Datasets:

bigbio

/

bionlp_st_2011_ge

like 0

[ { "id": "PMID-9115810__text", "type": "abstract", "text": [ "NF-kappa B-independent suppression of HIV expression by ascorbic acid. \nAscorbic acid (ascorbate or vitamin C) has been shown to suppress the induction of HIV in latently infected T lymphocytic cells following stimulation with a tumor promoter (PMA) and inflammatory cytokine (TNF-alpha). To assess whether this inhibition was mediated via modulation of the cellular transcription factor, NF-kappa B, we carried out gel shift analysis on nuclear extracts prepared under different conditions of cell stimulation in the presence or absence of ascorbate, N-acetylcysteine (NAC), or zidovudine (AZT). Pretreatment of ACH-2 T cells by NAC followed by stimulation with PMA, TNF-alpha, or hydrogen peroxide (H2O2) resulted in strong suppression of NF-kappa B activation. In contrast, neither ascorbate nor AZT affected NF-kappa B activity under all three induction conditions in the ACH-2 cell line. Ascorbate and AZT also had no effect on NF-kappa B activation following TNF-alpha- or PMA-induced stimulation of U1 promonocytic cells. These results suggest that the molecular mechanism of HIV inhibition by ascorbate is not mediated via NF-kappa B inhibition, unlike that seen with other antioxidants. " ], "offsets": [ [ 0, 1196 ] ] } ]

[ { "id": "PMID-9115810_T1", "type": "Protein", "text": [ "TNF-alpha" ], "offsets": [ [ 277, 286 ] ], "normalized": [] }, { "id": "PMID-9115810_T2", "type": "Protein", "text": [ "TNF-alpha" ], "offsets": [ [ 668, 677 ] ], "normalized": [] }, { "id": "PMID-9115810_T3", "type": "Protein", "text": [ "TNF-alpha" ], "offsets": [ [ 965, 974 ] ], "normalized": [] } ]

[]

[]

[]

[ { "id": "PMID-9116279__text", "type": "abstract", "text": [ "Lineage- and stage-specific expression of runt box polypeptides in primitive and definitive hematopoiesis. \nTranslocations involving the human CBFA2 locus have been associated with leukemia. This gene, originally named AML1, is a human homologue of the Drosophila gene runt that controls early events in fly embryogenesis. To clarify the role of mammalian runt products in normal and leukemic hematopoiesis, we have studied their pattern of expression in mouse hematopoietic tissues in the adult and during ontogeny using an anti-runt box antiserum. In the adult bone marrow, we found expression of runt polypeptides in differentiating myeloid cells and in B lymphocytes. Within the erythroid lineage, runt expression is biphasic, clearly present in the erythroblasts of early blood islands and of the fetal liver, but absent in the adult. Biochemical analysis by Western blotting of fetal and adult hematopoietic populations shows several runt isoforms. At least one of them appears to be myeloid specific. " ], "offsets": [ [ 0, 1008 ] ] } ]

[ { "id": "PMID-9116279_T1", "type": "Protein", "text": [ "runt" ], "offsets": [ [ 42, 46 ] ], "normalized": [] }, { "id": "PMID-9116279_T2", "type": "Protein", "text": [ "CBFA2" ], "offsets": [ [ 143, 148 ] ], "normalized": [] }, { "id": "PMID-9116279_T3", "type": "Protein", "text": [ "AML1" ], "offsets": [ [ 219, 223 ] ], "normalized": [] }, { "id": "PMID-9116279_T4", "type": "Protein", "text": [ "runt" ], "offsets": [ [ 269, 273 ] ], "normalized": [] }, { "id": "PMID-9116279_T5", "type": "Protein", "text": [ "runt" ], "offsets": [ [ 356, 360 ] ], "normalized": [] }, { "id": "PMID-9116279_T6", "type": "Protein", "text": [ "runt" ], "offsets": [ [ 702, 706 ] ], "normalized": [] } ]

[ { "id": "PMID-9116279_E1", "type": "Gene_expression", "trigger": { "text": [ "expression" ], "offsets": [ [ 707, 717 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "PMID-9116279_T6" } ] }, { "id": "PMID-9116279_E2", "type": "Gene_expression", "trigger": { "text": [ "absent" ], "offsets": [ [ 819, 825 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "PMID-9116279_T6" } ] } ]

[]

[]

[ { "id": "PMID-9119025__text", "type": "abstract", "text": [ "Cell-to-cell contact activates the long terminal repeat of human immunodeficiency virus 1 through its kappaB motif. \nCell-to-cell contact between peripheral blood lymphocytes and transfected human colonic carcinoma cell line HT29 activates transcription of the long terminal repeats (LTR) of human immunodeficiency virus. HIV-1 LTR transcription is controlled by a complex array of virus-encoded and cellular proteins. Using various constructs expressing a lacZ reporter gene under the control of the intact or three deleted forms of HIV-1 LTR, we obtained evidence that the kappaB regulatory elements located in the U3 region are involved in cell-to-cell activation of HIV-1 LTR. Cell-to-cell contact activates in vitro binding of the nuclear factor kappaB (NF-kappaB) p50/p65 heterodimer to an HIV-1 kappaB oligonucleotide. Cell-to-cell contact activation of NF-kappaB was only partially inhibited by 100 microM pyrrolidine dithiocarbamate and was not correlated with a significant decrease of cellular inhibitor kappaB alpha. NF-kappaB nuclear activation was not detectable before 1 h after cell contact and was dependent on protein synthesis. " ], "offsets": [ [ 0, 1147 ] ] } ]

[ { "id": "PMID-9119025_T1", "type": "Protein", "text": [ "p50" ], "offsets": [ [ 770, 773 ] ], "normalized": [] }, { "id": "PMID-9119025_T2", "type": "Protein", "text": [ "p65" ], "offsets": [ [ 774, 777 ] ], "normalized": [] }, { "id": "PMID-9119025_T3", "type": "Protein", "text": [ "inhibitor kappaB alpha" ], "offsets": [ [ 1005, 1027 ] ], "normalized": [] } ]

[ { "id": "PMID-9119025_E1", "type": "Positive_regulation", "trigger": { "text": [ "activates" ], "offsets": [ [ 702, 711 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "PMID-9119025_E4" } ] }, { "id": "PMID-9119025_E2", "type": "Positive_regulation", "trigger": { "text": [ "activates" ], "offsets": [ [ 702, 711 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "PMID-9119025_E3" } ] }, { "id": "PMID-9119025_E3", "type": "Binding", "trigger": { "text": [ "binding" ], "offsets": [ [ 721, 728 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "PMID-9119025_T2" } ] }, { "id": "PMID-9119025_E4", "type": "Binding", "trigger": { "text": [ "binding" ], "offsets": [ [ 721, 728 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "PMID-9119025_T1" } ] }, { "id": "PMID-9119025_E5", "type": "Negative_regulation", "trigger": { "text": [ "decrease" ], "offsets": [ [ 984, 992 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "PMID-9119025_T3" } ] } ]

[]

[]

[ { "id": "PMID-9119999__text", "type": "abstract", "text": [ "HIV does not replicate in naive CD4 T cells stimulated with CD3/CD28. \nIn this report, we demonstrate that the T cell tropic strain of HIV, LAI, does not replicate in naive CD4 T cells stimulated by cross-linking CD3 and CD28. In contrast, LAI replicates well in memory CD4 T cells stimulated in the same way. Unlike this physiologically relevant stimulation, PHA stimulates productive LAI replication in both naive and memory T cells. These studies were conducted with highly purified (FACS-isolated) subsets of CD4 T cells identified by expression of both CD45RA and CD62L. Remixing of purified T cells showed that naive T cells do not suppress LAI replication in memory T cells and that memory T cells do not restore LAI expression in naive T cells. The suppression of productive LAI replication in naive T cells is not due to differential expression of viral coreceptors, nor is it due to inhibition of activation of the important HIV transcription factors, nuclear factor-kappaB and activator protein-1. The inherent resistance of naive T cells to productive HIV infection, coupled with their proliferative advantage as demonstrated here, provides a sound basis for proposed clinical therapies using ex vivo expansion and reinfusion of CD4 T cells from HIV-infected adults. " ], "offsets": [ [ 0, 1279 ] ] } ]

[ { "id": "PMID-9119999_T1", "type": "Protein", "text": [ "CD4" ], "offsets": [ [ 32, 35 ] ], "normalized": [] }, { "id": "PMID-9119999_T2", "type": "Protein", "text": [ "CD28" ], "offsets": [ [ 64, 68 ] ], "normalized": [] }, { "id": "PMID-9119999_T3", "type": "Protein", "text": [ "CD4" ], "offsets": [ [ 173, 176 ] ], "normalized": [] }, { "id": "PMID-9119999_T4", "type": "Protein", "text": [ "CD28" ], "offsets": [ [ 221, 225 ] ], "normalized": [] }, { "id": "PMID-9119999_T5", "type": "Protein", "text": [ "CD4" ], "offsets": [ [ 270, 273 ] ], "normalized": [] }, { "id": "PMID-9119999_T6", "type": "Protein", "text": [ "PHA" ], "offsets": [ [ 360, 363 ] ], "normalized": [] }, { "id": "PMID-9119999_T7", "type": "Protein", "text": [ "CD4" ], "offsets": [ [ 513, 516 ] ], "normalized": [] }, { "id": "PMID-9119999_T8", "type": "Protein", "text": [ "CD45RA" ], "offsets": [ [ 558, 564 ] ], "normalized": [] }, { "id": "PMID-9119999_T9", "type": "Protein", "text": [ "CD62L" ], "offsets": [ [ 569, 574 ] ], "normalized": [] }, { "id": "PMID-9119999_T10", "type": "Protein", "text": [ "CD4" ], "offsets": [ [ 1241, 1244 ] ], "normalized": [] } ]

[ { "id": "PMID-9119999_E1", "type": "Binding", "trigger": { "text": [ "cross-linking" ], "offsets": [ [ 199, 212 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "PMID-9119999_T4" } ] } ]

[]

[]

[ { "id": "PMID-9121455__text", "type": "abstract", "text": [ "Control of NFATx1 nuclear translocation by a calcineurin-regulated inhibitory domain. \nThe nuclear factor of activated T cells (NFAT) regulates cytokine gene expression in T cells through cis-acting elements located in the promoters of several cytokine genes. NFATx1, which is preferentially expressed in the thymus and peripheral blood leukocytes, is one of four members of the NFAT family of transcription factors. We have performed domain analysis of NFATx1 by examining the effects of deletion mutations. We found that NFATx1 DNA binding activity and interaction with AP-1 polypeptides were dependent on its central Rel similarity region and that transcriptional activation was reduced by deletions of either its N-terminal domain or its C-terminal domain, suggesting the presence of intrinsic transcriptional activation motifs in both regions. We also identified a potent inhibitory sequence within its N-terminal domain. We show that the inactivation of the inhibition was dependent on the activity of calcineurin, a calcium-calmodulin-dependent phosphatase. We also show that calcineurin associated with the N-terminal domain of NFATx1 at multiple docking sites and caused a reduction of size, indicative of dephosphorylation, in NFATx1. We have mapped the inhibitory activity to less than 60 residues, containing motifs that are conserved in all NFAT proteins. Finally, we demonstrate that deletion in NFATx1 of the mapped 60 residues leads to its nuclear translocation independent of calcium signaling. Our results support the model proposing that the N-terminal domain confers calcium-signaling dependence on NFATx1 transactivation activity by regulating its intracellular localization through a protein module that associates with calcineurin and is a target of its phosphatase activity. " ], "offsets": [ [ 0, 1799 ] ] } ]

[ { "id": "PMID-9121455_T1", "type": "Protein", "text": [ "NFATx1" ], "offsets": [ [ 11, 17 ] ], "normalized": [] }, { "id": "PMID-9121455_T2", "type": "Protein", "text": [ "NFATx1" ], "offsets": [ [ 260, 266 ] ], "normalized": [] }, { "id": "PMID-9121455_T3", "type": "Protein", "text": [ "NFATx1" ], "offsets": [ [ 454, 460 ] ], "normalized": [] }, { "id": "PMID-9121455_T4", "type": "Protein", "text": [ "NFATx1" ], "offsets": [ [ 523, 529 ] ], "normalized": [] }, { "id": "PMID-9121455_T5", "type": "Protein", "text": [ "NFATx1" ], "offsets": [ [ 1136, 1142 ] ], "normalized": [] }, { "id": "PMID-9121455_T6", "type": "Protein", "text": [ "NFATx1" ], "offsets": [ [ 1237, 1243 ] ], "normalized": [] }, { "id": "PMID-9121455_T7", "type": "Protein", "text": [ "NFATx1" ], "offsets": [ [ 1410, 1416 ] ], "normalized": [] }, { "id": "PMID-9121455_T8", "type": "Protein", "text": [ "NFATx1" ], "offsets": [ [ 1619, 1625 ] ], "normalized": [] }, { "id": "PMID-9121455_T10", "type": "Entity", "text": [ "nuclear" ], "offsets": [ [ 18, 25 ] ], "normalized": [] }, { "id": "PMID-9121455_T19", "type": "Entity", "text": [ "nuclear" ], "offsets": [ [ 1456, 1463 ] ], "normalized": [] }, { "id": "PMID-9121455_T23", "type": "Entity", "text": [ "intracellular" ], "offsets": [ [ 1669, 1682 ] ], "normalized": [] } ]

[ { "id": "PMID-9121455_E1", "type": "Regulation", "trigger": { "text": [ "Control" ], "offsets": [ [ 0, 7 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "PMID-9121455_E2" } ] }, { "id": "PMID-9121455_E2", "type": "Localization", "trigger": { "text": [ "translocation" ], "offsets": [ [ 26, 39 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "PMID-9121455_T1" }, { "role": "ToLoc", "ref_id": "PMID-9121455_T10" } ] }, { "id": "PMID-9121455_E3", "type": "Gene_expression", "trigger": { "text": [ "expressed" ], "offsets": [ [ 292, 301 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "PMID-9121455_T2" } ] }, { "id": "PMID-9121455_E4", "type": "Binding", "trigger": { "text": [ "binding" ], "offsets": [ [ 534, 541 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "PMID-9121455_T4" } ] }, { "id": "PMID-9121455_E5", "type": "Positive_regulation", "trigger": { "text": [ "dependent" ], "offsets": [ [ 595, 604 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "PMID-9121455_E4" } ] }, { "id": "PMID-9121455_E6", "type": "Positive_regulation", "trigger": { "text": [ "transcriptional activation" ], "offsets": [ [ 651, 677 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "PMID-9121455_T4" } ] }, { "id": "PMID-9121455_E7", "type": "Negative_regulation", "trigger": { "text": [ "reduced" ], "offsets": [ [ 682, 689 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "PMID-9121455_E6" } ] }, { "id": "PMID-9121455_E8", "type": "Binding", "trigger": { "text": [ "associated" ], "offsets": [ [ 1095, 1105 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "PMID-9121455_T5" } ] }, { "id": "PMID-9121455_E9", "type": "Positive_regulation", "trigger": { "text": [ "leads" ], "offsets": [ [ 1443, 1448 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "PMID-9121455_E10" } ] }, { "id": "PMID-9121455_E10", "type": "Localization", "trigger": { "text": [ "translocation" ], "offsets": [ [ 1464, 1477 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "PMID-9121455_T7" }, { "role": "ToLoc", "ref_id": "PMID-9121455_T19" } ] }, { "id": "PMID-9121455_E11", "type": "Positive_regulation", "trigger": { "text": [ "independent" ], "offsets": [ [ 1478, 1489 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "PMID-9121455_E10" } ] }, { "id": "PMID-9121455_E12", "type": "Regulation", "trigger": { "text": [ "regulating" ], "offsets": [ [ 1654, 1664 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "PMID-9121455_E13" } ] }, { "id": "PMID-9121455_E13", "type": "Localization", "trigger": { "text": [ "localization" ], "offsets": [ [ 1683, 1695 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "PMID-9121455_T8" }, { "role": "AtLoc", "ref_id": "PMID-9121455_T23" } ] }, { "id": "PMID-9121455_E14", "type": "Regulation", "trigger": { "text": [ "through" ], "offsets": [ [ 1696, 1703 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "PMID-9121455_E12" } ] } ]

[]

[]

[ { "id": "PMID-9122255__text", "type": "abstract", "text": [ "Neuronal (type I) nitric oxide synthase regulates nuclear factor kappaB activity and immunologic (type II) nitric oxide synthase expression. \nNitric oxide subserves diverse physiologic roles in the nervous system. NO is produced from at least three different NO synthase (NOS) isoforms: neuronal NOS (nNOS), endothelial NOS, and immunologic NOS (iNOS). We show that nNOS is the predominant isoform constitutively expressed in glia. NO derived from nNOS in glia inhibits the transcription factor nuclear factor kappaB (NF kappaB) as NOS inhibitors enhance basal NF kappaB activation. Pyrrolidine dithiocarbamate (PDTC) is an inhibitor of NF kappaB in most cells; however, we show that PDTC is also a potent scavenger of NO through formation of mononitrosyl iron complexes with PDTC. In Jurkat cells, a human T-cell lymphoma cell line, tumor necrosis factor-alpha (TNF-alpha) induces NF kappaB activation that is inhibited by PDTC. Contrary to the results in Jurkat cells, PDTC did not inhibit tumor necrosis factor-alpha-induced NF kappaB activation in astrocytes; instead PDTC itself induces NF kappaB activation in astrocytes, and this may be related to scavenging of endogenously produced NO by the PDTC iron complex. In astrocytes PDTC also dramatically induces the NF kappaB-dependent enzyme, iNOS, supporting the physiologic relevance of endogenous NO regulation of NF kappaB. NF kappaB activation in glia from mice lacking nNOS responds more rapidly to PDTC compared with astrocytes from wild-type mice. Our data suggest that nNOS in astrocytes regulates NF kappaB activity and iNOS expression, and indicate a novel regulatory role for nNOS in tonically suppressing central nervous system, NF kappaB-regulated genes. " ], "offsets": [ [ 0, 1723 ] ] } ]

[ { "id": "PMID-9122255_T1", "type": "Protein", "text": [ "Neuronal (type I) nitric oxide synthase" ], "offsets": [ [ 0, 39 ] ], "normalized": [] }, { "id": "PMID-9122255_T2", "type": "Protein", "text": [ "immunologic (type II) nitric oxide synthase" ], "offsets": [ [ 85, 128 ] ], "normalized": [] }, { "id": "PMID-9122255_T3", "type": "Protein", "text": [ "neuronal NOS" ], "offsets": [ [ 287, 299 ] ], "normalized": [] }, { "id": "PMID-9122255_T4", "type": "Protein", "text": [ "nNOS" ], "offsets": [ [ 301, 305 ] ], "normalized": [] }, { "id": "PMID-9122255_T5", "type": "Protein", "text": [ "endothelial NOS" ], "offsets": [ [ 308, 323 ] ], "normalized": [] }, { "id": "PMID-9122255_T6", "type": "Protein", "text": [ "immunologic NOS" ], "offsets": [ [ 329, 344 ] ], "normalized": [] }, { "id": "PMID-9122255_T7", "type": "Protein", "text": [ "iNOS" ], "offsets": [ [ 346, 350 ] ], "normalized": [] }, { "id": "PMID-9122255_T8", "type": "Protein", "text": [ "nNOS" ], "offsets": [ [ 366, 370 ] ], "normalized": [] }, { "id": "PMID-9122255_T9", "type": "Protein", "text": [ "nNOS" ], "offsets": [ [ 448, 452 ] ], "normalized": [] }, { "id": "PMID-9122255_T10", "type": "Protein", "text": [ "tumor necrosis factor-alpha" ], "offsets": [ [ 834, 861 ] ], "normalized": [] }, { "id": "PMID-9122255_T11", "type": "Protein", "text": [ "TNF-alpha" ], "offsets": [ [ 863, 872 ] ], "normalized": [] }, { "id": "PMID-9122255_T12", "type": "Protein", "text": [ "tumor necrosis factor-alpha" ], "offsets": [ [ 992, 1019 ] ], "normalized": [] }, { "id": "PMID-9122255_T13", "type": "Protein", "text": [ "iNOS" ], "offsets": [ [ 1297, 1301 ] ], "normalized": [] }, { "id": "PMID-9122255_T14", "type": "Protein", "text": [ "nNOS" ], "offsets": [ [ 1429, 1433 ] ], "normalized": [] }, { "id": "PMID-9122255_T15", "type": "Protein", "text": [ "nNOS" ], "offsets": [ [ 1532, 1536 ] ], "normalized": [] }, { "id": "PMID-9122255_T16", "type": "Protein", "text": [ "iNOS" ], "offsets": [ [ 1584, 1588 ] ], "normalized": [] }, { "id": "PMID-9122255_T17", "type": "Protein", "text": [ "nNOS" ], "offsets": [ [ 1642, 1646 ] ], "normalized": [] } ]

[ { "id": "PMID-9122255_E1", "type": "Regulation", "trigger": { "text": [ "regulates" ], "offsets": [ [ 40, 49 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "PMID-9122255_E2" }, { "role": "Cause", "ref_id": "PMID-9122255_T1" } ] }, { "id": "PMID-9122255_E2", "type": "Gene_expression", "trigger": { "text": [ "expression" ], "offsets": [ [ 129, 139 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "PMID-9122255_T2" } ] }, { "id": "PMID-9122255_E3", "type": "Gene_expression", "trigger": { "text": [ "expressed" ], "offsets": [ [ 413, 422 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "PMID-9122255_T8" } ] }, { "id": "PMID-9122255_E4", "type": "Positive_regulation", "trigger": { "text": [ "induces" ], "offsets": [ [ 1257, 1264 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "PMID-9122255_T13" } ] }, { "id": "PMID-9122255_E5", "type": "Positive_regulation", "trigger": { "text": [ "dependent" ], "offsets": [ [ 1279, 1288 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "PMID-9122255_T13" } ] }, { "id": "PMID-9122255_E6", "type": "Negative_regulation", "trigger": { "text": [ "lacking" ], "offsets": [ [ 1421, 1428 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "PMID-9122255_T14" } ] }, { "id": "PMID-9122255_E7", "type": "Regulation", "trigger": { "text": [ "regulates" ], "offsets": [ [ 1551, 1560 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "PMID-9122255_E8" }, { "role": "Cause", "ref_id": "PMID-9122255_T15" } ] }, { "id": "PMID-9122255_E8", "type": "Gene_expression", "trigger": { "text": [ "expression" ], "offsets": [ [ 1589, 1599 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "PMID-9122255_T16" } ] } ]

[ { "id": "PMID-9122255_1", "entity_ids": [ "PMID-9122255_T3", "PMID-9122255_T4" ] }, { "id": "PMID-9122255_2", "entity_ids": [ "PMID-9122255_T10", "PMID-9122255_T11" ] }, { "id": "PMID-9122255_3", "entity_ids": [ "PMID-9122255_T6", "PMID-9122255_T7" ] } ]

[]

[ { "id": "PMID-9130477__text", "type": "abstract", "text": [ "Regulation of human epsilon germline transcription: role of B-cell-specific activator protein. \nGermline transcripts initiate from promoters upstream of the immunoglobulin switch region, and are necessary to target the appropriate switch region for recombination and switching. Different cytokines activate transcription at the appropriate germline promoter. Because binding sites for B-cell-specific activator protein (BSAP) are located upstream of several switch regions in the immunoglobulin heavy chain gene cluster, BSAP might play a role in the regulation of germline transcription and isotype switching. We investigated whether BSAP plays a role in the transcriptional regulation of the epsilon germline promoter in human B cells. Our results showed that BSAP plays a role in both IL-4-dependent induction and CD40-mediated upregulation of human epsilon germline transcription. BSAP is unique among the transcription factors that regulate epsilon germline expression, because it is B cell specific, and is at the merging point of two signalling pathways that are critical for IgE switching. " ], "offsets": [ [ 0, 1098 ] ] } ]

[ { "id": "PMID-9130477_T1", "type": "Protein", "text": [ "B-cell-specific activator protein" ], "offsets": [ [ 60, 93 ] ], "normalized": [] }, { "id": "PMID-9130477_T2", "type": "Protein", "text": [ "B-cell-specific activator protein" ], "offsets": [ [ 385, 418 ] ], "normalized": [] }, { "id": "PMID-9130477_T3", "type": "Protein", "text": [ "BSAP" ], "offsets": [ [ 420, 424 ] ], "normalized": [] }, { "id": "PMID-9130477_T4", "type": "Protein", "text": [ "BSAP" ], "offsets": [ [ 521, 525 ] ], "normalized": [] }, { "id": "PMID-9130477_T5", "type": "Protein", "text": [ "BSAP" ], "offsets": [ [ 635, 639 ] ], "normalized": [] }, { "id": "PMID-9130477_T6", "type": "Protein", "text": [ "BSAP" ], "offsets": [ [ 762, 766 ] ], "normalized": [] }, { "id": "PMID-9130477_T7", "type": "Protein", "text": [ "IL-4" ], "offsets": [ [ 788, 792 ] ], "normalized": [] }, { "id": "PMID-9130477_T8", "type": "Protein", "text": [ "CD40" ], "offsets": [ [ 817, 821 ] ], "normalized": [] }, { "id": "PMID-9130477_T9", "type": "Protein", "text": [ "BSAP" ], "offsets": [ [ 885, 889 ] ], "normalized": [] } ]

[]

[ { "id": "PMID-9130477_1", "entity_ids": [ "PMID-9130477_T2", "PMID-9130477_T3" ] } ]

[]

[ { "id": "PMID-9130512__text", "type": "abstract", "text": [ "Retinoic acid-induced modulation of IL-2 mRNA production and IL-2 receptor expression on T cells. \nBACKGROUND: Retinoic acid (RA) has important immune-modulating effects on both T and B cell function. Our laboratory has shown that RA can enhance in vitro polyclonal B cell immunoglobulin (Ig) response. Investigating cytokines known to affect B cell differentiation, we have recently shown that IL-6 production is augmented by RA. In the present study we have examined the immune modulating effects of RA on IL-2 mRNA, another important cytokine for B cell immunoglobulin production, the expression of IL-2 receptors on T cells, and the RA nuclear receptors. METHODS: Purified T cells were obtained from adenoidal tissues, and incubated with RA (10(-7) M) or DMSO solvent/media control for 0, 6-8, and 24 h. Total mRNA was extracted from T cells, and using RT-PCR, changes in the production of IL-2 and RA receptors (RAR)-alpha,beta,gamma mRNA were determined. The effects of RA on IL-2-alpha receptor expression was determined by flow cytometry on T cells. CONCLUSION: These studies suggest that RA can augment IL-2 mRNA production by T cells with a possible paracrine effect on IL-2R-alpha expression. These changes appear to be mediated by RAR-alpha. Thus, IL-2 may be another important cytokine modulated by RA in the immune response. " ], "offsets": [ [ 0, 1339 ] ] } ]

[ { "id": "PMID-9130512_T1", "type": "Protein", "text": [ "IL-2" ], "offsets": [ [ 36, 40 ] ], "normalized": [] }, { "id": "PMID-9130512_T2", "type": "Protein", "text": [ "IL-2" ], "offsets": [ [ 61, 65 ] ], "normalized": [] }, { "id": "PMID-9130512_T3", "type": "Protein", "text": [ "IL-6" ], "offsets": [ [ 395, 399 ] ], "normalized": [] }, { "id": "PMID-9130512_T4", "type": "Protein", "text": [ "IL-2" ], "offsets": [ [ 508, 512 ] ], "normalized": [] }, { "id": "PMID-9130512_T5", "type": "Protein", "text": [ "IL-2" ], "offsets": [ [ 602, 606 ] ], "normalized": [] }, { "id": "PMID-9130512_T6", "type": "Protein", "text": [ "RA receptors (RAR)-alpha" ], "offsets": [ [ 903, 927 ] ], "normalized": [] }, { "id": "PMID-9130512_T7", "type": "Protein", "text": [ "beta" ], "offsets": [ [ 928, 932 ] ], "normalized": [] }, { "id": "PMID-9130512_T8", "type": "Protein", "text": [ "gamma" ], "offsets": [ [ 933, 938 ] ], "normalized": [] }, { "id": "PMID-9130512_T9", "type": "Protein", "text": [ "IL-2-alpha receptor" ], "offsets": [ [ 982, 1001 ] ], "normalized": [] }, { "id": "PMID-9130512_T10", "type": "Protein", "text": [ "IL-2" ], "offsets": [ [ 1112, 1116 ] ], "normalized": [] }, { "id": "PMID-9130512_T11", "type": "Protein", "text": [ "IL-2R-alpha" ], "offsets": [ [ 1180, 1191 ] ], "normalized": [] }, { "id": "PMID-9130512_T12", "type": "Protein", "text": [ "RAR-alpha" ], "offsets": [ [ 1243, 1252 ] ], "normalized": [] }, { "id": "PMID-9130512_T13", "type": "Protein", "text": [ "IL-2" ], "offsets": [ [ 1260, 1264 ] ], "normalized": [] } ]

[ { "id": "PMID-9130512_E1", "type": "Regulation", "trigger": { "text": [ "modulation" ], "offsets": [ [ 22, 32 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "PMID-9130512_E2" } ] }, { "id": "PMID-9130512_E2", "type": "Transcription", "trigger": { "text": [ "production" ], "offsets": [ [ 46, 56 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "PMID-9130512_T1" } ] }, { "id": "PMID-9130512_E3", "type": "Gene_expression", "trigger": { "text": [ "production" ], "offsets": [ [ 400, 410 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "PMID-9130512_T3" } ] }, { "id": "PMID-9130512_E4", "type": "Positive_regulation", "trigger": { "text": [ "augmented" ], "offsets": [ [ 414, 423 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "PMID-9130512_E3" } ] }, { "id": "PMID-9130512_E5", "type": "Regulation", "trigger": { "text": [ "immune modulating effects" ], "offsets": [ [ 473, 498 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "PMID-9130512_E6" } ] }, { "id": "PMID-9130512_E6", "type": "Transcription", "trigger": { "text": [ "mRNA" ], "offsets": [ [ 513, 517 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "PMID-9130512_T4" } ] }, { "id": "PMID-9130512_E7", "type": "Regulation", "trigger": { "text": [ "changes" ], "offsets": [ [ 865, 872 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "PMID-9130512_E10" } ] }, { "id": "PMID-9130512_E8", "type": "Regulation", "trigger": { "text": [ "changes" ], "offsets": [ [ 865, 872 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "PMID-9130512_E11" } ] }, { "id": "PMID-9130512_E9", "type": "Regulation", "trigger": { "text": [ "changes" ], "offsets": [ [ 865, 872 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "PMID-9130512_E12" } ] }, { "id": "PMID-9130512_E10", "type": "Transcription", "trigger": { "text": [ "production" ], "offsets": [ [ 880, 890 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "PMID-9130512_T6" } ] }, { "id": "PMID-9130512_E11", "type": "Transcription", "trigger": { "text": [ "production" ], "offsets": [ [ 880, 890 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "PMID-9130512_T7" } ] }, { "id": "PMID-9130512_E12", "type": "Transcription", "trigger": { "text": [ "production" ], "offsets": [ [ 880, 890 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "PMID-9130512_T8" } ] }, { "id": "PMID-9130512_E13", "type": "Regulation", "trigger": { "text": [ "effects" ], "offsets": [ [ 965, 972 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "PMID-9130512_E14" } ] }, { "id": "PMID-9130512_E14", "type": "Gene_expression", "trigger": { "text": [ "expression" ], "offsets": [ [ 1002, 1012 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "PMID-9130512_T9" } ] }, { "id": "PMID-9130512_E15", "type": "Positive_regulation", "trigger": { "text": [ "augment" ], "offsets": [ [ 1104, 1111 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "PMID-9130512_E16" } ] }, { "id": "PMID-9130512_E16", "type": "Transcription", "trigger": { "text": [ "production" ], "offsets": [ [ 1122, 1132 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "PMID-9130512_T10" } ] }, { "id": "PMID-9130512_E17", "type": "Regulation", "trigger": { "text": [ "effect" ], "offsets": [ [ 1170, 1176 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "PMID-9130512_E18" } ] }, { "id": "PMID-9130512_E18", "type": "Gene_expression", "trigger": { "text": [ "expression" ], "offsets": [ [ 1192, 1202 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "PMID-9130512_T11" } ] }, { "id": "PMID-9130512_E19", "type": "Positive_regulation", "trigger": { "text": [ "mediated" ], "offsets": [ [ 1231, 1239 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "PMID-9130512_E16" }, { "role": "Cause", "ref_id": "PMID-9130512_T12" } ] }, { "id": "PMID-9130512_E20", "type": "Regulation", "trigger": { "text": [ "modulated" ], "offsets": [ [ 1299, 1308 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "PMID-9130512_T13" } ] } ]

[]

[]

[ { "id": "PMID-9130632__text", "type": "abstract", "text": [ "Itk, a T cell-specific tyrosine kinase, is required for CD2-mediated interleukin-2 promoter activation in the human T cell line Jurkat. \nWe investigated the functional role of Itk, a member of the cytoplasmic tyrosine kinase Tec family, in T cell activation. Stimulation of either CD2 or T cell receptor (TCR)/CD3 on Tcells by monoclonal antibody-mediated cross-linking induced tyrosine phosphorylation of Itk, which was maximal as early as 1 min after stimulation. The tyrosine kinase activity in the anti-Itk immunoprecipitate was significantly activated upon these stimulations. Interleukin-2 (IL-2) promoter activity stimulated by cross-linking of CD2, TCR/CD3, and CD28 with antibodies was significantly reduced by transient expression of an Itk mutant lacking the kinase activity. The reduction paralleled a decrease in tyrosine phosphorylation of endogenous wild-type Itk. Stimulation of CD2 or TCR/CD3 induced activation of the nuclear factor of activated T cells (NFAT), the binding site of which is included in the IL-2 gene promoter. The activation of NFAT was also impaired by expression of the Itk mutant. These results demonstrate that Itk plays a role in IL-2 production, indicating a critical involvement of Itk in the initial stage of T cell activation by mediating signals from the TCR/CD3 complex, CD2, and CD28. " ], "offsets": [ [ 0, 1332 ] ] } ]

