", "type": "Protein", "text": [ "c-fos" ], "offsets": [ [ 53, 58 ] ], "normalized": [] }, { "id": "PMID-7989745_T3", "type": "Protein", "text": [ "CD28" ], "offsets": [ [ 94, 98 ] ], "normalized": [] }, { "id": "PMID-7989745_T4", "type": "Protein", "text": [ "CD28" ], "offsets": [ [ 129, 133 ] ], "normalized": [] }, { "id": "PMID-7989745_T5", "type": "Protein", "text": [ "phospholipase C gamma 1" ], "offsets": [ [ 378, 401 ] ], "normalized": [] }, { "id": "PMID-7989745_T6", "type": "Protein", "text": [ "CD28" ], "offsets": [ [ 475, 479 ] ], "normalized": [] }, { "id": "PMID-7989745_T7", "type": "Protein", "text": [ "CD28" ], "offsets": [ [ 545, 549 ] ], "normalized": [] }, { "id": "PMID-7989745_T8", "type": "Protein", "text": [ "CD5" ], "offsets": [ [ 564, 567 ] ], "normalized": [] }, { "id": "PMID-7989745_T9", "type": "Protein", "text": [ "CD7" ], "offsets": [ [ 579, 582 ] ], "normalized": [] }, { "id": "PMID-7989745_T10", "type": "Protein", "text": [ "c-jun" ], "offsets": [ [ 609, 614 ] ], "normalized": [] }, { "id": "PMID-7989745_T11", "type": "Protein", "text": [ "c-fos" ], "offsets": [ [ 653, 658 ] ], "normalized": [] }, { "id": "PMID-7989745_T12", "type": "Protein", "text": [ "CD28" ], "offsets": [ [ 671, 675 ] ], "normalized": [] }, { "id": "PMID-7989745_T13", "type": "Protein", "text": [ "c-jun" ], "offsets": [ [ 699, 704 ] ], "normalized": [] }, { "id": "PMID-7989745_T14", "type": "Protein", "text": [ "CD28" ], "offsets": [ [ 888, 892 ] ], "normalized": [] }, { "id": "PMID-7989745_T15", "type": "Protein", "text": [ "c-jun" ], "offsets": [ [ 916, 921 ] ], "normalized": [] }, { "id": "PMID-7989745_T16", "type": "Protein", "text": [ "c-jun" ], "offsets": [ [ 1037, 1042 ] ], "normalized": [] }, { "id": "PMID-7989745_T17", "type": "Protein", "text": [ "junB" ], "offsets": [ [ 1047, 1051 ] ], "normalized": [] }, { "id": "PMID-7989745_T18", "type": "Protein", "text": [ "CD28" ], "offsets": [ [ 1168, 1172 ] ], "normalized": [] } ]

[ { "id": "PMID-7989745_E1", "type": "Regulation", "trigger": { "text": [ "regulation" ], "offsets": [ [ 13, 23 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "PMID-7989745_T2" } ] }, { "id": "PMID-7989745_E2", "type": "Regulation", "trigger": { "text": [ "regulation" ], "offsets": [ [ 13, 23 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "PMID-7989745_T1" } ] }, { "id": "PMID-7989745_E3", "type": "Binding", "trigger": { "text": [ "binds" ], "offsets": [ [ 134, 139 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "PMID-7989745_T4" } ] }, { "id": "PMID-7989745_E4", "type": "Positive_regulation", "trigger": { "text": [ "activation" ], "offsets": [ [ 364, 374 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "PMID-7989745_T5" }, { "role": "Cause", "ref_id": "PMID-7989745_E5" } ] }, { "id": "PMID-7989745_E5", "type": "Binding", "trigger": { "text": [ "ligation" ], "offsets": [ [ 403, 411 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "PMID-7989745_T6" } ] }, { "id": "PMID-7989745_E6", "type": "Binding", "trigger": { "text": [ "cross-linking" ], "offsets": [ [ 528, 541 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "PMID-7989745_T9" } ] }, { "id": "PMID-7989745_E7", "type": "Binding", "trigger": { "text": [ "cross-linking" ], "offsets": [ [ 528, 541 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "PMID-7989745_T8" } ] }, { "id": "PMID-7989745_E8", "type": "Binding", "trigger": { "text": [ "cross-linking" ], "offsets": [ [ 528, 541 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "PMID-7989745_T7" } ] }, { "id": "PMID-7989745_E9", "type": "Positive_regulation", "trigger": { "text": [ "leads" ], "offsets": [ [ 584, 589 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "PMID-7989745_E13" }, { "role": "Cause", "ref_id": "PMID-7989745_E7" } ] }, { "id": "PMID-7989745_E10", "type": "Positive_regulation", "trigger": { "text": [ "leads" ], "offsets": [ [ 584, 589 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "PMID-7989745_E13" }, { "role": "Cause", "ref_id": "PMID-7989745_E8" } ] }, { "id": "PMID-7989745_E11", "type": "Positive_regulation", "trigger": { "text": [ "leads" ], "offsets": [ [ 584, 589 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "PMID-7989745_E13" } ] }, { "id": "PMID-7989745_E12", "type": "Positive_regulation", "trigger": { "text": [ "leads" ], "offsets": [ [ 584, 589 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "PMID-7989745_E13" }, { "role": "Cause", "ref_id": "PMID-7989745_E6" } ] }, { "id": "PMID-7989745_E13", "type": "Positive_regulation", "trigger": { "text": [ "elevation" ], "offsets": [ [ 596, 605 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "PMID-7989745_T10" } ] }, { "id": "PMID-7989745_E14", "type": "Positive_regulation", "trigger": { "text": [ "activation" ], "offsets": [ [ 639, 649 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "PMID-7989745_E15" }, { "role": "Cause", "ref_id": "PMID-7989745_E8" } ] }, { "id": "PMID-7989745_E15", "type": "Gene_expression", "trigger": { "text": [ "expression" ], "offsets": [ [ 659, 669 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "PMID-7989745_T11" } ] }, { "id": "PMID-7989745_E16", "type": "Positive_regulation", "trigger": { "text": [ "induction" ], "offsets": [ [ 686, 695 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "PMID-7989745_E17" }, { "role": "Cause", "ref_id": "PMID-7989745_T12" } ] }, { "id": "PMID-7989745_E17", "type": "Gene_expression", "trigger": { "text": [ "expression" ], "offsets": [ [ 705, 715 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "PMID-7989745_T13" } ] }, { "id": "PMID-7989745_E18", "type": "Positive_regulation", "trigger": { "text": [ "requires" ], "offsets": [ [ 716, 724 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "PMID-7989745_E16" } ] }, { "id": "PMID-7989745_E19", "type": "Regulation", "trigger": { "text": [ "depend" ], "offsets": [ [ 772, 778 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "PMID-7989745_E16" } ] }, { "id": "PMID-7989745_E20", "type": "Positive_regulation", "trigger": { "text": [ "elevation" ], "offsets": [ [ 903, 912 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "PMID-7989745_T15" }, { "role": "Cause", "ref_id": "PMID-7989745_T14" } ] }, { "id": "PMID-7989745_E21", "type": "Positive_regulation", "trigger": { "text": [ "mediated" ], "offsets": [ [ 949, 957 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "PMID-7989745_E20" }, { "role": "Cause", "ref_id": "PMID-7989745_E22" } ] }, { "id": "PMID-7989745_E22", "type": "Regulation", "trigger": { "text": [ "stability" ], "offsets": [ [ 979, 988 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "PMID-7989745_T15" } ] }, { "id": "PMID-7989745_E23", "type": "Gene_expression", "trigger": { "text": [ "expression" ], "offsets": [ [ 1023, 1033 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "PMID-7989745_T17" } ] }, { "id": "PMID-7989745_E24", "type": "Gene_expression", "trigger": { "text": [ "expression" ], "offsets": [ [ 1023, 1033 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "PMID-7989745_T16" } ] }, { "id": "PMID-7989745_E25", "type": "Binding", "trigger": { "text": [ "ligation" ], "offsets": [ [ 1156, 1164 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "PMID-7989745_T18" } ] } ]

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[ { "id": "PMID-7998962__text", "type": "abstract", "text": [ "Constitutive nuclear NF-kappa B in cells of the monocyte lineage. \nIn monocytes, the nuclear factor NF-kappa B has been invoked as an important transcription factor in the expression of cytokine genes, of cell-surface receptors and in the expression of human immunodeficiency virus. In such cells, DNA binding activity of NF-kappa B can be detected without intentional stimulation. In our studies, cells of the human monocytic line Mono Mac 6, cultured in medium containing fetal-calf serum and low levels of lipopolysaccharide (LPS), also exhibit such 'constitutive' NF-kappa B, as demonstrated by mobility-shift analysis of nuclear extracts. This nuclear NF-kappa B was still present when contaminant LPS was removed by ultrafiltration and when serum was omitted. Protein-DNA complexes of constitutive NF-kappa B are similar in mobility to the LPS-induced NF-kappa B and both are recognized by an antibody specific to the p50 subunit of NF-kappa B. By contrast, treatment of cells with pyrrolidine dithiocarbamate (PDTC) will only block LPS-induced NF-kappa B, but not the constitutive binding protein. Using LPS-free and serum-free conditions, constitutive NF-kappa B can be detected in different cell lines of the monocytic lineage (HL60, U937, THP-1, Mono Mac 1 and Mono Mac 6), but not in Molt 4 T cells or K562 stem cells. When ordered according to stage of maturation, the amount of constitutive NF-kappa B was not increased in more mature cell lines. Furthermore, when inducing differentiation in Mono Mac 6 cells, with vitamin D3, no change in constitutive or inducible NF-kappa B can be detected. Analysis of primary cells revealed substantial constitutive NF-kappa B-binding activity in blood monocytes, pleural macrophages and alveolar macrophages. The constitutive NF-kappa B appears to be functionally active, since a low level of tumour necrosis factor (TNF) transcript is detectable in monocytes, and this level can be increased by blocking transcript degradation using cycloheximide. The level of constitutive NF-kappa B in these cells is variable and is frequently found to be lower in the more mature macrophages. Constitutive NF-kappa B was not maintained by autocrine action of cytokines TNF, interleukin 6, interleukin 10, granulocyte-macrophage colony-stimulating factor or macrophage colony-stimulating factor, since neutralizing antibodies did not reduce constitutive DNA-binding activity. Furthermore, blockade of prostaglandin or leukotriene biosynthesis did not affect constitutive NF-kappa B. (ABSTRACT TRUNCATED AT 400 WORDS) " ], "offsets": [ [ 0, 2557 ] ] } ]

[ { "id": "PMID-7998962_T1", "type": "Protein", "text": [ "p50 subunit" ], "offsets": [ [ 924, 935 ] ], "normalized": [] }, { "id": "PMID-7998962_T2", "type": "Protein", "text": [ "interleukin 6" ], "offsets": [ [ 2215, 2228 ] ], "normalized": [] }, { "id": "PMID-7998962_T3", "type": "Protein", "text": [ "interleukin 10" ], "offsets": [ [ 2230, 2244 ] ], "normalized": [] }, { "id": "PMID-7998962_T4", "type": "Protein", "text": [ "granulocyte-macrophage colony-stimulating factor" ], "offsets": [ [ 2246, 2294 ] ], "normalized": [] }, { "id": "PMID-7998962_T5", "type": "Protein", "text": [ "macrophage colony-stimulating factor" ], "offsets": [ [ 2298, 2334 ] ], "normalized": [] } ]

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[ { "id": "PMID-8011280__text", "type": "abstract", "text": [ "Function and activation of NF-kappa B in the immune system. \nNF-kappa B is a ubiquitous transcription factor. Nevertheless, its properties seem to be most extensively exploited in cells of the immune system. Among these properties are NF-kappa B's rapid posttranslational activation in response to many pathogenic signals, its direct participation in cytoplasmic/nuclear signaling, and its potency to activate transcription of a great variety of genes encoding immunologically relevant proteins. In vertebrates, five distinct DNA binding subunits are currently known which might extensively heterodimerize, thereby forming complexes with distinct transcriptional activity, DNA sequence specificity, and cell type- and cell stage-specific distribution. The activity of DNA binding NF-kappa B dimers is tightly controlled by accessory proteins called I kappa B subunits of which there are also five different species currently known in vertebrates. I kappa B proteins inhibit DNA binding and prevent nuclear uptake of NF-kappa B complexes. An exception is the Bcl-3 protein which in addition can function as a transcription activating subunit in th nucleus. Other I kappa B proteins are rather involved in terminating NF-kappa B's activity in the nucleus. The intracellular events that lead to the inactivation of I kappa B, i.e. the activation of NF-kappa B, are complex. They involve phosphorylation and proteolytic reactions and seem to be controlled by the cells' redox status. Interference with the activation or activity of NF-kappa B may be beneficial in suppressing toxic/septic shock, graft-vs-host reactions, acute inflammatory reactions, acute phase response, and radiation damage. The inhibition of NF-kappa B activation by antioxidants and specific protease inhibitors may provide a pharmacological basis for interfering with these acute processes. " ], "offsets": [ [ 0, 1860 ] ] } ]

[ { "id": "PMID-8011280_T1", "type": "Protein", "text": [ "Bcl-3" ], "offsets": [ [ 1058, 1063 ] ], "normalized": [] } ]

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[]

[ { "id": "PMID-8014029__text", "type": "abstract", "text": [ "Increased interleukin 2 transcription in murine lymphocytes by ciprofloxacin. \nThe fluoroquinolone antibiotic, ciprofloxacin (cipro), induces hyperproduction of interleukin 2 (IL-2) and interferon-gamma (IFN-gamma) in stimulated human peripheral blood lymphocytes. In this investigation an enhanced and prolonged IL-2 and IL-2 mRNA response was also detected in both stimulated (T cell mitogens or alloantigens) murine splenocytes and in the stimulated murine T cell line EL-4 in the presence of ciprofloxacin (5-80 micrograms/ml) as compared to control cells without antibiotics. However, in contrast to human lymphocytes, IFN-gamma production was inhibited and IFN-gamma mRNA levels were unaffected at 24 h and only slightly upregulated at 48 and 72 h of culture in murine splenocytes incubated with cipro (20 micrograms/ml). EL-4 cells were transfected with a plasmid containing the IL-2 promoter and enhancer region linked to the chloramphenicol acetyltransferase (CAT) reporter gene. Analysis of CAT activity revealed that cipro enhanced IL-2 gene induction. In addition, EL-4 cells incubated with ciprofloxacin showed an early peak and more activated nuclear factor of activated T cells (NFAT-1) as compared to control cells without antibiotics. Cipro did not affect the nuclear transcription factors AP-1 or NFIL-2A. Taken together, cipro inhibited IFN-gamma synthesis, but enhanced IL-2 production in murine lymphocytes by means of influencing NFAT-1 and causing an increased IL-2 transcription. " ], "offsets": [ [ 0, 1504 ] ] } ]

[ { "id": "PMID-8014029_T1", "type": "Protein", "text": [ "interleukin 2" ], "offsets": [ [ 10, 23 ] ], "normalized": [] }, { "id": "PMID-8014029_T2", "type": "Protein", "text": [ "interleukin 2" ], "offsets": [ [ 161, 174 ] ], "normalized": [] }, { "id": "PMID-8014029_T3", "type": "Protein", "text": [ "IL-2" ], "offsets": [ [ 176, 180 ] ], "normalized": [] }, { "id": "PMID-8014029_T4", "type": "Protein", "text": [ "interferon-gamma" ], "offsets": [ [ 186, 202 ] ], "normalized": [] }, { "id": "PMID-8014029_T5", "type": "Protein", "text": [ "IFN-gamma" ], "offsets": [ [ 204, 213 ] ], "normalized": [] }, { "id": "PMID-8014029_T6", "type": "Protein", "text": [ "IL-2" ], "offsets": [ [ 313, 317 ] ], "normalized": [] }, { "id": "PMID-8014029_T7", "type": "Protein", "text": [ "IL-2" ], "offsets": [ [ 322, 326 ] ], "normalized": [] }, { "id": "PMID-8014029_T8", "type": "Protein", "text": [ "IFN-gamma" ], "offsets": [ [ 624, 633 ] ], "normalized": [] }, { "id": "PMID-8014029_T9", "type": "Protein", "text": [ "IFN-gamma" ], "offsets": [ [ 663, 672 ] ], "normalized": [] }, { "id": "PMID-8014029_T10", "type": "Protein", "text": [ "IL-2" ], "offsets": [ [ 886, 890 ] ], "normalized": [] }, { "id": "PMID-8014029_T11", "type": "Protein", "text": [ "chloramphenicol acetyltransferase" ], "offsets": [ [ 934, 967 ] ], "normalized": [] }, { "id": "PMID-8014029_T12", "type": "Protein", "text": [ "CAT" ], "offsets": [ [ 969, 972 ] ], "normalized": [] }, { "id": "PMID-8014029_T13", "type": "Protein", "text": [ "CAT" ], "offsets": [ [ 1001, 1004 ] ], "normalized": [] }, { "id": "PMID-8014029_T14", "type": "Protein", "text": [ "IL-2" ], "offsets": [ [ 1043, 1047 ] ], "normalized": [] }, { "id": "PMID-8014029_T15", "type": "Protein", "text": [ "NFAT-1" ], "offsets": [ [ 1194, 1200 ] ], "normalized": [] }, { "id": "PMID-8014029_T16", "type": "Protein", "text": [ "NFIL-2A" ], "offsets": [ [ 1315, 1322 ] ], "normalized": [] }, { "id": "PMID-8014029_T17", "type": "Protein", "text": [ "IFN-gamma" ], "offsets": [ [ 1356, 1365 ] ], "normalized": [] }, { "id": "PMID-8014029_T18", "type": "Protein", "text": [ "IL-2" ], "offsets": [ [ 1390, 1394 ] ], "normalized": [] }, { "id": "PMID-8014029_T19", "type": "Protein", "text": [ "NFAT-1" ], "offsets": [ [ 1452, 1458 ] ], "normalized": [] }, { "id": "PMID-8014029_T20", "type": "Protein", "text": [ "IL-2" ], "offsets": [ [ 1484, 1488 ] ], "normalized": [] } ]

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"PMID-8014029_E6", "type": "Gene_expression", "trigger": { "text": [ "production" ], "offsets": [ [ 147, 157 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "PMID-8014029_T5" } ] }, { "id": "PMID-8014029_E7", "type": "Positive_regulation", "trigger": { "text": [ "enhanced and prolonged" ], "offsets": [ [ 290, 312 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "PMID-8014029_E10" } ] }, { "id": "PMID-8014029_E8", "type": "Positive_regulation", "trigger": { "text": [ "enhanced and prolonged" ], "offsets": [ [ 290, 312 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "PMID-8014029_E9" } ] }, { "id": "PMID-8014029_E9", "type": "Regulation", "trigger": { "text": [ "response" ], "offsets": [ [ 332, 340 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "PMID-8014029_T6" } ] }, { "id": "PMID-8014029_E10", "type": "Regulation", "trigger": { "text": [ "response" ], "offsets": [ [ 332, 340 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "PMID-8014029_T7" } ] }, { "id": "PMID-8014029_E11", "type": "Gene_expression", "trigger": { "text": [ "production" ], "offsets": [ [ 634, 644 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "PMID-8014029_T8" } ] }, { "id": "PMID-8014029_E12", "type": "Negative_regulation", "trigger": { "text": [ "inhibited" ], "offsets": [ [ 649, 658 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "PMID-8014029_E11" } ] }, { "id": "PMID-8014029_E13", "type": "Regulation", "trigger": { "text": [ "unaffected" ], "offsets": [ [ 690, 700 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "PMID-8014029_T9" } ] }, { "id": "PMID-8014029_E14", "type": "Positive_regulation", "trigger": { "text": [ "upregulated" ], "offsets": [ [ 727, 738 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "PMID-8014029_T9" } ] }, { "id": "PMID-8014029_E15", "type": "Positive_regulation", "trigger": { "text": [ "enhanced" ], "offsets": [ [ 1034, 1042 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "PMID-8014029_E16" } ] }, { "id": "PMID-8014029_E16", "type": "Gene_expression", "trigger": { "text": [ "induction" ], "offsets": [ [ 1053, 1062 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "PMID-8014029_T14" } ] }, { "id": "PMID-8014029_E17", "type": "Positive_regulation", "trigger": { "text": [ "showed an early peak and more activated" ], "offsets": [ [ 1117, 1156 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "PMID-8014029_T15" } ] }, { "id": "PMID-8014029_E18", "type": "Regulation", "trigger": { "text": [ "affect" ], "offsets": [ [ 1266, 1272 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "PMID-8014029_T16" } ] }, { "id": "PMID-8014029_E19", "type": "Negative_regulation", "trigger": { "text": [ "inhibited" ], "offsets": [ [ 1346, 1355 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "PMID-8014029_E20" } ] }, { "id": "PMID-8014029_E20", "type": "Gene_expression", "trigger": { "text": [ "synthesis" ], "offsets": [ [ 1366, 1375 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "PMID-8014029_T17" } ] }, { "id": "PMID-8014029_E21", "type": "Positive_regulation", "trigger": { "text": [ "enhanced" ], "offsets": [ [ 1381, 1389 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "PMID-8014029_E23" }, { "role": "Cause", "ref_id": "PMID-8014029_E24" } ] }, { "id": "PMID-8014029_E22", "type": "Positive_regulation", "trigger": { "text": [ "enhanced" ], "offsets": [ [ 1381, 1389 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "PMID-8014029_E23" }, { "role": "Cause", "ref_id": "PMID-8014029_E25" } ] }, { "id": "PMID-8014029_E23", "type": "Gene_expression", "trigger": { "text": [ "production" ], "offsets": [ [ 1395, 1405 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "PMID-8014029_T18" } ] }, { "id": "PMID-8014029_E24", "type": "Regulation", "trigger": { "text": [ "influencing" ], "offsets": [ [ 1440, 1451 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "PMID-8014029_T19" } ] }, { "id": "PMID-8014029_E25", "type": "Positive_regulation", "trigger": { "text": [ "causing an increased" ], "offsets": [ [ 1463, 1483 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "PMID-8014029_E26" }, { "role": "Cause", "ref_id": "PMID-8014029_T20" } ] }, { "id": "PMID-8014029_E26", "type": "Transcription", "trigger": { "text": [ "transcription" ], "offsets": [ [ 1489, 1502 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "PMID-8014029_T20" } ] } ]

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[]

[ { "id": "PMID-8015552__text", "type": "abstract", "text": [ "Multiple prolactin-responsive elements mediate G1 and S phase expression of the interferon regulatory factor-1 gene. \nThe interferon regulatory factor-1 (IRF-1) gene is both an immediate-early G1 phase gene and an S phase gene inducible by PRL in rat Nb2 T lymphocytes. To understand the mechanism by which PRL regulates the biphasic expression of IRF-1, we cloned the rat IRF-1 gene and functionally characterized the IRF-1 promoter. Upon transfection into Nb2 T cells, 1.7 kilobases (kb) of IRF-1 5'-flanking DNA linked to a chloramphenicol acetyl transferase (CAT) reporter gene mediated a 30-fold induction of CAT enzyme activity in response to 24 h of PRL stimulation. Deletion mutants containing 1.3, 0.6, and 0.2 kb 5'-flanking DNA were incrementally less transcriptionally active, although 0.2 kb still mediated a 12-fold induction by PRL. The sequence between -1.7 and -0.2 kb linked to a heterologous thymidine kinase promoter failed to respond to PRL stimulation, suggesting that the activity of upstream PRL response elements may require an interaction with promoter-proximal elements. By assaying CAT enzyme activity across a 24-h PRL induction time course, we were able to assign G1 vs. S phase PRL responses of the IRF-1 gene to different regions of the IRF-1 5'-flanking and promoter DNA. The 0.2-kb IRF-CAT construct was induced by PRL stimulation during the G1 phase of the cell cycle. In contrast, the 1.7-kb IRF-CAT construct was inducible by PRL during both G1 and S phase of the cell cycle. Hence, the PRL-induced biphasic expression of the IRF-1 gene appears to be controlled by separate PRL-responsive elements: elements in the first 0.2 kb of the IRF-1 promoter region act during early activation, and elements between 0.2 and 1.7 kb act in concert with the proximal 0.2-kb region during S phase progression. " ], "offsets": [ [ 0, 1834 ] ] } ]

[ { "id": "PMID-8015552_T1", "type": "Protein", "text": [ "prolactin" ], "offsets": [ [ 9, 18 ] ], "normalized": [] }, { "id": "PMID-8015552_T2", "type": "Protein", "text": [ "interferon regulatory factor-1" ], "offsets": [ [ 80, 110 ] ], "normalized": [] }, { "id": "PMID-8015552_T3", "type": "Protein", "text": [ "interferon regulatory factor-1" ], "offsets": [ [ 122, 152 ] ], "normalized": [] }, { "id": "PMID-8015552_T4", "type": "Protein", "text": [ "IRF-1" ], "offsets": [ [ 154, 159 ] ], "normalized": [] }, { "id": "PMID-8015552_T5", "type": "Protein", "text": [ "PRL" ], "offsets": [ [ 240, 243 ] ], "normalized": [] }, { "id": "PMID-8015552_T6", "type": "Protein", "text": [ "PRL" ], "offsets": [ [ 307, 310 ] ], "normalized": [] }, { "id": "PMID-8015552_T7", "type": "Protein", "text": [ "IRF-1" ], "offsets": [ [ 348, 353 ] ], "normalized": [] }, { "id": "PMID-8015552_T8", "type": "Protein", "text": [ "IRF-1" ], "offsets": [ [ 373, 378 ] ], "normalized": [] }, { "id": "PMID-8015552_T9", "type": "Protein", "text": [ "IRF-1" ], "offsets": [ [ 419, 424 ] ], "normalized": [] }, { "id": "PMID-8015552_T10", "type": "Protein", "text": [ "IRF-1" ], "offsets": [ [ 493, 498 ] ], "normalized": [] }, { "id": "PMID-8015552_T11", "type": "Protein", "text": [ "chloramphenicol acetyl transferase" ], "offsets": [ [ 527, 561 ] ], "normalized": [] }, { "id": "PMID-8015552_T12", "type": "Protein", "text": [ "CAT" ], "offsets": [ [ 563, 566 ] ], "normalized": [] }, { "id": "PMID-8015552_T13", "type": "Protein", "text": [ "CAT" ], "offsets": [ [ 614, 617 ] ], "normalized": [] }, { "id": "PMID-8015552_T14", "type": "Protein", "text": [ "PRL" ], "offsets": [ [ 657, 660 ] ], "normalized": [] }, { "id": "PMID-8015552_T15", "type": "Protein", "text": [ "PRL" ], "offsets": [ [ 843, 846 ] ], "normalized": [] }, { "id": "PMID-8015552_T16", "type": "Protein", "text": [ "PRL" ], "offsets": [ [ 958, 961 ] ], "normalized": [] }, { "id": "PMID-8015552_T17", "type": "Protein", "text": [ "PRL" ], "offsets": [ [ 1016, 1019 ] ], "normalized": [] }, { "id": "PMID-8015552_T18", "type": "Protein", "text": [ "CAT" ], "offsets": [ [ 1110, 1113 ] ], "normalized": [] }, { "id": "PMID-8015552_T19", "type": "Protein", "text": [ "PRL" ], "offsets": [ [ 1144, 1147 ] ], "normalized": [] }, { "id": "PMID-8015552_T20", "type": "Protein", "text": [ "PRL" ], "offsets": [ [ 1209, 1212 ] ], "normalized": [] }, { "id": "PMID-8015552_T21", "type": "Protein", "text": [ "IRF-1" ], "offsets": [ [ 1230, 1235 ] ], "normalized": [] }, { "id": "PMID-8015552_T22", "type": "Protein", "text": [ "IRF-1" ], "offsets": [ [ 1269, 1274 ] ], "normalized": [] }, { "id": "PMID-8015552_T23", "type": "Protein", "text": [ "PRL" ], "offsets": [ [ 1349, 1352 ] ], "normalized": [] }, { "id": "PMID-8015552_T24", "type": "Protein", "text": [ "PRL" ], "offsets": [ [ 1463, 1466 ] ], "normalized": [] }, { "id": "PMID-8015552_T25", "type": "Protein", "text": [ "PRL" ], "offsets": [ [ 1524, 1527 ] ], "normalized": [] }, { "id": "PMID-8015552_T26", "type": "Protein", "text": [ "IRF-1" ], "offsets": [ [ 1563, 1568 ] ], "normalized": [] }, { "id": "PMID-8015552_T27", "type": "Protein", "text": [ "PRL" ], "offsets": [ [ 1611, 1614 ] ], "normalized": [] }, { "id": "PMID-8015552_T28", "type": "Protein", "text": [ "IRF-1" ], "offsets": [ [ 1672, 1677 ] ], "normalized": [] }, { "id": "PMID-8015552_T40", "type": "Entity", "text": [ "promoter region" ], "offsets": [ [ 1678, 1693 ] ], "normalized": [] } ]