[ { "id": "PMID-9130632_T1", "type": "Protein", "text": [ "Itk" ], "offsets": [ [ 0, 3 ] ], "normalized": [] }, { "id": "PMID-9130632_T2", "type": "Protein", "text": [ "CD2" ], "offsets": [ [ 56, 59 ] ], "normalized": [] }, { "id": "PMID-9130632_T3", "type": "Protein", "text": [ "interleukin-2" ], "offsets": [ [ 69, 82 ] ], "normalized": [] }, { "id": "PMID-9130632_T4", "type": "Protein", "text": [ "Itk" ], "offsets": [ [ 176, 179 ] ], "normalized": [] }, { "id": "PMID-9130632_T5", "type": "Protein", "text": [ "CD2" ], "offsets": [ [ 281, 284 ] ], "normalized": [] }, { "id": "PMID-9130632_T6", "type": "Protein", "text": [ "Itk" ], "offsets": [ [ 406, 409 ] ], "normalized": [] }, { "id": "PMID-9130632_T7", "type": "Protein", "text": [ "Itk" ], "offsets": [ [ 507, 510 ] ], "normalized": [] }, { "id": "PMID-9130632_T8", "type": "Protein", "text": [ "Interleukin-2" ], "offsets": [ [ 582, 595 ] ], "normalized": [] }, { "id": "PMID-9130632_T9", "type": "Protein", "text": [ "IL-2" ], "offsets": [ [ 597, 601 ] ], "normalized": [] }, { "id": "PMID-9130632_T10", "type": "Protein", "text": [ "CD2" ], "offsets": [ [ 652, 655 ] ], "normalized": [] }, { "id": "PMID-9130632_T11", "type": "Protein", "text": [ "CD28" ], "offsets": [ [ 670, 674 ] ], "normalized": [] }, { "id": "PMID-9130632_T12", "type": "Protein", "text": [ "Itk" ], "offsets": [ [ 747, 750 ] ], "normalized": [] }, { "id": "PMID-9130632_T13", "type": "Protein", "text": [ "Itk" ], "offsets": [ [ 875, 878 ] ], "normalized": [] }, { "id": "PMID-9130632_T14", "type": "Protein", "text": [ "CD2" ], "offsets": [ [ 895, 898 ] ], "normalized": [] }, { "id": "PMID-9130632_T15", "type": "Protein", "text": [ "IL-2" ], "offsets": [ [ 1025, 1029 ] ], "normalized": [] }, { "id": "PMID-9130632_T16", "type": "Protein", "text": [ "Itk" ], "offsets": [ [ 1107, 1110 ] ], "normalized": [] }, { "id": "PMID-9130632_T17", "type": "Protein", "text": [ "Itk" ], "offsets": [ [ 1150, 1153 ] ], "normalized": [] }, { "id": "PMID-9130632_T18", "type": "Protein", "text": [ "IL-2" ], "offsets": [ [ 1170, 1174 ] ], "normalized": [] }, { "id": "PMID-9130632_T19", "type": "Protein", "text": [ "Itk" ], "offsets": [ [ 1224, 1227 ] ], "normalized": [] }, { "id": "PMID-9130632_T20", "type": "Protein", "text": [ "CD2" ], "offsets": [ [ 1317, 1320 ] ], "normalized": [] }, { "id": "PMID-9130632_T21", "type": "Protein", "text": [ "CD28" ], "offsets": [ [ 1326, 1330 ] ], "normalized": [] }, { "id": "PMID-9130632_T27", "type": "Entity", "text": [ "tyrosine" ], "offsets": [ [ 378, 386 ] ], "normalized": [] }, { "id": "PMID-9130632_T30", "type": "Entity", "text": [ "promoter" ], "offsets": [ [ 603, 611 ] ], "normalized": [] }, { "id": "PMID-9130632_T36", "type": "Entity", "text": [ "tyrosine" ], "offsets": [ [ 826, 834 ] ], "normalized": [] }, { "id": "PMID-9130632_T40", "type": "Entity", "text": [ "promoter" ], "offsets": [ [ 1035, 1043 ] ], "normalized": [] } ]

[ { "id": "PMID-9130632_E1", "type": "Positive_regulation", "trigger": { "text": [ "required" ], "offsets": [ [ 43, 51 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "PMID-9130632_E2" }, { "role": "Cause", "ref_id": "PMID-9130632_T1" } ] }, { "id": "PMID-9130632_E2", "type": "Positive_regulation", "trigger": { "text": [ "activation" ], "offsets": [ [ 92, 102 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "PMID-9130632_T3" }, { "role": "Cause", "ref_id": "PMID-9130632_T2" } ] }, { "id": "PMID-9130632_E3", "type": "Positive_regulation", "trigger": { "text": [ "Stimulation" ], "offsets": [ [ 259, 270 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "PMID-9130632_T5" }, { "role": "Cause", "ref_id": "PMID-9130632_E4" } ] }, { "id": "PMID-9130632_E4", "type": "Binding", "trigger": { "text": [ "cross-linking" ], "offsets": [ [ 356, 369 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "PMID-9130632_T5" } ] }, { "id": "PMID-9130632_E5", "type": "Positive_regulation", "trigger": { "text": [ "induced" ], "offsets": [ [ 370, 377 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "PMID-9130632_E7" } ] }, { "id": "PMID-9130632_E6", "type": "Positive_regulation", "trigger": { "text": [ "induced" ], "offsets": [ [ 370, 377 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "PMID-9130632_E7" }, { "role": "Cause", "ref_id": "PMID-9130632_E3" } ] }, { "id": "PMID-9130632_E7", "type": "Phosphorylation", "trigger": { "text": [ "phosphorylation" ], "offsets": [ [ 387, 402 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "PMID-9130632_T6" }, { "role": "Site", "ref_id": "PMID-9130632_T27" } ] }, { "id": "PMID-9130632_E8", "type": "Positive_regulation", "trigger": { "text": [ "maximal" ], "offsets": [ [ 421, 428 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "PMID-9130632_E5" } ] }, { "id": "PMID-9130632_E9", "type": "Positive_regulation", "trigger": { "text": [ "maximal" ], "offsets": [ [ 421, 428 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "PMID-9130632_E6" } ] }, { "id": "PMID-9130632_E10", "type": "Positive_regulation", "trigger": { "text": [ "stimulated" ], "offsets": [ [ 621, 631 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "PMID-9130632_T8" }, { "role": "Cause", "ref_id": "PMID-9130632_E13" }, { "role": "Site", "ref_id": "PMID-9130632_T30" } ] }, { "id": "PMID-9130632_E11", "type": "Positive_regulation", "trigger": { "text": [ "stimulated" ], "offsets": [ [ 621, 631 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "PMID-9130632_T8" }, { "role": "Site", "ref_id": "PMID-9130632_T30" } ] }, { "id": "PMID-9130632_E12", "type": "Positive_regulation", "trigger": { "text": [ "stimulated" ], "offsets": [ [ 621, 631 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "PMID-9130632_T8" }, { "role": "Cause", "ref_id": "PMID-9130632_E14" }, { "role": "Site", "ref_id": "PMID-9130632_T30" } ] }, { "id": "PMID-9130632_E13", "type": "Binding", "trigger": { "text": [ "cross-linking" ], "offsets": [ [ 635, 648 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "PMID-9130632_T11" } ] }, { "id": "PMID-9130632_E14", "type": "Binding", "trigger": { "text": [ "cross-linking" ], "offsets": [ [ 635, 648 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "PMID-9130632_T10" } ] }, { "id": "PMID-9130632_E15", "type": "Negative_regulation", "trigger": { "text": [ "reduced" ], "offsets": [ [ 709, 716 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "PMID-9130632_E10" }, { "role": "Cause", "ref_id": "PMID-9130632_E18" } ] }, { "id": "PMID-9130632_E16", "type": "Negative_regulation", "trigger": { "text": [ "reduced" ], "offsets": [ [ 709, 716 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "PMID-9130632_E12" }, { "role": "Cause", "ref_id": "PMID-9130632_E18" } ] }, { "id": "PMID-9130632_E17", "type": "Negative_regulation", "trigger": { "text": [ "reduced" ], "offsets": [ [ 709, 716 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "PMID-9130632_E11" }, { "role": "Cause", "ref_id": "PMID-9130632_E18" } ] }, { "id": "PMID-9130632_E18", "type": "Gene_expression", "trigger": { "text": [ "expression" ], "offsets": [ [ 730, 740 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "PMID-9130632_T12" } ] }, { "id": "PMID-9130632_E19", "type": "Negative_regulation", "trigger": { "text": [ "decrease" ], "offsets": [ [ 814, 822 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "PMID-9130632_E20" } ] }, { "id": "PMID-9130632_E20", "type": "Phosphorylation", "trigger": { "text": [ "phosphorylation" ], "offsets": [ [ 835, 850 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "PMID-9130632_T13" }, { "role": "Site", "ref_id": "PMID-9130632_T36" } ] }, { "id": "PMID-9130632_E21", "type": "Positive_regulation", "trigger": { "text": [ "Stimulation" ], "offsets": [ [ 880, 891 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "PMID-9130632_T14" } ] }, { "id": "PMID-9130632_E22", "type": "Positive_regulation", "trigger": { "text": [ "included" ], "offsets": [ [ 1009, 1017 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "PMID-9130632_T15" }, { "role": "Site", "ref_id": "PMID-9130632_T40" } ] }, { "id": "PMID-9130632_E23", "type": "Gene_expression", "trigger": { "text": [ "expression" ], "offsets": [ [ 1089, 1099 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "PMID-9130632_T16" } ] }, { "id": "PMID-9130632_E24", "type": "Regulation", "trigger": { "text": [ "plays a role" ], "offsets": [ [ 1154, 1166 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "PMID-9130632_E25" }, { "role": "Cause", "ref_id": "PMID-9130632_T17" } ] }, { "id": "PMID-9130632_E25", "type": "Gene_expression", "trigger": { "text": [ "production" ], "offsets": [ [ 1175, 1185 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "PMID-9130632_T18" } ] } ]

[ { "id": "PMID-9130632_1", "entity_ids": [ "PMID-9130632_T8", "PMID-9130632_T9" ] } ]

[]

[ { "id": "PMID-9133417__text", "type": "abstract", "text": [ "Jak3 is associated with CD40 and is critical for CD40 induction of gene expression in B cells. \nCD40 is a receptor that is critical for the survival, growth, differentiation, and isotype switching of B lymphocytes. Although CD40 lacks intrinsic tyrosine kinase activity, its ligation induces protein tyrosine phosphorylation, which is necessary for several CD40-mediated events. We show that engagement of CD40 induces tyrosine phosphorylation and activation of Jak3 as well as of STAT3. Jak3 is constitutively associated with CD40, and this interaction requires a proline-rich sequence in the membrane-proximal region of CD40. Deletion of this sequence abolishes the capacity of CD40 to induce expression of CD23, ICAM-1, and lymphotoxin-alpha genes in B cells. These results indicate that signaling through Jak3 is activated by CD40 and plays an important role in CD40-mediated functions. " ], "offsets": [ [ 0, 891 ] ] } ]

[ { "id": "PMID-9133417_T1", "type": "Protein", "text": [ "Jak3" ], "offsets": [ [ 0, 4 ] ], "normalized": [] }, { "id": "PMID-9133417_T2", "type": "Protein", "text": [ "CD40" ], "offsets": [ [ 24, 28 ] ], "normalized": [] }, { "id": "PMID-9133417_T3", "type": "Protein", "text": [ "CD40" ], "offsets": [ [ 49, 53 ] ], "normalized": [] }, { "id": "PMID-9133417_T4", "type": "Protein", "text": [ "CD40" ], "offsets": [ [ 96, 100 ] ], "normalized": [] }, { "id": "PMID-9133417_T5", "type": "Protein", "text": [ "CD40" ], "offsets": [ [ 224, 228 ] ], "normalized": [] }, { "id": "PMID-9133417_T6", "type": "Protein", "text": [ "CD40" ], "offsets": [ [ 357, 361 ] ], "normalized": [] }, { "id": "PMID-9133417_T7", "type": "Protein", "text": [ "CD40" ], "offsets": [ [ 406, 410 ] ], "normalized": [] }, { "id": "PMID-9133417_T8", "type": "Protein", "text": [ "Jak3" ], "offsets": [ [ 462, 466 ] ], "normalized": [] }, { "id": "PMID-9133417_T9", "type": "Protein", "text": [ "STAT3" ], "offsets": [ [ 481, 486 ] ], "normalized": [] }, { "id": "PMID-9133417_T10", "type": "Protein", "text": [ "Jak3" ], "offsets": [ [ 488, 492 ] ], "normalized": [] }, { "id": "PMID-9133417_T11", "type": "Protein", "text": [ "CD40" ], "offsets": [ [ 527, 531 ] ], "normalized": [] }, { "id": "PMID-9133417_T12", "type": "Protein", "text": [ "CD40" ], "offsets": [ [ 622, 626 ] ], "normalized": [] }, { "id": "PMID-9133417_T13", "type": "Protein", "text": [ "CD40" ], "offsets": [ [ 680, 684 ] ], "normalized": [] }, { "id": "PMID-9133417_T14", "type": "Protein", "text": [ "CD23" ], "offsets": [ [ 709, 713 ] ], "normalized": [] }, { "id": "PMID-9133417_T15", "type": "Protein", "text": [ "ICAM-1" ], "offsets": [ [ 715, 721 ] ], "normalized": [] }, { "id": "PMID-9133417_T16", "type": "Protein", "text": [ "lymphotoxin-alpha" ], "offsets": [ [ 727, 744 ] ], "normalized": [] }, { "id": "PMID-9133417_T17", "type": "Protein", "text": [ "Jak3" ], "offsets": [ [ 809, 813 ] ], "normalized": [] }, { "id": "PMID-9133417_T18", "type": "Protein", "text": [ "CD40" ], "offsets": [ [ 830, 834 ] ], "normalized": [] }, { "id": "PMID-9133417_T19", "type": "Protein", "text": [ "CD40" ], "offsets": [ [ 866, 870 ] ], "normalized": [] }, { "id": "PMID-9133417_T23", "type": "Entity", "text": [ "tyrosine" ], "offsets": [ [ 419, 427 ] ], "normalized": [] }, { "id": "PMID-9133417_T28", "type": "Entity", "text": [ "proline-rich sequence" ], "offsets": [ [ 565, 586 ] ], "normalized": [] } ]

[ { "id": "PMID-9133417_E1", "type": "Binding", "trigger": { "text": [ "associated" ], "offsets": [ [ 8, 18 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "PMID-9133417_T1" }, { "role": "Theme", "ref_id": "PMID-9133417_T2" } ] }, { "id": "PMID-9133417_E2", "type": "Binding", "trigger": { "text": [ "ligation" ], "offsets": [ [ 275, 283 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "PMID-9133417_T5" } ] }, { "id": "PMID-9133417_E3", "type": "Positive_regulation", "trigger": { "text": [ "induces" ], "offsets": [ [ 411, 418 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "PMID-9133417_E7" }, { "role": "Cause", "ref_id": "PMID-9133417_T7" } ] }, { "id": "PMID-9133417_E4", "type": "Positive_regulation", "trigger": { "text": [ "induces" ], "offsets": [ [ 411, 418 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "PMID-9133417_E10" }, { "role": "Cause", "ref_id": "PMID-9133417_T7" } ] }, { "id": "PMID-9133417_E5", "type": "Positive_regulation", "trigger": { "text": [ "induces" ], "offsets": [ [ 411, 418 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "PMID-9133417_E8" }, { "role": "Cause", "ref_id": "PMID-9133417_T7" } ] }, { "id": "PMID-9133417_E6", "type": "Positive_regulation", "trigger": { "text": [ "induces" ], "offsets": [ [ 411, 418 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "PMID-9133417_E9" }, { "role": "Cause", "ref_id": "PMID-9133417_T7" } ] }, { "id": "PMID-9133417_E7", "type": "Phosphorylation", "trigger": { "text": [ "phosphorylation" ], "offsets": [ [ 428, 443 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "PMID-9133417_T8" }, { "role": "Site", "ref_id": "PMID-9133417_T23" } ] }, { "id": "PMID-9133417_E8", "type": "Phosphorylation", "trigger": { "text": [ "phosphorylation" ], "offsets": [ [ 428, 443 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "PMID-9133417_T9" }, { "role": "Site", "ref_id": "PMID-9133417_T23" } ] }, { "id": "PMID-9133417_E9", "type": "Positive_regulation", "trigger": { "text": [ "activation" ], "offsets": [ [ 448, 458 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "PMID-9133417_T8" }, { "role": "Cause", "ref_id": "PMID-9133417_E7" } ] }, { "id": "PMID-9133417_E10", "type": "Positive_regulation", "trigger": { "text": [ "activation" ], "offsets": [ [ 448, 458 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "PMID-9133417_T9" }, { "role": "Cause", "ref_id": "PMID-9133417_E8" } ] }, { "id": "PMID-9133417_E11", "type": "Binding", "trigger": { "text": [ "associated" ], "offsets": [ [ 511, 521 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "PMID-9133417_T10" }, { "role": "Theme", "ref_id": "PMID-9133417_T11" } ] }, { "id": "PMID-9133417_E12", "type": "Positive_regulation", "trigger": { "text": [ "requires" ], "offsets": [ [ 554, 562 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "PMID-9133417_E11" }, { "role": "Cause", "ref_id": "PMID-9133417_T12" }, { "role": "CSite", "ref_id": "PMID-9133417_T28" } ] }, { "id": "PMID-9133417_E13", "type": "Negative_regulation", "trigger": { "text": [ "abolishes" ], "offsets": [ [ 654, 663 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "PMID-9133417_E16" } ] }, { "id": "PMID-9133417_E14", "type": "Negative_regulation", "trigger": { "text": [ "abolishes" ], "offsets": [ [ 654, 663 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "PMID-9133417_E17" } ] }, { "id": "PMID-9133417_E15", "type": "Negative_regulation", "trigger": { "text": [ "abolishes" ], "offsets": [ [ 654, 663 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "PMID-9133417_E18" } ] }, { "id": "PMID-9133417_E16", "type": "Positive_regulation", "trigger": { "text": [ "induce" ], "offsets": [ [ 688, 694 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "PMID-9133417_E20" }, { "role": "Cause", "ref_id": "PMID-9133417_T13" } ] }, { "id": "PMID-9133417_E17", "type": "Positive_regulation", "trigger": { "text": [ "induce" ], "offsets": [ [ 688, 694 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "PMID-9133417_E19" }, { "role": "Cause", "ref_id": "PMID-9133417_T13" } ] }, { "id": "PMID-9133417_E18", "type": "Positive_regulation", "trigger": { "text": [ "induce" ], "offsets": [ [ 688, 694 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "PMID-9133417_E21" }, { "role": "Cause", "ref_id": "PMID-9133417_T13" } ] }, { "id": "PMID-9133417_E19", "type": "Gene_expression", "trigger": { "text": [ "expression" ], "offsets": [ [ 695, 705 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "PMID-9133417_T16" } ] }, { "id": "PMID-9133417_E20", "type": "Gene_expression", "trigger": { "text": [ "expression" ], "offsets": [ [ 695, 705 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "PMID-9133417_T15" } ] }, { "id": "PMID-9133417_E21", "type": "Gene_expression", "trigger": { "text": [ "expression" ], "offsets": [ [ 695, 705 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "PMID-9133417_T14" } ] }, { "id": "PMID-9133417_E22", "type": "Regulation", "trigger": { "text": [ "role" ], "offsets": [ [ 858, 862 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "PMID-9133417_E20" } ] } ]

[]

[]

[ { "id": "PMID-9135552__text", "type": "abstract", "text": [ "The tumour associated cell surface antigen A6H is costimulatory for human CD4+ but not CD8+ T cells. \nThe A6H monoclonal antibody (mAb) recognizes a 120,000-140,000 MW antigen that is expressed at similar densities on 85-90% of human CD4+ and CD8+ T cells and on renal cell carcinomas. The binding of the A6H mAb induced a costimulatory signal in anti-CD3 activated T cells. In the present report, we show that A6H costimulated cell proliferation and cytokine production in purified CD4+ T cells. Unexpectedly, the CD8+ T-cell subpopulation failed to respond. CD4+ T cells costimulated with the A6H mAb upregulated CD80, CD86, CD71, interleukin-2 (IL-2)R alpha, IL-2R beta and IL-2R gamma, while no corresponding up-regulation of these cell surface molecules was seen in CD8+ T cells. In order to investigate the nature of the A6H mAb costimulus at the transcriptional level we have examined induction of the transcription factors OCT-1, AP-1 and NF-kappa B which are known to be transcriptional regulators of several cytokine and cytokine receptor genes, including the IL-2 and IL-2R genes. Co-ligation of the A6H antigen and the CD3 complex induced expression of the transcription factor AP-1 in CD4+ T cells, whereas no increase in NF-kappa B and octamer-binding (Oct) proteins was seen compared to T cells stimulated with anti-CD3 alone. Furthermore, no induction of AP-1 was seen in A6H costimulated CD8+ T cells. These results suggests that both proximal steps in CD8+ T-cell activation as well as the later phases are unresponsive to A6H ligation. Molecular differences of the A6H molecule or distinct regulation of the A6H transduced AP-1 activation pathway may exist in CD4+ and CD8+ T cell subpopulations. " ], "offsets": [ [ 0, 1716 ] ] } ]

[ { "id": "PMID-9135552_T1", "type": "Protein", "text": [ "CD4" ], "offsets": [ [ 74, 77 ] ], "normalized": [] }, { "id": "PMID-9135552_T2", "type": "Protein", "text": [ "CD4" ], "offsets": [ [ 234, 237 ] ], "normalized": [] }, { "id": "PMID-9135552_T3", "type": "Protein", "text": [ "CD4" ], "offsets": [ [ 483, 486 ] ], "normalized": [] }, { "id": "PMID-9135552_T4", "type": "Protein", "text": [ "CD4" ], "offsets": [ [ 560, 563 ] ], "normalized": [] }, { "id": "PMID-9135552_T5", "type": "Protein", "text": [ "CD80" ], "offsets": [ [ 615, 619 ] ], "normalized": [] }, { "id": "PMID-9135552_T6", "type": "Protein", "text": [ "CD86" ], "offsets": [ [ 621, 625 ] ], "normalized": [] }, { "id": "PMID-9135552_T7", "type": "Protein", "text": [ "CD71" ], "offsets": [ [ 627, 631 ] ], "normalized": [] }, { "id": "PMID-9135552_T8", "type": "Protein", "text": [ "interleukin-2 (IL-2)R alpha" ], "offsets": [ [ 633, 660 ] ], "normalized": [] }, { "id": "PMID-9135552_T9", "type": "Protein", "text": [ "IL-2R beta" ], "offsets": [ [ 662, 672 ] ], "normalized": [] }, { "id": "PMID-9135552_T10", "type": "Protein", "text": [ "IL-2R gamma" ], "offsets": [ [ 677, 688 ] ], "normalized": [] }, { "id": "PMID-9135552_T11", "type": "Protein", "text": [ "OCT-1" ], "offsets": [ [ 931, 936 ] ], "normalized": [] }, { "id": "PMID-9135552_T12", "type": "Protein", "text": [ "IL-2" ], "offsets": [ [ 1070, 1074 ] ], "normalized": [] }, { "id": "PMID-9135552_T13", "type": "Protein", "text": [ "CD4" ], "offsets": [ [ 1198, 1201 ] ], "normalized": [] }, { "id": "PMID-9135552_T14", "type": "Protein", "text": [ "CD4" ], "offsets": [ [ 1679, 1682 ] ], "normalized": [] } ]

[ { "id": "PMID-9135552_E1", "type": "Positive_regulation", "trigger": { "text": [ "upregulated" ], "offsets": [ [ 603, 614 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "PMID-9135552_T7" } ] }, { "id": "PMID-9135552_E2", "type": "Positive_regulation", "trigger": { "text": [ "upregulated" ], "offsets": [ [ 603, 614 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "PMID-9135552_T5" } ] }, { "id": "PMID-9135552_E3", "type": "Positive_regulation", "trigger": { "text": [ "upregulated" ], "offsets": [ [ 603, 614 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "PMID-9135552_T10" } ] }, { "id": "PMID-9135552_E4", "type": "Positive_regulation", "trigger": { "text": [ "upregulated" ], "offsets": [ [ 603, 614 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "PMID-9135552_T6" } ] }, { "id": "PMID-9135552_E5", "type": "Positive_regulation", "trigger": { "text": [ "upregulated" ], "offsets": [ [ 603, 614 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "PMID-9135552_T9" } ] }, { "id": "PMID-9135552_E6", "type": "Positive_regulation", "trigger": { "text": [ "upregulated" ], "offsets": [ [ 603, 614 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "PMID-9135552_T8" } ] }, { "id": "PMID-9135552_E7", "type": "Positive_regulation", "trigger": { "text": [ "up-regulation" ], "offsets": [ [ 713, 726 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "PMID-9135552_T5" } ] }, { "id": "PMID-9135552_E8", "type": "Positive_regulation", "trigger": { "text": [ "up-regulation" ], "offsets": [ [ 713, 726 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "PMID-9135552_T9" } ] }, { "id": "PMID-9135552_E9", "type": "Positive_regulation", "trigger": { "text": [ "up-regulation" ], "offsets": [ [ 713, 726 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "PMID-9135552_T8" } ] }, { "id": "PMID-9135552_E10", "type": "Positive_regulation", "trigger": { "text": [ "up-regulation" ], "offsets": [ [ 713, 726 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "PMID-9135552_T6" } ] }, { "id": "PMID-9135552_E11", "type": "Positive_regulation", "trigger": { "text": [ "up-regulation" ], "offsets": [ [ 713, 726 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "PMID-9135552_T10" } ] }, { "id": "PMID-9135552_E12", "type": "Positive_regulation", "trigger": { "text": [ "up-regulation" ], "offsets": [ [ 713, 726 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "PMID-9135552_T7" } ] }, { "id": "PMID-9135552_E13", "type": "Positive_regulation", "trigger": { "text": [ "induction" ], "offsets": [ [ 892, 901 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "PMID-9135552_T11" } ] }, { "id": "PMID-9135552_E14", "type": "Regulation", "trigger": { "text": [ "transcriptional regulators" ], "offsets": [ [ 980, 1006 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "PMID-9135552_T12" } ] }, { "id": "PMID-9135552_E15", "type": "Regulation", "trigger": { "text": [ "transcriptional regulators" ], "offsets": [ [ 980, 1006 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "PMID-9135552_T12" }, { "role": "Cause", "ref_id": "PMID-9135552_T11" } ] } ]

[]

[]

[ { "id": "PMID-9136080__text", "type": "abstract", "text": [ "Structure and function analysis of the human myeloid cell nuclear differentiation antigen promoter: evidence for the role of Sp1 and not of c-Myb or PU.1 in myelomonocytic lineage-specific expression. \nThe human myeloid nuclear differentiation antigen (MNDA) is expressed specifically in maturing cells of the myelomonocytic lineage and in monocytes and granulocytes. Epitope enhancement was used to confirm the strict lineage- and stage-specific expression of MNDA in bone marrow as well as in other paraffin-embedded fixed tissues. A 1-kb region of the gene that includes 5' flanking sequence was reported earlier to contain functional promoter activity and was specifically demethylated in expressing cells in contrast to null cells. Further analysis has revealed that this 1-kb fragment promotes higher reporter gene activity in MNDA-expressing cells than non-expressing cells, indicating cell-specific differences in transactivation. This sequence contains consensus elements consistent with myeloid-specific gene expression, including a PU.1 consensus site near the major transcription start site and a cluster of c-Myb sites located several hundred bases upstream of this region. However, analysis of deletion mutants localized nearly all of the promoter activity to a short region (-73 to -16) that did not include the cluster of c-Myb sites. A 4-bp mutation of the core Sp1 consensus element (GC box) (-20) reduced overall promoter activity of the 1-kb fragment. Mutation of the PU.1 site did not significantly affect promoter activity. Only a small region (-35 to +22) including the Sp1 element and transcription start site, but not the PU.1 site was footprinted. The 4-bp mutation of the core Sp1 consensus element abolished footprinting at the site and an antibody super-shift reaction showed that Sp1 is one of the factors binding the consensus site. The Sp1 site also co-localizes with a DNase I hypersensitive site. The results indicate that DNA methylation, chromatin structure, and transactivation at an Sp1 site contribute to the highly restricted expression of this myelomonocytic lineage specific gene. " ], "offsets": [ [ 0, 2123 ] ] } ]

[ { "id": "PMID-9136080_T1", "type": "Protein", "text": [ "myeloid cell nuclear differentiation antigen" ], "offsets": [ [ 45, 89 ] ], "normalized": [] }, { "id": "PMID-9136080_T2", "type": "Protein", "text": [ "Sp1" ], "offsets": [ [ 125, 128 ] ], "normalized": [] }, { "id": "PMID-9136080_T3", "type": "Protein", "text": [ "c-Myb" ], "offsets": [ [ 140, 145 ] ], "normalized": [] }, { "id": "PMID-9136080_T4", "type": "Protein", "text": [ "PU.1" ], "offsets": [ [ 149, 153 ] ], "normalized": [] }, { "id": "PMID-9136080_T5", "type": "Protein", "text": [ "myeloid nuclear differentiation antigen" ], "offsets": [ [ 212, 251 ] ], "normalized": [] }, { "id": "PMID-9136080_T6", "type": "Protein", "text": [ "MNDA" ], "offsets": [ [ 253, 257 ] ], "normalized": [] }, { "id": "PMID-9136080_T7", "type": "Protein", "text": [ "MNDA" ], "offsets": [ [ 461, 465 ] ], "normalized": [] }, { "id": "PMID-9136080_T8", "type": "Protein", "text": [ "MNDA" ], "offsets": [ [ 833, 837 ] ], "normalized": [] }, { "id": "PMID-9136080_T9", "type": "Protein", "text": [ "PU.1" ], "offsets": [ [ 1043, 1047 ] ], "normalized": [] }, { "id": "PMID-9136080_T10", "type": "Protein", "text": [ "c-Myb" ], "offsets": [ [ 1120, 1125 ] ], "normalized": [] }, { "id": "PMID-9136080_T11", "type": "Protein", "text": [ "c-Myb" ], "offsets": [ [ 1338, 1343 ] ], "normalized": [] }, { "id": "PMID-9136080_T12", "type": "Protein", "text": [ "Sp1" ], "offsets": [ [ 1379, 1382 ] ], "normalized": [] }, { "id": "PMID-9136080_T13", "type": "Protein", "text": [ "PU.1" ], "offsets": [ [ 1488, 1492 ] ], "normalized": [] }, { "id": "PMID-9136080_T14", "type": "Protein", "text": [ "Sp1" ], "offsets": [ [ 1593, 1596 ] ], "normalized": [] }, { "id": "PMID-9136080_T15", "type": "Protein", "text": [ "PU.1" ], "offsets": [ [ 1647, 1651 ] ], "normalized": [] }, { "id": "PMID-9136080_T16", "type": "Protein", "text": [ "Sp1" ], "offsets": [ [ 1704, 1707 ] ], "normalized": [] }, { "id": "PMID-9136080_T17", "type": "Protein", "text": [ "Sp1" ], "offsets": [ [ 1810, 1813 ] ], "normalized": [] }, { "id": "PMID-9136080_T18", "type": "Protein", "text": [ "Sp1" ], "offsets": [ [ 1868, 1871 ] ], "normalized": [] }, { "id": "PMID-9136080_T19", "type": "Protein", "text": [ "Sp1" ], "offsets": [ [ 2021, 2024 ] ], "normalized": [] } ]

[ { "id": "PMID-9136080_E1", "type": "Regulation", "trigger": { "text": [ "role" ], "offsets": [ [ 117, 121 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "PMID-9136080_E4" }, { "role": "Cause", "ref_id": "PMID-9136080_T2" } ] }, { "id": "PMID-9136080_E2", "type": "Regulation", "trigger": { "text": [ "role" ], "offsets": [ [ 117, 121 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "PMID-9136080_E4" }, { "role": "Cause", "ref_id": "PMID-9136080_T4" } ] }, { "id": "PMID-9136080_E3", "type": "Regulation", "trigger": { "text": [ "role" ], "offsets": [ [ 117, 121 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "PMID-9136080_E4" }, { "role": "Cause", "ref_id": "PMID-9136080_T3" } ] }, { "id": "PMID-9136080_E4", "type": "Gene_expression", "trigger": { "text": [ "expression" ], "offsets": [ [ 189, 199 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "PMID-9136080_T1" } ] }, { "id": "PMID-9136080_E5", "type": "Gene_expression", "trigger": { "text": [ "expressed" ], "offsets": [ [ 262, 271 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "PMID-9136080_T6" } ] }, { "id": "PMID-9136080_E6", "type": "Gene_expression", "trigger": { "text": [ "expression" ], "offsets": [ [ 447, 457 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "PMID-9136080_T7" } ] }, { "id": "PMID-9136080_E7", "type": "Positive_regulation", "trigger": { "text": [ "contain functional promoter activity" ], "offsets": [ [ 619, 655 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "PMID-9136080_T7" } ] }, { "id": "PMID-9136080_E8", "type": "Gene_expression", "trigger": { "text": [ "expressing" ], "offsets": [ [ 838, 848 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "PMID-9136080_T8" } ] }, { "id": "PMID-9136080_E9", "type": "Gene_expression", "trigger": { "text": [ "non-expressing" ], "offsets": [ [ 860, 874 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "PMID-9136080_T8" } ] }, { "id": "PMID-9136080_E10", "type": "Gene_expression", "trigger": { "text": [ "expression" ], "offsets": [ [ 1019, 1029 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "PMID-9136080_T8" } ] }, { "id": "PMID-9136080_E11", "type": "Positive_regulation", "trigger": { "text": [ "promoter activity" ], "offsets": [ [ 1253, 1270 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "PMID-9136080_T8" } ] }, { "id": "PMID-9136080_E12", "type": "Negative_regulation", "trigger": { "text": [ "reduced" ], "offsets": [ [ 1416, 1423 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "PMID-9136080_E13" } ] }, { "id": "PMID-9136080_E13", "type": "Positive_regulation", "trigger": { "text": [ "promoter activity" ], "offsets": [ [ 1432, 1449 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "PMID-9136080_T8" } ] }, { "id": "PMID-9136080_E14", "type": "Regulation", "trigger": { "text": [ "affect" ], "offsets": [ [ 1520, 1526 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "PMID-9136080_E13" } ] }, { "id": "PMID-9136080_E15", "type": "Binding", "trigger": { "text": [ "binding" ], "offsets": [ [ 1836, 1843 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "PMID-9136080_T17" } ] }, { "id": "PMID-9136080_E16", "type": "Regulation", "trigger": { "text": [ "contribute" ], "offsets": [ [ 2030, 2040 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "PMID-9136080_E18" } ] }, { "id": "PMID-9136080_E17", "type": "Positive_regulation", "trigger": { "text": [ "contribute" ], "offsets": [ [ 2030, 2040 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "PMID-9136080_E18" } ] }, { "id": "PMID-9136080_E18", "type": "Gene_expression", "trigger": { "text": [ "expression" ], "offsets": [ [ 2066, 2076 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "PMID-9136080_T8" } ] } ]