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[]

[ { "id": "PMID-8015553__text", "type": "abstract", "text": [ "Nonpituitary human prolactin gene transcription is independent of Pit-1 and differentially controlled in lymphocytes and in endometrial stroma. \nExpression of the human PRL (hPRL) gene in extrapituitary sites such as the uterus (decidualized endometrial stroma and myometrium) and cells of the hematopoietic lineage is directed by an alternative promoter which is located approximately 6 kilobases (kb) upstream of the pituitary-specific start site. In order to delineate the tissue-specific mechanisms governing the control of nonpituitary PRL gene expression, we have cloned and sequenced 3 kb 5'-flanking DNA of the upstream decidual/lymphoid (dPRL) promoter. Based on sequence homology we identified two binding motifs for Pit-1 and seven half-sites for glucocorticoid receptor/progesterone receptor (PR) binding. We focused our studies on the role of Pit-1 and of PR as potential transcriptional regulators, since the POU domain protein Pit-1 is essential in the control of pituitary PRL expression, and progesterone induces decidual transformation of the endometrial stroma, a differentiation process during which the decidual PRL gene is activated. We demonstrate in a variety of cell types, including lymphocytes and endometrial stroma, that Pit-1 is not involved in the regulation of dPRL promoter/reporter gene constructs carrying 3 kb 5'-flanking DNA. Our experiments also show that activated PR does not confer direct transcriptional control on the dPRL promoter. When we compared the activity of the transfected dPRL promoter in PRL-secreting and nonsecreting lymphoid cells, we found that the 3 kb 5'-flanking region of the dPRL promoter did not contain elements restricting expression to only those lymphocytes that produce PRL but allowed expression of fusion reporter genes irrespective of the status of the endogenous PRL gene. This was in sharp contrast to endometrial cells where 3 kb 5'-flanking DNA conferred strong transcriptional activation on the dPRL promoter in decidualized endometrial stromal cells actively secreting PRL, but did not allow transcription in undifferentiated non-PRL-secreting endometrial stromal cells. Activation of the dPRL promoter construct in these undifferentiated cells could however be induced by the addition of cAMP, in the absence of progesterone, suggesting that a signal transduced through the cAMP signaling pathway is a primary inducer of decidual PRL gene expression. " ], "offsets": [ [ 0, 2430 ] ] } ]

[ { "id": "PMID-8015553_T1", "type": "Protein", "text": [ "prolactin" ], "offsets": [ [ 19, 28 ] ], "normalized": [] }, { "id": "PMID-8015553_T2", "type": "Protein", "text": [ "Pit-1" ], "offsets": [ [ 66, 71 ] ], "normalized": [] }, { "id": "PMID-8015553_T3", "type": "Protein", "text": [ "PRL" ], "offsets": [ [ 169, 172 ] ], "normalized": [] }, { "id": "PMID-8015553_T4", "type": "Protein", "text": [ "hPRL" ], "offsets": [ [ 174, 178 ] ], "normalized": [] }, { "id": "PMID-8015553_T5", "type": "Protein", "text": [ "PRL" ], "offsets": [ [ 541, 544 ] ], "normalized": [] }, { "id": "PMID-8015553_T6", "type": "Protein", "text": [ "dPRL" ], "offsets": [ [ 647, 651 ] ], "normalized": [] }, { "id": "PMID-8015553_T7", "type": "Protein", "text": [ "Pit-1" ], "offsets": [ [ 727, 732 ] ], "normalized": [] }, { "id": "PMID-8015553_T8", "type": "Protein", "text": [ "glucocorticoid receptor" ], "offsets": [ [ 758, 781 ] ], "normalized": [] }, { "id": "PMID-8015553_T9", "type": "Protein", "text": [ "progesterone receptor" ], "offsets": [ [ 782, 803 ] ], "normalized": [] }, { "id": "PMID-8015553_T10", "type": "Protein", "text": [ "PR" ], "offsets": [ [ 805, 807 ] ], "normalized": [] }, { "id": "PMID-8015553_T11", "type": "Protein", "text": [ "Pit-1" ], "offsets": [ [ 856, 861 ] ], "normalized": [] }, { "id": "PMID-8015553_T12", "type": "Protein", "text": [ "PR" ], "offsets": [ [ 869, 871 ] ], "normalized": [] }, { "id": "PMID-8015553_T13", "type": "Protein", "text": [ "Pit-1" ], "offsets": [ [ 942, 947 ] ], "normalized": [] }, { "id": "PMID-8015553_T14", "type": "Protein", "text": [ "PRL" ], "offsets": [ [ 989, 992 ] ], "normalized": [] }, { "id": "PMID-8015553_T15", "type": "Protein", "text": [ "PRL" ], "offsets": [ [ 1133, 1136 ] ], "normalized": [] }, { "id": "PMID-8015553_T16", "type": "Protein", "text": [ "Pit-1" ], "offsets": [ [ 1250, 1255 ] ], "normalized": [] }, { "id": "PMID-8015553_T17", "type": "Protein", "text": [ "dPRL" ], "offsets": [ [ 1293, 1297 ] ], "normalized": [] }, { "id": "PMID-8015553_T18", "type": "Protein", "text": [ "PR" ], "offsets": [ [ 1404, 1406 ] ], "normalized": [] }, { "id": "PMID-8015553_T19", "type": "Protein", "text": [ "dPRL" ], "offsets": [ [ 1461, 1465 ] ], "normalized": [] }, { "id": "PMID-8015553_T20", "type": "Protein", "text": [ "dPRL" ], "offsets": [ [ 1525, 1529 ] ], "normalized": [] }, { "id": "PMID-8015553_T21", "type": "Protein", "text": [ "PRL" ], "offsets": [ [ 1542, 1545 ] ], "normalized": [] }, { "id": "PMID-8015553_T22", "type": "Protein", "text": [ "PRL" ], "offsets": [ [ 1739, 1742 ] ], "normalized": [] }, { "id": "PMID-8015553_T23", "type": "Protein", "text": [ "PRL" ], "offsets": [ [ 1836, 1839 ] ], "normalized": [] }, { "id": "PMID-8015553_T24", "type": "Protein", "text": [ "dPRL" ], "offsets": [ [ 1972, 1976 ] ], "normalized": [] }, { "id": "PMID-8015553_T25", "type": "Protein", "text": [ "PRL" ], "offsets": [ [ 2047, 2050 ] ], "normalized": [] }, { "id": "PMID-8015553_T26", "type": "Protein", "text": [ "PRL" ], "offsets": [ [ 2108, 2111 ] ], "normalized": [] }, { "id": "PMID-8015553_T27", "type": "Protein", "text": [ "dPRL" ], "offsets": [ [ 2167, 2171 ] ], "normalized": [] }, { "id": "PMID-8015553_T28", "type": "Protein", "text": [ "PRL" ], "offsets": [ [ 2409, 2412 ] ], "normalized": [] }, { "id": "PMID-8015553_T41", "type": "Entity", "text": [ "promoter" ], "offsets": [ [ 1466, 1474 ] ], "normalized": [] }, { "id": "PMID-8015553_T48", "type": "Entity", "text": [ "promoter" ], "offsets": [ [ 1977, 1985 ] ], "normalized": [] } ]

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] }, { "id": "PMID-8015553_E6", "type": "Regulation", "trigger": { "text": [ "control" ], "offsets": [ [ 517, 524 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "PMID-8015553_E7" } ] }, { "id": "PMID-8015553_E7", "type": "Gene_expression", "trigger": { "text": [ "expression" ], "offsets": [ [ 550, 560 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "PMID-8015553_T5" } ] }, { "id": "PMID-8015553_E8", "type": "Regulation", "trigger": { "text": [ "essential in the control" ], "offsets": [ [ 951, 975 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "PMID-8015553_E9" }, { "role": "Cause", "ref_id": "PMID-8015553_T13" } ] }, { "id": "PMID-8015553_E9", "type": "Gene_expression", "trigger": { "text": [ "expression" ], "offsets": [ [ 993, 1003 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "PMID-8015553_T14" } ] }, { "id": "PMID-8015553_E10", "type": "Positive_regulation", "trigger": { "text": [ "activated" ], "offsets": [ [ 1145, 1154 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "PMID-8015553_T15" } ] }, { "id": "PMID-8015553_E11", "type": "Positive_regulation", "trigger": { "text": [ "activated" ], "offsets": [ [ 1394, 1403 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "PMID-8015553_T18" } ] }, { "id": "PMID-8015553_E12", "type": "Regulation", "trigger": { "text": [ "confer direct transcriptional control" ], "offsets": [ [ 1416, 1453 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "PMID-8015553_T19" }, { "role": "Cause", "ref_id": "PMID-8015553_E11" }, { "role": "Site", "ref_id": "PMID-8015553_T41" } ] }, { "id": "PMID-8015553_E13", "type": "Gene_expression", "trigger": { "text": [ "secreting" ], "offsets": [ [ 1546, 1555 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "PMID-8015553_T21" } ] }, { "id": "PMID-8015553_E14", "type": "Gene_expression", "trigger": { "text": [ "nonsecreting" ], "offsets": [ [ 1560, 1572 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "PMID-8015553_T21" } ] }, { "id": "PMID-8015553_E15", "type": "Positive_regulation", "trigger": { "text": [ "restricting" ], "offsets": [ [ 1677, 1688 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "PMID-8015553_E16" } ] }, { "id": "PMID-8015553_E16", "type": "Gene_expression", "trigger": { "text": [ "expression" ], "offsets": [ [ 1689, 1699 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "PMID-8015553_T22" } ] }, { "id": "PMID-8015553_E17", "type": "Gene_expression", "trigger": { "text": [ "produce" ], "offsets": [ [ 1731, 1738 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "PMID-8015553_T22" } ] }, { "id": "PMID-8015553_E18", "type": "Positive_regulation", "trigger": { "text": [ "conferred strong transcriptional activation" ], "offsets": [ [ 1921, 1964 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "PMID-8015553_T24" }, { "role": "Site", "ref_id": "PMID-8015553_T48" } ] }, { "id": "PMID-8015553_E19", "type": "Gene_expression", "trigger": { "text": [ "secreting" ], "offsets": [ [ 2037, 2046 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "PMID-8015553_T25" } ] }, { "id": "PMID-8015553_E20", "type": "Positive_regulation", "trigger": { "text": [ "allow" ], "offsets": [ [ 2064, 2069 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "PMID-8015553_E21" } ] }, { "id": "PMID-8015553_E21", "type": "Transcription", "trigger": { "text": [ "transcription" ], "offsets": [ [ 2070, 2083 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "PMID-8015553_T26" } ] }, { "id": "PMID-8015553_E22", "type": "Gene_expression", "trigger": { "text": [ "secreting" ], "offsets": [ [ 2112, 2121 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "PMID-8015553_T26" } ] }, { "id": "PMID-8015553_E23", "type": "Positive_regulation", "trigger": { "text": [ "inducer" ], "offsets": [ [ 2389, 2396 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "PMID-8015553_E24" } ] }, { "id": "PMID-8015553_E24", "type": "Gene_expression", "trigger": { "text": [ "expression" ], "offsets": [ [ 2418, 2428 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "PMID-8015553_T28" } ] } ]

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[]

[ { "id": "PMID-8018558__text", "type": "abstract", "text": [ "Activation of early growth response 1 gene transcription and pp90rsk during induction of monocytic differentiation. \nThe present work has studied mechanisms responsible for induction of early growth response 1 (EGR-1) gene expression during monocytic differentiation of U-937 myeloid leukemia cells. Differentiation of U-937 cells with 12-O-tetradecanoylphorbol-13-acetate (TPA), an activator of the serine/threonine protein kinase C, was associated with transcriptional activation of EGR-1 promoter-reporter constructs. The EGR-1 promoter contains six CC(A/T)6GG (CArG) motifs. The two 5'-most distal CArG sequences conferred TPA inducibility. In contrast, there was little effect of TPA on EGR-1 transcription in a TPA-resistant U-937 cell variant, designated TUR. Treatment of both U-937 and TUR cells with okadaic acid, an inhibitor of serine/threonine protein phosphatases 1 and 2A, was associated with induction of monocytic differentiation and EGR-1 transcription through the 5'-most CArG element. Since these findings supported the involvement of serine/threonine protein phosphorylation in the regulation of EGR-1 expression, we studied activation of the 40S ribosomal protein S6 serine/threonine kinases, pp70S6K and pp90rsk. Although both kinases participate in regulating cell growth, there was no detectable activation of pp70S6K during TPA- or okadaic acid-induced monocytic differentiation. Moreover, rapamycin, an inhibitor of pp70S6K activation, had no effect on induction of EGR-1 expression. In contrast, analysis of pp90rsk activity by phosphorylation of a peptide derived from S6 protein demonstrated stimulation of this kinase in TPA-treated U-937, and not TUR, cells. Okadaic acid treatment of both cell types was associated with activation of pp90rsk. " ], "offsets": [ [ 0, 1776 ] ] } ]

[ { "id": "PMID-8018558_T1", "type": "Protein", "text": [ "early growth response 1" ], "offsets": [ [ 14, 37 ] ], "normalized": [] }, { "id": "PMID-8018558_T2", "type": "Protein", "text": [ "early growth response 1" ], "offsets": [ [ 186, 209 ] ], "normalized": [] }, { "id": "PMID-8018558_T3", "type": "Protein", "text": [ "EGR-1" ], "offsets": [ [ 211, 216 ] ], "normalized": [] }, { "id": "PMID-8018558_T4", "type": "Protein", "text": [ "EGR-1" ], "offsets": [ [ 485, 490 ] ], "normalized": [] }, { "id": "PMID-8018558_T5", "type": "Protein", "text": [ "EGR-1" ], "offsets": [ [ 525, 530 ] ], "normalized": [] }, { "id": "PMID-8018558_T6", "type": "Protein", "text": [ "EGR-1" ], "offsets": [ [ 692, 697 ] ], "normalized": [] }, { "id": "PMID-8018558_T7", "type": "Protein", "text": [ "EGR-1" ], "offsets": [ [ 951, 956 ] ], "normalized": [] }, { "id": "PMID-8018558_T8", "type": "Protein", "text": [ "EGR-1" ], "offsets": [ [ 1117, 1122 ] ], "normalized": [] }, { "id": "PMID-8018558_T9", "type": "Protein", "text": [ "EGR-1" ], "offsets": [ [ 1493, 1498 ] ], "normalized": [] } ]

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[]

[ { "id": "PMID-8018594__text", "type": "abstract", "text": [ "Effects of prostaglandin E2 on Th0-type human T cell clones: modulation of functions of nuclear proteins involved in cytokine production. \nThe effects of prostaglandin E2 (PGE2) on cytokine production and proliferation of the CD4+ human helper T cell clone SP-B21 were investigated. In cells stimulated with anti-CD3 mAb, PGE2 inhibited cell proliferation and the production of all the cytokines examined. Addition of rIL-2 fully restored the proliferative response and partially restored the production of IL-4 and IL-5, but not that of other cytokines. In contrast, in cells stimulated with phorbol myristate acetate (PMA)/A23187, PGE2 enhanced the production of IL-4 and IL-5, and only partially inhibited the production of other cytokines. Therefore, the effects of PGE2 vary depending on the mode of T cell activation, and the IL-4 and IL-5 are regulated differently from other cytokines. In a mobility shift assay, only the NF-kappa B (p50/p50) homodimer was observed in a complex formed with the kappa B sequence in unstimulated SP-B21 cells. When cells were stimulated with anti-CD3 mAb or PMA/A23187, a complex formation of NF-kappa B (p50/p65) heterodimer with the kappa B sequence was induced. Interestingly, PGE2 or di-butyryl (Bt2)cAMP abolished the binding of NF-kappa B (p50/p65) heterodimer to the kappa B sequence in cells stimulated with anti-CD3 mAb but not with PMA/A23187. Our results suggest that the target of PGE2 action is a component in the signal transduction pathway leading to the activation of protein kinase C. However, the inhibition of the T cell activation signals by PGE2 is selective. PGE2 enhanced the complex formation with NF-AT, AP-1 and CLE0 sequences when the cells were activated by either anti-CD3 mAb or PMA/A23187 stimulation. It seems therefore that PGE2, by elevating cAMP levels, interferes with the activation pathway for NF-kappa B but not for NF-AT, AP-1 or CLE0 binding protein. " ], "offsets": [ [ 0, 1932 ] ] } ]

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[ { "id": "PMID-8018594_1", "entity_ids": [ "PMID-8018594_T8", "PMID-8018594_T9" ] } ]

[]

[ { "id": "PMID-8038234__text", "type": "abstract", "text": [ "IL-4 down-regulates IL-2-, IL-3-, and GM-CSF-induced cytokine gene expression in peripheral blood monocytes. \nIL-4, a product of the T-helper 0 (Th0) and 2 (Th2) subset, was originally described as a B-cell stimulatory factor and has subsequently been found to suppress IL-1 alpha, IL-1 beta, IL-6, IL-8, and TNF-alpha gene expression in monocytes stimulated with LPS, and to upregulate IL-1 receptor antagonist (IL1-RA) gene expression. In this study we investigated the effect of IL-4 on the expression of cytokine genes in monocytes evoked by other T-helper cell cytokines: IL-2, IL-3, and GM-CSF. IL-4 down-regulated mRNA accumulation of the proinflammatory cytokines IL-1 beta, IL-8, and TNF-alpha in monocytes stimulated with IL-2, IL-3, and GM-CSF. IL-4 also suppressed the IL-2-induced IL-6 mRNA expression. Temporal analysis of the IL-4 down-regulatory effect on the IL-2-, IL-3-, or GM-CSF-induced proinflammatory cytokine gene expression in monocytes provided evidence that IL-4 acts predominantly on the post-transcriptional level. This was supported by the observation that the down-regulatory capacity of IL-4 appeared to be dependent on de novo protein synthesis. IL-4 did not exert significant influence on the induction of expression of IL-1-RA or various CSFs by IL-2, IL-3, and GM-CSF. (ABSTRACT TRUNCATED AT 250 WORDS) " ], "offsets": [ [ 0, 1339 ] ] } ]

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"text": [ "suppress" ], "offsets": [ [ 261, 269 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "PMID-8038234_E13" }, { "role": "Cause", "ref_id": "PMID-8038234_T5" } ] }, { "id": "PMID-8038234_E6", "type": "Negative_regulation", "trigger": { "text": [ "suppress" ], "offsets": [ [ 261, 269 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "PMID-8038234_E12" }, { "role": "Cause", "ref_id": "PMID-8038234_T5" } ] }, { "id": "PMID-8038234_E7", "type": "Gene_expression", "trigger": { "text": [ "expression" ], "offsets": [ [ 324, 334 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "PMID-8038234_T10" } ] }, { "id": "PMID-8038234_E8", "type": "Gene_expression", "trigger": { "text": [ "expression" ], "offsets": [ [ 324, 334 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "PMID-8038234_T6" } ] }, { "id": "PMID-8038234_E9", "type": "Gene_expression", "trigger": { "text": [ "expression" ], "offsets": [ [ 324, 334 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "PMID-8038234_T8" } ] }, { "id": "PMID-8038234_E10", "type": "Gene_expression", "trigger": { "text": [ "expression" ], "offsets": [ [ 324, 334 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "PMID-8038234_T9" } ] }, { "id": "PMID-8038234_E11", "type": "Gene_expression", "trigger": { "text": [ "expression" ], "offsets": [ [ 324, 334 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "PMID-8038234_T7" } ] }, { "id": "PMID-8038234_E12", "type": "Positive_regulation", "trigger": { "text": [ "stimulated" ], "offsets": [ [ 348, 358 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "PMID-8038234_E11" } ] }, { "id": "PMID-8038234_E13", "type": "Positive_regulation", "trigger": { "text": [ "stimulated" ], "offsets": [ [ 348, 358 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "PMID-8038234_E7" } ] }, { "id": "PMID-8038234_E14", "type": "Positive_regulation", "trigger": { "text": [ "stimulated" ], "offsets": [ [ 348, 358 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "PMID-8038234_E8" } ] }, { "id": "PMID-8038234_E15", "type": "Positive_regulation", "trigger": { "text": [ "stimulated" ], "offsets": [ [ 348, 358 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "PMID-8038234_E10" } ] }, { "id": "PMID-8038234_E16", "type": "Positive_regulation", "trigger": { "text": [ "stimulated" ], "offsets": [ [ 348, 358 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "PMID-8038234_E9" } ] }, { "id": "PMID-8038234_E17", "type": "Positive_regulation", "trigger": { "text": [ "upregulate" ], "offsets": [ [ 376, 386 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "PMID-8038234_E18" }, { "role": "Cause", "ref_id": "PMID-8038234_T5" } ] }, { "id": "PMID-8038234_E18", "type": "Gene_expression", "trigger": { "text": [ "expression" ], "offsets": [ [ 426, 436 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "PMID-8038234_T12" } ] }, { "id": "PMID-8038234_E19", "type": "Negative_regulation", "trigger": { "text": [ "down-regulated" ], "offsets": [ [ 606, 620 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "PMID-8038234_E22" }, { "role": "Cause", "ref_id": "PMID-8038234_T17" } ] }, { "id": "PMID-8038234_E20", "type": "Negative_regulation", "trigger": { "text": [ "down-regulated" ], "offsets": [ [ 606, 620 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "PMID-8038234_E23" }, { "role": "Cause", "ref_id": "PMID-8038234_T17" } ] }, { "id": "PMID-8038234_E21", "type": "Negative_regulation", "trigger": { "text": [ "down-regulated" ], "offsets": [ [ 606, 620 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "PMID-8038234_E24" }, { "role": "Cause", "ref_id": "PMID-8038234_T17" } ] }, { "id": "PMID-8038234_E22", "type": "Positive_regulation", "trigger": { "text": [ "mRNA accumulation" ], "offsets": [ [ 621, 638 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "PMID-8038234_T19" } ] }, { "id": "PMID-8038234_E23", "type": "Positive_regulation", "trigger": { "text": [ "mRNA accumulation" ], "offsets": [ [ 621, 638 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "PMID-8038234_T18" } ] }, { "id": "PMID-8038234_E24", "type": "Positive_regulation", "trigger": { "text": [ "mRNA accumulation" ], "offsets": [ [ 621, 638 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "PMID-8038234_T20" } ] }, { "id": "PMID-8038234_E25", "type": "Negative_regulation", "trigger": { "text": [ "suppressed" ], "offsets": [ [ 766, 776 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "PMID-8038234_E26" }, { "role": "Cause", "ref_id": "PMID-8038234_T24" } ] }, { "id": "PMID-8038234_E26", "type": "Positive_regulation", "trigger": { "text": [ "induced" ], "offsets": [ [ 786, 793 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "PMID-8038234_E27" }, { "role": "Cause", "ref_id": "PMID-8038234_T25" } ] }, { "id": "PMID-8038234_E27", "type": "Transcription", "trigger": { "text": [ "expression" ], "offsets": [ [ 804, 814 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "PMID-8038234_T26" } ] }, { "id": "PMID-8038234_E28", "type": "Regulation", "trigger": { "text": [ "influence" ], 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1227, 1236 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "PMID-8038234_E34" }, { "role": "Cause", "ref_id": "PMID-8038234_T37" } ] }, { "id": "PMID-8038234_E33", "type": "Positive_regulation", "trigger": { "text": [ "induction" ], "offsets": [ [ 1227, 1236 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "PMID-8038234_E34" }, { "role": "Cause", "ref_id": "PMID-8038234_T35" } ] }, { "id": "PMID-8038234_E34", "type": "Gene_expression", "trigger": { "text": [ "expression" ], "offsets": [ [ 1240, 1250 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "PMID-8038234_T34" } ] } ]

[ { "id": "PMID-8038234_1", "entity_ids": [ "PMID-8038234_T12", "PMID-8038234_T11" ] } ]

[]

[ { "id": "PMID-8039243__text", "type": "abstract", "text": [ "Long-term inositol phosphate release, but not tyrosine kinase activity, correlates with IL-2 secretion and NF-AT induction in anti-CD3-activated peripheral human T lymphocytes. \nThe cascade of events within the first few minutes of T cell stimulation has been well characterized. Although many second messengers have been shown to be necessary and sufficient for T cell activation in a number of model systems, the rate-limiting step in peripheral T cells has not been demonstrated. To model effective versus ineffective CD3-mediated stimulation in peripheral T cells, we used two anti-CD3 mAbs that differ in their ability to stimulate purified T cells: OKT3, which causes early second messenger generation but is unable to activate T cells without a second signal, and 64.1, which stimulates T cell proliferation on its own. We found that tyrosine kinase activity was similar for both mAbs over a period of hours. However, the inositol phosphate response was stronger for 64.1 than for OKT3. To tie these events to gene activation, we measured NF-kappa B and NF-AT activity in the nucleus after anti-CD3 stimulation. Both stimuli induced the appearance of the NF-kappa B components (c-Rel, p65 (RelA), and p50 (NF-kappa B1)) and NF-kappa B DNA binding activity in the nucleus. However, only 64.1 induced NF-AT in the nucleus, correlating with its ability to activate T cells. Thus, NF-AT induction and IL-2 secretion were correlated with the levels of inositol phosphate release but not with gross levels of tyrosine kinase activity induced late following the response. On the other hand, NF-kappa B induction and IL-2 receptor expression occurred even with the smaller second messenger response generated by OKT3. " ], "offsets": [ [ 0, 1717 ] ] } ]

[ { "id": "PMID-8039243_T1", "type": "Protein", "text": [ "IL-2" ], "offsets": [ [ 88, 92 ] ], "normalized": [] }, { "id": "PMID-8039243_T2", "type": "Protein", "text": [ "c-Rel" ], "offsets": [ [ 1185, 1190 ] ], "normalized": [] }, { "id": "PMID-8039243_T3", "type": "Protein", "text": [ "p65" ], "offsets": [ [ 1192, 1195 ] ], "normalized": [] }, { "id": "PMID-8039243_T4", "type": "Protein", "text": [ "RelA" ], "offsets": [ [ 1197, 1201 ] ], "normalized": [] }, { "id": "PMID-8039243_T5", "type": "Protein", "text": [ "p50" ], "offsets": [ [ 1208, 1211 ] ], "normalized": [] }, { "id": "PMID-8039243_T6", "type": "Protein", "text": [ "NF-kappa B1" ], "offsets": [ [ 1213, 1224 ] ], "normalized": [] }, { "id": "PMID-8039243_T7", "type": "Protein", "text": [ "IL-2" ], "offsets": [ [ 1404, 1408 ] ], "normalized": [] }, { "id": "PMID-8039243_T12", "type": "Entity", "text": [ "nucleus" ], "offsets": [ [ 1270, 1277 ] ], "normalized": [] } ]