[ { "id": "PMID-9136080_1", "entity_ids": [ "PMID-9136080_T6", "PMID-9136080_T5" ] } ]

[]

[ { "id": "PMID-9136989__text", "type": "abstract", "text": [ "Inhibitor (IK) of IFN-gamma induced HLA class II antigens expression also inhibits HLA class II constitutive expression in the human Raji B cell line. \nThe expression of major histocompatibility complex (MHC) class II antigens is constitutive in professional antigen presenting cells (APCs) but can also be induced by interferon-gamma (IFN-gamma) on the majority of the non professional APCs (e.g. fibroblasts). We have recently characterised a new factor called IK which is an efficient inhibitor of IFN-gamma induction of MHC class II antigens expression. Here, we demonstrate a novel role for IK in MHC class II expression since over-expression of this protein by stable transfection into human B cells led to a total disappearance of constitutive MHC class II mRNA expression. The class II transactivator (CIITA) is necessary for both constitutive and IFN-gamma induced MHC class II expressions. Examination of CIITA mRNA in IK stably transfected clones revealed a marked reduction of CIITA mRNA transcription. Taken together these results demonstrate that the IK protein plays a key role in the constitutive expression of MHC class II antigens and that inhibition induced by IK is upstream of CIITA in this regulatory pathway. " ], "offsets": [ [ 0, 1232 ] ] } ]

[ { "id": "PMID-9136989_T1", "type": "Protein", "text": [ "IK" ], "offsets": [ [ 11, 13 ] ], "normalized": [] }, { "id": "PMID-9136989_T2", "type": "Protein", "text": [ "IFN-gamma" ], "offsets": [ [ 18, 27 ] ], "normalized": [] }, { "id": "PMID-9136989_T3", "type": "Protein", "text": [ "interferon-gamma" ], "offsets": [ [ 318, 334 ] ], "normalized": [] }, { "id": "PMID-9136989_T4", "type": "Protein", "text": [ "IFN-gamma" ], "offsets": [ [ 336, 345 ] ], "normalized": [] }, { "id": "PMID-9136989_T5", "type": "Protein", "text": [ "IK" ], "offsets": [ [ 463, 465 ] ], "normalized": [] }, { "id": "PMID-9136989_T6", "type": "Protein", "text": [ "IFN-gamma" ], "offsets": [ [ 501, 510 ] ], "normalized": [] }, { "id": "PMID-9136989_T7", "type": "Protein", "text": [ "IK" ], "offsets": [ [ 596, 598 ] ], "normalized": [] }, { "id": "PMID-9136989_T8", "type": "Protein", "text": [ "class II transactivator" ], "offsets": [ [ 785, 808 ] ], "normalized": [] }, { "id": "PMID-9136989_T9", "type": "Protein", "text": [ "CIITA" ], "offsets": [ [ 810, 815 ] ], "normalized": [] }, { "id": "PMID-9136989_T10", "type": "Protein", "text": [ "IFN-gamma" ], "offsets": [ [ 856, 865 ] ], "normalized": [] }, { "id": "PMID-9136989_T11", "type": "Protein", "text": [ "CIITA" ], "offsets": [ [ 915, 920 ] ], "normalized": [] }, { "id": "PMID-9136989_T12", "type": "Protein", "text": [ "IK" ], "offsets": [ [ 929, 931 ] ], "normalized": [] }, { "id": "PMID-9136989_T13", "type": "Protein", "text": [ "CIITA" ], "offsets": [ [ 989, 994 ] ], "normalized": [] }, { "id": "PMID-9136989_T14", "type": "Protein", "text": [ "IK" ], "offsets": [ [ 1065, 1067 ] ], "normalized": [] }, { "id": "PMID-9136989_T15", "type": "Protein", "text": [ "IK" ], "offsets": [ [ 1180, 1182 ] ], "normalized": [] }, { "id": "PMID-9136989_T16", "type": "Protein", "text": [ "CIITA" ], "offsets": [ [ 1198, 1203 ] ], "normalized": [] } ]

[ { "id": "PMID-9136989_E1", "type": "Gene_expression", "trigger": { "text": [ "over-expression" ], "offsets": [ [ 632, 647 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "PMID-9136989_T7" } ] }, { "id": "PMID-9136989_E2", "type": "Positive_regulation", "trigger": { "text": [ "over-expression" ], "offsets": [ [ 632, 647 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "PMID-9136989_E1" } ] }, { "id": "PMID-9136989_E3", "type": "Transcription", "trigger": { "text": [ "mRNA" ], "offsets": [ [ 921, 925 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "PMID-9136989_T11" } ] }, { "id": "PMID-9136989_E4", "type": "Positive_regulation", "trigger": { "text": [ "transfected" ], "offsets": [ [ 939, 950 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "PMID-9136989_E5" } ] }, { "id": "PMID-9136989_E5", "type": "Gene_expression", "trigger": { "text": [ "transfected" ], "offsets": [ [ 939, 950 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "PMID-9136989_T12" } ] }, { "id": "PMID-9136989_E6", "type": "Negative_regulation", "trigger": { "text": [ "reduction" ], "offsets": [ [ 976, 985 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "PMID-9136989_E7" }, { "role": "Cause", "ref_id": "PMID-9136989_E4" } ] }, { "id": "PMID-9136989_E7", "type": "Transcription", "trigger": { "text": [ "transcription" ], "offsets": [ [ 1000, 1013 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "PMID-9136989_T13" } ] }, { "id": "PMID-9136989_E8", "type": "Negative_regulation", "trigger": { "text": [ "inhibition" ], "offsets": [ [ 1158, 1168 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "PMID-9136989_T16" }, { "role": "Cause", "ref_id": "PMID-9136989_T15" } ] } ]

[ { "id": "PMID-9136989_1", "entity_ids": [ "PMID-9136989_T8", "PMID-9136989_T9" ] }, { "id": "PMID-9136989_2", "entity_ids": [ "PMID-9136989_T3", "PMID-9136989_T4" ] } ]

[]

[ { "id": "PMID-9144218__text", "type": "abstract", "text": [ "An enhancer-blocking element between alpha and delta gene segments within the human T cell receptor alpha/delta locus. \nT cell receptor (TCR) alpha and delta gene segments are organized within a single genetic locus but are differentially regulated during T cell development. An enhancer-blocking element (BEAD-1, for blocking element alpha/delta 1) was localized to a 2.0-kb region 3' of TCR delta gene segments and 5' of TCR alpha joining gene segments within this locus. BEAD-1 blocked the ability of the TCR delta enhancer (Edelta) to activate a promoter when located between the two in a chromatin-integrated construct. We propose that BEAD-1 functions as a boundary that separates the TCR alpha/delta locus into distinct regulatory domains controlled by Edelta and the TCR alpha enhancer, and that it prevents Edelta from opening the chromatin of the TCR alpha joining gene segments for VDJ recombination at an early stage of T cell development. " ], "offsets": [ [ 0, 952 ] ] } ]

[]

[]

[]

[]

[ { "id": "PMID-9144338__text", "type": "abstract", "text": [ "Quantification of vitamin D receptor mRNA by competitive polymerase chain reaction in PBMC: lack of correspondence with common allelic variants. \nIt has been recently claimed that polymorphism for the vitamin D receptor (VDR) influences several aspects of calcium and bone metabolism. To evaluate the physiologic plausibility of these claims, we compared the abundance of the VDR mRNA in peripheral blood mononuclear cells (PBMCs) between different VDR genotypes using a quantitative reverse transcribed polymerase chain reaction-based method. The method is based on the coamplification of VDR cDNA and an internal standard consisting of known concentrations of a human VDR CDNA mutated at a BglII restriction site; the interassay coefficient of variation is 11%. To validate the method, we made use of earlier receptor binding studies indicating that normal human monocytes and activated, but not resting, lymphocytes expressed the VDR. The concentration of the VDR mRNA was 10(-8) to 10(-7) g/g of total RNA in cell-sorted monocytes and in in vitro activated lymphocytes, but only 10(-12) g/g of total mRNA in resting lymphocytes, establishing that the VDR mRNA determined by our method in PBMCs is due to constitutive expression in monocytes. Following an initial genotype screening of 85 normal volunteers by polymerase chain reaction or restriction fragment length polymorphism analysis, 14 individuals with the Bb genotype, 12 with the bb genotype, and 12 with the BB genotype were selected. The concentration of the VDR mRNA, corrected for the number of monocytes, was similar among the three genotype groups, as were the other variables examined: serum calcitriol, serum osteocalcin, and vertebral and hip bone density. We conclude that VDR polymorphism does not affect the abundance of the VDR mRNA. " ], "offsets": [ [ 0, 1809 ] ] } ]

[ { "id": "PMID-9144338_T1", "type": "Protein", "text": [ "vitamin D receptor" ], "offsets": [ [ 18, 36 ] ], "normalized": [] }, { "id": "PMID-9144338_T2", "type": "Protein", "text": [ "vitamin D receptor" ], "offsets": [ [ 201, 219 ] ], "normalized": [] }, { "id": "PMID-9144338_T3", "type": "Protein", "text": [ "VDR" ], "offsets": [ [ 221, 224 ] ], "normalized": [] }, { "id": "PMID-9144338_T4", "type": "Protein", "text": [ "VDR" ], "offsets": [ [ 376, 379 ] ], "normalized": [] }, { "id": "PMID-9144338_T5", "type": "Protein", "text": [ "VDR" ], "offsets": [ [ 449, 452 ] ], "normalized": [] }, { "id": "PMID-9144338_T6", "type": "Protein", "text": [ "VDR" ], "offsets": [ [ 590, 593 ] ], "normalized": [] }, { "id": "PMID-9144338_T7", "type": "Protein", "text": [ "VDR" ], "offsets": [ [ 670, 673 ] ], "normalized": [] }, { "id": "PMID-9144338_T8", "type": "Protein", "text": [ "VDR" ], "offsets": [ [ 933, 936 ] ], "normalized": [] }, { "id": "PMID-9144338_T9", "type": "Protein", "text": [ "VDR" ], "offsets": [ [ 963, 966 ] ], "normalized": [] }, { "id": "PMID-9144338_T10", "type": "Protein", "text": [ "VDR" ], "offsets": [ [ 1155, 1158 ] ], "normalized": [] }, { "id": "PMID-9144338_T11", "type": "Protein", "text": [ "VDR" ], "offsets": [ [ 1523, 1526 ] ], "normalized": [] }, { "id": "PMID-9144338_T12", "type": "Protein", "text": [ "serum osteocalcin" ], "offsets": [ [ 1673, 1690 ] ], "normalized": [] }, { "id": "PMID-9144338_T13", "type": "Protein", "text": [ "VDR" ], "offsets": [ [ 1745, 1748 ] ], "normalized": [] }, { "id": "PMID-9144338_T14", "type": "Protein", "text": [ "VDR" ], "offsets": [ [ 1799, 1802 ] ], "normalized": [] } ]

[ { "id": "PMID-9144338_E1", "type": "Transcription", "trigger": { "text": [ "abundance" ], "offsets": [ [ 359, 368 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "PMID-9144338_T4" } ] }, { "id": "PMID-9144338_E2", "type": "Gene_expression", "trigger": { "text": [ "expressed" ], "offsets": [ [ 919, 928 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "PMID-9144338_T8" } ] }, { "id": "PMID-9144338_E3", "type": "Transcription", "trigger": { "text": [ "expression" ], "offsets": [ [ 1221, 1231 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "PMID-9144338_T10" } ] }, { "id": "PMID-9144338_E4", "type": "Transcription", "trigger": { "text": [ "concentration" ], "offsets": [ [ 1502, 1515 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "PMID-9144338_T11" } ] }, { "id": "PMID-9144338_E5", "type": "Regulation", "trigger": { "text": [ "affect" ], "offsets": [ [ 1771, 1777 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "PMID-9144338_E6" } ] }, { "id": "PMID-9144338_E6", "type": "Transcription", "trigger": { "text": [ "abundance" ], "offsets": [ [ 1782, 1791 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "PMID-9144338_T14" } ] } ]

[ { "id": "PMID-9144338_1", "entity_ids": [ "PMID-9144338_T2", "PMID-9144338_T3" ] } ]

[]

[ { "id": "PMID-9144472__text", "type": "abstract", "text": [ "Regulation of CD95 (Fas) ligand expression by TCR-mediated signaling events. \nStimulation of mature peripheral T cells by TCR engagement results in activation of signals that drive induction of cytokine gene expression and clonal expansion. However, under some conditions, engagement of the TCR leads instead to apoptosis. Recent studies demonstrate that TCR-stimulated apoptosis requires expression of CD95 ligand on activated T cells followed by an interaction between CD95 ligand and the CD95 receptor also expressed on this population. The experiments reported in this study were designed to address the signaling events triggered by TCR engagement that are important for regulating CD95 ligand gene expression. To approach this, we generated a luciferase reporter construct containing elements of the CD95 ligand promoter. Using a previously described mutant of the Jurkat T cell line, we show that proximal signaling events dependent on the presence of the CD45 tyrosine phosphatase are required for TCR-stimulated CD95 ligand expression. Transient transfection studies demonstrate further that TCR-stimulated activation of the Ras signaling pathway is required for optimal activation of CD95 ligand. Next, in an effort to determine critical transcription factors that regulate CD95 ligand expression, we demonstrate a cyclosporin A-sensitive nuclear factor-AT response element in the promoter region of this gene that is critical for optimal CD95 ligand reporter activity in stimulated T cells. Together, these studies begin a dissection of the biochemical events that lead to expression of CD95 ligand, a required step for TCR-induced apoptosis. " ], "offsets": [ [ 0, 1654 ] ] } ]

[ { "id": "PMID-9144472_T1", "type": "Protein", "text": [ "CD95 (Fas) ligand" ], "offsets": [ [ 14, 31 ] ], "normalized": [] }, { "id": "PMID-9144472_T2", "type": "Protein", "text": [ "CD95 ligand" ], "offsets": [ [ 403, 414 ] ], "normalized": [] }, { "id": "PMID-9144472_T3", "type": "Protein", "text": [ "CD95 ligand" ], "offsets": [ [ 471, 482 ] ], "normalized": [] }, { "id": "PMID-9144472_T4", "type": "Protein", "text": [ "CD95" ], "offsets": [ [ 491, 495 ] ], "normalized": [] }, { "id": "PMID-9144472_T5", "type": "Protein", "text": [ "CD95 ligand" ], "offsets": [ [ 687, 698 ] ], "normalized": [] }, { "id": "PMID-9144472_T6", "type": "Protein", "text": [ "luciferase" ], "offsets": [ [ 749, 759 ] ], "normalized": [] }, { "id": "PMID-9144472_T7", "type": "Protein", "text": [ "CD95 ligand" ], "offsets": [ [ 806, 817 ] ], "normalized": [] }, { "id": "PMID-9144472_T8", "type": "Protein", "text": [ "CD45 tyrosine phosphatase" ], "offsets": [ [ 963, 988 ] ], "normalized": [] }, { "id": "PMID-9144472_T9", "type": "Protein", "text": [ "CD95 ligand" ], "offsets": [ [ 1021, 1032 ] ], "normalized": [] }, { "id": "PMID-9144472_T10", "type": "Protein", "text": [ "CD95 ligand" ], "offsets": [ [ 1194, 1205 ] ], "normalized": [] }, { "id": "PMID-9144472_T11", "type": "Protein", "text": [ "CD95 ligand" ], "offsets": [ [ 1284, 1295 ] ], "normalized": [] }, { "id": "PMID-9144472_T12", "type": "Protein", "text": [ "cyclosporin A" ], "offsets": [ [ 1325, 1338 ] ], "normalized": [] }, { "id": "PMID-9144472_T13", "type": "Protein", "text": [ "CD95 ligand" ], "offsets": [ [ 1449, 1460 ] ], "normalized": [] }, { "id": "PMID-9144472_T14", "type": "Protein", "text": [ "CD95 ligand" ], "offsets": [ [ 1598, 1609 ] ], "normalized": [] } ]

[ { "id": "PMID-9144472_E1", "type": "Regulation", "trigger": { "text": [ "Regulation" ], "offsets": [ [ 0, 10 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "PMID-9144472_E2" } ] }, { "id": "PMID-9144472_E2", "type": "Gene_expression", "trigger": { "text": [ "expression" ], "offsets": [ [ 32, 42 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "PMID-9144472_T1" } ] }, { "id": "PMID-9144472_E3", "type": "Gene_expression", "trigger": { "text": [ "expression" ], "offsets": [ [ 389, 399 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "PMID-9144472_T2" } ] }, { "id": "PMID-9144472_E4", "type": "Binding", "trigger": { "text": [ "interaction" ], "offsets": [ [ 451, 462 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "PMID-9144472_T3" } ] }, { "id": "PMID-9144472_E5", "type": "Regulation", "trigger": { "text": [ "important for regulating" ], "offsets": [ [ 662, 686 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "PMID-9144472_E6" } ] }, { "id": "PMID-9144472_E6", "type": "Gene_expression", "trigger": { "text": [ "expression" ], "offsets": [ [ 704, 714 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "PMID-9144472_T5" } ] }, { "id": "PMID-9144472_E7", "type": "Positive_regulation", "trigger": { "text": [ "required" ], "offsets": [ [ 993, 1001 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "PMID-9144472_E8" } ] }, { "id": "PMID-9144472_E8", "type": "Positive_regulation", "trigger": { "text": [ "stimulated" ], "offsets": [ [ 1010, 1020 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "PMID-9144472_E9" } ] }, { "id": "PMID-9144472_E9", "type": "Gene_expression", "trigger": { "text": [ "expression" ], "offsets": [ [ 1033, 1043 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "PMID-9144472_T9" } ] }, { "id": "PMID-9144472_E10", "type": "Positive_regulation", "trigger": { "text": [ "required" ], "offsets": [ [ 1159, 1167 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "PMID-9144472_E11" } ] }, { "id": "PMID-9144472_E11", "type": "Positive_regulation", "trigger": { "text": [ "activation" ], "offsets": [ [ 1180, 1190 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "PMID-9144472_T10" } ] }, { "id": "PMID-9144472_E12", "type": "Regulation", "trigger": { "text": [ "regulate" ], "offsets": [ [ 1275, 1283 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "PMID-9144472_E13" } ] }, { "id": "PMID-9144472_E13", "type": "Gene_expression", "trigger": { "text": [ "expression" ], "offsets": [ [ 1296, 1306 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "PMID-9144472_T11" } ] }, { "id": "PMID-9144472_E14", "type": "Positive_regulation", "trigger": { "text": [ "critical" ], "offsets": [ [ 1428, 1436 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "PMID-9144472_T13" } ] }, { "id": "PMID-9144472_E15", "type": "Gene_expression", "trigger": { "text": [ "expression" ], "offsets": [ [ 1584, 1594 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "PMID-9144472_T14" } ] } ]

[]

[]

[ { "id": "PMID-9144479__text", "type": "abstract", "text": [ "CD40 is a functional activation antigen and B7-independent T cell costimulatory molecule on normal human lung fibroblasts. \nCD40 is an important signaling and activation Ag found on certain bone marrow-derived cells. Recently, CD40 also has been shown to be expressed by mesenchymal cells, including human fibroblasts. Little is known about the role of CD40 in fibroblasts. The current study investigates the hypothesis that CD40 expressed on lung fibroblasts is an activation structure and mechanism for interaction with hemopoietic cells. Communication between resident tissue fibroblasts and T cells is necessary for normal wound healing, and can be pathologic, resulting in tissue fibrosis. Signaling through CD40 with soluble CD40 ligand stimulated fibroblast activation, as evidenced by mobilization of nuclear factor-kappaB and by induction of the proinflammatory and chemoattractant cytokines IL-6 and IL-8. IFN-gamma-primed lung fibroblasts costimulate T lymphocyte proliferation utilizing CD40, but not the well-studied costimulatory molecules B7-1 and B7-2. Data reported herein support the hypothesis that cognate interactions between tissue fibroblasts and infiltrating T lymphocytes, via the CD40/CD40L pathway, augment inflammation and may promote fibrogenesis by activating both cell types. " ], "offsets": [ [ 0, 1307 ] ] } ]

[ { "id": "PMID-9144479_T1", "type": "Protein", "text": [ "CD40" ], "offsets": [ [ 0, 4 ] ], "normalized": [] }, { "id": "PMID-9144479_T2", "type": "Protein", "text": [ "B7" ], "offsets": [ [ 44, 46 ] ], "normalized": [] }, { "id": "PMID-9144479_T3", "type": "Protein", "text": [ "CD40" ], "offsets": [ [ 124, 128 ] ], "normalized": [] }, { "id": "PMID-9144479_T4", "type": "Protein", "text": [ "CD40" ], "offsets": [ [ 227, 231 ] ], "normalized": [] }, { "id": "PMID-9144479_T5", "type": "Protein", "text": [ "CD40" ], "offsets": [ [ 353, 357 ] ], "normalized": [] }, { "id": "PMID-9144479_T6", "type": "Protein", "text": [ "CD40" ], "offsets": [ [ 425, 429 ] ], "normalized": [] }, { "id": "PMID-9144479_T7", "type": "Protein", "text": [ "CD40" ], "offsets": [ [ 713, 717 ] ], "normalized": [] }, { "id": "PMID-9144479_T8", "type": "Protein", "text": [ "CD40 ligand" ], "offsets": [ [ 731, 742 ] ], "normalized": [] }, { "id": "PMID-9144479_T9", "type": "Protein", "text": [ "IL-6" ], "offsets": [ [ 901, 905 ] ], "normalized": [] }, { "id": "PMID-9144479_T10", "type": "Protein", "text": [ "IL-8" ], "offsets": [ [ 910, 914 ] ], "normalized": [] }, { "id": "PMID-9144479_T11", "type": "Protein", "text": [ "IFN-gamma" ], "offsets": [ [ 916, 925 ] ], "normalized": [] }, { "id": "PMID-9144479_T12", "type": "Protein", "text": [ "CD40" ], "offsets": [ [ 999, 1003 ] ], "normalized": [] }, { "id": "PMID-9144479_T13", "type": "Protein", "text": [ "B7-1" ], "offsets": [ [ 1054, 1058 ] ], "normalized": [] }, { "id": "PMID-9144479_T14", "type": "Protein", "text": [ "B7-2" ], "offsets": [ [ 1063, 1067 ] ], "normalized": [] }, { "id": "PMID-9144479_T15", "type": "Protein", "text": [ "CD40" ], "offsets": [ [ 1206, 1210 ] ], "normalized": [] }, { "id": "PMID-9144479_T16", "type": "Protein", "text": [ "CD40L" ], "offsets": [ [ 1211, 1216 ] ], "normalized": [] } ]

[ { "id": "PMID-9144479_E1", "type": "Gene_expression", "trigger": { "text": [ "found" ], "offsets": [ [ 173, 178 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "PMID-9144479_T3" } ] }, { "id": "PMID-9144479_E2", "type": "Gene_expression", "trigger": { "text": [ "expressed" ], "offsets": [ [ 258, 267 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "PMID-9144479_T4" } ] }, { "id": "PMID-9144479_E3", "type": "Gene_expression", "trigger": { "text": [ "expressed" ], "offsets": [ [ 430, 439 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "PMID-9144479_T6" } ] }, { "id": "PMID-9144479_E4", "type": "Positive_regulation", "trigger": { "text": [ "induction" ], "offsets": [ [ 838, 847 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "PMID-9144479_T9" } ] }, { "id": "PMID-9144479_E5", "type": "Positive_regulation", "trigger": { "text": [ "induction" ], "offsets": [ [ 838, 847 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "PMID-9144479_T10" } ] } ]

[]

[]

[ { "id": "PMID-9175835__text", "type": "abstract", "text": [ "Tap: a novel cellular protein that interacts with tip of herpesvirus saimiri and induces lymphocyte aggregation. \nTip of herpesvirus saimiri associates with Lck and down-regulates Lck-mediated activation. We identified a novel cellular Tip-associated protein (Tap) by a yeast two-hybrid screen. Tap associated with Tip following transient expression in COS-1 cells and stable expression in human Jurkat-T cells. Expression of Tip and Tap in Jurkat-T cells induced dramatic cell aggregation. Aggregation was likely caused by the up-regulated surface expression of adhesion molecules including integrin alpha, L-selectin, ICAM-3, and H-CAM. Furthermore, NF-kappaB transcriptional factor of aggregated cells had approximately 40-fold higher activity than that of parental cells. Thus, Tap is likely to be an important cellular mediator of Tip function in T cell transformation by herpesvirus saimiri. " ], "offsets": [ [ 0, 898 ] ] } ]

[ { "id": "PMID-9175835_T1", "type": "Protein", "text": [ "Lck" ], "offsets": [ [ 157, 160 ] ], "normalized": [] }, { "id": "PMID-9175835_T2", "type": "Protein", "text": [ "Lck" ], "offsets": [ [ 180, 183 ] ], "normalized": [] }, { "id": "PMID-9175835_T3", "type": "Protein", "text": [ "L-selectin" ], "offsets": [ [ 608, 618 ] ], "normalized": [] }, { "id": "PMID-9175835_T4", "type": "Protein", "text": [ "ICAM-3" ], "offsets": [ [ 620, 626 ] ], "normalized": [] }, { "id": "PMID-9175835_T5", "type": "Protein", "text": [ "H-CAM" ], "offsets": [ [ 632, 637 ] ], "normalized": [] } ]

[ { "id": "PMID-9175835_E1", "type": "Binding", "trigger": { "text": [ "associates" ], "offsets": [ [ 141, 151 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "PMID-9175835_T1" } ] }, { "id": "PMID-9175835_E2", "type": "Positive_regulation", "trigger": { "text": [ "up-regulated" ], "offsets": [ [ 528, 540 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "PMID-9175835_E7" } ] }, { "id": "PMID-9175835_E3", "type": "Positive_regulation", "trigger": { "text": [ "up-regulated" ], "offsets": [ [ 528, 540 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "PMID-9175835_E6" } ] }, { "id": "PMID-9175835_E4", "type": "Positive_regulation", "trigger": { "text": [ "up-regulated" ], "offsets": [ [ 528, 540 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "PMID-9175835_E5" } ] }, { "id": "PMID-9175835_E5", "type": "Gene_expression", "trigger": { "text": [ "expression" ], "offsets": [ [ 549, 559 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "PMID-9175835_T5" } ] }, { "id": "PMID-9175835_E6", "type": "Gene_expression", "trigger": { "text": [ "expression" ], "offsets": [ [ 549, 559 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "PMID-9175835_T3" } ] }, { "id": "PMID-9175835_E7", "type": "Gene_expression", "trigger": { "text": [ "expression" ], "offsets": [ [ 549, 559 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "PMID-9175835_T4" } ] } ]

[]

[]

[ { "id": "PMID-9177216__text", "type": "abstract", "text": [ "Transactivation by CIITA, the type II bare lymphocyte syndrome-associated factor, requires participation of multiple regions of the TATA box binding protein. \nCIITA is a positive regulator of class II major histocompatibility complex gene transcription that has been found to be defective in one of the five complementation groups of class II major histocompatibility complex-negative cell lines. Its N-terminal region is capable of activating transcription from a reporter gene when fused to a DNA binding domain. We have investigated the mechanism of transactivation mediated by the CIITA activation domain by studying its role in the process of transcription initiation and elongation. Specifically the altered specificity TBP (TATA box binding protein) assay has been used to analyze the response of the CIITA activation domain to mutations in TBP known to disrupt its interaction with its associated general factors. Transactivation by CIITA was extremely sensitive to a mutation in TBP that in yeast is known to abolish VP16-mediated transcription but leaves basal transcription unaffected. A TBP mutant defective in interaction with TBP-associated factor TAFII250 also failed to mediate transactivation through the CIITA activation domain. Certain interactions between TBP and general factors that are specifically required for acidic activation domains were also required for CIITA-mediated transactivation to reach its full potential. Finally, like VP16, CIITA was able to stimulate elongation of transcription. Overall the mechanism of transactivation by the human B-cell-specific CIITA is very similar to that mediated by the herpes virus transactivator VP16 in the ways that have been tested. " ], "offsets": [ [ 0, 1705 ] ] } ]

[ { "id": "PMID-9177216_T1", "type": "Protein", "text": [ "CIITA" ], "offsets": [ [ 19, 24 ] ], "normalized": [] }, { "id": "PMID-9177216_T2", "type": "Protein", "text": [ "TATA box binding protein" ], "offsets": [ [ 132, 156 ] ], "normalized": [] }, { "id": "PMID-9177216_T3", "type": "Protein", "text": [ "CIITA" ], "offsets": [ [ 159, 164 ] ], "normalized": [] }, { "id": "PMID-9177216_T4", "type": "Protein", "text": [ "CIITA" ], "offsets": [ [ 585, 590 ] ], "normalized": [] }, { "id": "PMID-9177216_T5", "type": "Protein", "text": [ "TBP" ], "offsets": [ [ 726, 729 ] ], "normalized": [] }, { "id": "PMID-9177216_T6", "type": "Protein", "text": [ "TATA box binding protein" ], "offsets": [ [ 731, 755 ] ], "normalized": [] }, { "id": "PMID-9177216_T7", "type": "Protein", "text": [ "CIITA" ], "offsets": [ [ 808, 813 ] ], "normalized": [] }, { "id": "PMID-9177216_T8", "type": "Protein", "text": [ "TBP" ], "offsets": [ [ 848, 851 ] ], "normalized": [] }, { "id": "PMID-9177216_T9", "type": "Protein", "text": [ "CIITA" ], "offsets": [ [ 941, 946 ] ], "normalized": [] }, { "id": "PMID-9177216_T10", "type": "Protein", "text": [ "TBP" ], "offsets": [ [ 988, 991 ] ], "normalized": [] }, { "id": "PMID-9177216_T11", "type": "Protein", "text": [ "VP16" ], "offsets": [ [ 1026, 1030 ] ], "normalized": [] }, { "id": "PMID-9177216_T12", "type": "Protein", "text": [ "TBP" ], "offsets": [ [ 1099, 1102 ] ], "normalized": [] }, { "id": "PMID-9177216_T13", "type": "Protein", "text": [ "TBP" ], "offsets": [ [ 1140, 1143 ] ], "normalized": [] }, { "id": "PMID-9177216_T14", "type": "Protein", "text": [ "TAFII250" ], "offsets": [ [ 1162, 1170 ] ], "normalized": [] }, { "id": "PMID-9177216_T15", "type": "Protein", "text": [ "CIITA" ], "offsets": [ [ 1222, 1227 ] ], "normalized": [] }, { "id": "PMID-9177216_T16", "type": "Protein", "text": [ "TBP" ], "offsets": [ [ 1276, 1279 ] ], "normalized": [] }, { "id": "PMID-9177216_T17", "type": "Protein", "text": [ "CIITA" ], "offsets": [ [ 1384, 1389 ] ], "normalized": [] }, { "id": "PMID-9177216_T18", "type": "Protein", "text": [ "VP16" ], "offsets": [ [ 1458, 1462 ] ], "normalized": [] }, { "id": "PMID-9177216_T19", "type": "Protein", "text": [ "CIITA" ], "offsets": [ [ 1464, 1469 ] ], "normalized": [] }, { "id": "PMID-9177216_T20", "type": "Protein", "text": [ "CIITA" ], "offsets": [ [ 1591, 1596 ] ], "normalized": [] }, { "id": "PMID-9177216_T21", "type": "Protein", "text": [ "VP16" ], "offsets": [ [ 1665, 1669 ] ], "normalized": [] } ]

[ { "id": "PMID-9177216_E1", "type": "Negative_regulation", "trigger": { "text": [ "defective" ], "offsets": [ [ 279, 288 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "PMID-9177216_T3" } ] }, { "id": "PMID-9177216_E2", "type": "Negative_regulation", "trigger": { "text": [ "disrupt" ], "offsets": [ [ 861, 868 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "PMID-9177216_E3" } ] }, { "id": "PMID-9177216_E3", "type": "Binding", "trigger": { "text": [ "interaction" ], "offsets": [ [ 873, 884 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "PMID-9177216_T8" } ] }, { "id": "PMID-9177216_E4", "type": "Binding", "trigger": { "text": [ "interaction" ], "offsets": [ [ 1123, 1134 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "PMID-9177216_T12" }, { "role": "Theme", "ref_id": "PMID-9177216_T14" } ] }, { "id": "PMID-9177216_E5", "type": "Binding", "trigger": { "text": [ "interactions" ], "offsets": [ [ 1255, 1267 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "PMID-9177216_T16" } ] } ]

[ { "id": "PMID-9177216_1", "entity_ids": [ "PMID-9177216_T5", "PMID-9177216_T6" ] } ]

[]

[ { "id": "PMID-9177217__text", "type": "abstract", "text": [ "Specific complex formation between the type II bare lymphocyte syndrome-associated transactivators CIITA and RFX5. \nTwo of the genes defective in the five complementation groups identified in the class II-negative bare lymphocyte syndrome or corresponding laboratory mutants have been cloned. One gene encodes a protein, RFX5, that is a member of the RFX family of DNA binding proteins. The other, CIITA, encodes a large protein with a defined acidic transcriptional activation domain; this protein does not interact with DNA. Expression plasmids encoding regions of RFX5 fused to the GAL4 DNA binding domain activated transcription from a reporter construct containing GAL4 sites in a cotransfection assay in the Raji human B cell line. However, these plasmids produced transcriptional activity in HeLa cells only in conjunction with interferon gamma stimulation, a condition in which expression of both CIITA and class II major histocompatibility complex surface proteins are induced. Furthermore, these plasmids were not active in RJ2.2.5, an in vitro mutagenized derivative of Raji in which both copies of CIITA are defective. Transcriptional activation by the RFX5 fusion protein could be restored in RJ2.2.5 by cotransfection with a CIITA expression plasmid. Finally, a direct interaction between RFX5 and CIITA was detected with the yeast two-hybrid and far-Western blot assays. Thus, RFX5 can activate transcription only in cooperation with CIITA. RFX5 and CIITA associate to form a complex capable of activating transcription from class II major histocompatibility complex promoters. In this complex, promoter specificity is determined by the DNA binding domain of RFX5 and the general transcription apparatus is recruited by the acidic activation domain of CIITA. " ], "offsets": [ [ 0, 1774 ] ] } ]

[ { "id": "PMID-9177217_T1", "type": "Protein", "text": [ "CIITA" ], "offsets": [ [ 99, 104 ] ], "normalized": [] }, { "id": "PMID-9177217_T2", "type": "Protein", "text": [ "RFX5" ], "offsets": [ [ 109, 113 ] ], "normalized": [] }, { "id": "PMID-9177217_T3", "type": "Protein", "text": [ "RFX5" ], "offsets": [ [ 321, 325 ] ], "normalized": [] }, { "id": "PMID-9177217_T4", "type": "Protein", "text": [ "CIITA" ], "offsets": [ [ 398, 403 ] ], "normalized": [] }, { "id": "PMID-9177217_T5", "type": "Protein", "text": [ "RFX5" ], "offsets": [ [ 567, 571 ] ], "normalized": [] }, { "id": "PMID-9177217_T6", "type": "Protein", "text": [ "GAL4" ], "offsets": [ [ 585, 589 ] ], "normalized": [] }, { "id": "PMID-9177217_T7", "type": "Protein", "text": [ "GAL4" ], "offsets": [ [ 670, 674 ] ], "normalized": [] }, { "id": "PMID-9177217_T8", "type": "Protein", "text": [ "interferon gamma" ], "offsets": [ [ 835, 851 ] ], "normalized": [] }, { "id": "PMID-9177217_T9", "type": "Protein", "text": [ "CIITA" ], "offsets": [ [ 905, 910 ] ], "normalized": [] }, { "id": "PMID-9177217_T10", "type": "Protein", "text": [ "CIITA" ], "offsets": [ [ 1110, 1115 ] ], "normalized": [] }, { "id": "PMID-9177217_T11", "type": "Protein", "text": [ "RFX5" ], "offsets": [ [ 1165, 1169 ] ], "normalized": [] }, { "id": "PMID-9177217_T12", "type": "Protein", "text": [ "CIITA" ], "offsets": [ [ 1239, 1244 ] ], "normalized": [] }, { "id": "PMID-9177217_T13", "type": "Protein", "text": [ "RFX5" ], "offsets": [ [ 1303, 1307 ] ], "normalized": [] }, { "id": "PMID-9177217_T14", "type": "Protein", "text": [ "CIITA" ], "offsets": [ [ 1312, 1317 ] ], "normalized": [] }, { "id": "PMID-9177217_T15", "type": "Protein", "text": [ "RFX5" ], "offsets": [ [ 1392, 1396 ] ], "normalized": [] }, { "id": "PMID-9177217_T16", "type": "Protein", "text": [ "CIITA" ], "offsets": [ [ 1449, 1454 ] ], "normalized": [] }, { "id": "PMID-9177217_T17", "type": "Protein", "text": [ "RFX5" ], "offsets": [ [ 1456, 1460 ] ], "normalized": [] }, { "id": "PMID-9177217_T18", "type": "Protein", "text": [ "CIITA" ], "offsets": [ [ 1465, 1470 ] ], "normalized": [] }, { "id": "PMID-9177217_T19", "type": "Protein", "text": [ "RFX5" ], "offsets": [ [ 1674, 1678 ] ], "normalized": [] }, { "id": "PMID-9177217_T20", "type": "Protein", "text": [ "CIITA" ], "offsets": [ [ 1767, 1772 ] ], "normalized": [] }, { "id": "PMID-9177217_T32", "type": "Entity", "text": [ "DNA binding domain" ], "offsets": [ [ 1652, 1670 ] ], "normalized": [] } ]

[ { "id": "PMID-9177217_E1", "type": "Binding", "trigger": { "text": [ "complex formation" ], "offsets": [ [ 9, 26 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "PMID-9177217_T1" }, { "role": "Theme", "ref_id": "PMID-9177217_T2" } ] }, { "id": "PMID-9177217_E2", "type": "Negative_regulation", "trigger": { "text": [ "defective" ], "offsets": [ [ 133, 142 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "PMID-9177217_T1" } ] }, { "id": "PMID-9177217_E3", "type": "Negative_regulation", "trigger": { "text": [ "defective" ], "offsets": [ [ 133, 142 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "PMID-9177217_T2" } ] }, { "id": "PMID-9177217_E4", "type": "Binding", "trigger": { "text": [ "interact" ], "offsets": [ [ 508, 516 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "PMID-9177217_T4" } ] }, { "id": "PMID-9177217_E5", "type": "Gene_expression", "trigger": { "text": [ "expression" ], "offsets": [ [ 886, 896 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "PMID-9177217_T9" } ] }, { "id": "PMID-9177217_E6", "type": "Positive_regulation", "trigger": { "text": [ "induced" ], "offsets": [ [ 978, 985 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "PMID-9177217_E5" } ] }, { "id": "PMID-9177217_E7", "type": "Negative_regulation", "trigger": { "text": [ "defective" ], "offsets": [ [ 1120, 1129 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "PMID-9177217_T10" } ] }, { "id": "PMID-9177217_E8", "type": "Positive_regulation", "trigger": { "text": [ "cotransfection" ], "offsets": [ [ 1217, 1231 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "PMID-9177217_E9" } ] }, { "id": "PMID-9177217_E9", "type": "Gene_expression", "trigger": { "text": [ "expression" ], "offsets": [ [ 1245, 1255 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "PMID-9177217_T12" } ] }, { "id": "PMID-9177217_E10", "type": "Binding", "trigger": { "text": [ "interaction" ], "offsets": [ [ 1283, 1294 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "PMID-9177217_T13" }, { "role": "Theme", "ref_id": "PMID-9177217_T14" } ] }, { "id": "PMID-9177217_E11", "type": "Binding", "trigger": { "text": [ "associate to form a complex" ], "offsets": [ [ 1471, 1498 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "PMID-9177217_T17" }, { "role": "Theme", "ref_id": "PMID-9177217_T18" } ] }, { "id": "PMID-9177217_E12", "type": "Binding", "trigger": { "text": [ "specificity" ], "offsets": [ [ 1619, 1630 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "PMID-9177217_T19" }, { "role": "Site", "ref_id": "PMID-9177217_T32" } ] } ]

[]

[]

[ { "id": "PMID-9178107__text", "type": "abstract", "text": [ "Reactive oxygen species and antioxidants in inflammatory diseases. \nThis paper aims to review the role of free radical-induced tissue damage and antioxidant defence mechanisms in inflammatory diseases that involve pathogenic processes similar to the periodontal diseases. There is a clearly defined and substantial role for free radicals or reactive oxygen species (ROS) in periodontitis, but little research has been performed in this area. This paper reviews the considerable data available relating ROS activity and antioxidant defence to inflammatory diseases and attempts to draw parallels with periodontitis, in an effort to stimulate more periodontal research in this important area. The recent discovery of the transcription factor nuclear factor kappa B (NF-kappa B) is reviewed and several potential pathways for cytokine-induced periodontal tissue damage, mediated by NF-kappa B1 are discussed. Emphasis is placed on cytokines that have been studied in periodontitis, principally TNF-alpha, IL-1, IL-6, IL-8 and beta-interferon. The link between cellular production of such important mediators of inflammation and the antioxidant (AO) thiols, cysteine and reduced glutathione (GSH), is discussed and it is hypothesised that NF-kappa B antagonists may offer important therapeutic benefits. " ], "offsets": [ [ 0, 1300 ] ] } ]

[ { "id": "PMID-9178107_T1", "type": "Protein", "text": [ "NF-kappa B1" ], "offsets": [ [ 879, 890 ] ], "normalized": [] }, { "id": "PMID-9178107_T2", "type": "Protein", "text": [ "TNF-alpha" ], "offsets": [ [ 991, 1000 ] ], "normalized": [] }, { "id": "PMID-9178107_T3", "type": "Protein", "text": [ "IL-6" ], "offsets": [ [ 1008, 1012 ] ], "normalized": [] }, { "id": "PMID-9178107_T4", "type": "Protein", "text": [ "IL-8" ], "offsets": [ [ 1014, 1018 ] ], "normalized": [] }, { "id": "PMID-9178107_T5", "type": "Protein", "text": [ "beta-interferon" ], "offsets": [ [ 1023, 1038 ] ], "normalized": [] } ]

[ { "id": "PMID-9178107_E1", "type": "Gene_expression", "trigger": { "text": [ "production" ], "offsets": [ [ 1066, 1076 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "PMID-9178107_T2" } ] }, { "id": "PMID-9178107_E2", "type": "Gene_expression", "trigger": { "text": [ "production" ], "offsets": [ [ 1066, 1076 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "PMID-9178107_T4" } ] }, { "id": "PMID-9178107_E3", "type": "Gene_expression", "trigger": { "text": [ "production" ], "offsets": [ [ 1066, 1076 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "PMID-9178107_T5" } ] }, { "id": "PMID-9178107_E4", "type": "Gene_expression", "trigger": { "text": [ "production" ], "offsets": [ [ 1066, 1076 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "PMID-9178107_T3" } ] } ]

[]

[]

[ { "id": "PMID-9180266__text", "type": "abstract", "text": [ "Transcriptional activity and constitutive nuclear localization of the ETS protein Elf-1. \nElf-1 is a lymphoid-specific transcription factor that belongs to the ETS protein family. It can bind to DNA target sequences within a variety of cytokine genes. We demonstrate that Elf-1 is constitutively localized in the nucleus which is dependent on the presence of amino acids 86-265. Analysis of Gal4-Elf-1 fusion proteins revealed that the N-terminal 86 amino acids of Elf-1 contain a transcriptional activation domain, the activity of which is attenuated by an internal repression domain. Furthermore, Elf-1 interacts specifically with the E74 target sequence and can stimulate transcription driven by the E74 site independent of mitogenic signaling. Thus, Elf-1 is able to stimulate gene transcription which may be required for the development and activity of lymphocytes. " ], "offsets": [ [ 0, 871 ] ] } ]

[ { "id": "PMID-9180266_T1", "type": "Protein", "text": [ "Elf-1" ], "offsets": [ [ 82, 87 ] ], "normalized": [] }, { "id": "PMID-9180266_T2", "type": "Protein", "text": [ "Elf-1" ], "offsets": [ [ 90, 95 ] ], "normalized": [] }, { "id": "PMID-9180266_T3", "type": "Protein", "text": [ "Elf-1" ], "offsets": [ [ 272, 277 ] ], "normalized": [] }, { "id": "PMID-9180266_T4", "type": "Protein", "text": [ "Gal4" ], "offsets": [ [ 391, 395 ] ], "normalized": [] }, { "id": "PMID-9180266_T5", "type": "Protein", "text": [ "Elf-1" ], "offsets": [ [ 396, 401 ] ], "normalized": [] }, { "id": "PMID-9180266_T6", "type": "Protein", "text": [ "Elf-1" ], "offsets": [ [ 465, 470 ] ], "normalized": [] }, { "id": "PMID-9180266_T7", "type": "Protein", "text": [ "Elf-1" ], "offsets": [ [ 599, 604 ] ], "normalized": [] }, { "id": "PMID-9180266_T8", "type": "Protein", "text": [ "Elf-1" ], "offsets": [ [ 754, 759 ] ], "normalized": [] }, { "id": "PMID-9180266_T9", "type": "Entity", "text": [ "nuclear" ], "offsets": [ [ 42, 49 ] ], "normalized": [] }, { "id": "PMID-9180266_T13", "type": "Entity", "text": [ "nucleus" ], "offsets": [ [ 313, 320 ] ], "normalized": [] } ]

[ { "id": "PMID-9180266_E1", "type": "Localization", "trigger": { "text": [ "localization" ], "offsets": [ [ 50, 62 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "PMID-9180266_T1" }, { "role": "AtLoc", "ref_id": "PMID-9180266_T9" } ] }, { "id": "PMID-9180266_E2", "type": "Binding", "trigger": { "text": [ "bind" ], "offsets": [ [ 187, 191 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "PMID-9180266_T2" } ] }, { "id": "PMID-9180266_E3", "type": "Localization", "trigger": { "text": [ "localized" ], "offsets": [ [ 296, 305 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "PMID-9180266_T3" }, { "role": "AtLoc", "ref_id": "PMID-9180266_T13" } ] }, { "id": "PMID-9180266_E4", "type": "Positive_regulation", "trigger": { "text": [ "dependent" ], "offsets": [ [ 330, 339 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "PMID-9180266_E3" } ] }, { "id": "PMID-9180266_E5", "type": "Binding", "trigger": { "text": [ "interacts" ], "offsets": [ [ 605, 614 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "PMID-9180266_T7" } ] } ]

[]

[]

[ { "id": "PMID-9182556__text", "type": "abstract", "text": [ "Overexpression of HSF2-beta inhibits hemin-induced heat shock gene expression and erythroid differentiation in K562 cells. \nAcquisition of heat shock factor 2 (HSF2) DNA binding activity is accompanied by induced transcription of heat shock genes in hemin-treated K562 cells undergoing erythroid differentiation. Previous studies revealed that HSF2 consists of two alternatively spliced isoforms, HSF2-alpha and HSF2-beta, whose relative abundance is developmentally regulated and varies between different tissues. To investigate whether the molar ratio of HSF2-alpha and HSF2-beta isoforms is crucial for the activation of HSF2 and whether the HSF2 isoforms play functionally distinct roles during the hemin-mediated erythroid differentiation, we generated cell clones expressing different levels of HSF2-alpha and HSF2-beta. We show that in parental K562 cells, the HSF2-alpha isoform is predominantly expressed and HSF2 can be activated upon hemin treatment. In contrast, when HSF2-beta is expressed at levels exceeding those of endogenous HSF2-alpha, the hemin-induced DNA binding activity and transcription of heat shock genes are repressed, whereas overexpression of HSF2-alpha results in an enhanced hemin response. Furthermore, the hemin-induced accumulation of globin, known as a marker of erythroid differentiation, is decreased in cells overexpressing HSF2-beta. We suggest that HSF2-beta acts as a negative regulator of HSF2 activity during hemin-mediated erythroid differentiation of K562 cells. " ], "offsets": [ [ 0, 1509 ] ] } ]

[ { "id": "PMID-9182556_T1", "type": "Protein", "text": [ "HSF2-beta" ], "offsets": [ [ 18, 27 ] ], "normalized": [] }, { "id": "PMID-9182556_T2", "type": "Protein", "text": [ "heat shock factor 2" ], "offsets": [ [ 139, 158 ] ], "normalized": [] }, { "id": "PMID-9182556_T3", "type": "Protein", "text": [ "HSF2" ], "offsets": [ [ 160, 164 ] ], "normalized": [] }, { "id": "PMID-9182556_T4", "type": "Protein", "text": [ "HSF2" ], "offsets": [ [ 344, 348 ] ], "normalized": [] }, { "id": "PMID-9182556_T5", "type": "Protein", "text": [ "HSF2-alpha" ], "offsets": [ [ 397, 407 ] ], "normalized": [] }, { "id": "PMID-9182556_T6", "type": "Protein", "text": [ "HSF2-beta" ], "offsets": [ [ 412, 421 ] ], "normalized": [] }, { "id": "PMID-9182556_T7", "type": "Protein", "text": [ "HSF2-alpha" ], "offsets": [ [ 557, 567 ] ], "normalized": [] }, { "id": "PMID-9182556_T8", "type": "Protein", "text": [ "HSF2-beta" ], "offsets": [ [ 572, 581 ] ], "normalized": [] }, { "id": "PMID-9182556_T9", "type": "Protein", "text": [ "HSF2" ], "offsets": [ [ 624, 628 ] ], "normalized": [] }, { "id": "PMID-9182556_T10", "type": "Protein", "text": [ "HSF2" ], "offsets": [ [ 645, 649 ] ], "normalized": [] }, { "id": "PMID-9182556_T11", "type": "Protein", "text": [ "HSF2-alpha" ], "offsets": [ [ 801, 811 ] ], "normalized": [] }, { "id": "PMID-9182556_T12", "type": "Protein", "text": [ "HSF2-beta" ], "offsets": [ [ 816, 825 ] ], "normalized": [] }, { "id": "PMID-9182556_T13", "type": "Protein", "text": [ "HSF2-alpha" ], "offsets": [ [ 868, 878 ] ], "normalized": [] }, { "id": "PMID-9182556_T14", "type": "Protein", "text": [ "HSF2" ], "offsets": [ [ 918, 922 ] ], "normalized": [] }, { "id": "PMID-9182556_T15", "type": "Protein", "text": [ "HSF2-beta" ], "offsets": [ [ 980, 989 ] ], "normalized": [] }, { "id": "PMID-9182556_T16", "type": "Protein", "text": [ "HSF2-alpha" ], "offsets": [ [ 1043, 1053 ] ], "normalized": [] }, { "id": "PMID-9182556_T17", "type": "Protein", "text": [ "HSF2-alpha" ], "offsets": [ [ 1173, 1183 ] ], "normalized": [] }, { "id": "PMID-9182556_T18", "type": "Protein", "text": [ "HSF2-beta" ], "offsets": [ [ 1363, 1372 ] ], "normalized": [] }, { "id": "PMID-9182556_T19", "type": "Protein", "text": [ "HSF2-beta" ], "offsets": [ [ 1390, 1399 ] ], "normalized": [] }, { "id": "PMID-9182556_T20", "type": "Protein", "text": [ "HSF2" ], "offsets": [ [ 1432, 1436 ] ], "normalized": [] } ]

[ { "id": "PMID-9182556_E1", "type": "Positive_regulation", "trigger": { "text": [ "Overexpression" ], "offsets": [ [ 0, 14 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "PMID-9182556_E2" } ] }, { "id": "PMID-9182556_E2", "type": "Gene_expression", "trigger": { "text": [ "Overexpression" ], "offsets": [ [ 0, 14 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "PMID-9182556_T1" } ] }, { "id": "PMID-9182556_E3", "type": "Binding", "trigger": { "text": [ "binding" ], "offsets": [ [ 170, 177 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "PMID-9182556_T3" } ] }, { "id": "PMID-9182556_E4", "type": "Regulation", "trigger": { "text": [ "accompanied" ], "offsets": [ [ 190, 201 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "PMID-9182556_E3" } ] }, { "id": "PMID-9182556_E5", "type": "Regulation", "trigger": { "text": [ "regulated" ], "offsets": [ [ 467, 476 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "PMID-9182556_T6" } ] }, { "id": "PMID-9182556_E6", "type": "Regulation", "trigger": { "text": [ "regulated" ], "offsets": [ [ 467, 476 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "PMID-9182556_T5" } ] }, { "id": "PMID-9182556_E7", "type": "Regulation", "trigger": { "text": [ "varies" ], "offsets": [ [ 481, 487 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "PMID-9182556_T5" } ] }, { "id": "PMID-9182556_E8", "type": "Regulation", "trigger": { "text": [ "varies" ], "offsets": [ [ 481, 487 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "PMID-9182556_T6" } ] }, { "id": "PMID-9182556_E9", "type": "Regulation", "trigger": { "text": [ "crucial" ], "offsets": [ [ 594, 601 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "PMID-9182556_E11" }, { "role": "Cause", "ref_id": "PMID-9182556_T7" } ] }, { "id": "PMID-9182556_E10", "type": "Regulation", "trigger": { "text": [ "crucial" ], "offsets": [ [ 594, 601 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "PMID-9182556_E11" }, { "role": "Cause", "ref_id": "PMID-9182556_T8" } ] }, { "id": "PMID-9182556_E11", "type": "Positive_regulation", "trigger": { "text": [ "activation" ], "offsets": [ [ 610, 620 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "PMID-9182556_T9" } ] }, { "id": "PMID-9182556_E12", "type": "Gene_expression", "trigger": { "text": [ "expressing" ], "offsets": [ [ 770, 780 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "PMID-9182556_T11" } ] }, { "id": "PMID-9182556_E13", "type": "Gene_expression", "trigger": { "text": [ "expressing" ], "offsets": [ [ 770, 780 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "PMID-9182556_T12" } ] }, { "id": "PMID-9182556_E14", "type": "Gene_expression", "trigger": { "text": [ "expressed" ], "offsets": [ [ 904, 913 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "PMID-9182556_T13" } ] }, { "id": "PMID-9182556_E15", "type": "Positive_regulation", "trigger": { "text": [ "activated" ], "offsets": [ [ 930, 939 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "PMID-9182556_T14" } ] }, { "id": "PMID-9182556_E16", "type": "Gene_expression", "trigger": { "text": [ "expressed" ], "offsets": [ [ 993, 1002 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "PMID-9182556_T16" } ] }, { "id": "PMID-9182556_E17", "type": "Gene_expression", "trigger": { "text": [ "expressed" ], "offsets": [ [ 993, 1002 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "PMID-9182556_T15" } ] }, { "id": "PMID-9182556_E18", "type": "Positive_regulation", "trigger": { "text": [ "levels" ], "offsets": [ [ 1006, 1012 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "PMID-9182556_E17" } ] }, { "id": "PMID-9182556_E19", "type": "Positive_regulation", "trigger": { "text": [ "overexpression" ], "offsets": [ [ 1155, 1169 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "PMID-9182556_E20" } ] }, { "id": "PMID-9182556_E20", "type": "Gene_expression", "trigger": { "text": [ "overexpression" ], "offsets": [ [ 1155, 1169 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "PMID-9182556_T17" } ] }, { "id": "PMID-9182556_E21", "type": "Negative_regulation", "trigger": { "text": [ "decreased" ], "offsets": [ [ 1329, 1338 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "PMID-9182556_E23" } ] }, { "id": "PMID-9182556_E22", "type": "Gene_expression", "trigger": { "text": [ "overexpressing" ], "offsets": [ [ 1348, 1362 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "PMID-9182556_T18" } ] }, { "id": "PMID-9182556_E23", "type": "Positive_regulation", "trigger": { "text": [ "overexpressing" ], "offsets": [ [ 1348, 1362 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "PMID-9182556_E22" } ] }, { "id": "PMID-9182556_E24", "type": "Negative_regulation", "trigger": { "text": [ "negative regulator" ], "offsets": [ [ 1410, 1428 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "PMID-9182556_T20" }, { "role": "Cause", "ref_id": "PMID-9182556_T19" } ] } ]

[ { "id": "PMID-9182556_1", "entity_ids": [ "PMID-9182556_T3", "PMID-9182556_T2" ] } ]

[]

[ { "id": "PMID-9185506__text", "type": "abstract", "text": [ "Glucocorticoid-mediated repression of cytokine gene transcription in human arteritis-SCID chimeras. \nGiant cell arteritis (GCA) is a vasculitic syndrome that preferentially affects medium and large-sized arteries. Glucocorticoid therapy resolves clinical symptoms within hours to days, but therapy has to be continued over several years to prevent disease relapses. It is not known whether and how glucocorticoids affect the function of the inflammatory infiltrate or why the disease persists subclinically despite chronic treatment. GCA is self-sustained in temporal arteries engrafted into SCID mice, providing a model in which the mechanisms of action and limitations of glucocorticoid therapy can be examined in vivo. Administration of dexamethasone to temporal artery-SCID chimeras for 1 wk induced a partial suppression of T cell and macrophage function as indicated by the reduced tissue concentrations of IL-2, IL-1beta, and IL-6 mRNA, and by the diminished expression of inducible NO synthase. In contrast, synthesis of IFN-gamma mRNA was only slightly decreased, and expression of TGF-beta1 was unaffected. These findings correlated with activation of the IkappaBalpha gene and blockade of the nuclear translocation of NFkappaB in the xenotransplanted tissue. Dose-response experiments suggested that steroid doses currently used in clinical medicine are suboptimal in repressing NFkappaB-mediated cytokine production in the inflammatory lesions. Chronic steroid therapy was able to deplete the T cell products IL-2 and IFN-gamma, whereas the activation of tissue-infiltrating macrophages was only partially affected. IL-1beta transcription was abrogated; in contrast, TGF-beta1 mRNA synthesis was steroid resistant. The persistence of TGF-beta1-transcribing macrophages, despite paralysis of T cell function, may provide an explanation for the chronicity of the disease, and may identify a novel therapeutic target in this inflammatory vasculopathy. " ], "offsets": [ [ 0, 1961 ] ] } ]

[ { "id": "PMID-9185506_T1", "type": "Protein", "text": [ "IL-2" ], "offsets": [ [ 913, 917 ] ], "normalized": [] }, { "id": "PMID-9185506_T2", "type": "Protein", "text": [ "IL-1beta" ], "offsets": [ [ 919, 927 ] ], "normalized": [] }, { "id": "PMID-9185506_T3", "type": "Protein", "text": [ "IL-6" ], "offsets": [ [ 933, 937 ] ], "normalized": [] }, { "id": "PMID-9185506_T4", "type": "Protein", "text": [ "IFN-gamma" ], "offsets": [ [ 1029, 1038 ] ], "normalized": [] }, { "id": "PMID-9185506_T5", "type": "Protein", "text": [ "TGF-beta1" ], "offsets": [ [ 1091, 1100 ] ], "normalized": [] }, { "id": "PMID-9185506_T6", "type": "Protein", "text": [ "IkappaBalpha" ], "offsets": [ [ 1166, 1178 ] ], "normalized": [] }, { "id": "PMID-9185506_T7", "type": "Protein", "text": [ "IL-2" ], "offsets": [ [ 1521, 1525 ] ], "normalized": [] }, { "id": "PMID-9185506_T8", "type": "Protein", "text": [ "IFN-gamma" ], "offsets": [ [ 1530, 1539 ] ], "normalized": [] }, { "id": "PMID-9185506_T9", "type": "Protein", "text": [ "IL-1beta" ], "offsets": [ [ 1628, 1636 ] ], "normalized": [] }, { "id": "PMID-9185506_T10", "type": "Protein", "text": [ "TGF-beta1" ], "offsets": [ [ 1679, 1688 ] ], "normalized": [] }, { "id": "PMID-9185506_T11", "type": "Protein", "text": [ "TGF-beta1" ], "offsets": [ [ 1746, 1755 ] ], "normalized": [] } ]

[ { "id": "PMID-9185506_E1", "type": "Negative_regulation", "trigger": { "text": [ "reduced" ], "offsets": [ [ 880, 887 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "PMID-9185506_T2" } ] }, { "id": "PMID-9185506_E2", "type": "Negative_regulation", "trigger": { "text": [ "reduced" ], "offsets": [ [ 880, 887 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "PMID-9185506_T1" } ] }, { "id": "PMID-9185506_E3", "type": "Negative_regulation", "trigger": { "text": [ "reduced" ], "offsets": [ [ 880, 887 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "PMID-9185506_T3" } ] }, { "id": "PMID-9185506_E4", "type": "Transcription", "trigger": { "text": [ "synthesis" ], "offsets": [ [ 1016, 1025 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "PMID-9185506_T4" } ] }, { "id": "PMID-9185506_E5", "type": "Negative_regulation", "trigger": { "text": [ "decreased" ], "offsets": [ [ 1062, 1071 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "PMID-9185506_E4" } ] }, { "id": "PMID-9185506_E6", "type": "Gene_expression", "trigger": { "text": [ "expression" ], "offsets": [ [ 1077, 1087 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "PMID-9185506_T5" } ] }, { "id": "PMID-9185506_E7", "type": "Negative_regulation", "trigger": { "text": [ "unaffected" ], "offsets": [ [ 1105, 1115 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "PMID-9185506_E6" } ] }, { "id": "PMID-9185506_E8", "type": "Positive_regulation", "trigger": { "text": [ "activation" ], "offsets": [ [ 1148, 1158 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "PMID-9185506_T6" } ] }, { "id": "PMID-9185506_E9", "type": "Negative_regulation", "trigger": { "text": [ "deplete" ], "offsets": [ [ 1493, 1500 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "PMID-9185506_E11" } ] }, { "id": "PMID-9185506_E10", "type": "Negative_regulation", "trigger": { "text": [ "deplete" ], "offsets": [ [ 1493, 1500 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "PMID-9185506_E12" } ] }, { "id": "PMID-9185506_E11", "type": "Gene_expression", "trigger": { "text": [ "products" ], "offsets": [ [ 1512, 1520 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "PMID-9185506_T7" } ] }, { "id": "PMID-9185506_E12", "type": "Gene_expression", "trigger": { "text": [ "products" ], "offsets": [ [ 1512, 1520 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "PMID-9185506_T8" } ] }, { "id": "PMID-9185506_E13", "type": "Transcription", "trigger": { "text": [ "transcription" ], "offsets": [ [ 1637, 1650 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "PMID-9185506_T9" } ] }, { "id": "PMID-9185506_E14", "type": "Negative_regulation", "trigger": { "text": [ "abrogated" ], "offsets": [ [ 1655, 1664 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "PMID-9185506_E13" } ] }, { "id": "PMID-9185506_E15", "type": "Transcription", "trigger": { "text": [ "synthesis" ], "offsets": [ [ 1694, 1703 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "PMID-9185506_T10" } ] }, { "id": "PMID-9185506_E16", "type": "Regulation", "trigger": { "text": [ "resistant" ], "offsets": [ [ 1716, 1725 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "PMID-9185506_E15" } ] }, { "id": "PMID-9185506_E17", "type": "Negative_regulation", "trigger": { "text": [ "persistence" ], "offsets": [ [ 1731, 1742 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "PMID-9185506_E18" } ] }, { "id": "PMID-9185506_E18", "type": "Transcription", "trigger": { "text": [ "transcribing" ], "offsets": [ [ 1756, 1768 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "PMID-9185506_T11" } ] } ]

[]

[]

[ { "id": "PMID-9187264__text", "type": "abstract", "text": [ "Histamine modulates the expression of c-fos through cyclic AMP production via the H2 receptor in the human promonocytic cell line U937. \nWe examined the effects of histamine and its agonists on the expression of the c-fos and c-myc proto-oncogenes at the transcriptional and translational levels in the human promonocytic U937 cell line. Histamine transiently increased cAMP and c-fos expression through H2 receptors. Dibutyryl cAMP also increased c-fos mRNA and protein, and levels remained elevated even after 12 hr of treatment. Dose-dependence studies using histamine and dimaprit showed that the EC50 values for cAMP production and c-fos increase were similar, suggesting that cAMP might be involved in c-fos induction via H2 receptors. Furthermore, studies carried out using H7, a protein kinase A/protein kinase C inhibitor, blocked c-fos induction, whereas no effect was observed with bisindolylmaleimide, a specific protein kinase C inhibitor. No modification of c-myc expression could be detected on treatment with histamine or its analogues. Nevertheless, dibutyryl cAMP induced a down-regulation of the levels of this proto-oncogene. In addition, dibutyryl cAMP inhibited cell growth in a dose-dependent manner, whereas histamine failed to affect proliferation and differentiation of U937 cells. Cells pretreated with dimaprit showed a decrease in the cAMP response to subsequent addition of H2 agonists, whereas the cAMP response to prostaglandin E2 remained unaltered. This homologous mechanism of H2 receptor desensitization was time dependent. These results indicate that histamine activates several mechanisms involved in the induction of differentiation, such as cAMP and c-fos production, but fails to promote differentiation of U937 cells, apparently due to the rapid desensitization of H2 receptors. " ], "offsets": [ [ 0, 1821 ] ] } ]

[ { "id": "PMID-9187264_T1", "type": "Protein", "text": [ "c-fos" ], "offsets": [ [ 38, 43 ] ], "normalized": [] }, { "id": "PMID-9187264_T2", "type": "Protein", "text": [ "H2 receptor" ], "offsets": [ [ 82, 93 ] ], "normalized": [] }, { "id": "PMID-9187264_T3", "type": "Protein", "text": [ "c-fos" ], "offsets": [ [ 216, 221 ] ], "normalized": [] }, { "id": "PMID-9187264_T4", "type": "Protein", "text": [ "c-myc" ], "offsets": [ [ 226, 231 ] ], "normalized": [] }, { "id": "PMID-9187264_T5", "type": "Protein", "text": [ "c-fos" ], "offsets": [ [ 379, 384 ] ], "normalized": [] }, { "id": "PMID-9187264_T6", "type": "Protein", "text": [ "H2 receptors" ], "offsets": [ [ 404, 416 ] ], "normalized": [] }, { "id": "PMID-9187264_T7", "type": "Protein", "text": [ "c-fos" ], "offsets": [ [ 448, 453 ] ], "normalized": [] }, { "id": "PMID-9187264_T8", "type": "Protein", "text": [ "c-fos" ], "offsets": [ [ 637, 642 ] ], "normalized": [] }, { "id": "PMID-9187264_T9", "type": "Protein", "text": [ "c-fos" ], "offsets": [ [ 708, 713 ] ], "normalized": [] }, { "id": "PMID-9187264_T10", "type": "Protein", "text": [ "H2 receptors" ], "offsets": [ [ 728, 740 ] ], "normalized": [] }, { "id": "PMID-9187264_T11", "type": "Protein", "text": [ "c-fos" ], "offsets": [ [ 840, 845 ] ], "normalized": [] }, { "id": "PMID-9187264_T12", "type": "Protein", "text": [ "c-myc" ], "offsets": [ [ 972, 977 ] ], "normalized": [] }, { "id": "PMID-9187264_T13", "type": "Protein", "text": [ "H2 receptor" ], "offsets": [ [ 1512, 1523 ] ], "normalized": [] }, { "id": "PMID-9187264_T14", "type": "Protein", "text": [ "c-fos" ], "offsets": [ [ 1690, 1695 ] ], "normalized": [] }, { "id": "PMID-9187264_T15", "type": "Protein", "text": [ "H2 receptors" ], "offsets": [ [ 1807, 1819 ] ], "normalized": [] } ]