[ { "id": "PMID-8039243_E1", "type": "Localization", "trigger": { "text": [ "secretion" ], "offsets": [ [ 93, 102 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "PMID-8039243_T1" } ] }, { "id": "PMID-8039243_E2", "type": "Positive_regulation", "trigger": { "text": [ "induced" ], "offsets": [ [ 1132, 1139 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "PMID-8039243_E6" } ] }, { "id": "PMID-8039243_E3", "type": "Positive_regulation", "trigger": { "text": [ "induced" ], "offsets": [ [ 1132, 1139 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "PMID-8039243_E8" } ] }, { "id": "PMID-8039243_E4", "type": "Positive_regulation", "trigger": { "text": [ "induced" ], "offsets": [ [ 1132, 1139 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "PMID-8039243_E9" } ] }, { "id": "PMID-8039243_E5", "type": "Positive_regulation", "trigger": { "text": [ "induced" ], "offsets": [ [ 1132, 1139 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "PMID-8039243_E7" } ] }, { "id": "PMID-8039243_E6", "type": "Localization", "trigger": { "text": [ "appearance" ], "offsets": [ [ 1144, 1154 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "PMID-8039243_T5" }, { "role": "AtLoc", "ref_id": "PMID-8039243_T12" } ] }, { "id": "PMID-8039243_E7", "type": "Localization", "trigger": { "text": [ "appearance" ], "offsets": [ [ 1144, 1154 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "PMID-8039243_T3" }, { "role": "AtLoc", "ref_id": "PMID-8039243_T12" } ] }, { "id": "PMID-8039243_E8", "type": "Positive_regulation", "trigger": { "text": [ "appearance" ], "offsets": [ [ 1144, 1154 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "PMID-8039243_T2" } ] }, { "id": "PMID-8039243_E9", "type": "Localization", "trigger": { "text": [ "appearance" ], "offsets": [ [ 1144, 1154 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "PMID-8039243_T2" }, { "role": "AtLoc", "ref_id": "PMID-8039243_T12" } ] }, { "id": "PMID-8039243_E10", "type": "Localization", "trigger": { "text": [ "secretion" ], "offsets": [ [ 1409, 1418 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "PMID-8039243_T7" } ] } ]

[ { "id": "PMID-8039243_1", "entity_ids": [ "PMID-8039243_T3", "PMID-8039243_T4" ] }, { "id": "PMID-8039243_2", "entity_ids": [ "PMID-8039243_T5", "PMID-8039243_T6" ] } ]

[]

[ { "id": "PMID-8051172__text", "type": "abstract", "text": [ "ZAP-70 tyrosine kinase, CD45, and T cell receptor involvement in UV- and H2O2-induced T cell signal transduction. \nSeveral mammalian responses to UV irradiation, including the activation of NF-kappa B, are believed to involve tyrosine phosphorylation. UV irradiation and H2O2 treatment of T lymphocytes induce protein tyrosine phosphorylation and Ca2+ signals similar to those observed following biological stimulation. We have examined the role of cell surface molecules in these responses. Normal T lymphocytes whose surface expression of CD3 was depleted showed impaired UV-induced tyrosine phosphorylation and Ca2+ signals. Similarly, Jurkat T cell lines deficient in CD3 or CD45 expression also gave impaired UV responses. However, all these cell types still gave strong Ca2+ and tyrosine phosphorylation responses to H2O2. The T cell tyrosine kinase ZAP-70 was found to be highly responsive to UV and H2O2 treatment. ZAP-70 responsiveness to UV required expression of both CD3 and CD45, whereas only CD3 was required for the response to H2O2. UV-induced activation of NF-kappa B was blocked by CD3 depletion, indicating the importance of such cell surface molecules in biological responses to UV. In nonlymphoid cells, the epidermal growth factor receptor displayed increased tyrosine phosphorylation within seconds of UV irradiation. These results suggest that UV-induced signal transduction is mediated via cell surface receptors that normally respond to biological stimulation, whereas H2O2 is able to partially bypass this requirement. " ], "offsets": [ [ 0, 1546 ] ] } ]

[ { "id": "PMID-8051172_T1", "type": "Protein", "text": [ "ZAP-70" ], "offsets": [ [ 0, 6 ] ], "normalized": [] }, { "id": "PMID-8051172_T2", "type": "Protein", "text": [ "CD45" ], "offsets": [ [ 24, 28 ] ], "normalized": [] }, { "id": "PMID-8051172_T3", "type": "Protein", "text": [ "CD45" ], "offsets": [ [ 679, 683 ] ], "normalized": [] }, { "id": "PMID-8051172_T4", "type": "Protein", "text": [ "ZAP-70" ], "offsets": [ [ 856, 862 ] ], "normalized": [] }, { "id": "PMID-8051172_T5", "type": "Protein", "text": [ "ZAP-70" ], "offsets": [ [ 923, 929 ] ], "normalized": [] }, { "id": "PMID-8051172_T6", "type": "Protein", "text": [ "CD45" ], "offsets": [ [ 987, 991 ] ], "normalized": [] }, { "id": "PMID-8051172_T7", "type": "Protein", "text": [ "epidermal growth factor receptor" ], "offsets": [ [ 1229, 1261 ] ], "normalized": [] }, { "id": "PMID-8051172_T15", "type": "Entity", "text": [ "tyrosine" ], "offsets": [ [ 1282, 1290 ] ], "normalized": [] } ]

[ { "id": "PMID-8051172_E1", "type": "Negative_regulation", "trigger": { "text": [ "deficient" ], "offsets": [ [ 659, 668 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "PMID-8051172_E2" } ] }, { "id": "PMID-8051172_E2", "type": "Gene_expression", "trigger": { "text": [ "expression" ], "offsets": [ [ 684, 694 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "PMID-8051172_T3" } ] }, { "id": "PMID-8051172_E3", "type": "Regulation", "trigger": { "text": [ "responsive" ], "offsets": [ [ 886, 896 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "PMID-8051172_T4" } ] }, { "id": "PMID-8051172_E4", "type": "Regulation", "trigger": { "text": [ "responsive" ], "offsets": [ [ 886, 896 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "PMID-8051172_T5" } ] }, { "id": "PMID-8051172_E5", "type": "Regulation", "trigger": { "text": [ "responsiveness" ], "offsets": [ [ 930, 944 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "PMID-8051172_T5" } ] }, { "id": "PMID-8051172_E6", "type": "Gene_expression", "trigger": { "text": [ "expression" ], "offsets": [ [ 960, 970 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "PMID-8051172_T6" } ] }, { "id": "PMID-8051172_E7", "type": "Regulation", "trigger": { "text": [ "response" ], "offsets": [ [ 1031, 1039 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "PMID-8051172_T5" } ] }, { "id": "PMID-8051172_E8", "type": "Positive_regulation", "trigger": { "text": [ "increased" ], "offsets": [ [ 1272, 1281 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "PMID-8051172_E9" } ] }, { "id": "PMID-8051172_E9", "type": "Phosphorylation", "trigger": { "text": [ "phosphorylation" ], "offsets": [ [ 1291, 1306 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "PMID-8051172_T7" }, { "role": "Site", "ref_id": "PMID-8051172_T15" } ] } ]

[]

[]

[ { "id": "PMID-8052854__text", "type": "abstract", "text": [ "Inhibition of NF-kappa B by sodium salicylate and aspirin [see comments] \nThe transcription factor nuclear factor-kappa B (NF-kappa B) is critical for the inducible expression of multiple cellular and viral genes involved in inflammation and infection including interleukin-1 (IL-1), IL-6, and adhesion molecules. The anti-inflammatory drugs sodium salicylate and aspirin inhibited the activation of NF-kappa B, which further explains the mechanism of action of these drugs. This inhibition prevented the degradation of the NF-kappa B inhibitor, I kappa B, and therefore NF-kappa B was retained in the cytosol. Sodium salicylate and aspirin also inhibited NF-kappa B-dependent transcription from the Ig kappa enhancer and the human immunodeficiency virus (HIV) long terminal repeat (LTR) in transfected T cells. " ], "offsets": [ [ 0, 812 ] ] } ]

[ { "id": "PMID-8052854_T1", "type": "Protein", "text": [ "IL-6" ], "offsets": [ [ 284, 288 ] ], "normalized": [] }, { "id": "PMID-8052854_T2", "type": "Protein", "text": [ "Ig kappa" ], "offsets": [ [ 700, 708 ] ], "normalized": [] } ]

[ { "id": "PMID-8052854_E1", "type": "Negative_regulation", "trigger": { "text": [ "inhibited" ], "offsets": [ [ 646, 655 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "PMID-8052854_E2" } ] }, { "id": "PMID-8052854_E2", "type": "Positive_regulation", "trigger": { "text": [ "dependent" ], "offsets": [ [ 667, 676 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "PMID-8052854_E3" } ] }, { "id": "PMID-8052854_E3", "type": "Transcription", "trigger": { "text": [ "transcription" ], "offsets": [ [ 677, 690 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "PMID-8052854_T2" } ] } ]

[]

[]

[ { "id": "PMID-8054477__text", "type": "abstract", "text": [ "Positive and negative regulation of IL-2 gene expression: role of multiple regulatory sites. \nInterleukin 2 (IL-2) is an important lymphokine required in the process of T cell activation, proliferation, clonal expansion and differentiation. The IL-2 gene displays both T cell specific and inducible expression: it is only expressed in CD4+ T cells after antigenic or mitogenic stimulation. Several cis-acting regulatory sites are required for induction of the IL-2 gene after stimulation. In this study, we have analysed the function of these cis-acting regulatory sites in the context of the native IL-2 enhancer and promoter sequence. The results of this study suggest that the NFAT (-276 to -261), the distal octamer (-256 to -248) and the proximal octamer (-75 to -66) sites not only act as enhancers of IL-2 gene transcription in the presence of cellular stimulation, but also have a silencing effect on IL-2 gene expression in resting cells. Two other sites display disparate effects on IL-2 gene expression in different T leukemia cell lines: the distal purine box (-291 to -277) and the proximal purine box sites (-145 to -128). Finally, the AP-1 (-186 to -176) and the kappa B sites (-206 to -195) respond to different cellular activation in EL4 cells. The AP-1 site mediated the response to PMA stimulation while the kappa B site responded to IL-1 stimulation. These data suggest that the regulation of IL-2 gene expression is a complex process and multiple cis-acting regulatory sites interact to exert different effects in T cells representative of alternative stages of differentiation. " ], "offsets": [ [ 0, 1600 ] ] } ]

[ { "id": "PMID-8054477_T1", "type": "Protein", "text": [ "IL-2" ], "offsets": [ [ 36, 40 ] ], "normalized": [] }, { "id": "PMID-8054477_T2", "type": "Protein", "text": [ "Interleukin 2" ], "offsets": [ [ 94, 107 ] ], "normalized": [] }, { "id": "PMID-8054477_T3", "type": "Protein", "text": [ "IL-2" ], "offsets": [ [ 109, 113 ] ], "normalized": [] }, { "id": "PMID-8054477_T4", "type": "Protein", "text": [ "IL-2" ], "offsets": [ [ 245, 249 ] ], "normalized": [] }, { "id": "PMID-8054477_T5", "type": "Protein", "text": [ "CD4" ], "offsets": [ [ 335, 338 ] ], "normalized": [] }, { "id": "PMID-8054477_T6", "type": "Protein", "text": [ "IL-2" ], "offsets": [ [ 460, 464 ] ], "normalized": [] }, { "id": "PMID-8054477_T7", "type": "Protein", "text": [ "IL-2" ], "offsets": [ [ 600, 604 ] ], "normalized": [] }, { "id": "PMID-8054477_T8", "type": "Protein", "text": [ "IL-2" ], "offsets": [ [ 808, 812 ] ], "normalized": [] }, { "id": "PMID-8054477_T9", "type": "Protein", "text": [ "IL-2" ], "offsets": [ [ 909, 913 ] ], "normalized": [] }, { "id": "PMID-8054477_T10", "type": "Protein", "text": [ "IL-2" ], "offsets": [ [ 993, 997 ] ], "normalized": [] }, { "id": "PMID-8054477_T11", "type": "Protein", "text": [ "IL-2" ], "offsets": [ [ 1413, 1417 ] ], "normalized": [] } ]

[ { "id": "PMID-8054477_E1", "type": "Positive_regulation", "trigger": { "text": [ "Positive" ], "offsets": [ [ 0, 8 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "PMID-8054477_E3" } ] }, { "id": "PMID-8054477_E2", "type": "Negative_regulation", "trigger": { "text": [ "negative regulation" ], "offsets": [ [ 13, 32 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "PMID-8054477_E3" } ] }, { "id": "PMID-8054477_E3", "type": "Gene_expression", "trigger": { "text": [ "expression" ], "offsets": [ [ 46, 56 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "PMID-8054477_T1" } ] }, { "id": "PMID-8054477_E4", "type": "Regulation", "trigger": { "text": [ "role" ], "offsets": [ [ 58, 62 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "PMID-8054477_E1" } ] }, { "id": "PMID-8054477_E5", "type": "Regulation", "trigger": { "text": [ "role" ], "offsets": [ [ 58, 62 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "PMID-8054477_E2" } ] }, { "id": "PMID-8054477_E6", "type": "Positive_regulation", "trigger": { "text": [ "inducible" ], "offsets": [ [ 289, 298 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "PMID-8054477_E7" } ] }, { "id": "PMID-8054477_E7", "type": "Gene_expression", "trigger": { "text": [ "expression" ], "offsets": [ [ 299, 309 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "PMID-8054477_T4" } ] }, { "id": "PMID-8054477_E8", "type": "Positive_regulation", "trigger": { "text": [ "expressed" ], "offsets": [ [ 322, 331 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "PMID-8054477_T4" } ] }, { "id": "PMID-8054477_E9", "type": "Positive_regulation", "trigger": { "text": [ "required" ], "offsets": [ [ 430, 438 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "PMID-8054477_E10" } ] }, { "id": "PMID-8054477_E10", "type": "Positive_regulation", "trigger": { "text": [ "induction" ], "offsets": [ [ 443, 452 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "PMID-8054477_T6" } ] }, { "id": "PMID-8054477_E11", "type": "Positive_regulation", "trigger": { "text": [ "act as enhancers" ], "offsets": [ [ 788, 804 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "PMID-8054477_E13" } ] }, { "id": "PMID-8054477_E12", "type": "Transcription", "trigger": { "text": [ "transcription" ], "offsets": [ [ 818, 831 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "PMID-8054477_T8" } ] }, { "id": "PMID-8054477_E13", "type": "Positive_regulation", "trigger": { "text": [ "in the presence of" ], "offsets": [ [ 832, 850 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "PMID-8054477_E12" } ] }, { "id": "PMID-8054477_E14", "type": "Negative_regulation", "trigger": { "text": [ "have a silencing effect" ], "offsets": [ [ 882, 905 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "PMID-8054477_E15" } ] }, { "id": "PMID-8054477_E15", "type": "Gene_expression", "trigger": { "text": [ "expression" ], "offsets": [ [ 919, 929 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "PMID-8054477_T9" } ] }, { "id": "PMID-8054477_E16", "type": "Regulation", "trigger": { "text": [ "display disparate effects" ], "offsets": [ [ 964, 989 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "PMID-8054477_E17" } ] }, { "id": "PMID-8054477_E17", "type": "Gene_expression", "trigger": { "text": [ "expression" ], "offsets": [ [ 1003, 1013 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "PMID-8054477_T10" } ] }, { "id": "PMID-8054477_E18", "type": "Regulation", "trigger": { "text": [ "regulation" ], "offsets": [ [ 1399, 1409 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "PMID-8054477_E19" } ] }, { "id": "PMID-8054477_E19", "type": "Gene_expression", "trigger": { "text": [ "expression" ], "offsets": [ [ 1423, 1433 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "PMID-8054477_T11" } ] }, { "id": "PMID-8054477_E20", "type": "Regulation", "trigger": { "text": [ "interact to exert different effects" ], "offsets": [ [ 1496, 1531 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "PMID-8054477_E18" } ] } ]