[ { "id": "PMID-9187264_E1", "type": "Regulation", "trigger": { "text": [ "modulates" ], "offsets": [ [ 10, 19 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "PMID-9187264_T2" } ] }, { "id": "PMID-9187264_E2", "type": "Regulation", "trigger": { "text": [ "modulates" ], "offsets": [ [ 10, 19 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "PMID-9187264_E3" } ] }, { "id": "PMID-9187264_E3", "type": "Gene_expression", "trigger": { "text": [ "expression" ], "offsets": [ [ 24, 34 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "PMID-9187264_T1" } ] }, { "id": "PMID-9187264_E4", "type": "Regulation", "trigger": { "text": [ "effects" ], "offsets": [ [ 153, 160 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "PMID-9187264_E6" } ] }, { "id": "PMID-9187264_E5", "type": "Regulation", "trigger": { "text": [ "effects" ], "offsets": [ [ 153, 160 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "PMID-9187264_E7" } ] }, { "id": "PMID-9187264_E6", "type": "Transcription", "trigger": { "text": [ "transcriptional" ], "offsets": [ [ 255, 270 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "PMID-9187264_T4" } ] }, { "id": "PMID-9187264_E7", "type": "Transcription", "trigger": { "text": [ "transcriptional" ], "offsets": [ [ 255, 270 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "PMID-9187264_T3" } ] }, { "id": "PMID-9187264_E8", "type": "Positive_regulation", "trigger": { "text": [ "increased" ], "offsets": [ [ 360, 369 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "PMID-9187264_E10" }, { "role": "Cause", "ref_id": "PMID-9187264_E9" } ] }, { "id": "PMID-9187264_E9", "type": "Positive_regulation", "trigger": { "text": [ "increased" ], "offsets": [ [ 360, 369 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "PMID-9187264_T6" } ] }, { "id": "PMID-9187264_E10", "type": "Gene_expression", "trigger": { "text": [ "expression" ], "offsets": [ [ 385, 395 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "PMID-9187264_T5" } ] }, { "id": "PMID-9187264_E11", "type": "Positive_regulation", "trigger": { "text": [ "increased" ], "offsets": [ [ 438, 447 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "PMID-9187264_T7" } ] }, { "id": "PMID-9187264_E12", "type": "Positive_regulation", "trigger": { "text": [ "remained elevated" ], "offsets": [ [ 483, 500 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "PMID-9187264_T7" } ] }, { "id": "PMID-9187264_E13", "type": "Regulation", "trigger": { "text": [ "EC50 values" ], "offsets": [ [ 601, 612 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "PMID-9187264_E14" } ] }, { "id": "PMID-9187264_E14", "type": "Positive_regulation", "trigger": { "text": [ "increase" ], "offsets": [ [ 643, 651 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "PMID-9187264_T8" } ] }, { "id": "PMID-9187264_E15", "type": "Positive_regulation", "trigger": { "text": [ "induction" ], "offsets": [ [ 714, 723 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "PMID-9187264_T9" }, { "role": "Cause", "ref_id": "PMID-9187264_T10" } ] }, { "id": "PMID-9187264_E16", "type": "Negative_regulation", "trigger": { "text": [ "blocked" ], "offsets": [ [ 832, 839 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "PMID-9187264_E17" } ] }, { "id": "PMID-9187264_E17", "type": "Positive_regulation", "trigger": { "text": [ "induction" ], "offsets": [ [ 846, 855 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "PMID-9187264_T11" } ] }, { "id": "PMID-9187264_E18", "type": "Regulation", "trigger": { "text": [ "effect" ], "offsets": [ [ 868, 874 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "PMID-9187264_E17" } ] }, { "id": "PMID-9187264_E19", "type": "Regulation", "trigger": { "text": [ "modification" ], "offsets": [ [ 956, 968 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "PMID-9187264_E20" } ] }, { "id": "PMID-9187264_E20", "type": "Gene_expression", "trigger": { "text": [ "expression" ], "offsets": [ [ 978, 988 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "PMID-9187264_T12" } ] }, { "id": "PMID-9187264_E21", "type": "Negative_regulation", "trigger": { "text": [ "induced a down-regulation" ], "offsets": [ [ 1082, 1107 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "PMID-9187264_T12" } ] }, { "id": "PMID-9187264_E22", "type": "Negative_regulation", "trigger": { "text": [ "desensitization" ], "offsets": [ [ 1524, 1539 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "PMID-9187264_T13" } ] }, { "id": "PMID-9187264_E23", "type": "Positive_regulation", "trigger": { "text": [ "activates" ], "offsets": [ [ 1598, 1607 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "PMID-9187264_E24" } ] }, { "id": "PMID-9187264_E24", "type": "Gene_expression", "trigger": { "text": [ "production" ], "offsets": [ [ 1696, 1706 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "PMID-9187264_T14" } ] }, { "id": "PMID-9187264_E25", "type": "Negative_regulation", "trigger": { "text": [ "desensitization" ], "offsets": [ [ 1788, 1803 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "PMID-9187264_T15" } ] } ]

[]

[]

[ { "id": "PMID-9188651__text", "type": "abstract", "text": [ "Human cytomegalovirus induces interleukin-8 production by a human monocytic cell line, THP-1, through acting concurrently on AP-1- and NF-kappaB-binding sites of the interleukin-8 gene. \nCytomegalovirus (CMV) infection induced interleukin-8 (IL-8) gene transcription in a human monocytic cell line, THP-1 cells, leading to IL-8 secretion. The functional analysis of the IL-8 gene revealed that both AP-1- and NF-kappaB factor-binding elements were involved in conferring the responsiveness to CMV. Moreover, electrophoretic mobility shift assays demonstrated that CMV induced the formation of NF-kappaB and AP-1 complexes. These results suggest that CMV activates these transcriptional factors, resulting in IL-8 gene expression. " ], "offsets": [ [ 0, 730 ] ] } ]

[ { "id": "PMID-9188651_T1", "type": "Protein", "text": [ "interleukin-8" ], "offsets": [ [ 30, 43 ] ], "normalized": [] }, { "id": "PMID-9188651_T2", "type": "Protein", "text": [ "interleukin-8" ], "offsets": [ [ 166, 179 ] ], "normalized": [] }, { "id": "PMID-9188651_T3", "type": "Protein", "text": [ "interleukin-8" ], "offsets": [ [ 227, 240 ] ], "normalized": [] }, { "id": "PMID-9188651_T4", "type": "Protein", "text": [ "IL-8" ], "offsets": [ [ 242, 246 ] ], "normalized": [] }, { "id": "PMID-9188651_T5", "type": "Protein", "text": [ "IL-8" ], "offsets": [ [ 323, 327 ] ], "normalized": [] }, { "id": "PMID-9188651_T6", "type": "Protein", "text": [ "IL-8" ], "offsets": [ [ 370, 374 ] ], "normalized": [] }, { "id": "PMID-9188651_T7", "type": "Protein", "text": [ "IL-8" ], "offsets": [ [ 708, 712 ] ], "normalized": [] } ]

[ { "id": "PMID-9188651_E1", "type": "Positive_regulation", "trigger": { "text": [ "induces" ], "offsets": [ [ 22, 29 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "PMID-9188651_E2" } ] }, { "id": "PMID-9188651_E2", "type": "Gene_expression", "trigger": { "text": [ "production" ], "offsets": [ [ 44, 54 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "PMID-9188651_T1" } ] }, { "id": "PMID-9188651_E3", "type": "Positive_regulation", "trigger": { "text": [ "induced" ], "offsets": [ [ 219, 226 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "PMID-9188651_E4" } ] }, { "id": "PMID-9188651_E4", "type": "Transcription", "trigger": { "text": [ "transcription" ], "offsets": [ [ 253, 266 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "PMID-9188651_T4" } ] }, { "id": "PMID-9188651_E5", "type": "Positive_regulation", "trigger": { "text": [ "leading" ], "offsets": [ [ 312, 319 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "PMID-9188651_E6" }, { "role": "Cause", "ref_id": "PMID-9188651_E3" } ] }, { "id": "PMID-9188651_E6", "type": "Localization", "trigger": { "text": [ "secretion" ], "offsets": [ [ 328, 337 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "PMID-9188651_T5" } ] }, { "id": "PMID-9188651_E7", "type": "Positive_regulation", "trigger": { "text": [ "resulting" ], "offsets": [ [ 695, 704 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "PMID-9188651_E8" } ] }, { "id": "PMID-9188651_E8", "type": "Gene_expression", "trigger": { "text": [ "expression" ], "offsets": [ [ 718, 728 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "PMID-9188651_T7" } ] } ]

[ { "id": "PMID-9188651_1", "entity_ids": [ "PMID-9188651_T4", "PMID-9188651_T3" ] } ]

[]

[ { "id": "PMID-9188842__text", "type": "abstract", "text": [ "Concomitant downregulation of IgH 3' enhancer activity and c-myc expression in a plasmacytoma x fibroblast environment: implications for dysregulation of translocated c-myc. \nRegulation of immunoglobulin heavy chain (IgH) gene expression is controlled by a B cell-specific promoter, intronic enhancer and additional B cell-specific enhancer elements identified recently in the 3' end of the IgH locus. One of the latter elements, the IgH 3' enhancer, is of particular interest: (1) it is B cell-specific and active only in late B cell development; (2) in rodent plasmacytomas and in some human Burkitt's lymphomas it is part of a locus control region (LCR) that is involved in deregulation of the c-myc oncogene as a result of translocation into the IgH locus; and (3) it has been implicated in the mechanisms that control Ig gene class switch recombination. We have used a somatic cell hybridization approach to genetically analyse regulation of the activity of the IgH 3' enhancer. When mouse MPC11 plasmacytoma cells, in which the IgH 3' enhancer is active, are fused with fibroblasts, Ig expression is extinguished at the level of transcription. Here we show that in a MPC11 plasmacytoma x fibroblast environment, the IgH 3' enhancer is transcriptionally inactive. Furthermore, we demonstrate that binding of several B cell-specific transcription factors, essential for IgH 3' enhancer activity, is lacking, which may explain 3' enhancer inactivity, although the binding of repressors cannot be excluded. Moreover, the high expression level of c-myc, characteristic of the parental MPC11 cells carrying the t(12;15) translocation, is down-regulated in the hybrids to that in unfused fibroblasts. Therefore, inactivation of the IgH 3' enhancer is a multifactorial process affecting several transcription factors that control the cell-specific and developmental activity of the enhancer. " ], "offsets": [ [ 0, 1890 ] ] } ]

[ { "id": "PMID-9188842_T1", "type": "Protein", "text": [ "c-myc" ], "offsets": [ [ 59, 64 ] ], "normalized": [] }, { "id": "PMID-9188842_T2", "type": "Protein", "text": [ "c-myc" ], "offsets": [ [ 167, 172 ] ], "normalized": [] }, { "id": "PMID-9188842_T3", "type": "Protein", "text": [ "c-myc" ], "offsets": [ [ 697, 702 ] ], "normalized": [] }, { "id": "PMID-9188842_T4", "type": "Protein", "text": [ "c-myc" ], "offsets": [ [ 1548, 1553 ] ], "normalized": [] }, { "id": "PMID-9188842_T13", "type": "Entity", "text": [ "IgH locus" ], "offsets": [ [ 750, 759 ] ], "normalized": [] } ]

[ { "id": "PMID-9188842_E1", "type": "Negative_regulation", "trigger": { "text": [ "downregulation" ], "offsets": [ [ 12, 26 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "PMID-9188842_E2" } ] }, { "id": "PMID-9188842_E2", "type": "Gene_expression", "trigger": { "text": [ "expression" ], "offsets": [ [ 65, 75 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "PMID-9188842_T1" } ] }, { "id": "PMID-9188842_E3", "type": "Regulation", "trigger": { "text": [ "dysregulation" ], "offsets": [ [ 137, 150 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "PMID-9188842_E4" } ] }, { "id": "PMID-9188842_E4", "type": "Localization", "trigger": { "text": [ "translocated" ], "offsets": [ [ 154, 166 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "PMID-9188842_T2" } ] }, { "id": "PMID-9188842_E5", "type": "Regulation", "trigger": { "text": [ "involved" ], "offsets": [ [ 665, 673 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "PMID-9188842_E6" } ] }, { "id": "PMID-9188842_E6", "type": "Regulation", "trigger": { "text": [ "deregulation" ], "offsets": [ [ 677, 689 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "PMID-9188842_T3" } ] }, { "id": "PMID-9188842_E7", "type": "Regulation", "trigger": { "text": [ "result" ], "offsets": [ [ 717, 723 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "PMID-9188842_E6" }, { "role": "Cause", "ref_id": "PMID-9188842_E8" } ] }, { "id": "PMID-9188842_E8", "type": "Localization", "trigger": { "text": [ "translocation" ], "offsets": [ [ 727, 740 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "PMID-9188842_T3" }, { "role": "ToLoc", "ref_id": "PMID-9188842_T13" } ] }, { "id": "PMID-9188842_E9", "type": "Gene_expression", "trigger": { "text": [ "expression" ], "offsets": [ [ 1528, 1538 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "PMID-9188842_T4" } ] }, { "id": "PMID-9188842_E10", "type": "Negative_regulation", "trigger": { "text": [ "down-regulated" ], "offsets": [ [ 1638, 1652 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "PMID-9188842_E9" } ] } ]

[]

[]

[ { "id": "PMID-9190901__text", "type": "abstract", "text": [ "ETS1, NFkappaB and AP1 synergistically transactivate the human GM-CSF promoter. \nActivation of helper T cells results in coordinate expression of a number of cytokines involved in differentiation, proliferation and activation of the haematopoietic system. Granulocyte-macrophage colony stimulating factor (GM-CSF) is one such cytokine, whose increased expression results mostly from increases in transcription. Cis-acting elements with NFkappaB, AP1 and ETS-like binding motifs have been identified in the promoter region of the GM-CSF gene, and are important or essential for transcriptional activity following T cell activation. ETS1 is a transcription factor of the ETS family that is expressed in T cells. We have previously shown that ETS1 can transactivate GM-CSF in Jurkat T cells, but only after the cells have been stimulated by treatment with PMA and ionomycin, agents that mimic T cell activation. Thus we proposed that ETS1, which is expressed constitutively in Jurkat cells, may act in concert with PMA/ionomycin inducible factors. Here we show that ETS1 can transactivate a GM-CSF reporter construct in unstimulated Jurkat cells, providing that either NFkappaB or AP1 transcription factors are supplied by co-transfection. We confirm that binding of endogenous NFkappaB and AP1 is induced following PMA/ionomycin treatment of T cells. Transactivation by ETS1, NFkappaB and AP1 is synergistic, and mutation of the individual binding sites reveals that the transcriptional activities of these factors are interdependent. Our results suggest that constitutive ETS1, and inducible NFkappaB and AP1, cooperate as part of a higher order transcriptional complex in activated T cells. " ], "offsets": [ [ 0, 1691 ] ] } ]

[ { "id": "PMID-9190901_T1", "type": "Protein", "text": [ "ETS1" ], "offsets": [ [ 0, 4 ] ], "normalized": [] }, { "id": "PMID-9190901_T2", "type": "Protein", "text": [ "GM-CSF" ], "offsets": [ [ 63, 69 ] ], "normalized": [] }, { "id": "PMID-9190901_T3", "type": "Protein", "text": [ "Granulocyte-macrophage colony stimulating factor" ], "offsets": [ [ 256, 304 ] ], "normalized": [] }, { "id": "PMID-9190901_T4", "type": "Protein", "text": [ "GM-CSF" ], "offsets": [ [ 306, 312 ] ], "normalized": [] }, { "id": "PMID-9190901_T5", "type": "Protein", "text": [ "GM-CSF" ], "offsets": [ [ 529, 535 ] ], "normalized": [] }, { "id": "PMID-9190901_T6", "type": "Protein", "text": [ "ETS1" ], "offsets": [ [ 631, 635 ] ], "normalized": [] }, { "id": "PMID-9190901_T7", "type": "Protein", "text": [ "ETS1" ], "offsets": [ [ 740, 744 ] ], "normalized": [] }, { "id": "PMID-9190901_T8", "type": "Protein", "text": [ "GM-CSF" ], "offsets": [ [ 763, 769 ] ], "normalized": [] }, { "id": "PMID-9190901_T9", "type": "Protein", "text": [ "ETS1" ], "offsets": [ [ 931, 935 ] ], "normalized": [] }, { "id": "PMID-9190901_T10", "type": "Protein", "text": [ "ETS1" ], "offsets": [ [ 1063, 1067 ] ], "normalized": [] }, { "id": "PMID-9190901_T11", "type": "Protein", "text": [ "GM-CSF" ], "offsets": [ [ 1088, 1094 ] ], "normalized": [] }, { "id": "PMID-9190901_T12", "type": "Protein", "text": [ "ETS1" ], "offsets": [ [ 1368, 1372 ] ], "normalized": [] }, { "id": "PMID-9190901_T13", "type": "Protein", "text": [ "ETS1" ], "offsets": [ [ 1571, 1575 ] ], "normalized": [] }, { "id": "PMID-9190901_T15", "type": "Entity", "text": [ "promoter" ], "offsets": [ [ 70, 78 ] ], "normalized": [] }, { "id": "PMID-9190901_T20", "type": "Entity", "text": [ "Cis-acting elements" ], "offsets": [ [ 411, 430 ] ], "normalized": [] } ]

[ { "id": "PMID-9190901_E1", "type": "Positive_regulation", "trigger": { "text": [ "synergistically transactivate" ], "offsets": [ [ 23, 52 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "PMID-9190901_T2" }, { "role": "Cause", "ref_id": "PMID-9190901_T1" }, { "role": "Site", "ref_id": "PMID-9190901_T15" } ] }, { "id": "PMID-9190901_E2", "type": "Positive_regulation", "trigger": { "text": [ "increased" ], "offsets": [ [ 342, 351 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "PMID-9190901_E3" }, { "role": "Cause", "ref_id": "PMID-9190901_E4" } ] }, { "id": "PMID-9190901_E3", "type": "Gene_expression", "trigger": { "text": [ "expression" ], "offsets": [ [ 352, 362 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "PMID-9190901_T4" } ] }, { "id": "PMID-9190901_E4", "type": "Positive_regulation", "trigger": { "text": [ "increases" ], "offsets": [ [ 383, 392 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "PMID-9190901_E5" } ] }, { "id": "PMID-9190901_E5", "type": "Transcription", "trigger": { "text": [ "transcription" ], "offsets": [ [ 396, 409 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "PMID-9190901_T4" } ] }, { "id": "PMID-9190901_E6", "type": "Positive_regulation", "trigger": { "text": [ "important or essential" ], "offsets": [ [ 550, 572 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "PMID-9190901_E8" }, { "role": "Cause", "ref_id": "PMID-9190901_T5" }, { "role": "CSite", "ref_id": "PMID-9190901_T20" } ] }, { "id": "PMID-9190901_E7", "type": "Transcription", "trigger": { "text": [ "transcriptional activity" ], "offsets": [ [ 577, 601 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "PMID-9190901_T5" } ] }, { "id": "PMID-9190901_E8", "type": "Positive_regulation", "trigger": { "text": [ "following" ], "offsets": [ [ 602, 611 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "PMID-9190901_E7" } ] }, { "id": "PMID-9190901_E9", "type": "Gene_expression", "trigger": { "text": [ "expressed" ], "offsets": [ [ 688, 697 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "PMID-9190901_T6" } ] }, { "id": "PMID-9190901_E10", "type": "Positive_regulation", "trigger": { "text": [ "transactivate" ], "offsets": [ [ 749, 762 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "PMID-9190901_T8" }, { "role": "Cause", "ref_id": "PMID-9190901_T7" } ] }, { "id": "PMID-9190901_E11", "type": "Gene_expression", "trigger": { "text": [ "expressed" ], "offsets": [ [ 946, 955 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "PMID-9190901_T9" } ] } ]

[ { "id": "PMID-9190901_1", "entity_ids": [ "PMID-9190901_T4", "PMID-9190901_T3" ] } ]

[]

[ { "id": "PMID-9191057__text", "type": "abstract", "text": [ "Relief of cyclin A gene transcriptional inhibition during activation of human primary T lymphocytes via CD2 and CD28 adhesion molecules. \nCyclin A transcription is cell cycle regulated and induced by cell proliferative signals. To understand the mechanisms underlined in this regulation in normal human cells, we have analysed in vivo protein-DNA interactions at the Cyclin A locus in primary T lymphocytes. Stimulation of purified T lymphocytes by a combination of monoclonal antibodies directed at CD2 and CD28 adhesion molecules gives rise to a long lasting proliferation in the absence of accessory cells. Cyclin A was observed after 4 days of costimulation with anti CD2 + CD28 whereas stimulation by anti CD2 or anti CD28 alone was not effective. In vivo genomic DMS footprinting revealed upstream of the major transcription initiation sites, the presence of at least three protein binding sites, two of which were constitutively occupied. They bind in vitro respectively ATF-1 and NF-Y proteins. The third site was occupied in quiescent cells or in cells stimulated by anti CD2 or anti CD28 alone. The mitogenic combination of anti CD2 + anti CD28 released the footprint as cells were committed to proliferation. Consistent with theses results, nuclear extracts prepared from quiescent cells formed a specific complex with this element, whereas extracts prepared from cells treated with anti CD2 + anti CD28 failed to do so after cells entered a proliferative state. " ], "offsets": [ [ 0, 1474 ] ] } ]

[ { "id": "PMID-9191057_T1", "type": "Protein", "text": [ "cyclin A" ], "offsets": [ [ 10, 18 ] ], "normalized": [] }, { "id": "PMID-9191057_T2", "type": "Protein", "text": [ "CD2" ], "offsets": [ [ 104, 107 ] ], "normalized": [] }, { "id": "PMID-9191057_T3", "type": "Protein", "text": [ "CD28" ], "offsets": [ [ 112, 116 ] ], "normalized": [] }, { "id": "PMID-9191057_T4", "type": "Protein", "text": [ "Cyclin A" ], "offsets": [ [ 138, 146 ] ], "normalized": [] }, { "id": "PMID-9191057_T5", "type": "Protein", "text": [ "Cyclin A" ], "offsets": [ [ 367, 375 ] ], "normalized": [] }, { "id": "PMID-9191057_T6", "type": "Protein", "text": [ "CD2" ], "offsets": [ [ 500, 503 ] ], "normalized": [] }, { "id": "PMID-9191057_T7", "type": "Protein", "text": [ "CD28" ], "offsets": [ [ 508, 512 ] ], "normalized": [] }, { "id": "PMID-9191057_T8", "type": "Protein", "text": [ "Cyclin A" ], "offsets": [ [ 610, 618 ] ], "normalized": [] }, { "id": "PMID-9191057_T9", "type": "Protein", "text": [ "CD2" ], "offsets": [ [ 672, 675 ] ], "normalized": [] }, { "id": "PMID-9191057_T10", "type": "Protein", "text": [ "CD28" ], "offsets": [ [ 678, 682 ] ], "normalized": [] }, { "id": "PMID-9191057_T11", "type": "Protein", "text": [ "CD2" ], "offsets": [ [ 711, 714 ] ], "normalized": [] }, { "id": "PMID-9191057_T12", "type": "Protein", "text": [ "CD28" ], "offsets": [ [ 723, 727 ] ], "normalized": [] }, { "id": "PMID-9191057_T13", "type": "Protein", "text": [ "ATF-1" ], "offsets": [ [ 978, 983 ] ], "normalized": [] }, { "id": "PMID-9191057_T14", "type": "Protein", "text": [ "CD2" ], "offsets": [ [ 1081, 1084 ] ], "normalized": [] }, { "id": "PMID-9191057_T15", "type": "Protein", "text": [ "CD28" ], "offsets": [ [ 1093, 1097 ] ], "normalized": [] }, { "id": "PMID-9191057_T16", "type": "Protein", "text": [ "CD2" ], "offsets": [ [ 1139, 1142 ] ], "normalized": [] }, { "id": "PMID-9191057_T17", "type": "Protein", "text": [ "CD28" ], "offsets": [ [ 1150, 1154 ] ], "normalized": [] }, { "id": "PMID-9191057_T18", "type": "Protein", "text": [ "CD2" ], "offsets": [ [ 1399, 1402 ] ], "normalized": [] }, { "id": "PMID-9191057_T19", "type": "Protein", "text": [ "CD28" ], "offsets": [ [ 1410, 1414 ] ], "normalized": [] } ]

[ { "id": "PMID-9191057_E1", "type": "Negative_regulation", "trigger": { "text": [ "Relief" ], "offsets": [ [ 0, 6 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "PMID-9191057_E2" } ] }, { "id": "PMID-9191057_E2", "type": "Negative_regulation", "trigger": { "text": [ "transcriptional inhibition" ], "offsets": [ [ 24, 50 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "PMID-9191057_T1" } ] }, { "id": "PMID-9191057_E3", "type": "Transcription", "trigger": { "text": [ "transcription" ], "offsets": [ [ 147, 160 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "PMID-9191057_T4" } ] }, { "id": "PMID-9191057_E4", "type": "Regulation", "trigger": { "text": [ "regulated" ], "offsets": [ [ 175, 184 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "PMID-9191057_E3" } ] }, { "id": "PMID-9191057_E5", "type": "Positive_regulation", "trigger": { "text": [ "induced" ], "offsets": [ [ 189, 196 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "PMID-9191057_E3" } ] }, { "id": "PMID-9191057_E6", "type": "Binding", "trigger": { "text": [ "interactions" ], "offsets": [ [ 347, 359 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "PMID-9191057_T5" } ] }, { "id": "PMID-9191057_E7", "type": "Transcription", "trigger": { "text": [ "observed" ], "offsets": [ [ 623, 631 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "PMID-9191057_T8" } ] }, { "id": "PMID-9191057_E8", "type": "Positive_regulation", "trigger": { "text": [ "effective" ], "offsets": [ [ 742, 751 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "PMID-9191057_E3" } ] }, { "id": "PMID-9191057_E9", "type": "Binding", "trigger": { "text": [ "bind" ], "offsets": [ [ 951, 955 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "PMID-9191057_T13" } ] } ]

[]

[]

[ { "id": "PMID-9195127__text", "type": "abstract", "text": [ "Biphasic control of NF-kappa B activation induced by the triggering of HLA-DR antigens expressed on B cells. \nThe regulation of NF-kappa B activation following the triggering of HLA-DR antigens by mAb L243 has been studied at various times in Raji cells. Electrophoretic mobility shift assays demonstrated a strong increase of NF-kappa B DNA binding after triggering of HLA-DR antigens. Using TNF-alpha-activity neutralizing antibodies, the authors demonstrated that the upregulation of NF-kappa B was found to depend, at later time point, on an autocrine effect of TNF-alpha secreted following triggering of HLA-DR antigens. In contrast, it was found to be TNF-alpha independent in the early time point. Moreover, the upregulation of NF-kappa B binding activity is regulated by the triggering of selected epitopes of HLA-DR antigens. In fact, mAb L243 but not the staphylococcal superantigens, staphylococcal exotoxin toxic shock syndrome toxin-I or staphylococcal enterotoxin B, regulate the NF-kappa B binding activity. " ], "offsets": [ [ 0, 1023 ] ] } ]

[ { "id": "PMID-9195127_T1", "type": "Protein", "text": [ "TNF-alpha" ], "offsets": [ [ 393, 402 ] ], "normalized": [] }, { "id": "PMID-9195127_T2", "type": "Protein", "text": [ "TNF-alpha" ], "offsets": [ [ 566, 575 ] ], "normalized": [] }, { "id": "PMID-9195127_T3", "type": "Protein", "text": [ "TNF-alpha" ], "offsets": [ [ 658, 667 ] ], "normalized": [] }, { "id": "PMID-9195127_T4", "type": "Protein", "text": [ "toxic shock syndrome toxin-I" ], "offsets": [ [ 919, 947 ] ], "normalized": [] }, { "id": "PMID-9195127_T5", "type": "Protein", "text": [ "staphylococcal enterotoxin B" ], "offsets": [ [ 951, 979 ] ], "normalized": [] } ]

[ { "id": "PMID-9195127_E1", "type": "Localization", "trigger": { "text": [ "secreted" ], "offsets": [ [ 576, 584 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "PMID-9195127_T2" } ] }, { "id": "PMID-9195127_E2", "type": "Positive_regulation", "trigger": { "text": [ "following" ], "offsets": [ [ 585, 594 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "PMID-9195127_E1" } ] } ]

[]

[]

[ { "id": "PMID-9199300__text", "type": "abstract", "text": [ "Comparison of the transactivation domains of Stat5 and Stat6 in lymphoid cells and mammary epithelial cells. \nStat (signal transducers and activators of transcription) and Jak (Janus kinases) proteins are central components in the signal transduction events in hematopoietic and epithelial cells. They are rapidly activated by various cytokines, hormones, and growth factors. Upon ligand binding and cytokine receptor dimerization, Stat proteins are phosphorylated on tyrosine residues by Jak kinases. Activated Stat proteins form homo- or heterodimers, translocate to the nucleus, and induce transcription from responsive genes. Stat5 and Stat6 are transcription factors active in mammary epithelial cells and immune cells. Prolactin activates Stat5, and interleukin-4 (IL-4) activates Stat6. Both cytokines are able to stimulate cell proliferation, differentiation, and survival. We investigated the transactivation potential of Stat6 and found that it is not restricted to lymphocytes. IL-4-dependent activation of Stat6 was also observed in HC11 mammary epithelial cells. In these cells, Stat6 activation led to the induction of the beta-casein gene promoter. The induction of this promoter was confirmed in COS7 cells. The glucocorticoid receptor was able to further enhance IL-4-induced gene transcription through the action of Stat6. Deletion analysis of the carboxyl-terminal region of Stat6 and recombination of this region with a heterologous DNA binding domain allowed the delimitation and characterization of the transactivation domain of Stat6. The potencies of the transactivation domains of Stat5, Stat6, and viral protein VP16 were compared. Stat6 had a transactivation domain which was about 10-fold stronger than that of Stat5. In pre-B cells (Ba/F3), the transactivation domain of Stat6 was IL-4 regulated, independently from its DNA binding function. " ], "offsets": [ [ 0, 1871 ] ] } ]

[ { "id": "PMID-9199300_T1", "type": "Protein", "text": [ "Stat5" ], "offsets": [ [ 45, 50 ] ], "normalized": [] }, { "id": "PMID-9199300_T2", "type": "Protein", "text": [ "Stat6" ], "offsets": [ [ 55, 60 ] ], "normalized": [] }, { "id": "PMID-9199300_T3", "type": "Protein", "text": [ "Stat5" ], "offsets": [ [ 630, 635 ] ], "normalized": [] }, { "id": "PMID-9199300_T4", "type": "Protein", "text": [ "Stat6" ], "offsets": [ [ 640, 645 ] ], "normalized": [] }, { "id": "PMID-9199300_T5", "type": "Protein", "text": [ "Prolactin" ], "offsets": [ [ 725, 734 ] ], "normalized": [] }, { "id": "PMID-9199300_T6", "type": "Protein", "text": [ "Stat5" ], "offsets": [ [ 745, 750 ] ], "normalized": [] }, { "id": "PMID-9199300_T7", "type": "Protein", "text": [ "interleukin-4" ], "offsets": [ [ 756, 769 ] ], "normalized": [] }, { "id": "PMID-9199300_T8", "type": "Protein", "text": [ "IL-4" ], "offsets": [ [ 771, 775 ] ], "normalized": [] }, { "id": "PMID-9199300_T9", "type": "Protein", "text": [ "Stat6" ], "offsets": [ [ 787, 792 ] ], "normalized": [] }, { "id": "PMID-9199300_T10", "type": "Protein", "text": [ "Stat6" ], "offsets": [ [ 931, 936 ] ], "normalized": [] }, { "id": "PMID-9199300_T11", "type": "Protein", "text": [ "IL-4" ], "offsets": [ [ 989, 993 ] ], "normalized": [] }, { "id": "PMID-9199300_T12", "type": "Protein", "text": [ "Stat6" ], "offsets": [ [ 1018, 1023 ] ], "normalized": [] }, { "id": "PMID-9199300_T13", "type": "Protein", "text": [ "Stat6" ], "offsets": [ [ 1092, 1097 ] ], "normalized": [] }, { "id": "PMID-9199300_T14", "type": "Protein", "text": [ "glucocorticoid receptor" ], "offsets": [ [ 1228, 1251 ] ], "normalized": [] }, { "id": "PMID-9199300_T15", "type": "Protein", "text": [ "IL-4" ], "offsets": [ [ 1280, 1284 ] ], "normalized": [] }, { "id": "PMID-9199300_T16", "type": "Protein", "text": [ "Stat6" ], "offsets": [ [ 1334, 1339 ] ], "normalized": [] }, { "id": "PMID-9199300_T17", "type": "Protein", "text": [ "Stat6" ], "offsets": [ [ 1394, 1399 ] ], "normalized": [] }, { "id": "PMID-9199300_T18", "type": "Protein", "text": [ "Stat6" ], "offsets": [ [ 1551, 1556 ] ], "normalized": [] }, { "id": "PMID-9199300_T19", "type": "Protein", "text": [ "Stat5" ], "offsets": [ [ 1606, 1611 ] ], "normalized": [] }, { "id": "PMID-9199300_T20", "type": "Protein", "text": [ "Stat6" ], "offsets": [ [ 1613, 1618 ] ], "normalized": [] }, { "id": "PMID-9199300_T21", "type": "Protein", "text": [ "VP16" ], "offsets": [ [ 1638, 1642 ] ], "normalized": [] }, { "id": "PMID-9199300_T22", "type": "Protein", "text": [ "Stat6" ], "offsets": [ [ 1658, 1663 ] ], "normalized": [] }, { "id": "PMID-9199300_T23", "type": "Protein", "text": [ "Stat5" ], "offsets": [ [ 1739, 1744 ] ], "normalized": [] }, { "id": "PMID-9199300_T24", "type": "Protein", "text": [ "Stat6" ], "offsets": [ [ 1800, 1805 ] ], "normalized": [] }, { "id": "PMID-9199300_T25", "type": "Protein", "text": [ "IL-4" ], "offsets": [ [ 1810, 1814 ] ], "normalized": [] }, { "id": "PMID-9199300_T34", "type": "Entity", "text": [ "transactivation domain" ], "offsets": [ [ 1774, 1796 ] ], "normalized": [] } ]