[ { "id": "PMID-8054477_1", "entity_ids": [ "PMID-8054477_T2", "PMID-8054477_T3" ] } ]

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[ { "id": "PMID-8062448__text", "type": "abstract", "text": [ "Superantigens activate HIV-1 gene expression in monocytic cells. \nBinding of superantigens to MHC class II molecules results in transduction of biochemical signals leading to cellular activation and gene expression. We demonstrate that the staphylococcal superantigens toxic shock syndrome toxin-1 (TSST-1) and staphylococcal enterotoxin A (SEA) activate HIV-1-LTR-driven transcription of chloramphenicol acetyl transferase in the human monocytic cell line THP-1. Induction of HIV-1-LTR-driven transcription in THP-1 cells by superantigens was associated with the induction of nuclear factor-kappa B DNA-binding activity. Superantigens also increased viral protein secretion from the granulocyte-macrophage colony-stimulating factor-pretreated chronically infected human monocytic cell line U1. Induction of HIV-1 gene expression in monocytic cells by superantigens occurred via tumor necrosis factor-alpha-dependent and -independent mechanisms. Our results suggest that superantigens and other MHC class II ligands may activate HIV-1 gene expression in monocytes/macrophages. " ], "offsets": [ [ 0, 1077 ] ] } ]

[ { "id": "PMID-8062448_T1", "type": "Protein", "text": [ "toxic shock syndrome toxin-1" ], "offsets": [ [ 269, 297 ] ], "normalized": [] }, { "id": "PMID-8062448_T2", "type": "Protein", "text": [ "TSST-1" ], "offsets": [ [ 299, 305 ] ], "normalized": [] }, { "id": "PMID-8062448_T3", "type": "Protein", "text": [ "staphylococcal enterotoxin A" ], "offsets": [ [ 311, 339 ] ], "normalized": [] }, { "id": "PMID-8062448_T4", "type": "Protein", "text": [ "SEA" ], "offsets": [ [ 341, 344 ] ], "normalized": [] }, { "id": "PMID-8062448_T5", "type": "Protein", "text": [ "chloramphenicol acetyl transferase" ], "offsets": [ [ 389, 423 ] ], "normalized": [] }, { "id": "PMID-8062448_T6", "type": "Protein", "text": [ "granulocyte-macrophage colony-stimulating factor" ], "offsets": [ [ 684, 732 ] ], "normalized": [] }, { "id": "PMID-8062448_T7", "type": "Protein", "text": [ "tumor necrosis factor-alpha" ], "offsets": [ [ 879, 906 ] ], "normalized": [] } ]

[ { "id": "PMID-8062448_E1", "type": "Positive_regulation", "trigger": { "text": [ "activate" ], "offsets": [ [ 346, 354 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "PMID-8062448_E3" }, { "role": "Cause", "ref_id": "PMID-8062448_T4" } ] }, { "id": "PMID-8062448_E2", "type": "Positive_regulation", "trigger": { "text": [ "activate" ], "offsets": [ [ 346, 354 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "PMID-8062448_E3" }, { "role": "Cause", "ref_id": "PMID-8062448_T2" } ] }, { "id": "PMID-8062448_E3", "type": "Positive_regulation", "trigger": { "text": [ "driven" ], "offsets": [ [ 365, 371 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "PMID-8062448_E4" } ] }, { "id": "PMID-8062448_E4", "type": "Transcription", "trigger": { "text": [ "transcription" ], "offsets": [ [ 372, 385 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "PMID-8062448_T5" } ] } ]

[ { "id": "PMID-8062448_1", "entity_ids": [ "PMID-8062448_T4", "PMID-8062448_T3" ] }, { "id": "PMID-8062448_2", "entity_ids": [ "PMID-8062448_T2", "PMID-8062448_T1" ] } ]

[]

[ { "id": "PMID-8067997__text", "type": "abstract", "text": [ "Inhibition of activation of transcription factor AP-1 by CD28 signalling in human T-cells. \nCo-stimulation of T-lymphocytes by T-cell receptor (TcR) occupancy and activation of the CD28 surface molecule results in enhanced proliferation and interleukin 2 (IL-2) production. The increase in IL-2 gene expression triggered by CD28 involves a kappa B-like sequence in the 5'-regulatory region of the IL-2 promoter, called CD28-responsive element. Stimulation of T-cells by agonistic anti-CD28 antibodies in conjunction with phorbol 12-myristate 13-acetate (PMA)- or TcR-derived signals induces the enhanced activation of the transcription factor NF-kappa B. Here we report that CD28 engagement, however, exerts opposite effects on the transcription factor AP-1. Whereas anti-CD28 together with PMA increased the DNA binding and trans-activation activity of NF-kappa B, PMA-induced activation of AP-1 was significantly suppressed. The inhibitory effect exerted by anti-CD28 was observed at the level of DNA binding as well as in functional reporter-gene assays. These results suggest that the two transcription factors are independently regulated and may perform different functions during T-cell activation. " ], "offsets": [ [ 0, 1205 ] ] } ]

[ { "id": "PMID-8067997_T1", "type": "Protein", "text": [ "CD28" ], "offsets": [ [ 57, 61 ] ], "normalized": [] }, { "id": "PMID-8067997_T2", "type": "Protein", "text": [ "CD28" ], "offsets": [ [ 181, 185 ] ], "normalized": [] }, { "id": "PMID-8067997_T3", "type": "Protein", "text": [ "interleukin 2" ], "offsets": [ [ 241, 254 ] ], "normalized": [] }, { "id": "PMID-8067997_T4", "type": "Protein", "text": [ "IL-2" ], "offsets": [ [ 256, 260 ] ], "normalized": [] }, { "id": "PMID-8067997_T5", "type": "Protein", "text": [ "IL-2" ], "offsets": [ [ 290, 294 ] ], "normalized": [] }, { "id": "PMID-8067997_T6", "type": "Protein", "text": [ "CD28" ], "offsets": [ [ 324, 328 ] ], "normalized": [] }, { "id": "PMID-8067997_T7", "type": "Protein", "text": [ "IL-2" ], "offsets": [ [ 397, 401 ] ], "normalized": [] }, { "id": "PMID-8067997_T8", "type": "Protein", "text": [ "CD28" ], "offsets": [ [ 419, 423 ] ], "normalized": [] }, { "id": "PMID-8067997_T9", "type": "Protein", "text": [ "CD28" ], "offsets": [ [ 485, 489 ] ], "normalized": [] }, { "id": "PMID-8067997_T10", "type": "Protein", "text": [ "CD28" ], "offsets": [ [ 675, 679 ] ], "normalized": [] }, { "id": "PMID-8067997_T11", "type": "Protein", "text": [ "CD28" ], "offsets": [ [ 772, 776 ] ], "normalized": [] }, { "id": "PMID-8067997_T12", "type": "Protein", "text": [ "CD28" ], "offsets": [ [ 965, 969 ] ], "normalized": [] } ]

[ { "id": "PMID-8067997_E1", "type": "Positive_regulation", "trigger": { "text": [ "activation" ], "offsets": [ [ 163, 173 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "PMID-8067997_T2" } ] }, { "id": "PMID-8067997_E2", "type": "Gene_expression", "trigger": { "text": [ "production" ], "offsets": [ [ 262, 272 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "PMID-8067997_T4" } ] }, { "id": "PMID-8067997_E3", "type": "Positive_regulation", "trigger": { "text": [ "increase" ], "offsets": [ [ 278, 286 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "PMID-8067997_E4" }, { "role": "Cause", "ref_id": "PMID-8067997_T6" } ] }, { "id": "PMID-8067997_E4", "type": "Gene_expression", "trigger": { "text": [ "expression" ], "offsets": [ [ 300, 310 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "PMID-8067997_T5" } ] }, { "id": "PMID-8067997_E5", "type": "Binding", "trigger": { "text": [ "engagement" ], "offsets": [ [ 680, 690 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "PMID-8067997_T10" } ] } ]

[ { "id": "PMID-8067997_1", "entity_ids": [ "PMID-8067997_T4", "PMID-8067997_T3" ] } ]

[]

[ { "id": "PMID-8077662__text", "type": "abstract", "text": [ "Induction of IL-8 expression in T cells uses the CD28 costimulatory pathway. \nIL-8, a potent chemotactic factor for neutrophil granulocytes and lymphocytes, is a proinflammatory cytokine secreted by a variety of cell types, including T cells. Stimulation of the CD28 cell surface molecule delivers costimulatory signals essential for lymphokine production in activated T cells via a conserved sequence element found in the promoter of several lymphokine genes. Anti-CD28-stimulated T cells produced significant amounts of IL-8; additionally, costimulation with anti-CD3 and anti-CD28 Abs resulted in a synergistic induction of IL-8 secretion. Sequence homology, single nucleotide mutations, and anti-CD28 Ab stimulation studies established that the NF-kappa B-like sequence in the promoter of the IL-8 gene functioned as a CD28 response element. Furthermore, cyclosporin A, but not rapamycin, blocked the synergistic induction of IL-8 expression achieved with anti-CD3 and anti-CD28 costimulation. The involvement of a CD28 response element in the induction of IL-8 expression in activated T cells may provide new insights into the pathogenesis and persistence of immune disorders characterized by increased levels of IL-8, such as psoriasis and rheumatoid arthritis. " ], "offsets": [ [ 0, 1268 ] ] } ]

[ { "id": "PMID-8077662_T1", "type": "Protein", "text": [ "IL-8" ], "offsets": [ [ 13, 17 ] ], "normalized": [] }, { "id": "PMID-8077662_T2", "type": "Protein", "text": [ "CD28" ], "offsets": [ [ 49, 53 ] ], "normalized": [] }, { "id": "PMID-8077662_T3", "type": "Protein", "text": [ "IL-8" ], "offsets": [ [ 78, 82 ] ], "normalized": [] }, { "id": "PMID-8077662_T4", "type": "Protein", "text": [ "CD28" ], "offsets": [ [ 262, 266 ] ], "normalized": [] }, { "id": "PMID-8077662_T5", "type": "Protein", "text": [ "CD28" ], "offsets": [ [ 466, 470 ] ], "normalized": [] }, { "id": "PMID-8077662_T6", "type": "Protein", "text": [ "IL-8" ], "offsets": [ [ 522, 526 ] ], "normalized": [] }, { "id": "PMID-8077662_T7", "type": "Protein", "text": [ "CD28" ], "offsets": [ [ 579, 583 ] ], "normalized": [] }, { "id": "PMID-8077662_T8", "type": "Protein", "text": [ "IL-8" ], "offsets": [ [ 627, 631 ] ], "normalized": [] }, { "id": "PMID-8077662_T9", "type": "Protein", "text": [ "CD28" ], "offsets": [ [ 700, 704 ] ], "normalized": [] }, { "id": "PMID-8077662_T10", "type": "Protein", "text": [ "IL-8" ], "offsets": [ [ 797, 801 ] ], "normalized": [] }, { "id": "PMID-8077662_T11", "type": "Protein", "text": [ "CD28" ], "offsets": [ [ 823, 827 ] ], "normalized": [] }, { "id": "PMID-8077662_T12", "type": "Protein", "text": [ "IL-8" ], "offsets": [ [ 930, 934 ] ], "normalized": [] }, { "id": "PMID-8077662_T13", "type": "Protein", "text": [ "CD28" ], "offsets": [ [ 978, 982 ] ], "normalized": [] }, { "id": "PMID-8077662_T14", "type": "Protein", "text": [ "CD28" ], "offsets": [ [ 1019, 1023 ] ], "normalized": [] }, { "id": "PMID-8077662_T15", "type": "Protein", "text": [ "IL-8" ], "offsets": [ [ 1061, 1065 ] ], "normalized": [] }, { "id": "PMID-8077662_T16", "type": "Protein", "text": [ "IL-8" ], "offsets": [ [ 1218, 1222 ] ], "normalized": [] }, { "id": "PMID-8077662_T26", "type": "Entity", "text": [ "NF-kappa B-like sequence" ], "offsets": [ [ 749, 773 ] ], "normalized": [] } ]

[ { "id": "PMID-8077662_E1", "type": "Positive_regulation", "trigger": { "text": [ "Induction" ], "offsets": [ [ 0, 9 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "PMID-8077662_E2" } ] }, { "id": "PMID-8077662_E2", "type": "Gene_expression", "trigger": { "text": [ "expression" ], "offsets": [ [ 18, 28 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "PMID-8077662_T1" } ] }, { "id": "PMID-8077662_E3", "type": "Positive_regulation", "trigger": { "text": [ "uses" ], "offsets": [ [ 40, 44 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "PMID-8077662_E1" } ] }, { "id": "PMID-8077662_E4", "type": "Localization", "trigger": { "text": [ "secreted" ], "offsets": [ [ 187, 195 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "PMID-8077662_T3" } ] }, { "id": "PMID-8077662_E5", "type": "Positive_regulation", "trigger": { "text": [ "Stimulation" ], "offsets": [ [ 243, 254 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "PMID-8077662_T4" } ] }, { "id": "PMID-8077662_E6", "type": "Gene_expression", "trigger": { "text": [ "produced" ], "offsets": [ [ 490, 498 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "PMID-8077662_T6" } ] }, { "id": "PMID-8077662_E7", "type": "Positive_regulation", "trigger": { "text": [ "resulted" ], "offsets": [ [ 588, 596 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "PMID-8077662_E8" } ] }, { "id": "PMID-8077662_E8", "type": "Positive_regulation", "trigger": { "text": [ "synergistic induction" ], "offsets": [ [ 602, 623 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "PMID-8077662_E9" } ] }, { "id": "PMID-8077662_E9", "type": "Localization", "trigger": { "text": [ "secretion" ], "offsets": [ [ 632, 641 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "PMID-8077662_T8" } ] }, { "id": "PMID-8077662_E10", "type": "Regulation", "trigger": { "text": [ "response" ], "offsets": [ [ 828, 836 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "PMID-8077662_T10" }, { "role": "Cause", "ref_id": "PMID-8077662_T11" }, { "role": "Site", "ref_id": "PMID-8077662_T26" } ] }, { "id": "PMID-8077662_E11", "type": "Negative_regulation", "trigger": { "text": [ "blocked" ], "offsets": [ [ 893, 900 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "PMID-8077662_E12" } ] }, { "id": "PMID-8077662_E12", "type": "Positive_regulation", "trigger": { "text": [ "synergistic induction" ], "offsets": [ [ 905, 926 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "PMID-8077662_E13" } ] }, { "id": "PMID-8077662_E13", "type": "Gene_expression", "trigger": { "text": [ "expression" ], "offsets": [ [ 935, 945 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "PMID-8077662_T12" } ] }, { "id": "PMID-8077662_E14", "type": "Positive_regulation", "trigger": { "text": [ "involvement" ], "offsets": [ [ 1002, 1013 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "PMID-8077662_E15" } ] }, { "id": "PMID-8077662_E15", "type": "Positive_regulation", "trigger": { "text": [ "induction" ], "offsets": [ [ 1048, 1057 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "PMID-8077662_E16" } ] }, { "id": "PMID-8077662_E16", "type": "Gene_expression", "trigger": { "text": [ "expression" ], "offsets": [ [ 1066, 1076 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "PMID-8077662_T15" } ] }, { "id": "PMID-8077662_E17", "type": "Positive_regulation", "trigger": { "text": [ "increased" ], "offsets": [ [ 1198, 1207 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "PMID-8077662_E18" } ] }, { "id": "PMID-8077662_E18", "type": "Gene_expression", "trigger": { "text": [ "levels" ], "offsets": [ [ 1208, 1214 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "PMID-8077662_T16" } ] } ]

[]

[]

[ { "id": "PMID-8079992__text", "type": "abstract", "text": [ "The severe phenotype of females with tiny ring X chromosomes is associated with inability of these chromosomes to undergo X inactivation. \nMental retardation and a constellation of congenital malformations not usually associated with Turner syndrome are seen in some females with a mosaic 45,X/46,X,r(X) karyotype. Studies of these females show that the XIST locus on their tiny ring X chromosomes is either not present or not expressed. As XIST transcription is well correlated with inactivation of the X chromosome in female somatic cells and spermatogonia, nonexpression of the locus even when it is present suggests that these chromosomes are transcriptionally active. We examined the transcriptional activity of ring X chromosomes lacking XIST expression (XISTE-), from three females with severe phenotypes. The two tiny ring X chromosomes studied with an antibody specific for the acetylated isoforms of histone H4 marking transcribed chromatin domains were labeled at a level consistent with their being active. We also examined tow of the XISTE- ring chromosomes to determine whether genes that are normally silent on an inactive X are expressed from these chromosomes. Analyses of hybrid cells show that TIMP, ZXDA, and ZXDB loci on the proximal short arm, and AR and PHKA1 loci on the long arm, are well expressed from the tiny ring X chromosome lacking XIST DNA. Studies of the ring chromosome that has XIST DNA but does not transcribe it show that its AR allele is transcribed along with the one on the normal X allele. (ABSTRACT TRUNCATED AT 250 WORDS) " ], "offsets": [ [ 0, 1566 ] ] } ]

[ { "id": "PMID-8079992_T1", "type": "Protein", "text": [ "XIST" ], "offsets": [ [ 354, 358 ] ], "normalized": [] }, { "id": "PMID-8079992_T2", "type": "Protein", "text": [ "XIST" ], "offsets": [ [ 441, 445 ] ], "normalized": [] }, { "id": "PMID-8079992_T3", "type": "Protein", "text": [ "XIST" ], "offsets": [ [ 744, 748 ] ], "normalized": [] }, { "id": "PMID-8079992_T4", "type": "Protein", "text": [ "histone H4" ], "offsets": [ [ 910, 920 ] ], "normalized": [] }, { "id": "PMID-8079992_T5", "type": "Protein", "text": [ "ZXDA" ], "offsets": [ [ 1219, 1223 ] ], "normalized": [] }, { "id": "PMID-8079992_T6", "type": "Protein", "text": [ "ZXDB" ], "offsets": [ [ 1229, 1233 ] ], "normalized": [] }, { "id": "PMID-8079992_T7", "type": "Protein", "text": [ "PHKA1" ], "offsets": [ [ 1277, 1282 ] ], "normalized": [] }, { "id": "PMID-8079992_T8", "type": "Protein", "text": [ "XIST" ], "offsets": [ [ 1364, 1368 ] ], "normalized": [] }, { "id": "PMID-8079992_T9", "type": "Protein", "text": [ "XIST" ], "offsets": [ [ 1414, 1418 ] ], "normalized": [] } ]

[ { "id": "PMID-8079992_E1", "type": "Negative_regulation", "trigger": { "text": [ "present" ], "offsets": [ [ 412, 419 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "PMID-8079992_T1" } ] }, { "id": "PMID-8079992_E2", "type": "Gene_expression", "trigger": { "text": [ "expressed" ], "offsets": [ [ 427, 436 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "PMID-8079992_T1" } ] }, { "id": "PMID-8079992_E3", "type": "Transcription", "trigger": { "text": [ "transcription" ], "offsets": [ [ 446, 459 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "PMID-8079992_T2" } ] }, { "id": "PMID-8079992_E4", "type": "Gene_expression", "trigger": { "text": [ "nonexpression" ], "offsets": [ [ 560, 573 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "PMID-8079992_T2" } ] }, { "id": "PMID-8079992_E5", "type": "Gene_expression", "trigger": { "text": [ "expression" ], "offsets": [ [ 749, 759 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "PMID-8079992_T3" } ] }, { "id": "PMID-8079992_E6", "type": "Gene_expression", "trigger": { "text": [ "expressed" ], "offsets": [ [ 1314, 1323 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "PMID-8079992_T6" } ] }, { "id": "PMID-8079992_E7", "type": "Gene_expression", "trigger": { "text": [ "expressed" ], "offsets": [ [ 1314, 1323 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "PMID-8079992_T5" } ] }, { "id": "PMID-8079992_E8", "type": "Gene_expression", "trigger": { "text": [ "expressed" ], "offsets": [ [ 1314, 1323 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "PMID-8079992_T7" } ] }, { "id": "PMID-8079992_E9", "type": "Negative_regulation", "trigger": { "text": [ "lacking" ], "offsets": [ [ 1356, 1363 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "PMID-8079992_T8" } ] }, { "id": "PMID-8079992_E10", "type": "Transcription", "trigger": { "text": [ "transcribe" ], "offsets": [ [ 1436, 1446 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "PMID-8079992_T9" } ] } ]

[]

[]

[ { "id": "PMID-8083467__text", "type": "abstract", "text": [ "Signals and nuclear factors that regulate the expression of interleukin-4 and interleukin-5 genes in helper T cells. \nMouse thymoma line EL-4 cells produce cytokines such as interleukin (IL)-2, IL-3, IL-4, IL-10, and granulocyte-macrophage colony-stimulating factor in response to phorbol 12-myristate 13-acetate (PMA). EL-4 cells also produce low levels of IL-5 when stimulated by PMA alone; however, cAMP greatly augments PMA-dependent IL-5 production. A transient transfection assay revealed that two signals, PMA and cAMP, are required for optimal activation of the IL-5 promoter. In contrast, cAMP almost completely inhibited the PMA-dependent activation of the endogenous IL-2 gene, as well as the transfected IL-2 promoter. These results indicate that the IL-5 gene is positively regulated by cAMP in a manner opposite to that for the IL-2 gene. One of the nuclear factors (NFs) that regulates the response of the IL-5 promoter to cAMP and PMA has properties similar to NF for activated t cell. The P sequence of the IL-4 gene, defined as a responsive element for PMA and calcium ionophore (A23187), shares sequence similarity with the NF kappa B and the NF-activated T cell binding sites. We attempted to determine whether NF(P), a nuclear factor specific for the P sequence, is related to NF-kappa B and nuclear factor for activated T cell (NF-AT). In electromobility shift assays both NF-kappa B (P65 or P65/P50 heterodimer) and NF-AT bound to the P sequence. However, sequence specificity of NF-AT was more similar to that of NF(P), and only a small amount of P65 was detected in NF(P). These results indicate that a component or components of NF-AT have the potential to reconstitute NF(P), whereas NF-kappa B alone does not account for NF(P) in Jurkat crude extract. Taken together, these results suggest that NF-AT-like factors are involved in the regulation of IL-4 and IL-5 genes. " ], "offsets": [ [ 0, 1897 ] ] } ]

[ { "id": "PMID-8083467_T1", "type": "Protein", "text": [ "interleukin-4" ], "offsets": [ [ 60, 73 ] ], "normalized": [] }, { "id": "PMID-8083467_T2", "type": "Protein", "text": [ "interleukin-5" ], "offsets": [ [ 78, 91 ] ], "normalized": [] }, { "id": "PMID-8083467_T3", "type": "Protein", "text": [ "interleukin (IL)-2" ], "offsets": [ [ 174, 192 ] ], "normalized": [] }, { "id": "PMID-8083467_T4", "type": "Protein", "text": [ "IL-3" ], "offsets": [ [ 194, 198 ] ], "normalized": [] }, { "id": "PMID-8083467_T5", "type": "Protein", "text": [ "IL-4" ], "offsets": [ [ 200, 204 ] ], "normalized": [] }, { "id": "PMID-8083467_T6", "type": "Protein", "text": [ "IL-10" ], "offsets": [ [ 206, 211 ] ], "normalized": [] }, { "id": "PMID-8083467_T7", "type": "Protein", "text": [ "granulocyte-macrophage colony-stimulating factor" ], "offsets": [ [ 217, 265 ] ], "normalized": [] }, { "id": "PMID-8083467_T8", "type": "Protein", "text": [ "IL-5" ], "offsets": [ [ 358, 362 ] ], "normalized": [] }, { "id": "PMID-8083467_T9", "type": "Protein", "text": [ "IL-5" ], "offsets": [ [ 438, 442 ] ], "normalized": [] }, { "id": "PMID-8083467_T10", "type": "Protein", "text": [ "IL-5" ], "offsets": [ [ 570, 574 ] ], "normalized": [] }, { "id": "PMID-8083467_T11", "type": "Protein", "text": [ "IL-2" ], "offsets": [ [ 678, 682 ] ], "normalized": [] }, { "id": "PMID-8083467_T12", "type": "Protein", "text": [ "IL-2" ], "offsets": [ [ 716, 720 ] ], "normalized": [] }, { "id": "PMID-8083467_T13", "type": "Protein", "text": [ "IL-5" ], "offsets": [ [ 763, 767 ] ], "normalized": [] }, { "id": "PMID-8083467_T14", "type": "Protein", "text": [ "IL-2" ], "offsets": [ [ 842, 846 ] ], "normalized": [] }, { "id": "PMID-8083467_T15", "type": "Protein", "text": [ "IL-5" ], "offsets": [ [ 921, 925 ] ], "normalized": [] }, { "id": "PMID-8083467_T16", "type": "Protein", "text": [ "IL-4" ], "offsets": [ [ 1024, 1028 ] ], "normalized": [] }, { "id": "PMID-8083467_T17", "type": "Protein", "text": [ "P65" ], "offsets": [ [ 1407, 1410 ] ], "normalized": [] }, { "id": "PMID-8083467_T18", "type": "Protein", "text": [ "P65" ], "offsets": [ [ 1414, 1417 ] ], "normalized": [] }, { "id": "PMID-8083467_T19", "type": "Protein", "text": [ "P50" ], "offsets": [ [ 1418, 1421 ] ], "normalized": [] }, { "id": "PMID-8083467_T20", "type": "Protein", "text": [ "P65" ], "offsets": [ [ 1571, 1574 ] ], "normalized": [] }, { "id": "PMID-8083467_T21", "type": "Protein", "text": [ "IL-4" ], "offsets": [ [ 1876, 1880 ] ], "normalized": [] }, { "id": "PMID-8083467_T22", "type": "Protein", "text": [ "IL-5" ], "offsets": [ [ 1885, 1889 ] ], "normalized": [] }, { "id": "PMID-8083467_T34", "type": "Entity", "text": [ "promoter" ], "offsets": [ [ 575, 583 ] ], "normalized": [] }, { "id": "PMID-8083467_T37", "type": "Entity", "text": [ "promoter" ], "offsets": [ [ 721, 729 ] ], "normalized": [] }, { "id": "PMID-8083467_T42", "type": "Entity", "text": [ "promoter" ], "offsets": [ [ 926, 934 ] ], "normalized": [] }, { "id": "PMID-8083467_T43", "type": "Entity", "text": [ "P sequence" ], "offsets": [ [ 1006, 1016 ] ], "normalized": [] } ]