[ { "id": "PMID-9199300_E1", "type": "Positive_regulation", "trigger": { "text": [ "active" ], "offsets": [ [ 672, 678 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "PMID-9199300_T4" } ] }, { "id": "PMID-9199300_E2", "type": "Positive_regulation", "trigger": { "text": [ "active" ], "offsets": [ [ 672, 678 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "PMID-9199300_T3" } ] }, { "id": "PMID-9199300_E3", "type": "Positive_regulation", "trigger": { "text": [ "activates" ], "offsets": [ [ 735, 744 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "PMID-9199300_T6" }, { "role": "Cause", "ref_id": "PMID-9199300_T5" } ] }, { "id": "PMID-9199300_E4", "type": "Positive_regulation", "trigger": { "text": [ "activates" ], "offsets": [ [ 777, 786 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "PMID-9199300_T9" }, { "role": "Cause", "ref_id": "PMID-9199300_T8" } ] }, { "id": "PMID-9199300_E5", "type": "Positive_regulation", "trigger": { "text": [ "transactivation" ], "offsets": [ [ 902, 917 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "PMID-9199300_T10" } ] }, { "id": "PMID-9199300_E6", "type": "Negative_regulation", "trigger": { "text": [ "restricted" ], "offsets": [ [ 962, 972 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "PMID-9199300_E5" } ] }, { "id": "PMID-9199300_E7", "type": "Positive_regulation", "trigger": { "text": [ "activation" ], "offsets": [ [ 1004, 1014 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "PMID-9199300_T12" }, { "role": "Cause", "ref_id": "PMID-9199300_T11" } ] }, { "id": "PMID-9199300_E8", "type": "Positive_regulation", "trigger": { "text": [ "activation" ], "offsets": [ [ 1098, 1108 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "PMID-9199300_T13" } ] }, { "id": "PMID-9199300_E9", "type": "Positive_regulation", "trigger": { "text": [ "enhance" ], "offsets": [ [ 1272, 1279 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "PMID-9199300_T16" }, { "role": "Cause", "ref_id": "PMID-9199300_T14" } ] }, { "id": "PMID-9199300_E10", "type": "Regulation", "trigger": { "text": [ "regulated" ], "offsets": [ [ 1815, 1824 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "PMID-9199300_T24" }, { "role": "Cause", "ref_id": "PMID-9199300_T25" }, { "role": "Site", "ref_id": "PMID-9199300_T34" } ] }, { "id": "PMID-9199300_E11", "type": "Positive_regulation", "trigger": { "text": [ "independently" ], "offsets": [ [ 1826, 1839 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "PMID-9199300_E10" }, { "role": "Cause", "ref_id": "PMID-9199300_E12" } ] }, { "id": "PMID-9199300_E12", "type": "Binding", "trigger": { "text": [ "binding" ], "offsets": [ [ 1853, 1860 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "PMID-9199300_T24" }, { "role": "Site", "ref_id": "PMID-9199300_T34" } ] } ]

[ { "id": "PMID-9199300_1", "entity_ids": [ "PMID-9199300_T8", "PMID-9199300_T7" ] } ]

[]

[ { "id": "PMID-9199305__text", "type": "abstract", "text": [ "The immediate-early gene product Egr-1 regulates the human interleukin-2 receptor beta-chain promoter through noncanonical Egr and Sp1 binding sites. \nThe interleukin-2 IL-2 receptor beta-chain (IL-2Rbeta) is an essential component of the receptors for IL-2 and IL-15. Although IL-2Rbeta is constitutively expressed by lymphocytes, its expression can be further induced by a number of stimuli, including phorbol 12-myristate 13-acetate (PMA). We have now characterized factors that bind to an enhancer region located between nucleotides -170 and -139 of the human IL-2Rbeta promoter. Both Sp1 and Sp3 bound to the 5' portion of this region, whereas a PMA-inducible factor (PIF) mainly bound to its 3' portion and bound to the Sp binding motifs as well. In Jurkat T cells, induction of PIF DNA binding activity was rapidly induced, required de novo protein synthesis, and was sustained at a high level for at least 23 h. Interestingly, PIF was constitutively activated in human T-cell leukemia virus type 1-transformed MT-2 cells. In this paper, we demonstrate that PIF is Egr-1 based on its recognition by anti-Egr-1 antisera in gel mobility shift assays, even though the IL-2Rbeta DNA binding motif differed substantially from the canonical Egr-1 binding site. In addition, Egr-1 bound to the Sp binding site. In Jurkat cells, both sites were required for maximal IL-2Rbeta promoter activity, and in HeLaS3 cells, transfection of Egr-1 could drive activity of a reporter construct containing both sites. Moreover, Sp1 and Egr-1 could form a complex with kinetics that correlated with the production of Egr-1 in Jurkat cells upon PMA stimulation. Thus, Sp1 and Egr-1 physically and functionally cooperate to mediate maximal IL-2Rbeta promoter activity. " ], "offsets": [ [ 0, 1753 ] ] } ]

[ { "id": "PMID-9199305_T1", "type": "Protein", "text": [ "Egr-1" ], "offsets": [ [ 33, 38 ] ], "normalized": [] }, { "id": "PMID-9199305_T2", "type": "Protein", "text": [ "interleukin-2 receptor beta-chain" ], "offsets": [ [ 59, 92 ] ], "normalized": [] }, { "id": "PMID-9199305_T3", "type": "Protein", "text": [ "interleukin-2 IL-2 receptor beta-chain" ], "offsets": [ [ 155, 193 ] ], "normalized": [] }, { "id": "PMID-9199305_T4", "type": "Protein", "text": [ "IL-2Rbeta" ], "offsets": [ [ 195, 204 ] ], "normalized": [] }, { "id": "PMID-9199305_T5", "type": "Protein", "text": [ "IL-2" ], "offsets": [ [ 253, 257 ] ], "normalized": [] }, { "id": "PMID-9199305_T6", "type": "Protein", "text": [ "IL-15" ], "offsets": [ [ 262, 267 ] ], "normalized": [] }, { "id": "PMID-9199305_T7", "type": "Protein", "text": [ "IL-2Rbeta" ], "offsets": [ [ 278, 287 ] ], "normalized": [] }, { "id": "PMID-9199305_T8", "type": "Protein", "text": [ "IL-2Rbeta" ], "offsets": [ [ 564, 573 ] ], "normalized": [] }, { "id": "PMID-9199305_T9", "type": "Protein", "text": [ "Sp1" ], "offsets": [ [ 589, 592 ] ], "normalized": [] }, { "id": "PMID-9199305_T10", "type": "Protein", "text": [ "Sp3" ], "offsets": [ [ 597, 600 ] ], "normalized": [] }, { "id": "PMID-9199305_T11", "type": "Protein", "text": [ "Egr-1" ], "offsets": [ [ 1072, 1077 ] ], "normalized": [] }, { "id": "PMID-9199305_T12", "type": "Protein", "text": [ "Egr-1" ], "offsets": [ [ 1111, 1116 ] ], "normalized": [] }, { "id": "PMID-9199305_T13", "type": "Protein", "text": [ "IL-2Rbeta" ], "offsets": [ [ 1172, 1181 ] ], "normalized": [] }, { "id": "PMID-9199305_T14", "type": "Protein", "text": [ "Egr-1" ], "offsets": [ [ 1242, 1247 ] ], "normalized": [] }, { "id": "PMID-9199305_T15", "type": "Protein", "text": [ "Egr-1" ], "offsets": [ [ 1275, 1280 ] ], "normalized": [] }, { "id": "PMID-9199305_T16", "type": "Protein", "text": [ "IL-2Rbeta" ], "offsets": [ [ 1365, 1374 ] ], "normalized": [] }, { "id": "PMID-9199305_T17", "type": "Protein", "text": [ "Egr-1" ], "offsets": [ [ 1431, 1436 ] ], "normalized": [] }, { "id": "PMID-9199305_T18", "type": "Protein", "text": [ "Sp1" ], "offsets": [ [ 1515, 1518 ] ], "normalized": [] }, { "id": "PMID-9199305_T19", "type": "Protein", "text": [ "Egr-1" ], "offsets": [ [ 1523, 1528 ] ], "normalized": [] }, { "id": "PMID-9199305_T20", "type": "Protein", "text": [ "Egr-1" ], "offsets": [ [ 1603, 1608 ] ], "normalized": [] }, { "id": "PMID-9199305_T21", "type": "Protein", "text": [ "Sp1" ], "offsets": [ [ 1653, 1656 ] ], "normalized": [] }, { "id": "PMID-9199305_T22", "type": "Protein", "text": [ "Egr-1" ], "offsets": [ [ 1661, 1666 ] ], "normalized": [] }, { "id": "PMID-9199305_T23", "type": "Protein", "text": [ "IL-2Rbeta" ], "offsets": [ [ 1724, 1733 ] ], "normalized": [] }, { "id": "PMID-9199305_T28", "type": "Entity", "text": [ "promoter" ], "offsets": [ [ 574, 582 ] ], "normalized": [] }, { "id": "PMID-9199305_T33", "type": "Entity", "text": [ "promoter" ], "offsets": [ [ 1375, 1383 ] ], "normalized": [] } ]

[ { "id": "PMID-9199305_E1", "type": "Regulation", "trigger": { "text": [ "through" ], "offsets": [ [ 102, 109 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "PMID-9199305_T2" } ] }, { "id": "PMID-9199305_E2", "type": "Gene_expression", "trigger": { "text": [ "expressed" ], "offsets": [ [ 306, 315 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "PMID-9199305_T7" } ] }, { "id": "PMID-9199305_E3", "type": "Positive_regulation", "trigger": { "text": [ "induced" ], "offsets": [ [ 362, 369 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "PMID-9199305_E2" } ] }, { "id": "PMID-9199305_E4", "type": "Binding", "trigger": { "text": [ "bind" ], "offsets": [ [ 482, 486 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "PMID-9199305_T8" }, { "role": "Site", "ref_id": "PMID-9199305_T28" } ] }, { "id": "PMID-9199305_E5", "type": "Binding", "trigger": { "text": [ "bound" ], "offsets": [ [ 601, 606 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "PMID-9199305_T10" } ] }, { "id": "PMID-9199305_E6", "type": "Binding", "trigger": { "text": [ "bound" ], "offsets": [ [ 601, 606 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "PMID-9199305_T9" } ] }, { "id": "PMID-9199305_E7", "type": "Binding", "trigger": { "text": [ "recognition" ], "offsets": [ [ 1091, 1102 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "PMID-9199305_T11" } ] }, { "id": "PMID-9199305_E8", "type": "Binding", "trigger": { "text": [ "bound" ], "offsets": [ [ 1281, 1286 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "PMID-9199305_T15" } ] }, { "id": "PMID-9199305_E9", "type": "Positive_regulation", "trigger": { "text": [ "required" ], "offsets": [ [ 1344, 1352 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "PMID-9199305_T16" }, { "role": "Site", "ref_id": "PMID-9199305_T33" } ] }, { "id": "PMID-9199305_E10", "type": "Gene_expression", "trigger": { "text": [ "transfection" ], "offsets": [ [ 1415, 1427 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "PMID-9199305_T17" } ] }, { "id": "PMID-9199305_E11", "type": "Positive_regulation", "trigger": { "text": [ "transfection" ], "offsets": [ [ 1415, 1427 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "PMID-9199305_E10" } ] }, { "id": "PMID-9199305_E12", "type": "Binding", "trigger": { "text": [ "form a complex" ], "offsets": [ [ 1535, 1549 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "PMID-9199305_T18" }, { "role": "Theme", "ref_id": "PMID-9199305_T19" } ] }, { "id": "PMID-9199305_E13", "type": "Gene_expression", "trigger": { "text": [ "production" ], "offsets": [ [ 1589, 1599 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "PMID-9199305_T20" } ] }, { "id": "PMID-9199305_E14", "type": "Positive_regulation", "trigger": { "text": [ "mediate" ], "offsets": [ [ 1708, 1715 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "PMID-9199305_T23" }, { "role": "Cause", "ref_id": "PMID-9199305_T21" } ] }, { "id": "PMID-9199305_E15", "type": "Positive_regulation", "trigger": { "text": [ "mediate" ], "offsets": [ [ 1708, 1715 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "PMID-9199305_T23" }, { "role": "Cause", "ref_id": "PMID-9199305_T22" } ] } ]

[ { "id": "PMID-9199305_1", "entity_ids": [ "PMID-9199305_T3", "PMID-9199305_T4" ] } ]

[]

[ { "id": "PMID-9199464__text", "type": "abstract", "text": [ "Anti-Ehrlichia chaffeensis antibody complexed with E. chaffeensis induces potent proinflammatory cytokine mRNA expression in human monocytes through sustained reduction of IkappaB-alpha and activation of NF-kappaB. \nEhrlichia chaffeensis is an obligatory intracellular bacterium that infects monocytes and macrophages and is the etiologic agent of human ehrlichiosis in the United States. Our previous studies showed that the exposure of human monocytes to E. chaffeensis induces the expression of interleukin-1beta (IL-1beta), IL-8, and IL-10 genes in vitro but not the expression of tumor necrosis factor alpha (TNF-alpha) and IL-6 mRNAs. In this study, the effect of anti-E. chaffeensis antibody complexed with E. chaffeensis on the expression of major proinflammatory cytokines in human monocytes was examined. Human monocytic cell line THP-1 was treated with E. chaffeensis which had been preincubated with human anti-E. chaffeensis serum for 2 h, and the levels of cytokine mRNAs were evaluated by competitive reverse transcription-PCR. Anti-E. chaffeensis antibody complexed with E. chaffeensis significantly enhanced mRNA expression of IL-1beta in THP-1 cells. The expression of TNF-alpha and IL-6 mRNAs was also induced. The levels of secreted IL-1beta, TNF-alpha, and IL-6 during 24 h of stimulation were comparable to those induced by Escherichia coli lipopolysaccharide at 1 microg/ml. Fab fragment of anti-E. chaffeensis immunoglobulin G complexed with E. chaffeensis did not induce any of these three cytokines, indicating that ehrlichial binding is required for IL-1beta mRNA expression and that binding of the immune complex to the Fc gamma receptor is required for TNF-alpha and IL-6 mRNA expression and enhanced IL-1beta mRNA expression. Furthermore, prolonged degradation of IkappaB-alpha and activation of NF-kappaB were demonstrated in THP-1 cells exposed to anti-E. chaffeensis serum and E. chaffeensis. This result implies that development of anti-E. chaffeensis antibody in patients can result in the production of major proinflammatory cytokines, which may play an important role in the pathophysiology of ehrlichiosis and immune responses to it. " ], "offsets": [ [ 0, 2172 ] ] } ]

[ { "id": "PMID-9199464_T1", "type": "Protein", "text": [ "IkappaB-alpha" ], "offsets": [ [ 172, 185 ] ], "normalized": [] }, { "id": "PMID-9199464_T2", "type": "Protein", "text": [ "interleukin-1beta" ], "offsets": [ [ 498, 515 ] ], "normalized": [] }, { "id": "PMID-9199464_T3", "type": "Protein", "text": [ "IL-1beta" ], "offsets": [ [ 517, 525 ] ], "normalized": [] }, { "id": "PMID-9199464_T4", "type": "Protein", "text": [ "IL-8" ], "offsets": [ [ 528, 532 ] ], "normalized": [] }, { "id": "PMID-9199464_T5", "type": "Protein", "text": [ "IL-10" ], "offsets": [ [ 538, 543 ] ], "normalized": [] }, { "id": "PMID-9199464_T6", "type": "Protein", "text": [ "tumor necrosis factor alpha" ], "offsets": [ [ 585, 612 ] ], "normalized": [] }, { "id": "PMID-9199464_T7", "type": "Protein", "text": [ "TNF-alpha" ], "offsets": [ [ 614, 623 ] ], "normalized": [] }, { "id": "PMID-9199464_T8", "type": "Protein", "text": [ "IL-6" ], "offsets": [ [ 629, 633 ] ], "normalized": [] }, { "id": "PMID-9199464_T9", "type": "Protein", "text": [ "IL-1beta" ], "offsets": [ [ 1144, 1152 ] ], "normalized": [] }, { "id": "PMID-9199464_T10", "type": "Protein", "text": [ "TNF-alpha" ], "offsets": [ [ 1187, 1196 ] ], "normalized": [] }, { "id": "PMID-9199464_T11", "type": "Protein", "text": [ "IL-6" ], "offsets": [ [ 1201, 1205 ] ], "normalized": [] }, { "id": "PMID-9199464_T12", "type": "Protein", "text": [ "IL-1beta" ], "offsets": [ [ 1253, 1261 ] ], "normalized": [] }, { "id": "PMID-9199464_T13", "type": "Protein", "text": [ "TNF-alpha" ], "offsets": [ [ 1263, 1272 ] ], "normalized": [] }, { "id": "PMID-9199464_T14", "type": "Protein", "text": [ "IL-6" ], "offsets": [ [ 1278, 1282 ] ], "normalized": [] }, { "id": "PMID-9199464_T15", "type": "Protein", "text": [ "IL-1beta" ], "offsets": [ [ 1577, 1585 ] ], "normalized": [] }, { "id": "PMID-9199464_T16", "type": "Protein", "text": [ "Fc gamma receptor" ], "offsets": [ [ 1648, 1665 ] ], "normalized": [] }, { "id": "PMID-9199464_T17", "type": "Protein", "text": [ "TNF-alpha" ], "offsets": [ [ 1682, 1691 ] ], "normalized": [] }, { "id": "PMID-9199464_T18", "type": "Protein", "text": [ "IL-6" ], "offsets": [ [ 1696, 1700 ] ], "normalized": [] }, { "id": "PMID-9199464_T19", "type": "Protein", "text": [ "IL-1beta" ], "offsets": [ [ 1730, 1738 ] ], "normalized": [] }, { "id": "PMID-9199464_T20", "type": "Protein", "text": [ "IkappaB-alpha" ], "offsets": [ [ 1794, 1807 ] ], "normalized": [] } ]

[ { "id": "PMID-9199464_E1", "type": "Negative_regulation", "trigger": { "text": [ "reduction" ], "offsets": [ [ 159, 168 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "PMID-9199464_T1" } ] }, { "id": "PMID-9199464_E2", "type": "Positive_regulation", "trigger": { "text": [ "induces" ], "offsets": [ [ 472, 479 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "PMID-9199464_E9" } ] }, { "id": "PMID-9199464_E3", "type": "Positive_regulation", "trigger": { "text": [ "induces" ], "offsets": [ [ 472, 479 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "PMID-9199464_E10" } ] }, { "id": "PMID-9199464_E4", "type": "Positive_regulation", "trigger": { "text": [ "induces" ], "offsets": [ [ 472, 479 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "PMID-9199464_E7" } ] }, { "id": "PMID-9199464_E5", "type": "Positive_regulation", "trigger": { "text": [ "induces" ], "offsets": [ [ 472, 479 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "PMID-9199464_E8" } ] }, { "id": "PMID-9199464_E6", "type": "Positive_regulation", "trigger": { "text": [ "induces" ], "offsets": [ [ 472, 479 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "PMID-9199464_E11" } ] }, { "id": "PMID-9199464_E7", "type": "Gene_expression", "trigger": { "text": [ "expression" ], "offsets": [ [ 484, 494 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "PMID-9199464_T3" } ] }, { "id": "PMID-9199464_E8", "type": "Gene_expression", "trigger": { "text": [ "expression" ], "offsets": [ [ 484, 494 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "PMID-9199464_T4" } ] }, { "id": "PMID-9199464_E9", "type": "Gene_expression", "trigger": { "text": [ "expression" ], "offsets": [ [ 484, 494 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "PMID-9199464_T5" } ] }, { "id": "PMID-9199464_E10", "type": "Transcription", "trigger": { "text": [ "expression" ], "offsets": [ [ 571, 581 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "PMID-9199464_T8" } ] }, { "id": "PMID-9199464_E11", "type": "Transcription", "trigger": { "text": [ "expression" ], "offsets": [ [ 571, 581 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "PMID-9199464_T7" } ] }, { "id": "PMID-9199464_E12", "type": "Positive_regulation", "trigger": { "text": [ "enhanced" ], "offsets": [ [ 1116, 1124 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "PMID-9199464_E13" } ] }, { "id": "PMID-9199464_E13", "type": "Transcription", "trigger": { "text": [ "mRNA expression" ], "offsets": [ [ 1125, 1140 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "PMID-9199464_T9" } ] }, { "id": "PMID-9199464_E14", "type": "Transcription", "trigger": { "text": [ "expression" ], "offsets": [ [ 1173, 1183 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "PMID-9199464_T10" } ] }, { "id": "PMID-9199464_E15", "type": "Transcription", "trigger": { "text": [ "expression" ], "offsets": [ [ 1173, 1183 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "PMID-9199464_T11" } ] }, { "id": "PMID-9199464_E16", "type": "Positive_regulation", "trigger": { "text": [ "induced" ], "offsets": [ [ 1221, 1228 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "PMID-9199464_E14" } ] }, { "id": "PMID-9199464_E17", "type": "Positive_regulation", "trigger": { "text": [ "induce" ], "offsets": [ [ 1489, 1495 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "PMID-9199464_T12" } ] }, { "id": "PMID-9199464_E18", "type": "Positive_regulation", "trigger": { "text": [ "induce" ], "offsets": [ [ 1489, 1495 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "PMID-9199464_T14" } ] }, { "id": "PMID-9199464_E19", "type": "Positive_regulation", "trigger": { "text": [ "induce" ], "offsets": [ [ 1489, 1495 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "PMID-9199464_T13" } ] }, { "id": "PMID-9199464_E20", "type": "Positive_regulation", "trigger": { "text": [ "required" ], "offsets": [ [ 1564, 1572 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "PMID-9199464_E21" } ] }, { "id": "PMID-9199464_E21", "type": "Transcription", "trigger": { "text": [ "expression" ], "offsets": [ [ 1591, 1601 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "PMID-9199464_T15" } ] }, { "id": "PMID-9199464_E22", "type": "Binding", "trigger": { "text": [ "binding" ], "offsets": [ [ 1611, 1618 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "PMID-9199464_T16" } ] }, { "id": "PMID-9199464_E23", "type": "Positive_regulation", "trigger": { "text": [ "required" ], "offsets": [ [ 1669, 1677 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "PMID-9199464_E26" }, { "role": "Cause", "ref_id": "PMID-9199464_E22" } ] }, { "id": "PMID-9199464_E24", "type": "Positive_regulation", "trigger": { "text": [ "required" ], "offsets": [ [ 1669, 1677 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "PMID-9199464_E25" }, { "role": "Cause", "ref_id": "PMID-9199464_E22" } ] }, { "id": "PMID-9199464_E25", "type": "Transcription", "trigger": { "text": [ "expression" ], "offsets": [ [ 1706, 1716 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "PMID-9199464_T17" } ] }, { "id": "PMID-9199464_E26", "type": "Transcription", "trigger": { "text": [ "expression" ], "offsets": [ [ 1706, 1716 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "PMID-9199464_T18" } ] }, { "id": "PMID-9199464_E27", "type": "Positive_regulation", "trigger": { "text": [ "enhanced" ], "offsets": [ [ 1721, 1729 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "PMID-9199464_E28" }, { "role": "Cause", "ref_id": "PMID-9199464_E22" } ] }, { "id": "PMID-9199464_E28", "type": "Transcription", "trigger": { "text": [ "expression" ], "offsets": [ [ 1744, 1754 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "PMID-9199464_T19" } ] }, { "id": "PMID-9199464_E29", "type": "Protein_catabolism", "trigger": { "text": [ "degradation" ], "offsets": [ [ 1779, 1790 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "PMID-9199464_T20" } ] }, { "id": "PMID-9199464_E30", "type": "Positive_regulation", "trigger": { "text": [ "demonstrated" ], "offsets": [ [ 1841, 1853 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "PMID-9199464_E29" } ] } ]

[ { "id": "PMID-9199464_1", "entity_ids": [ "PMID-9199464_T3", "PMID-9199464_T2" ] }, { "id": "PMID-9199464_2", "entity_ids": [ "PMID-9199464_T7", "PMID-9199464_T6" ] } ]

[]

[ { "id": "PMID-9199898__text", "type": "abstract", "text": [ "S-allyl cysteine inhibits activation of nuclear factor kappa B in human T cells. \nReactive oxygen species are involved in signal transduction pathways leading to nuclear factor kappa B (NF-kappa B) activation which has been implicated in the regulation of gene transcription. We recently reported that a garlic compound, S-allyl cysteine (SAC), protects bovine pulmonary artery endothelial cells from oxidant injury induced by hydrogen peroxide (H2O2). In this study we determined the effects of SAC on NF-kappa B activation in human T lymphocytes (Jurkat cells) induced by tumor necrosis factor alpha (TNF- alpha) and H2O2. Activated NF-kappa B in nuclear extracts was measured by an electrophoretic mobility shift assay using 32P-labeled probe. SAC consistently exhibited a dose-dependent inhibition of NF-kappa B activation induced by both TNF-alpha and H2O2. Supershift with specific antibodies to NF-kappa B subunits confirmed that the inducible retarded bands observed in the EMSA and p65-p50 heterodimer of the NF-kappa B/Rel protein. Our data suggest that SAC may act via antioxidant mechanisms to block NF-kappa B activation in Jurkat cells. " ], "offsets": [ [ 0, 1151 ] ] } ]

[ { "id": "PMID-9199898_T1", "type": "Protein", "text": [ "tumor necrosis factor alpha" ], "offsets": [ [ 574, 601 ] ], "normalized": [] }, { "id": "PMID-9199898_T2", "type": "Protein", "text": [ "TNF- alpha" ], "offsets": [ [ 603, 613 ] ], "normalized": [] }, { "id": "PMID-9199898_T3", "type": "Protein", "text": [ "TNF-alpha" ], "offsets": [ [ 843, 852 ] ], "normalized": [] }, { "id": "PMID-9199898_T4", "type": "Protein", "text": [ "p65" ], "offsets": [ [ 991, 994 ] ], "normalized": [] }, { "id": "PMID-9199898_T5", "type": "Protein", "text": [ "p50" ], "offsets": [ [ 995, 998 ] ], "normalized": [] } ]

[ { "id": "PMID-9199898_E1", "type": "Binding", "trigger": { "text": [ "heterodimer" ], "offsets": [ [ 999, 1010 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "PMID-9199898_T4" }, { "role": "Theme", "ref_id": "PMID-9199898_T5" } ] } ]

[ { "id": "PMID-9199898_1", "entity_ids": [ "PMID-9199898_T1", "PMID-9199898_T2" ] } ]

[]

[ { "id": "PMID-9201242__text", "type": "abstract", "text": [ "Effect of adenovirus 2 on cellular gene activation in blood-derived monocytes and macrophages. \nWe have investigated the effect of adenovirus 2 (Ad2) infection on human monocytes and monocyte-derived macrophages with regard to expression of TNF-alpha and IL-1 beta. In monocytes, the virus was bound to the surface without being internalized. On the other hand, Ad2 was internalized by macrophages. No virus replication and no transcription of the Ad2 early genes was observed in either of the cells. Ad2 infection induced transient increase in the mRNA levels for TNF-alpha and IL-1 beta in both monocytes and in macrophages, although the kinetics of the transcription was slightly different. The production of both cytokines, measured by ELISA tests, was enhanced in monocytes. In macrophages, a slight enhancement of TNF-alpha production was seen, whereas IL-1 beta was not detected. The data indicate that cellular genes might be activated by Ad2 virus infection in nonpermissive cells where no viral gene products could be detected. " ], "offsets": [ [ 0, 1038 ] ] } ]

[ { "id": "PMID-9201242_T1", "type": "Protein", "text": [ "TNF-alpha" ], "offsets": [ [ 241, 250 ] ], "normalized": [] }, { "id": "PMID-9201242_T2", "type": "Protein", "text": [ "IL-1 beta" ], "offsets": [ [ 255, 264 ] ], "normalized": [] }, { "id": "PMID-9201242_T3", "type": "Protein", "text": [ "TNF-alpha" ], "offsets": [ [ 565, 574 ] ], "normalized": [] }, { "id": "PMID-9201242_T4", "type": "Protein", "text": [ "IL-1 beta" ], "offsets": [ [ 579, 588 ] ], "normalized": [] }, { "id": "PMID-9201242_T5", "type": "Protein", "text": [ "TNF-alpha" ], "offsets": [ [ 820, 829 ] ], "normalized": [] }, { "id": "PMID-9201242_T6", "type": "Protein", "text": [ "IL-1 beta" ], "offsets": [ [ 859, 868 ] ], "normalized": [] } ]

[ { "id": "PMID-9201242_E1", "type": "Regulation", "trigger": { "text": [ "effect" ], "offsets": [ [ 121, 127 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "PMID-9201242_E4" } ] }, { "id": "PMID-9201242_E2", "type": "Regulation", "trigger": { "text": [ "effect" ], "offsets": [ [ 121, 127 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "PMID-9201242_E3" } ] }, { "id": "PMID-9201242_E3", "type": "Gene_expression", "trigger": { "text": [ "expression" ], "offsets": [ [ 227, 237 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "PMID-9201242_T1" } ] }, { "id": "PMID-9201242_E4", "type": "Gene_expression", "trigger": { "text": [ "expression" ], "offsets": [ [ 227, 237 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "PMID-9201242_T2" } ] }, { "id": "PMID-9201242_E5", "type": "Positive_regulation", "trigger": { "text": [ "induced" ], "offsets": [ [ 515, 522 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "PMID-9201242_E8" } ] }, { "id": "PMID-9201242_E6", "type": "Positive_regulation", "trigger": { "text": [ "induced" ], "offsets": [ [ 515, 522 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "PMID-9201242_E7" } ] }, { "id": "PMID-9201242_E7", "type": "Positive_regulation", "trigger": { "text": [ "increase" ], "offsets": [ [ 533, 541 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "PMID-9201242_E9" } ] }, { "id": "PMID-9201242_E8", "type": "Positive_regulation", "trigger": { "text": [ "increase" ], "offsets": [ [ 533, 541 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "PMID-9201242_E10" } ] }, { "id": "PMID-9201242_E9", "type": "Transcription", "trigger": { "text": [ "mRNA levels" ], "offsets": [ [ 549, 560 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "PMID-9201242_T4" } ] }, { "id": "PMID-9201242_E10", "type": "Transcription", "trigger": { "text": [ "mRNA levels" ], "offsets": [ [ 549, 560 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "PMID-9201242_T3" } ] }, { "id": "PMID-9201242_E11", "type": "Gene_expression", "trigger": { "text": [ "production" ], "offsets": [ [ 698, 708 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "PMID-9201242_T4" } ] }, { "id": "PMID-9201242_E12", "type": "Gene_expression", "trigger": { "text": [ "production" ], "offsets": [ [ 698, 708 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "PMID-9201242_T3" } ] }, { "id": "PMID-9201242_E13", "type": "Positive_regulation", "trigger": { "text": [ "enhanced" ], "offsets": [ [ 757, 765 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "PMID-9201242_E12" } ] }, { "id": "PMID-9201242_E14", "type": "Positive_regulation", "trigger": { "text": [ "enhanced" ], "offsets": [ [ 757, 765 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "PMID-9201242_E11" } ] }, { "id": "PMID-9201242_E15", "type": "Positive_regulation", "trigger": { "text": [ "enhancement" ], "offsets": [ [ 805, 816 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "PMID-9201242_E16" } ] }, { "id": "PMID-9201242_E16", "type": "Gene_expression", "trigger": { "text": [ "production" ], "offsets": [ [ 830, 840 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "PMID-9201242_T5" } ] }, { "id": "PMID-9201242_E17", "type": "Gene_expression", "trigger": { "text": [ "detected" ], "offsets": [ [ 877, 885 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "PMID-9201242_T6" } ] } ]

[]

[]

[ { "id": "PMID-9209268__text", "type": "abstract", "text": [ "Activation of nuclear factor-kappa B by beta-amyloid peptides and interferon-gamma in murine microglia. \nAn increasing body of evidence suggests that amyloid-beta (A beta) peptides and microglia are crucially involved in the pathogenesis of Alzheimer's disease. In an effort to further elucidate the biological effects of A beta towards microglia, we investigated the ability of A beta peptides to activate nuclear factor (NF)-kappa B in the N9 murine microglial cell line. Co-stimulation of microglia with suboptimal concentrations of A beta(25-35) and 100 U/ml IFN gamma resulted in the detection of a specific NF-kappa B DNA-binding activity in nuclear extracts, as determined in gel mobility shift assays. This response required at least 120 min to be evident and supershift experiments revealed that the NF-kappa B complex contains both RelA and p50. Accordingly, immunoblot experiments showed that amongst NF-kappa B/Rel proteins, RelA and p50 are mobilized to the nucleus following microglial cell stimulation with A beta(25-35) plus IFN gamma. Higher concentrations of A beta(25-35) were effective by themselves in inducing NF-kappa B activation, both in the N9 microglial cell line and in rat primary microglia, as well as in human monocytes. For purposes of comparison, microglia were also stimulated with bacterial LPS, a known NF-kappa B inducer. As expected, LPS strongly induced the formation of two NF-kappa B DNA-binding activities, one of which was identified as RelA/p50. The LPS response was also more rapid, as it was already evident by 40 min and remained sustained for up to 3 h. Collectively, these findings indicate that NF-kappa B activation might constitute one of the mechanisms underlying the inducible expression of kappa B-dependent genes in microglia stimulated by A beta peptides and IFN gamma, or by LPS. " ], "offsets": [ [ 0, 1838 ] ] } ]

[ { "id": "PMID-9209268_T1", "type": "Protein", "text": [ "interferon-gamma" ], "offsets": [ [ 66, 82 ] ], "normalized": [] }, { "id": "PMID-9209268_T2", "type": "Protein", "text": [ "IFN gamma" ], "offsets": [ [ 563, 572 ] ], "normalized": [] }, { "id": "PMID-9209268_T3", "type": "Protein", "text": [ "RelA" ], "offsets": [ [ 842, 846 ] ], "normalized": [] }, { "id": "PMID-9209268_T4", "type": "Protein", "text": [ "p50" ], "offsets": [ [ 851, 854 ] ], "normalized": [] }, { "id": "PMID-9209268_T5", "type": "Protein", "text": [ "RelA" ], "offsets": [ [ 937, 941 ] ], "normalized": [] }, { "id": "PMID-9209268_T6", "type": "Protein", "text": [ "p50" ], "offsets": [ [ 946, 949 ] ], "normalized": [] }, { "id": "PMID-9209268_T7", "type": "Protein", "text": [ "IFN gamma" ], "offsets": [ [ 1041, 1050 ] ], "normalized": [] }, { "id": "PMID-9209268_T8", "type": "Protein", "text": [ "RelA" ], "offsets": [ [ 1480, 1484 ] ], "normalized": [] }, { "id": "PMID-9209268_T9", "type": "Protein", "text": [ "p50" ], "offsets": [ [ 1485, 1488 ] ], "normalized": [] }, { "id": "PMID-9209268_T10", "type": "Protein", "text": [ "IFN gamma" ], "offsets": [ [ 1816, 1825 ] ], "normalized": [] }, { "id": "PMID-9209268_T12", "type": "Entity", "text": [ "nucleus" ], "offsets": [ [ 971, 978 ] ], "normalized": [] } ]