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"trigger": { "text": [ "produce" ], "offsets": [ [ 148, 155 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "PMID-8083467_T4" } ] }, { "id": "PMID-8083467_E7", "type": "Gene_expression", "trigger": { "text": [ "produce" ], "offsets": [ [ 148, 155 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "PMID-8083467_T6" } ] }, { "id": "PMID-8083467_E8", "type": "Gene_expression", "trigger": { "text": [ "produce" ], "offsets": [ [ 148, 155 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "PMID-8083467_T7" } ] }, { "id": "PMID-8083467_E9", "type": "Gene_expression", "trigger": { "text": [ "produce" ], "offsets": [ [ 148, 155 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "PMID-8083467_T5" } ] }, { "id": "PMID-8083467_E10", "type": "Positive_regulation", "trigger": { "text": [ "in response" ], "offsets": [ [ 266, 277 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "PMID-8083467_E6" } ] }, { "id": "PMID-8083467_E11", "type": "Positive_regulation", "trigger": { "text": [ "in response" 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363, 367 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "PMID-8083467_E15" } ] }, { "id": "PMID-8083467_E17", "type": "Positive_regulation", "trigger": { "text": [ "augments" ], "offsets": [ [ 415, 423 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "PMID-8083467_E18" } ] }, { "id": "PMID-8083467_E18", "type": "Positive_regulation", "trigger": { "text": [ "dependent" ], "offsets": [ [ 428, 437 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "PMID-8083467_E19" } ] }, { "id": "PMID-8083467_E19", "type": "Gene_expression", "trigger": { "text": [ "production" ], "offsets": [ [ 443, 453 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "PMID-8083467_T9" } ] }, { "id": "PMID-8083467_E20", "type": "Positive_regulation", "trigger": { "text": [ "required" ], "offsets": [ [ 531, 539 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "PMID-8083467_E21" } ] }, { "id": "PMID-8083467_E21", "type": "Positive_regulation", "trigger": { "text": [ "activation" ], "offsets": [ [ 552, 562 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "PMID-8083467_T10" }, { "role": "Site", "ref_id": "PMID-8083467_T34" } ] }, { "id": "PMID-8083467_E22", "type": "Negative_regulation", "trigger": { "text": [ "inhibited" ], "offsets": [ [ 621, 630 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "PMID-8083467_E24" } ] }, { "id": "PMID-8083467_E23", "type": "Negative_regulation", "trigger": { "text": [ "inhibited" ], "offsets": [ [ 621, 630 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "PMID-8083467_E25" } ] }, { "id": "PMID-8083467_E24", "type": "Positive_regulation", "trigger": { "text": [ "activation" ], "offsets": [ [ 649, 659 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "PMID-8083467_T11" } ] }, { "id": "PMID-8083467_E25", "type": "Positive_regulation", "trigger": { "text": [ "activation" ], "offsets": [ [ 649, 659 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "PMID-8083467_T12" }, { "role": "Site", "ref_id": "PMID-8083467_T37" } ] }, { "id": "PMID-8083467_E26", "type": "Positive_regulation", "trigger": { "text": [ "positively regulated" ], "offsets": [ [ 776, 796 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "PMID-8083467_T13" } ] }, { "id": "PMID-8083467_E27", "type": "Negative_regulation", "trigger": { "text": [ "opposite" ], "offsets": [ [ 817, 825 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "PMID-8083467_T14" } ] }, { "id": "PMID-8083467_E28", "type": "Regulation", "trigger": { "text": [ "regulates" ], "offsets": [ [ 891, 900 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "PMID-8083467_E29" } ] }, { "id": "PMID-8083467_E29", "type": "Regulation", "trigger": { "text": [ "response" ], "offsets": [ [ 905, 913 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "PMID-8083467_T15" }, { "role": "Site", "ref_id": "PMID-8083467_T42" } ] }, { "id": "PMID-8083467_E30", "type": "Regulation", "trigger": { "text": [ "defined as a responsive element" ], "offsets": [ [ 1035, 1066 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "PMID-8083467_T16" }, { "role": "Site", "ref_id": "PMID-8083467_T43" } ] }, { "id": "PMID-8083467_E31", "type": "Binding", "trigger": { "text": [ "bound" ], "offsets": [ [ 1445, 1450 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "PMID-8083467_T17" } ] }, { "id": "PMID-8083467_E32", "type": "Binding", "trigger": { "text": [ "bound" ], "offsets": [ [ 1445, 1450 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "PMID-8083467_T19" } ] }, { "id": "PMID-8083467_E33", "type": "Binding", "trigger": { "text": [ "bound" ], "offsets": [ [ 1445, 1450 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "PMID-8083467_T18" } ] }, { "id": "PMID-8083467_E34", "type": "Regulation", "trigger": { "text": [ "regulation" ], "offsets": [ [ 1862, 1872 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "PMID-8083467_T22" } ] }, { "id": "PMID-8083467_E35", "type": "Regulation", "trigger": { "text": [ "regulation" ], "offsets": [ [ 1862, 1872 ] ] }, "arguments": [ { "role": "Theme", "ref_id": 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[ { "id": "PMID-8088776__text", "type": "abstract", "text": [ "Structure and expression of the human GATA3 gene. \nGATA3, a member of the GATA family that is abundantly expressed in the T-lymphocyte lineage, is thought to participate in T-cell receptor gene activation through binding to enhancers. To understand GATA3 gene regulation, we cloned the human gene and the 5' end of the mouse GATA3 gene. We show that the human GATA3 gene contains six exons distributed over 17 kb of DNA. The two human GATA3 zinc fingers are encoded by two separate exons highly conserved with those of GATA1, but no other structural homologies between these two genes can be found. The human and mouse GATA3 transcription units start at a major initiation site. The promoter sequence analysis of these two genes revealed that they are embedded within a CpG island and share structural features often found in the promoters of housekeeping genes. Finally, we show that a DNA fragment containing the human GATA3 transcription unit, 3 kb upstream from the initiation site and 4 kb downstream from the polyadenylation site, displays T-cell specificity. " ], "offsets": [ [ 0, 1066 ] ] } ]

[ { "id": "PMID-8088776_T1", "type": "Protein", "text": [ "GATA3" ], "offsets": [ [ 38, 43 ] ], "normalized": [] }, { "id": "PMID-8088776_T2", "type": "Protein", "text": [ "GATA3" ], "offsets": [ [ 51, 56 ] ], "normalized": [] }, { "id": "PMID-8088776_T3", "type": "Protein", "text": [ "GATA3" ], "offsets": [ [ 249, 254 ] ], "normalized": [] }, { "id": "PMID-8088776_T4", "type": "Protein", "text": [ "GATA3" ], "offsets": [ [ 325, 330 ] ], "normalized": [] }, { "id": "PMID-8088776_T5", "type": "Protein", "text": [ "GATA3" ], "offsets": [ [ 360, 365 ] ], "normalized": [] }, { "id": "PMID-8088776_T6", "type": "Protein", "text": [ "GATA3" ], "offsets": [ [ 435, 440 ] ], "normalized": [] }, { "id": "PMID-8088776_T7", "type": "Protein", "text": [ "GATA1" ], "offsets": [ [ 519, 524 ] ], "normalized": [] }, { "id": "PMID-8088776_T8", "type": "Protein", "text": [ "GATA3" ], "offsets": [ [ 619, 624 ] ], "normalized": [] }, { "id": "PMID-8088776_T9", "type": "Protein", "text": [ "GATA3" ], "offsets": [ [ 921, 926 ] ], "normalized": [] } ]

[ { "id": "PMID-8088776_E1", "type": "Gene_expression", "trigger": { "text": [ "expression" ], "offsets": [ [ 14, 24 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "PMID-8088776_T1" } ] }, { "id": "PMID-8088776_E2", "type": "Gene_expression", "trigger": { "text": [ "expressed" ], "offsets": [ [ 105, 114 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "PMID-8088776_T2" } ] }, { "id": "PMID-8088776_E3", "type": "Binding", "trigger": { "text": [ "binding" ], "offsets": [ [ 213, 220 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "PMID-8088776_T2" } ] }, { "id": "PMID-8088776_E4", "type": "Regulation", "trigger": { "text": [ "regulation" ], "offsets": [ [ 260, 270 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "PMID-8088776_T3" } ] } ]

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[ { "id": "PMID-8135784__text", "type": "abstract", "text": [ "Characterization of NF(P), the nuclear factor that interacts with the regulatory P sequence (5'-CGAAAATTTCC-3') of the human interleukin-4 gene: relationship to NF-kappa B and NF-AT. \nThe P sequence of the human interleukin-4 (IL-4) gene, which was defined as a responsive element for phorbol 12-myristate 13-acetate and calcium ionophore (A23187) in Jurkat T cells, shares sequence similarity with the NF-kappa B and the NF-AT binding sites. We examined whether NF(P), a nuclear factor specific for the P sequence, is related to NF-kappa B and NF-AT. NF-kappa B (P65 or P65/P50 heterodimer) bound to the P sequence in electrophoretic mobility shift assays (EMSA) and activated transcription through the P sequence when expression plasmids were cotransfected with P sequence-driven reporter plasmids in Jurkat T cells. In EMSAs, NF(P) binding was inhibited by the unlabeled NF-AT binding site but not by the unlabeled AP1 binding site and purified NF-AT contained an activity that bound to the P sequence. Both mobility shift and sequence specificity of NF-AT were similar to those of NF(P) and only a small amount of P65 was detected in NF(P) in crude nuclear extracts. These results indicate that the component(s) of NF-AT has the potential to reconstitute NF(P) whereas NF-kappa B alone cannot account for NF(P) in crude extracts. Unlike NF-AT, NF(P) does not contain AP1 as its DNA binding component. " ], "offsets": [ [ 0, 1405 ] ] } ]

[ { "id": "PMID-8135784_T1", "type": "Protein", "text": [ "interleukin-4" ], "offsets": [ [ 125, 138 ] ], "normalized": [] }, { "id": "PMID-8135784_T2", "type": "Protein", "text": [ "interleukin-4" ], "offsets": [ [ 212, 225 ] ], "normalized": [] }, { "id": "PMID-8135784_T3", "type": "Protein", "text": [ "IL-4" ], "offsets": [ [ 227, 231 ] ], "normalized": [] }, { "id": "PMID-8135784_T4", "type": "Protein", "text": [ "P65" ], "offsets": [ [ 564, 567 ] ], "normalized": [] }, { "id": "PMID-8135784_T5", "type": "Protein", "text": [ "P65" ], "offsets": [ [ 571, 574 ] ], "normalized": [] }, { "id": "PMID-8135784_T6", "type": "Protein", "text": [ "P50" ], "offsets": [ [ 575, 578 ] ], "normalized": [] }, { "id": "PMID-8135784_T7", "type": "Protein", "text": [ "P65" ], "offsets": [ [ 1118, 1121 ] ], "normalized": [] }, { "id": "PMID-8135784_T9", "type": "Entity", "text": [ "P sequence" ], "offsets": [ [ 81, 91 ] ], "normalized": [] }, { "id": "PMID-8135784_T10", "type": "Entity", "text": [ "P sequence" ], "offsets": [ [ 188, 198 ] ], "normalized": [] } ]

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[ { "id": "PMID-8135784_1", "entity_ids": [ "PMID-8135784_T2", "PMID-8135784_T3" ] } ]

[]

[ { "id": "PMID-8137243__text", "type": "abstract", "text": [ "Hypoxia causes the activation of nuclear factor kappa B through the phosphorylation of I kappa B alpha on tyrosine residues. \nThe response of mammalian cells to stress is controlled by transcriptional regulatory proteins such as nuclear factor kappa B (NF-kappa B) to induce a wide variety of early response genes. In this report, we show that exposure of cells to hypoxia (0.02% O2) results in I kappa B alpha degradation, increased NF-kappa B DNA binding activity, and transactivation of a reporter gene construct containing two NF-kappa B DNA binding sites. Pretreatment of cells with protein tyrosine kinase inhibitors and the dominant negative allele of c-Raf-1 (Raf 301) inhibited I kappa B alpha degradation, NF-kappa B binding, and transactivation of kappa B reporter constructs by hypoxia. To demonstrate a direct link between changes in the phosphorylation pattern of I kappa B alpha with NF-kappa B activation, we immunoprecipitated I kappa B alpha after varying times of hypoxic exposure and found that its tyrosine phosphorylation status increased during hypoxic exposure. Inhibition of the transfer of tyrosine phosphoryl groups onto I kappa B alpha prevented I kappa B alpha degradation and NF-kappa B binding. In comparison to other activators of NF-kappa B such as phorbol myristate acetate or tumor necrosis factor, we did not detect changes in the tyrosine phosphorylation status of I kappa B alpha following treatment with either of these agents. These results suggest that tyrosine phosphorylation of I kappa B alpha during hypoxia is an important proximal step which precedes its dissociation and degradation from NF-kappa B. " ], "offsets": [ [ 0, 1648 ] ] } ]

[ { "id": "PMID-8137243_T1", "type": "Protein", "text": [ "I kappa B alpha" ], "offsets": [ [ 87, 102 ] ], "normalized": [] }, { "id": "PMID-8137243_T2", "type": "Protein", "text": [ "I kappa B alpha" ], "offsets": [ [ 395, 410 ] ], "normalized": [] }, { "id": "PMID-8137243_T3", "type": "Protein", "text": [ "I kappa B alpha" ], "offsets": [ [ 687, 702 ] ], "normalized": [] }, { "id": "PMID-8137243_T4", "type": "Protein", "text": [ "I kappa B alpha" ], "offsets": [ [ 878, 893 ] ], "normalized": [] }, { "id": "PMID-8137243_T5", "type": "Protein", "text": [ "I kappa B alpha" ], "offsets": [ [ 944, 959 ] ], "normalized": [] }, { "id": "PMID-8137243_T6", "type": "Protein", "text": [ "I kappa B alpha" ], "offsets": [ [ 1148, 1163 ] ], "normalized": [] }, { "id": "PMID-8137243_T7", "type": "Protein", "text": [ "I kappa B alpha" ], "offsets": [ [ 1174, 1189 ] ], "normalized": [] }, { "id": "PMID-8137243_T8", "type": "Protein", "text": [ "I kappa B alpha" ], "offsets": [ [ 1402, 1417 ] ], "normalized": [] }, { "id": "PMID-8137243_T9", "type": "Protein", "text": [ "I kappa B alpha" ], "offsets": [ [ 1522, 1537 ] ], "normalized": [] }, { "id": "PMID-8137243_T18", "type": "Entity", "text": [ "tyrosine" ], "offsets": [ [ 1019, 1027 ] ], "normalized": [] }, { "id": "PMID-8137243_T26", "type": "Entity", "text": [ "tyrosine" ], "offsets": [ [ 1367, 1375 ] ], "normalized": [] }, { "id": "PMID-8137243_T28", "type": "Entity", "text": [ "tyrosine" ], "offsets": [ [ 1494, 1502 ] ], "normalized": [] } ]

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