[ { "id": "PMID-9209268_E1", "type": "Localization", "trigger": { "text": [ "mobilized" ], "offsets": [ [ 954, 963 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "PMID-9209268_T6" }, { "role": "ToLoc", "ref_id": "PMID-9209268_T12" } ] }, { "id": "PMID-9209268_E2", "type": "Localization", "trigger": { "text": [ "mobilized" ], "offsets": [ [ 954, 963 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "PMID-9209268_T5" }, { "role": "ToLoc", "ref_id": "PMID-9209268_T12" } ] }, { "id": "PMID-9209268_E3", "type": "Positive_regulation", "trigger": { "text": [ "following" ], "offsets": [ [ 979, 988 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "PMID-9209268_E2" } ] }, { "id": "PMID-9209268_E4", "type": "Positive_regulation", "trigger": { "text": [ "following" ], "offsets": [ [ 979, 988 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "PMID-9209268_E1" } ] }, { "id": "PMID-9209268_E5", "type": "Positive_regulation", "trigger": { "text": [ "induced the formation" ], "offsets": [ [ 1385, 1406 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "PMID-9209268_E8" } ] }, { "id": "PMID-9209268_E6", "type": "Positive_regulation", "trigger": { "text": [ "induced the formation" ], "offsets": [ [ 1385, 1406 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "PMID-9209268_E7" } ] }, { "id": "PMID-9209268_E7", "type": "Binding", "trigger": { "text": [ "binding" ], "offsets": [ [ 1429, 1436 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "PMID-9209268_T9" } ] }, { "id": "PMID-9209268_E8", "type": "Binding", "trigger": { "text": [ "binding" ], "offsets": [ [ 1429, 1436 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "PMID-9209268_T8" } ] } ]

[]

[]

[ { "id": "PMID-9209284__text", "type": "abstract", "text": [ "AP-1 derived from mature monocytes and astrocytes preferentially interacts with the HTLV-I promoter central 21 bp repeat. \nCharacterization of the cellular transcription factors interacting with the human T cell lymphotropic virus type I (HTLV-I) long terminal repeat (LTR) is essential to dissecting the mechanisms involved in viral transcription that may be pertinent to the oncogenic and neuropathogenic processes associated with HTLV-I infection in both the immune and nervous systems. Electrophoretic mobility shift (EMS) analyses utilizing oligonucleotides homologous to each of the 21 bp repeat elements reacted with nuclear extracts derived from cell lines of lymphocytic, monocytic, neuronal, and glial cell origin have demonstrated differential binding of cellular factors to the three 21 bp repeats (1-4). ATF/CREB and Sp family members interacted with the 21 bp repeats to form DNA-protein complexes common to all cell types examined. However, a unique DNA-protein complex was detected when the promoter central 21 bp repeat was reacted with nuclear extracts derived from either the U-373 MG glioblastoma cell line or the THP-1 mature monocytic cell line. Based on nucleotide sequence requirements and immunoreactivity, we demonstrate that this DNA-protein complex is comprised of the AP-1 components, Fos and Jun. " ], "offsets": [ [ 0, 1327 ] ] } ]

[]

[]

[]

[]

[ { "id": "PMID-9209438__text", "type": "abstract", "text": [ "Of the GATA-binding proteins, only GATA-4 selectively regulates the human IL-5 gene promoter in IL-5 producing cells which express multiple GATA-binding proteins. \nInterleukin-5 (IL-5) is produced by T lymphocytes and known to support B cell growth and eosinophilic differentiation of the progenitor cells. Using ATL-16T cells which express IL-5 mRNA, we have identified a region, within the human IL-5 gene promoter, that regulates IL-5 gene transcription. This cis-acting sequence contains the core binding motif, (A/T)GATA(A/G), for GATA-binding family proteins and thus suggests the involvement of these family members. In this report, we describe the cloning of human GATA-4 (hGATA-4) and show that hGATA-4 selectively interacts with the -70 GATA site within the IL-5 proximal promoter region. By promoter deletion and mutation analyses, we established this region as a positive regulatory element. Cotransfection experiments revealed that both hGATA-4 and PMA/A23187 stimulation are necessary for the IL-5 promoter activation. The requirement of another regulatory element called CLE0, which lies downstream of the -70 GATA site, was also demonstrated. ATL-16T cells express mRNA of three GATA-binding proteins, hGATA-2, hGATA-3 and hGATA-4, and each of them has a potential to bind to the consensus (A/T)GATA(G/ A) motif. However, using ATL-16T nuclear extract, we demonstrated that GATA-4 is the only GATA-binding protein that forms specific DNA-protein complex with the -70 GATA site. The electrophoretic mobility shift assay with extracts of COS cells expressing GATA-binding proteins showed that GATA-4 has the highest binding affinity to the -70 GATA site among the three GATA-binding proteins. When the transactivation ability was compared among the three, GATA-4 showed the highest activity. These results demonstrate the selective role of GATA-4 in the transcriptional regulation of the IL-5 gene in a circumstance where multiple members of the GATA-binding proteins are expressed. " ], "offsets": [ [ 0, 1997 ] ] } ]

[ { "id": "PMID-9209438_T1", "type": "Protein", "text": [ "GATA-4" ], "offsets": [ [ 35, 41 ] ], "normalized": [] }, { "id": "PMID-9209438_T2", "type": "Protein", "text": [ "IL-5" ], "offsets": [ [ 74, 78 ] ], "normalized": [] }, { "id": "PMID-9209438_T3", "type": "Protein", "text": [ "IL-5" ], "offsets": [ [ 96, 100 ] ], "normalized": [] }, { "id": "PMID-9209438_T4", "type": "Protein", "text": [ "Interleukin-5" ], "offsets": [ [ 164, 177 ] ], "normalized": [] }, { "id": "PMID-9209438_T5", "type": "Protein", "text": [ "IL-5" ], "offsets": [ [ 179, 183 ] ], "normalized": [] }, { "id": "PMID-9209438_T6", "type": "Protein", "text": [ "IL-5" ], "offsets": [ [ 341, 345 ] ], "normalized": [] }, { "id": "PMID-9209438_T7", "type": "Protein", "text": [ "IL-5" ], "offsets": [ [ 398, 402 ] ], "normalized": [] }, { "id": "PMID-9209438_T8", "type": "Protein", "text": [ "IL-5" ], "offsets": [ [ 433, 437 ] ], "normalized": [] }, { "id": "PMID-9209438_T9", "type": "Protein", "text": [ "human GATA-4" ], "offsets": [ [ 667, 679 ] ], "normalized": [] }, { "id": "PMID-9209438_T10", "type": "Protein", "text": [ "hGATA-4" ], "offsets": [ [ 681, 688 ] ], "normalized": [] }, { "id": "PMID-9209438_T11", "type": "Protein", "text": [ "hGATA-4" ], "offsets": [ [ 704, 711 ] ], "normalized": [] }, { "id": "PMID-9209438_T12", "type": "Protein", "text": [ "IL-5" ], "offsets": [ [ 768, 772 ] ], "normalized": [] }, { "id": "PMID-9209438_T13", "type": "Protein", "text": [ "hGATA-4" ], "offsets": [ [ 950, 957 ] ], "normalized": [] }, { "id": "PMID-9209438_T14", "type": "Protein", "text": [ "IL-5" ], "offsets": [ [ 1007, 1011 ] ], "normalized": [] }, { "id": "PMID-9209438_T15", "type": "Protein", "text": [ "hGATA-2" ], "offsets": [ [ 1218, 1225 ] ], "normalized": [] }, { "id": "PMID-9209438_T16", "type": "Protein", "text": [ "hGATA-3" ], "offsets": [ [ 1227, 1234 ] ], "normalized": [] }, { "id": "PMID-9209438_T17", "type": "Protein", "text": [ "hGATA-4" ], "offsets": [ [ 1239, 1246 ] ], "normalized": [] }, { "id": "PMID-9209438_T18", "type": "Protein", "text": [ "GATA-4" ], "offsets": [ [ 1390, 1396 ] ], "normalized": [] }, { "id": "PMID-9209438_T19", "type": "Protein", "text": [ "GATA-4" ], "offsets": [ [ 1607, 1613 ] ], "normalized": [] }, { "id": "PMID-9209438_T20", "type": "Protein", "text": [ "GATA-4" ], "offsets": [ [ 1770, 1776 ] ], "normalized": [] }, { "id": "PMID-9209438_T21", "type": "Protein", "text": [ "GATA-4" ], "offsets": [ [ 1854, 1860 ] ], "normalized": [] }, { "id": "PMID-9209438_T22", "type": "Protein", "text": [ "IL-5" ], "offsets": [ [ 1902, 1906 ] ], "normalized": [] }, { "id": "PMID-9209438_T24", "type": "Entity", "text": [ "promoter" ], "offsets": [ [ 84, 92 ] ], "normalized": [] }, { "id": "PMID-9209438_T28", "type": "Entity", "text": [ "region" ], "offsets": [ [ 373, 379 ] ], "normalized": [] }, { "id": "PMID-9209438_T32", "type": "Entity", "text": [ "-70 GATA site" ], "offsets": [ [ 743, 756 ] ], "normalized": [] }, { "id": "PMID-9209438_T34", "type": "Entity", "text": [ "promoter" ], "offsets": [ [ 1012, 1020 ] ], "normalized": [] } ]

[ { "id": "PMID-9209438_E1", "type": "Regulation", "trigger": { "text": [ "regulates" ], "offsets": [ [ 54, 63 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "PMID-9209438_T2" }, { "role": "Cause", "ref_id": "PMID-9209438_T1" }, { "role": "Site", "ref_id": "PMID-9209438_T24" } ] }, { "id": "PMID-9209438_E2", "type": "Gene_expression", "trigger": { "text": [ "producing" ], "offsets": [ [ 101, 110 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "PMID-9209438_T3" } ] }, { "id": "PMID-9209438_E3", "type": "Gene_expression", "trigger": { "text": [ "produced" ], "offsets": [ [ 188, 196 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "PMID-9209438_T5" } ] }, { "id": "PMID-9209438_E4", "type": "Transcription", "trigger": { "text": [ "express" ], "offsets": [ [ 333, 340 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "PMID-9209438_T6" } ] }, { "id": "PMID-9209438_E5", "type": "Regulation", "trigger": { "text": [ "regulates" ], "offsets": [ [ 423, 432 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "PMID-9209438_E6" }, { "role": "Cause", "ref_id": "PMID-9209438_T7" }, { "role": "CSite", "ref_id": "PMID-9209438_T28" } ] }, { "id": "PMID-9209438_E6", "type": "Transcription", "trigger": { "text": [ "transcription" ], "offsets": [ [ 443, 456 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "PMID-9209438_T8" } ] }, { "id": "PMID-9209438_E7", "type": "Binding", "trigger": { "text": [ "interacts" ], "offsets": [ [ 724, 733 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "PMID-9209438_T11" }, { "role": "Theme", "ref_id": "PMID-9209438_T12" }, { "role": "Site", "ref_id": "PMID-9209438_T32" } ] }, { "id": "PMID-9209438_E8", "type": "Positive_regulation", "trigger": { "text": [ "necessary" ], "offsets": [ [ 989, 998 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "PMID-9209438_E9" }, { "role": "Cause", "ref_id": "PMID-9209438_T13" } ] }, { "id": "PMID-9209438_E9", "type": "Positive_regulation", "trigger": { "text": [ "activation" ], "offsets": [ [ 1021, 1031 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "PMID-9209438_T14" }, { "role": "Site", "ref_id": "PMID-9209438_T34" } ] }, { "id": "PMID-9209438_E10", "type": "Positive_regulation", "trigger": { "text": [ "requirement" ], "offsets": [ [ 1037, 1048 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "PMID-9209438_E9" } ] }, { "id": "PMID-9209438_E11", "type": "Gene_expression", "trigger": { "text": [ "express" ], "offsets": [ [ 1173, 1180 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "PMID-9209438_T17" } ] }, { "id": "PMID-9209438_E12", "type": "Gene_expression", "trigger": { "text": [ "express" ], "offsets": [ [ 1173, 1180 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "PMID-9209438_T15" } ] }, { "id": "PMID-9209438_E13", "type": "Gene_expression", "trigger": { "text": [ "express" ], "offsets": [ [ 1173, 1180 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "PMID-9209438_T16" } ] }, { "id": "PMID-9209438_E14", "type": "Binding", "trigger": { "text": [ "bind" ], "offsets": [ [ 1284, 1288 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "PMID-9209438_T15" } ] }, { "id": "PMID-9209438_E15", "type": "Binding", "trigger": { "text": [ "bind" ], "offsets": [ [ 1284, 1288 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "PMID-9209438_T17" } ] }, { "id": "PMID-9209438_E16", "type": "Binding", "trigger": { "text": [ "bind" ], "offsets": [ [ 1284, 1288 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "PMID-9209438_T16" } ] }, { "id": "PMID-9209438_E17", "type": "Binding", "trigger": { "text": [ "forms specific DNA-protein complex" ], "offsets": [ [ 1435, 1469 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "PMID-9209438_T18" } ] }, { "id": "PMID-9209438_E18", "type": "Binding", "trigger": { "text": [ "has the highest binding affinity" ], "offsets": [ [ 1614, 1646 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "PMID-9209438_T19" } ] }, { "id": "PMID-9209438_E19", "type": "Regulation", "trigger": { "text": [ "role" ], "offsets": [ [ 1846, 1850 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "PMID-9209438_E20" }, { "role": "Cause", "ref_id": "PMID-9209438_T21" } ] }, { "id": "PMID-9209438_E20", "type": "Regulation", "trigger": { "text": [ "transcriptional regulation" ], "offsets": [ [ 1868, 1894 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "PMID-9209438_T22" } ] } ]

[ { "id": "PMID-9209438_1", "entity_ids": [ "PMID-9209438_T9", "PMID-9209438_T10" ] }, { "id": "PMID-9209438_2", "entity_ids": [ "PMID-9209438_T5", "PMID-9209438_T4" ] } ]

[]

[ { "id": "PMID-9211847__text", "type": "abstract", "text": [ "Inducible expression and phosphorylation of coactivator BOB.1/OBF.1 in T cells [see comments] \nBOB.1/OBF.1 is a transcriptional coactivator that is constitutively expressed in B cells and interacts with the Oct1 and Oct2 transcription factors. Upon activation of Jurkat T cells and primary murine thymocytes with phorbol esters and ionomycin, BOB.1/OBF.1 expression and transactivation function were induced. BOB.1/OBF.1 was phosphorylated at Ser184 both in vivo and in vitro, and this modification was required for inducible activation. Mutation of Ser184 also diminished transactivation function in B cells, suggesting that the activating phosphorylation that is inducible in T cells is constitutively present in B cells. Thus, BOB.1/OBF.1 is a transcriptional coactivator that is critically regulated by posttranslational modifications to mediate cell type-specific gene expression. " ], "offsets": [ [ 0, 886 ] ] } ]

[ { "id": "PMID-9211847_T1", "type": "Protein", "text": [ "BOB.1" ], "offsets": [ [ 56, 61 ] ], "normalized": [] }, { "id": "PMID-9211847_T2", "type": "Protein", "text": [ "OBF.1" ], "offsets": [ [ 62, 67 ] ], "normalized": [] }, { "id": "PMID-9211847_T3", "type": "Protein", "text": [ "BOB.1" ], "offsets": [ [ 95, 100 ] ], "normalized": [] }, { "id": "PMID-9211847_T4", "type": "Protein", "text": [ "OBF.1" ], "offsets": [ [ 101, 106 ] ], "normalized": [] }, { "id": "PMID-9211847_T5", "type": "Protein", "text": [ "Oct1" ], "offsets": [ [ 207, 211 ] ], "normalized": [] }, { "id": "PMID-9211847_T6", "type": "Protein", "text": [ "Oct2" ], "offsets": [ [ 216, 220 ] ], "normalized": [] }, { "id": "PMID-9211847_T7", "type": "Protein", "text": [ "BOB.1" ], "offsets": [ [ 343, 348 ] ], "normalized": [] }, { "id": "PMID-9211847_T8", "type": "Protein", "text": [ "OBF.1" ], "offsets": [ [ 349, 354 ] ], "normalized": [] }, { "id": "PMID-9211847_T9", "type": "Protein", "text": [ "BOB.1" ], "offsets": [ [ 409, 414 ] ], "normalized": [] }, { "id": "PMID-9211847_T10", "type": "Protein", "text": [ "OBF.1" ], "offsets": [ [ 415, 420 ] ], "normalized": [] }, { "id": "PMID-9211847_T11", "type": "Protein", "text": [ "BOB.1" ], "offsets": [ [ 730, 735 ] ], "normalized": [] }, { "id": "PMID-9211847_T12", "type": "Protein", "text": [ "OBF.1" ], "offsets": [ [ 736, 741 ] ], "normalized": [] }, { "id": "PMID-9211847_T21", "type": "Entity", "text": [ "Ser184" ], "offsets": [ [ 443, 449 ] ], "normalized": [] } ]

[ { "id": "PMID-9211847_E1", "type": "Positive_regulation", "trigger": { "text": [ "Inducible" ], "offsets": [ [ 0, 9 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "PMID-9211847_E3" } ] }, { "id": "PMID-9211847_E2", "type": "Positive_regulation", "trigger": { "text": [ "Inducible" ], "offsets": [ [ 0, 9 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "PMID-9211847_E4" } ] }, { "id": "PMID-9211847_E3", "type": "Gene_expression", "trigger": { "text": [ "expression" ], "offsets": [ [ 10, 20 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "PMID-9211847_T1" } ] }, { "id": "PMID-9211847_E4", "type": "Phosphorylation", "trigger": { "text": [ "phosphorylation" ], "offsets": [ [ 25, 40 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "PMID-9211847_T1" } ] }, { "id": "PMID-9211847_E5", "type": "Gene_expression", "trigger": { "text": [ "expressed" ], "offsets": [ [ 163, 172 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "PMID-9211847_T3" } ] }, { "id": "PMID-9211847_E6", "type": "Binding", "trigger": { "text": [ "interacts" ], "offsets": [ [ 188, 197 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "PMID-9211847_T3" }, { "role": "Theme", "ref_id": "PMID-9211847_T6" } ] }, { "id": "PMID-9211847_E7", "type": "Binding", "trigger": { "text": [ "interacts" ], "offsets": [ [ 188, 197 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "PMID-9211847_T3" }, { "role": "Theme", "ref_id": "PMID-9211847_T5" } ] }, { "id": "PMID-9211847_E8", "type": "Gene_expression", "trigger": { "text": [ "expression" ], "offsets": [ [ 355, 365 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "PMID-9211847_T7" } ] }, { "id": "PMID-9211847_E9", "type": "Positive_regulation", "trigger": { "text": [ "induced" ], "offsets": [ [ 400, 407 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "PMID-9211847_E8" } ] }, { "id": "PMID-9211847_E10", "type": "Phosphorylation", "trigger": { "text": [ "phosphorylated" ], "offsets": [ [ 425, 439 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "PMID-9211847_T9" }, { "role": "Site", "ref_id": "PMID-9211847_T21" } ] }, { "id": "PMID-9211847_E11", "type": "Positive_regulation", "trigger": { "text": [ "required" ], "offsets": [ [ 503, 511 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "PMID-9211847_T9" }, { "role": "Cause", "ref_id": "PMID-9211847_E10" } ] }, { "id": "PMID-9211847_E12", "type": "Positive_regulation", "trigger": { "text": [ "activating" ], "offsets": [ [ 630, 640 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "PMID-9211847_E10" } ] }, { "id": "PMID-9211847_E13", "type": "Positive_regulation", "trigger": { "text": [ "inducible" ], "offsets": [ [ 665, 674 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "PMID-9211847_E12" } ] }, { "id": "PMID-9211847_E14", "type": "Regulation", "trigger": { "text": [ "regulated" ], "offsets": [ [ 794, 803 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "PMID-9211847_T11" } ] } ]

[ { "id": "PMID-9211847_1", "entity_ids": [ "PMID-9211847_T1", "PMID-9211847_T2" ] }, { "id": "PMID-9211847_2", "entity_ids": [ "PMID-9211847_T11", "PMID-9211847_T12" ] }, { "id": "PMID-9211847_3", "entity_ids": [ "PMID-9211847_T9", "PMID-9211847_T10" ] }, { "id": "PMID-9211847_4", "entity_ids": [ "PMID-9211847_T3", "PMID-9211847_T4" ] }, { "id": "PMID-9211847_5", "entity_ids": [ "PMID-9211847_T7", "PMID-9211847_T8" ] } ]

[]

[ { "id": "PMID-9218534__text", "type": "abstract", "text": [ "Role of the X2 box in activated transcription from the DRA promoter in B cells. \nWe investigated the function of the evolutionary conserved X2 box in the promoter of the HLA-DRA gene from the human major histocompatibility complex (MHC) in resting and activated B cells. NF-X2, which contains members of the AP-1/ATF/CREB families of transcription factors, interacts with the X2 box (5'-TGCGTCA-3') from positions -97 to -91 in the DRA promoter. In resting Raji cells, little to no binding to the X2 box was observed. In sharp contrast, in B cells treated with the phorbol ester 12-O-tetradecanoylphorbol-13-acetate (TPA), strong interactions between the X2 box and NF-X2 containing c-Fos were observed. As determined by transient expression and RNA analyses, the activation of protein kinase C (PKC) also increased rates of transcription from the wild-type DRA promoter but not from a DRA promoter bearing clustered point mutations in the X2 box. Since the co-expression with a dominant negative c-Fos abolished the responsiveness to TPA, we conclude that activated transcription of the DRA gene depends on interactions between the X2 box and NF-X2, which contains c-Fos. " ], "offsets": [ [ 0, 1173 ] ] } ]

[ { "id": "PMID-9218534_T1", "type": "Protein", "text": [ "c-Fos" ], "offsets": [ [ 683, 688 ] ], "normalized": [] }, { "id": "PMID-9218534_T2", "type": "Protein", "text": [ "c-Fos" ], "offsets": [ [ 997, 1002 ] ], "normalized": [] }, { "id": "PMID-9218534_T3", "type": "Protein", "text": [ "c-Fos" ], "offsets": [ [ 1166, 1171 ] ], "normalized": [] } ]

[ { "id": "PMID-9218534_E1", "type": "Gene_expression", "trigger": { "text": [ "co-expression" ], "offsets": [ [ 958, 971 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "PMID-9218534_T2" } ] } ]

[]

[]

[ { "id": "PMID-9218843__text", "type": "abstract", "text": [ "Rescue by cytokines of apoptotic cell death induced by IL-2 deprivation of human antigen-specific T cell clones. \nThe control of cell survival and cell death is of central importance in tissues with high cell turnover such as the lymphoid system. We have examined the effect of cytokines on IL-2 deprivation-induced apoptosis of human antigen-specific T helper clones with different cytokine production profiles. We found that IL-2, interferon-alpha (IFN-alpha), and IFN-beta inhibited IL-2 deprivation apoptosis in Th0, Th1, and Th2 clones. We also found that IL-2 protects T cell clones from IL-2 deprivation apoptosis accompanying active proliferation and enhanced expression of P53, Rb and Bcl-xL proteins. In contrast, IFN-alpha/beta rescued T cell clones from apoptosis without active proliferation, and expression of apoptosis-associated proteins tested so far was unaffected. This may be due to the fact that T cells treated with IL-2 contained those located in S + G2/M phases of the cell cycle, whereas the vast majority of T cells treated with IFN-alpha/beta were located in G0/G1 phase. IFN-alpha/beta specifically induced tyrosine phosphorylation and translocation into nucleus of signal transducers and activators of transcription (STAT) 2 protein in the T cell clones. In addition, over-expression of STAT2 by transfection of the cDNA prevented apoptosis of the T cell clones. Our present study shows that IFN-alpha and -beta mediate anti-apoptotic effect through other pathways than that of IL-2 in growth factor deprivation apoptosis. " ], "offsets": [ [ 0, 1552 ] ] } ]

[ { "id": "PMID-9218843_T1", "type": "Protein", "text": [ "IL-2" ], "offsets": [ [ 55, 59 ] ], "normalized": [] }, { "id": "PMID-9218843_T2", "type": "Protein", "text": [ "IL-2" ], "offsets": [ [ 291, 295 ] ], "normalized": [] }, { "id": "PMID-9218843_T3", "type": "Protein", "text": [ "IL-2" ], "offsets": [ [ 427, 431 ] ], "normalized": [] }, { "id": "PMID-9218843_T4", "type": "Protein", "text": [ "IFN-beta" ], "offsets": [ [ 467, 475 ] ], "normalized": [] }, { "id": "PMID-9218843_T5", "type": "Protein", "text": [ "IL-2" ], "offsets": [ [ 486, 490 ] ], "normalized": [] }, { "id": "PMID-9218843_T6", "type": "Protein", "text": [ "IL-2" ], "offsets": [ [ 561, 565 ] ], "normalized": [] }, { "id": "PMID-9218843_T7", "type": "Protein", "text": [ "IL-2" ], "offsets": [ [ 594, 598 ] ], "normalized": [] }, { "id": "PMID-9218843_T8", "type": "Protein", "text": [ "P53" ], "offsets": [ [ 682, 685 ] ], "normalized": [] }, { "id": "PMID-9218843_T9", "type": "Protein", "text": [ "Rb" ], "offsets": [ [ 687, 689 ] ], "normalized": [] }, { "id": "PMID-9218843_T10", "type": "Protein", "text": [ "Bcl-xL" ], "offsets": [ [ 694, 700 ] ], "normalized": [] }, { "id": "PMID-9218843_T11", "type": "Protein", "text": [ "IL-2" ], "offsets": [ [ 938, 942 ] ], "normalized": [] }, { "id": "PMID-9218843_T12", "type": "Protein", "text": [ "signal transducers and activators of transcription (STAT) 2" ], "offsets": [ [ 1194, 1253 ] ], "normalized": [] }, { "id": "PMID-9218843_T13", "type": "Protein", "text": [ "STAT2" ], "offsets": [ [ 1316, 1321 ] ], "normalized": [] }, { "id": "PMID-9218843_T14", "type": "Protein", "text": [ "IL-2" ], "offsets": [ [ 1507, 1511 ] ], "normalized": [] }, { "id": "PMID-9218843_T22", "type": "Entity", "text": [ "tyrosine" ], "offsets": [ [ 1135, 1143 ] ], "normalized": [] }, { "id": "PMID-9218843_T25", "type": "Entity", "text": [ "nucleus" ], "offsets": [ [ 1183, 1190 ] ], "normalized": [] } ]

[ { "id": "PMID-9218843_E1", "type": "Negative_regulation", "trigger": { "text": [ "deprivation" ], "offsets": [ [ 60, 71 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "PMID-9218843_T1" } ] }, { "id": "PMID-9218843_E2", "type": "Negative_regulation", "trigger": { "text": [ "deprivation" ], "offsets": [ [ 296, 307 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "PMID-9218843_T2" } ] }, { "id": "PMID-9218843_E3", "type": "Negative_regulation", "trigger": { "text": [ "deprivation" ], "offsets": [ [ 491, 502 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "PMID-9218843_T5" } ] }, { "id": "PMID-9218843_E4", "type": "Negative_regulation", "trigger": { "text": [ "deprivation" ], "offsets": [ [ 599, 610 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "PMID-9218843_T7" } ] }, { "id": "PMID-9218843_E5", "type": "Positive_regulation", "trigger": { "text": [ "enhanced" ], "offsets": [ [ 659, 667 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "PMID-9218843_E10" }, { "role": "Cause", "ref_id": "PMID-9218843_T6" } ] }, { "id": "PMID-9218843_E6", "type": "Positive_regulation", "trigger": { "text": [ "enhanced" ], "offsets": [ [ 659, 667 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "PMID-9218843_E9" }, { "role": "Cause", "ref_id": "PMID-9218843_T6" } ] }, { "id": "PMID-9218843_E7", "type": "Positive_regulation", "trigger": { "text": [ "enhanced" ], "offsets": [ [ 659, 667 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "PMID-9218843_E8" }, { "role": "Cause", "ref_id": "PMID-9218843_T6" } ] }, { "id": "PMID-9218843_E8", "type": "Gene_expression", "trigger": { "text": [ "expression" ], "offsets": [ [ 668, 678 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "PMID-9218843_T8" } ] }, { "id": "PMID-9218843_E9", "type": "Gene_expression", "trigger": { "text": [ "expression" ], "offsets": [ [ 668, 678 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "PMID-9218843_T10" } ] }, { "id": "PMID-9218843_E10", "type": "Gene_expression", "trigger": { "text": [ "expression" ], "offsets": [ [ 668, 678 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "PMID-9218843_T9" } ] }, { "id": "PMID-9218843_E11", "type": "Positive_regulation", "trigger": { "text": [ "induced" ], "offsets": [ [ 1127, 1134 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "PMID-9218843_E13" } ] }, { "id": "PMID-9218843_E12", "type": "Positive_regulation", "trigger": { "text": [ "induced" ], "offsets": [ [ 1127, 1134 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "PMID-9218843_E14" } ] }, { "id": "PMID-9218843_E13", "type": "Phosphorylation", "trigger": { "text": [ "phosphorylation" ], "offsets": [ [ 1144, 1159 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "PMID-9218843_T12" }, { "role": "Site", "ref_id": "PMID-9218843_T22" } ] }, { "id": "PMID-9218843_E14", "type": "Localization", "trigger": { "text": [ "translocation" ], "offsets": [ [ 1164, 1177 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "PMID-9218843_T12" }, { "role": "ToLoc", "ref_id": "PMID-9218843_T25" } ] }, { "id": "PMID-9218843_E15", "type": "Gene_expression", "trigger": { "text": [ "over-expression" ], "offsets": [ [ 1297, 1312 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "PMID-9218843_T13" } ] }, { "id": "PMID-9218843_E16", "type": "Positive_regulation", "trigger": { "text": [ "over-expression" ], "offsets": [ [ 1297, 1312 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "PMID-9218843_E15" } ] } ]

[]

[]

[ { "id": "PMID-9219058__text", "type": "abstract", "text": [ "Association between expression of intercellular adhesion molecule-1 and integration of human T-cell-leukemia virus type 1 in adult T-cell leukemia cells. \nIt is known that the expression levels of intercellular adhesion molecule-1 (ICAM-1) in adult T cell leukemia(ATL) cells are high, whereas those in T-lymphoid cells are not. In order to investigate the factors that influence the induction of ICAM-1 molecules, Northern blot analysis to measure the expression level of ICAM-1 mRNAs and Southern blot hybridization to analyze the integration of human T-cell-leukemia virus type 1 (HTLV-1) provirus were done. The levels of ICAM-1 mRNA expression of ATL cells were generally higher than those of T-lymphoid cells. However, ILT-mat cells and ATL16T(-) cells, although they were ATL cells, showed rather low surface ICAM-1 expression and ICAM-1 mRNA expression. Southern blot hybridization showed that only two and four bands were found in ILT-mat and ATL16T(-) cells, respectively, whereas > 10 bands were detected in other ATL cells. These results suggest that monoclonal integration of HTLV-1 provirus to the genome of T cell, especially the number of integration sites, is one of the factors for induction of ICAM-1 molecules. " ], "offsets": [ [ 0, 1231 ] ] } ]

[ { "id": "PMID-9219058_T1", "type": "Protein", "text": [ "intercellular adhesion molecule-1" ], "offsets": [ [ 34, 67 ] ], "normalized": [] }, { "id": "PMID-9219058_T2", "type": "Protein", "text": [ "intercellular adhesion molecule-1" ], "offsets": [ [ 197, 230 ] ], "normalized": [] }, { "id": "PMID-9219058_T3", "type": "Protein", "text": [ "ICAM-1" ], "offsets": [ [ 232, 238 ] ], "normalized": [] }, { "id": "PMID-9219058_T4", "type": "Protein", "text": [ "ICAM-1" ], "offsets": [ [ 397, 403 ] ], "normalized": [] }, { "id": "PMID-9219058_T5", "type": "Protein", "text": [ "ICAM-1" ], "offsets": [ [ 473, 479 ] ], "normalized": [] }, { "id": "PMID-9219058_T6", "type": "Protein", "text": [ "ICAM-1" ], "offsets": [ [ 626, 632 ] ], "normalized": [] }, { "id": "PMID-9219058_T7", "type": "Protein", "text": [ "ICAM-1" ], "offsets": [ [ 816, 822 ] ], "normalized": [] }, { "id": "PMID-9219058_T8", "type": "Protein", "text": [ "ICAM-1" ], "offsets": [ [ 838, 844 ] ], "normalized": [] }, { "id": "PMID-9219058_T9", "type": "Protein", "text": [ "ICAM-1" ], "offsets": [ [ 1213, 1219 ] ], "normalized": [] } ]

[ { "id": "PMID-9219058_E1", "type": "Gene_expression", "trigger": { "text": [ "expression" ], "offsets": [ [ 20, 30 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "PMID-9219058_T1" } ] }, { "id": "PMID-9219058_E2", "type": "Gene_expression", "trigger": { "text": [ "expression" ], "offsets": [ [ 176, 186 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "PMID-9219058_T3" } ] }, { "id": "PMID-9219058_E3", "type": "Regulation", "trigger": { "text": [ "influence" ], "offsets": [ [ 370, 379 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "PMID-9219058_E4" } ] }, { "id": "PMID-9219058_E4", "type": "Positive_regulation", "trigger": { "text": [ "induction" ], "offsets": [ [ 384, 393 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "PMID-9219058_T4" } ] }, { "id": "PMID-9219058_E5", "type": "Transcription", "trigger": { "text": [ "expression" ], "offsets": [ [ 453, 463 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "PMID-9219058_T5" } ] }, { "id": "PMID-9219058_E6", "type": "Transcription", "trigger": { "text": [ "expression" ], "offsets": [ [ 638, 648 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "PMID-9219058_T6" } ] }, { "id": "PMID-9219058_E7", "type": "Gene_expression", "trigger": { "text": [ "expression" ], "offsets": [ [ 823, 833 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "PMID-9219058_T7" } ] }, { "id": "PMID-9219058_E8", "type": "Transcription", "trigger": { "text": [ "expression" ], "offsets": [ [ 850, 860 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "PMID-9219058_T8" } ] }, { "id": "PMID-9219058_E9", "type": "Positive_regulation", "trigger": { "text": [ "induction" ], "offsets": [ [ 1200, 1209 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "PMID-9219058_T9" } ] } ]

[ { "id": "PMID-9219058_1", "entity_ids": [ "PMID-9219058_T3", "PMID-9219058_T2" ] } ]

[]

[ { "id": "PMID-9223506__text", "type": "abstract", "text": [ "Transcription factor binding sites downstream of the human immunodeficiency virus type 1 transcription start site are important for virus infectivity. \nWhen transcriptionally active, the human immunodeficiency virus (HIV) promoter contains a nucleosome-free region encompassing both the promoter/enhancer region and a large region (255 nucleotides [nt]) downstream of the transcription start site. We have previously identified new binding sites for transcription factors downstream of the transcription start site (nt 465 to 720): three AP-1 sites (I, II, and III), an AP3-like motif (AP3-L), a downstream binding factor (DBF) site, and juxtaposed Sp1 sites. Here, we show that the DBF site is an interferon-responsive factor (IRF) binding site and that the AP3-L motif binds the T-cell-specific factor NF-AT. Mutations that abolish the binding of each factor to its cognate site are introduced in an infectious HIV-1 molecular clone to study their effect on HIV-1 transcription and replication. Individual mutation of the DBF or AP3-L site as well as the double mutation AP-1(III)/AP3-L did not affect HIV-1 replication compared to that of the wild-type virus. In contrast, proviruses carrying mutations in the Sp1 sites were totally defective in terms of replication. Virus production occurred with slightly delayed kinetics for viruses containing combined mutations in the AP-1(III), AP3-L, and DBF sites and in the AP3-L and DBF-sites, whereas viruses mutated in the AP-1(I,II,III) and AP3-L sites and in the AP-1(I,II,III), AP3-L, and DBF sites exhibited a severely defective replicative phenotype. No RNA-packaging defect could be measured for any of the mutant viruses as determined by quantification of their HIV genomic RNA. Measurement of the transcriptional activity of the HIV-1 promoter after transient transfection of the HIV-1 provirus DNA or of long terminal repeat-luciferase constructs showed a positive correlation between the transcriptional and the replication defects for most mutants. " ], "offsets": [ [ 0, 2009 ] ] } ]

[ { "id": "PMID-9223506_T1", "type": "Protein", "text": [ "Sp1" ], "offsets": [ [ 649, 652 ] ], "normalized": [] }, { "id": "PMID-9223506_T2", "type": "Protein", "text": [ "Sp1" ], "offsets": [ [ 1213, 1216 ] ], "normalized": [] } ]

[]

[]

[]

[ { "id": "PMID-9224203__text", "type": "abstract", "text": [ "The role of nuclear factor-kappa B in cytokine gene regulation. \nTranscription factors are DNA-binding proteins that regulate gene expression. Nuclear factor-kappa B (NF-kappa B) is a critical transcription factor for maximal expression of many cytokines that are involved in the pathogenesis of inflammatory diseases, such as adult respiratory distress syndrome (ARDS) and sepsis syndrome. Activation and regulation of NF-kappa B are tightly controlled by a group of inhibitory proteins (I kappa B) that sequester NF-kappa B in the cytoplasm of immune/inflammatory effector cells. NF-kappa B activation involves signaled phosphorylation, ubiquitination, and proteolysis of I kappa B. Liberated NF-kappa B migrates to the nucleus, where it binds to specific promoter sites and activates gene transcription. The activation of NF-kappa B initiates both extracellular and intracellular regulatory events that result in autoregulation of the inflammatory cascade through modulation of NF-kappa B activation. Recently, activation of NF-kappa B has been linked to ARDS and has been shown to be a critical proximal step in the initiation of neutrophilic inflammation in animal models. Activation of NF-kappa B can be inhibited in vivo by treatment with antioxidants, corticosteroids, and the induction of endotoxin tolerance. Identification of more specific and efficacious inhibitors of NF-kappa B activation might prove beneficial for the treatment of cytokine-mediated inflammatory diseases. " ], "offsets": [ [ 0, 1488 ] ] } ]

[]

[]

[]

[]

[ { "id": "PMID-9224625__text", "type": "abstract", "text": [ "Role of ascorbate in the activation of NF-kappaB by tumour necrosis factor-alpha in T-cells. \nThe first product of ascorbate oxidation, the ascorbate free radical (AFR), acts in biological systems mainly as an oxidant, and through its role in the plasma membrane redox system exerts different effects on the cell. We have investigated the role of ascorbate, AFR and dehydroascorbate (DHA) in the activation of the NF-kappaB transcription factor in Jurkat T-cells stimulated by tumour necrosis factor-alpha (TNF-alpha). Here we show, by electrophoretic mobility shift assays, that ascorbate increases the binding of NF-kappaB to DNA in TNF-alpha-stimulated Jurkat cells. The ability of ascorbate to enhance cytoplasmic inhibitory IkBalpha protein degradation correlates completely with its capacity to induce NF-kappaB binding to DNA and to potentiate NF-kappaB-mediated transactivation of the HIV-1 long terminal repeat promoter in TNF-alpha-stimulated Jurkat cells but not in cells stimulated with PMA plus ionomycin. AFR behaves like ascorbate, while DHA and ascorbate phosphate do not affect TNF-alpha-mediated NF-kappaB activation. These results provide new evidence for a possible relationship between the activation of the electron-transport system at the plasma membrane by ascorbate or its free radical and redox-dependent gene transcription in T-cells. " ], "offsets": [ [ 0, 1362 ] ] } ]

[ { "id": "PMID-9224625_T1", "type": "Protein", "text": [ "tumour necrosis factor-alpha" ], "offsets": [ [ 52, 80 ] ], "normalized": [] }, { "id": "PMID-9224625_T2", "type": "Protein", "text": [ "tumour necrosis factor-alpha" ], "offsets": [ [ 477, 505 ] ], "normalized": [] }, { "id": "PMID-9224625_T3", "type": "Protein", "text": [ "TNF-alpha" ], "offsets": [ [ 507, 516 ] ], "normalized": [] }, { "id": "PMID-9224625_T4", "type": "Protein", "text": [ "TNF-alpha" ], "offsets": [ [ 635, 644 ] ], "normalized": [] }, { "id": "PMID-9224625_T5", "type": "Protein", "text": [ "IkBalpha" ], "offsets": [ [ 729, 737 ] ], "normalized": [] }, { "id": "PMID-9224625_T6", "type": "Protein", "text": [ "TNF-alpha" ], "offsets": [ [ 932, 941 ] ], "normalized": [] }, { "id": "PMID-9224625_T7", "type": "Protein", "text": [ "TNF-alpha" ], "offsets": [ [ 1095, 1104 ] ], "normalized": [] } ]

[ { "id": "PMID-9224625_E1", "type": "Positive_regulation", "trigger": { "text": [ "enhance" ], "offsets": [ [ 698, 705 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "PMID-9224625_E2" } ] }, { "id": "PMID-9224625_E2", "type": "Protein_catabolism", "trigger": { "text": [ "degradation" ], "offsets": [ [ 746, 757 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "PMID-9224625_T5" } ] } ]

[ { "id": "PMID-9224625_1", "entity_ids": [ "PMID-9224625_T2", "PMID-9224625_T3" ] } ]

[]

[ { "id": "PMID-9231664__text", "type": "abstract", "text": [ "Pancreatic islet expression studies and polymorphic DNA markers in the genes encoding hepatocyte nuclear factor-3alpha, -3beta, -3gamma, -4gamma, and -6. \nThe genes encoding the functionally related hepatocyte nuclear factors HNF-1alpha and HNF-4alpha play a critical role in normal pancreatic beta-cell function. Mutations in these liver-enriched transcription factors result in two forms of early-onset type 2 diabetes (maturity-onset diabetes of the young [MODY]), MODY3 and MODY1, which are characterized by impaired glucose-stimulated insulin secretion, early disease onset, and autosomal dominant inheritance. The transcriptional hierarchy of HNFs suggests that other proteins of the regulatory cascade might be responsible for other forms of MODY and/or late-onset type 2 diabetes. In this study, we show that HNF-3alpha, -3beta, -3gamma, -4gamma, and -6 are expressed in pancreatic beta-cells. We report the identification and characterization of simple tandem repeat DNA polymorphisms in the genes encoding HNF-3alpha, -3beta, -3gamma, -4gamma, and -6 and the mapping of HNF-6 to chromosome bands 15q21.1-21.2 by fluorescence in situ hybridization. These markers will be useful to study the role of genetic variation in these genes in the pathogenesis of type 2 diabetes. " ], "offsets": [ [ 0, 1281 ] ] } ]

[ { "id": "PMID-9231664_T1", "type": "Protein", "text": [ "hepatocyte nuclear factor-3alpha" ], "offsets": [ [ 86, 118 ] ], "normalized": [] }, { "id": "PMID-9231664_T2", "type": "Protein", "text": [ "-3beta" ], "offsets": [ [ 120, 126 ] ], "normalized": [] }, { "id": "PMID-9231664_T3", "type": "Protein", "text": [ "-3gamma" ], "offsets": [ [ 128, 135 ] ], "normalized": [] }, { "id": "PMID-9231664_T4", "type": "Protein", "text": [ "-4gamma" ], "offsets": [ [ 137, 144 ] ], "normalized": [] }, { "id": "PMID-9231664_T5", "type": "Protein", "text": [ "-6" ], "offsets": [ [ 150, 152 ] ], "normalized": [] }, { "id": "PMID-9231664_T6", "type": "Protein", "text": [ "HNF-1alpha" ], "offsets": [ [ 226, 236 ] ], "normalized": [] }, { "id": "PMID-9231664_T7", "type": "Protein", "text": [ "HNF-4alpha" ], "offsets": [ [ 241, 251 ] ], "normalized": [] }, { "id": "PMID-9231664_T8", "type": "Protein", "text": [ "HNF-3alpha" ], "offsets": [ [ 817, 827 ] ], "normalized": [] }, { "id": "PMID-9231664_T9", "type": "Protein", "text": [ "-3beta" ], "offsets": [ [ 829, 835 ] ], "normalized": [] }, { "id": "PMID-9231664_T10", "type": "Protein", "text": [ "-3gamma" ], "offsets": [ [ 837, 844 ] ], "normalized": [] }, { "id": "PMID-9231664_T11", "type": "Protein", "text": [ "-4gamma" ], "offsets": [ [ 846, 853 ] ], "normalized": [] }, { "id": "PMID-9231664_T12", "type": "Protein", "text": [ "-6" ], "offsets": [ [ 859, 861 ] ], "normalized": [] }, { "id": "PMID-9231664_T13", "type": "Protein", "text": [ "HNF-3alpha" ], "offsets": [ [ 1016, 1026 ] ], "normalized": [] }, { "id": "PMID-9231664_T14", "type": "Protein", "text": [ "-3beta" ], "offsets": [ [ 1028, 1034 ] ], "normalized": [] }, { "id": "PMID-9231664_T15", "type": "Protein", "text": [ "-3gamma" ], "offsets": [ [ 1036, 1043 ] ], "normalized": [] }, { "id": "PMID-9231664_T16", "type": "Protein", "text": [ "-4gamma" ], "offsets": [ [ 1045, 1052 ] ], "normalized": [] }, { "id": "PMID-9231664_T17", "type": "Protein", "text": [ "-6" ], "offsets": [ [ 1058, 1060 ] ], "normalized": [] }, { "id": "PMID-9231664_T18", "type": "Protein", "text": [ "HNF-6" ], "offsets": [ [ 1080, 1085 ] ], "normalized": [] } ]

[ { "id": "PMID-9231664_E1", "type": "Gene_expression", "trigger": { "text": [ "expression studies" ], "offsets": [ [ 17, 35 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "PMID-9231664_T2" } ] }, { "id": "PMID-9231664_E2", "type": "Gene_expression", "trigger": { "text": [ "expression studies" ], "offsets": [ [ 17, 35 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "PMID-9231664_T3" } ] }, { "id": "PMID-9231664_E3", "type": "Gene_expression", "trigger": { "text": [ "expression studies" ], "offsets": [ [ 17, 35 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "PMID-9231664_T4" } ] }, { "id": "PMID-9231664_E4", "type": "Gene_expression", "trigger": { "text": [ "expression studies" ], "offsets": [ [ 17, 35 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "PMID-9231664_T1" } ] }, { "id": "PMID-9231664_E5", "type": "Gene_expression", "trigger": { "text": [ "expression studies" ], "offsets": [ [ 17, 35 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "PMID-9231664_T5" } ] }, { "id": "PMID-9231664_E6", "type": "Gene_expression", "trigger": { "text": [ "expressed" ], "offsets": [ [ 866, 875 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "PMID-9231664_T12" } ] }, { "id": "PMID-9231664_E7", "type": "Gene_expression", "trigger": { "text": [ "expressed" ], "offsets": [ [ 866, 875 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "PMID-9231664_T9" } ] }, { "id": "PMID-9231664_E8", "type": "Gene_expression", "trigger": { "text": [ "expressed" ], "offsets": [ [ 866, 875 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "PMID-9231664_T8" } ] }, { "id": "PMID-9231664_E9", "type": "Gene_expression", "trigger": { "text": [ "expressed" ], "offsets": [ [ 866, 875 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "PMID-9231664_T10" } ] }, { "id": "PMID-9231664_E10", "type": "Gene_expression", "trigger": { "text": [ "expressed" ], "offsets": [ [ 866, 875 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "PMID-9231664_T11" } ] } ]

[]

[]

[ { "id": "PMID-9233623__text", "type": "abstract", "text": [ "RP1, a new member of the adenomatous polyposis coli-binding EB1-like gene family, is differentially expressed in activated T cells. \nCross-linking of the CD3 and CD28 molecules on T lymphocytes represents one of the most effective signals for T lymphocyte activation and triggering of their cytotoxic effector function. To identify genes that are expressed in T cells after stimulation, mRNA from T lymphocytes that had been activated by the simultaneous stimulation of the CD3 and CD28 trigger molecules was transcribed for a differential mRNA display analysis into cDNA and was compared with cDNA from CD28- or CD3-activated or resting lymphocytes. Differential expression was confirmed subsequently by Northern blot analysis. One of the cDNA fragments expressed specifically in CD3- and CD28-activated T cells was designated RP1. The predictive protein-coding region of RP1 had a significant homology to members of the recently found adenomatous polyposis coli (APC) protein-binding EB1 gene family, which codes for yet unknown protein(s). Bacterially expressed RP1 protein revealed specific binding to wild-type but not to mutated APC protein. The rapid up-regulation of RP1 mRNA in properly activated T cells suggests that this gene might belong to the immediate/early gene family, which controls the signal transduction cascade downstream of the TCR. As the expression level of the RP1 gene in activated T cells and a spectrum of tumor-derived cell lines correlates with the proliferative status of the cells, members of the EB1-like gene family may not only be involved in the tumorigenesis of colorectal cancers but may also play a role in the proliferative control of normal cells. " ], "offsets": [ [ 0, 1691 ] ] } ]

[ { "id": "PMID-9233623_T1", "type": "Protein", "text": [ "RP1" ], "offsets": [ [ 0, 3 ] ], "normalized": [] }, { "id": "PMID-9233623_T2", "type": "Protein", "text": [ "CD28" ], "offsets": [ [ 162, 166 ] ], "normalized": [] }, { "id": "PMID-9233623_T3", "type": "Protein", "text": [ "CD28" ], "offsets": [ [ 482, 486 ] ], "normalized": [] }, { "id": "PMID-9233623_T4", "type": "Protein", "text": [ "CD28" ], "offsets": [ [ 604, 608 ] ], "normalized": [] }, { "id": "PMID-9233623_T5", "type": "Protein", "text": [ "CD28" ], "offsets": [ [ 790, 794 ] ], "normalized": [] }, { "id": "PMID-9233623_T6", "type": "Protein", "text": [ "RP1" ], "offsets": [ [ 873, 876 ] ], "normalized": [] }, { "id": "PMID-9233623_T7", "type": "Protein", "text": [ "adenomatous polyposis coli (APC) protein" ], "offsets": [ [ 937, 977 ] ], "normalized": [] }, { "id": "PMID-9233623_T8", "type": "Protein", "text": [ "EB1" ], "offsets": [ [ 986, 989 ] ], "normalized": [] }, { "id": "PMID-9233623_T9", "type": "Protein", "text": [ "RP1" ], "offsets": [ [ 1065, 1068 ] ], "normalized": [] }, { "id": "PMID-9233623_T10", "type": "Protein", "text": [ "APC" ], "offsets": [ [ 1135, 1138 ] ], "normalized": [] }, { "id": "PMID-9233623_T11", "type": "Protein", "text": [ "RP1" ], "offsets": [ [ 1175, 1178 ] ], "normalized": [] }, { "id": "PMID-9233623_T12", "type": "Protein", "text": [ "RP1" ], "offsets": [ [ 1388, 1391 ] ], "normalized": [] } ]

[ { "id": "PMID-9233623_E1", "type": "Gene_expression", "trigger": { "text": [ "expressed" ], "offsets": [ [ 100, 109 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "PMID-9233623_T1" } ] }, { "id": "PMID-9233623_E2", "type": "Binding", "trigger": { "text": [ "Cross-linking" ], "offsets": [ [ 133, 146 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "PMID-9233623_T2" } ] }, { "id": "PMID-9233623_E3", "type": "Gene_expression", "trigger": { "text": [ "expressed" ], "offsets": [ [ 1055, 1064 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "PMID-9233623_T9" } ] }, { "id": "PMID-9233623_E4", "type": "Binding", "trigger": { "text": [ "binding" ], "offsets": [ [ 1095, 1102 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "PMID-9233623_T9" } ] }, { "id": "PMID-9233623_E5", "type": "Binding", "trigger": { "text": [ "binding" ], "offsets": [ [ 1095, 1102 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "PMID-9233623_T9" }, { "role": "Theme", "ref_id": "PMID-9233623_T10" } ] }, { "id": "PMID-9233623_E6", "type": "Positive_regulation", "trigger": { "text": [ "up-regulation" ], "offsets": [ [ 1158, 1171 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "PMID-9233623_T11" } ] }, { "id": "PMID-9233623_E7", "type": "Gene_expression", "trigger": { "text": [ "expression" ], "offsets": [ [ 1364, 1374 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "PMID-9233623_T12" } ] } ]

[]

[]

[ { "id": "PMID-9237716__text", "type": "abstract", "text": [ "Induction of human immunodeficiency virus type 1 expression in monocytic cells by Cryptococcus neoformans and Candida albicans. \nBecause candidiasis and cryptococcosis are common in human immunodeficiency virus (HIV)-infected persons, the effect of Cryptococcus neoformans and Candida albicans on HIV expression in monocytic cells was examined. Stimulation of the latently HIV-infected myelomonocytic cell line OM-10.1 with C. neoformans and C. albicans in the presence of pooled human serum caused a ratio-dependent increase in HIV production. Induction of HIV by C. neoformans was enhanced by anti-capsular antibody, while induction by both organisms was inhibited by anti-TNF-alpha antibody. In THP-1 cells transfected with HIV plasmid constructs, both organisms induced transcription from the HIV long terminal repeat that was dependent on intact NF-kappaB binding sequences. Thus, C. neoformans and C. albicans enhance HIV expression in monocytic cells through a TNF-alpha- and NF-kappaB-dependent mechanism. In HIV-infected patients, such enhancement may further impair host immunity and could accelerate the course of HIV disease. " ], "offsets": [ [ 0, 1138 ] ] } ]

[ { "id": "PMID-9237716_T1", "type": "Protein", "text": [ "TNF-alpha" ], "offsets": [ [ 675, 684 ] ], "normalized": [] }, { "id": "PMID-9237716_T2", "type": "Protein", "text": [ "TNF-alpha" ], "offsets": [ [ 968, 977 ] ], "normalized": [] } ]

[]

[]

[]

[ { "id": "PMID-9242431__text", "type": "abstract", "text": [ "Bcl-2 protein inhibits bufalin-induced apoptosis through inhibition of mitogen-activated protein kinase activation in human leukemia U937 cells. \nIn a previous study, we demonstrated that bufalin, which is an active principle of Chinese medicine, chan'su, caused apoptosis in human leukemia U937 cells by anomalous activation of mitogen-activated protein kinase (MAPK) via the signaling pathway of Ras, Raf-1, and MAPK kinase-1. Here, we report the effect of overexpression of bcl-2 in U937 cells on the signaling pathway of apoptosis that is induced by bufalin. The results indicated that the apoptosis induced by bufalin in U937 cells was significantly inhibited by overexpression of the Bcl-2 protein. No significant difference was detected in the activation of MAPK kinase-1 that is induced by bufalin in wild-type or Bcl-2-overexpressed U937 cells; however, the activation of MAPK by bufalin was significantly attenuated in the cells overexpressing Bcl-2. Bufalin treatment activated activator protein-1 transcriptional activity; however, this activation was decreased to 40% in bcl-2-overexpressed U937 cells. These results indicate that Bcl-2 acts downstream of MAPK kinase-1 but upstream of MAPK and suggest that, in the signaling pathway of the apoptotic process induced by bufalin, the transcriptional activity of activator protein-1 may be down-regulated through the inhibition of MAPK activity by Bcl-2. " ], "offsets": [ [ 0, 1416 ] ] } ]

[ { "id": "PMID-9242431_T1", "type": "Protein", "text": [ "Bcl-2" ], "offsets": [ [ 0, 5 ] ], "normalized": [] }, { "id": "PMID-9242431_T2", "type": "Protein", "text": [ "Raf-1" ], "offsets": [ [ 403, 408 ] ], "normalized": [] }, { "id": "PMID-9242431_T3", "type": "Protein", "text": [ "MAPK kinase-1" ], "offsets": [ [ 414, 427 ] ], "normalized": [] }, { "id": "PMID-9242431_T4", "type": "Protein", "text": [ "bcl-2" ], "offsets": [ [ 477, 482 ] ], "normalized": [] }, { "id": "PMID-9242431_T5", "type": "Protein", "text": [ "Bcl-2" ], "offsets": [ [ 690, 695 ] ], "normalized": [] }, { "id": "PMID-9242431_T6", "type": "Protein", "text": [ "MAPK kinase-1" ], "offsets": [ [ 765, 778 ] ], "normalized": [] }, { "id": "PMID-9242431_T7", "type": "Protein", "text": [ "Bcl-2" ], "offsets": [ [ 822, 827 ] ], "normalized": [] }, { "id": "PMID-9242431_T8", "type": "Protein", "text": [ "Bcl-2" ], "offsets": [ [ 954, 959 ] ], "normalized": [] }, { "id": "PMID-9242431_T9", "type": "Protein", "text": [ "bcl-2" ], "offsets": [ [ 1084, 1089 ] ], "normalized": [] }, { "id": "PMID-9242431_T10", "type": "Protein", "text": [ "Bcl-2" ], "offsets": [ [ 1144, 1149 ] ], "normalized": [] }, { "id": "PMID-9242431_T11", "type": "Protein", "text": [ "MAPK kinase-1" ], "offsets": [ [ 1169, 1182 ] ], "normalized": [] }, { "id": "PMID-9242431_T12", "type": "Protein", "text": [ "Bcl-2" ], "offsets": [ [ 1409, 1414 ] ], "normalized": [] } ]

[ { "id": "PMID-9242431_E1", "type": "Gene_expression", "trigger": { "text": [ "overexpression" ], "offsets": [ [ 459, 473 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "PMID-9242431_T4" } ] }, { "id": "PMID-9242431_E2", "type": "Positive_regulation", "trigger": { "text": [ "overexpression" ], "offsets": [ [ 459, 473 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "PMID-9242431_E1" } ] }, { "id": "PMID-9242431_E3", "type": "Gene_expression", "trigger": { "text": [ "overexpression" ], "offsets": [ [ 668, 682 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "PMID-9242431_T5" } ] }, { "id": "PMID-9242431_E4", "type": "Positive_regulation", "trigger": { "text": [ "overexpression" ], "offsets": [ [ 668, 682 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "PMID-9242431_E3" } ] }, { "id": "PMID-9242431_E5", "type": "Positive_regulation", "trigger": { "text": [ "activation" ], "offsets": [ [ 751, 761 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "PMID-9242431_T6" } ] }, { "id": "PMID-9242431_E6", "type": "Positive_regulation", "trigger": { "text": [ "overexpressed" ], "offsets": [ [ 828, 841 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "PMID-9242431_E7" } ] }, { "id": "PMID-9242431_E7", "type": "Gene_expression", "trigger": { "text": [ "overexpressed" ], "offsets": [ [ 828, 841 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "PMID-9242431_T7" } ] }, { "id": "PMID-9242431_E8", "type": "Positive_regulation", "trigger": { "text": [ "overexpressing" ], "offsets": [ [ 939, 953 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "PMID-9242431_E9" } ] }, { "id": "PMID-9242431_E9", "type": "Gene_expression", "trigger": { "text": [ "overexpressing" ], "offsets": [ [ 939, 953 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "PMID-9242431_T8" } ] }, { "id": "PMID-9242431_E10", "type": "Positive_regulation", "trigger": { "text": [ "overexpressed" ], "offsets": [ [ 1090, 1103 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "PMID-9242431_E11" } ] }, { "id": "PMID-9242431_E11", "type": "Gene_expression", "trigger": { "text": [ "overexpressed" ], "offsets": [ [ 1090, 1103 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "PMID-9242431_T9" } ] }, { "id": "PMID-9242431_E12", "type": "Regulation", "trigger": { "text": [ "acts" ], "offsets": [ [ 1150, 1154 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "PMID-9242431_T10" }, { "role": "Cause", "ref_id": "PMID-9242431_T11" } ] } ]

[]

[]

[ { "id": "PMID-9242564__text", "type": "abstract", "text": [ "A shortened life span of EKLF-/- adult erythrocytes, due to a deficiency of beta-globin chains, is ameliorated by human gamma-globin chains. \nUsing homologous recombination, both EKLF alleles in murine embryonic stem (ES) cells were inactivated. These EKLF-/- ES cells were capable of undergoing in vitro differentiation to form definitive erythroid colonies that were similar in size and number to those formed by wild-type ES cells. However, the EKLF-/- colonies were poorly hemoglobinized and enucleated erythrocytes in these colonies contained numerous Heinz bodies. Reverse transcriptase-polymerase chain reaction (RT-PCR) analyses revealed that adult and embryonic globin genes were appropriately regulated, with the exception of beta h1-globin, which continued to be expressed at a very low level. The ratio of adult beta-globin/alpha-globin mRNA in the mutant ES cells was 1/15 of that in wild-type ES cells. When the EKLF-/- cells were injected into blastocysts, they did not contribute at a detectable level to the mature erythrocyte compartment of the chimeric animals, based on analysis of glucose phosphate isomerase-1 (GPI-1) isozymes and hemoglobins that distinguish ES cell-derived erythrocytes from host blastocyst-derived erythrocytes. In contrast, semiquantitative RT-PCR analysis of RNA from reticulocytes of the same chimeric animals suggested that the ES cell-derived reticulocytes were present at a level of 6% to 8%. This indicated that the EKLF-/- erythrocytes in adult animals must be short-lived, apparently due to the imbalance of beta- versus alpha-globin chains, leading to the precipitation of excess alpha-globin chains to form Heinz bodies. Consistent with this hypothesis, the short life span was ameliorated by introduction into the EKLF-/- ES cells of a human LCR/gamma-globin gene, as evidenced by the presence of ES cell-derived reticulocytes as well as mature erythrocytes in the blood of the chimeric animals. " ], "offsets": [ [ 0, 1950 ] ] } ]

[ { "id": "PMID-9242564_T1", "type": "Protein", "text": [ "EKLF" ], "offsets": [ [ 25, 29 ] ], "normalized": [] }, { "id": "PMID-9242564_T2", "type": "Protein", "text": [ "beta-globin" ], "offsets": [ [ 76, 87 ] ], "normalized": [] }, { "id": "PMID-9242564_T3", "type": "Protein", "text": [ "gamma-globin" ], "offsets": [ [ 120, 132 ] ], "normalized": [] }, { "id": "PMID-9242564_T4", "type": "Protein", "text": [ "EKLF alleles" ], "offsets": [ [ 179, 191 ] ], "normalized": [] }, { "id": "PMID-9242564_T5", "type": "Protein", "text": [ "EKLF" ], "offsets": [ [ 252, 256 ] ], "normalized": [] }, { "id": "PMID-9242564_T6", "type": "Protein", "text": [ "EKLF" ], "offsets": [ [ 448, 452 ] ], "normalized": [] }, { "id": "PMID-9242564_T7", "type": "Protein", "text": [ "beta h1-globin" ], "offsets": [ [ 736, 750 ] ], "normalized": [] }, { "id": "PMID-9242564_T8", "type": "Protein", "text": [ "beta-globin" ], "offsets": [ [ 824, 835 ] ], "normalized": [] }, { "id": "PMID-9242564_T9", "type": "Protein", "text": [ "alpha-globin" ], "offsets": [ [ 836, 848 ] ], "normalized": [] }, { "id": "PMID-9242564_T10", "type": "Protein", "text": [ "EKLF" ], "offsets": [ [ 926, 930 ] ], "normalized": [] }, { "id": "PMID-9242564_T11", "type": "Protein", "text": [ "glucose phosphate isomerase-1" ], "offsets": [ [ 1102, 1131 ] ], "normalized": [] }, { "id": "PMID-9242564_T12", "type": "Protein", "text": [ "GPI-1" ], "offsets": [ [ 1133, 1138 ] ], "normalized": [] }, { "id": "PMID-9242564_T13", "type": "Protein", "text": [ "EKLF" ], "offsets": [ [ 1465, 1469 ] ], "normalized": [] }, { "id": "PMID-9242564_T14", "type": "Protein", "text": [ "beta-" ], "offsets": [ [ 1559, 1564 ] ], "normalized": [] }, { "id": "PMID-9242564_T15", "type": "Protein", "text": [ "alpha-globin chains" ], "offsets": [ [ 1572, 1591 ] ], "normalized": [] }, { "id": "PMID-9242564_T16", "type": "Protein", "text": [ "alpha-globin" ], "offsets": [ [ 1632, 1644 ] ], "normalized": [] }, { "id": "PMID-9242564_T17", "type": "Protein", "text": [ "EKLF" ], "offsets": [ [ 1768, 1772 ] ], "normalized": [] }, { "id": "PMID-9242564_T18", "type": "Protein", "text": [ "gamma-globin" ], "offsets": [ [ 1800, 1812 ] ], "normalized": [] }, { "id": "PMID-9242564_T26", "type": "Entity", "text": [ "Heinz bodies" ], "offsets": [ [ 1660, 1672 ] ], "normalized": [] } ]

[ { "id": "PMID-9242564_E1", "type": "Negative_regulation", "trigger": { "text": [ "deficiency" ], "offsets": [ [ 62, 72 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "PMID-9242564_T2" } ] }, { "id": "PMID-9242564_E2", "type": "Regulation", "trigger": { "text": [ "regulated" ], "offsets": [ [ 703, 712 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "PMID-9242564_T7" } ] }, { "id": "PMID-9242564_E3", "type": "Negative_regulation", "trigger": { "text": [ "continued to" ], "offsets": [ [ 758, 770 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "PMID-9242564_E4" } ] }, { "id": "PMID-9242564_E4", "type": "Gene_expression", "trigger": { "text": [ "expressed" ], "offsets": [ [ 774, 783 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "PMID-9242564_T7" } ] }, { "id": "PMID-9242564_E5", "type": "Positive_regulation", "trigger": { "text": [ "leading" ], "offsets": [ [ 1593, 1600 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "PMID-9242564_E6" } ] }, { "id": "PMID-9242564_E6", "type": "Localization", "trigger": { "text": [ "precipitation" ], "offsets": [ [ 1608, 1621 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "PMID-9242564_T16" }, { "role": "AtLoc", "ref_id": "PMID-9242564_T26" } ] }, { "id": "PMID-9242564_E7", "type": "Positive_regulation", "trigger": { "text": [ "excess" ], "offsets": [ [ 1625, 1631 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "PMID-9242564_T16" } ] } ]

[ { "id": "PMID-9242564_1", "entity_ids": [ "PMID-9242564_T11", "PMID-9242564_T12" ] } ]

[]

[ { "id": "PMID-9243748__text", "type": "abstract", "text": [ "Induction of nuclear factor kappa B/Rel nuclear activity in human peripheral blood T lymphocytes by anti-HLA class I monoclonal antibodies. \nMonoclonal antibodies against either monomorphic or polymorphic determinants of class I antigen induced in PBMC and highly purified T lymphocytes the nuclear activity of NF-kappa B/Rel complexes. These included both p50/p50 and p50/p65 dimers, recognized by specific antibodies in EMSA. The induced complexes were detectable in extracts of cells incubated with anti-class I monoclonal antibody (mAb) for 1.5 h; the induction was maximal at 5 h, persistent at 16 h and no longer observed at 40 h. The mAb failed to induce NF-kappa B/Rel nuclear activity in cells incubated in the presence of 3,4-dichloroisocoumarin, an inhibitor of I kappa B-alpha degradation. Together, these results suggest that class I triggering can induce the activity of NF-kappa B/Rel nuclear activity in peripheral blood T lymphocytes, thereby modulating the expression of genes regulated by these transcription factors. " ], "offsets": [ [ 0, 1037 ] ] } ]

[ { "id": "PMID-9243748_T1", "type": "Protein", "text": [ "p50" ], "offsets": [ [ 357, 360 ] ], "normalized": [] }, { "id": "PMID-9243748_T2", "type": "Protein", "text": [ "p50" ], "offsets": [ [ 361, 364 ] ], "normalized": [] }, { "id": "PMID-9243748_T3", "type": "Protein", "text": [ "p50" ], "offsets": [ [ 369, 372 ] ], "normalized": [] }, { "id": "PMID-9243748_T4", "type": "Protein", "text": [ "p65" ], "offsets": [ [ 373, 376 ] ], "normalized": [] }, { "id": "PMID-9243748_T5", "type": "Protein", "text": [ "I kappa B-alpha" ], "offsets": [ [ 773, 788 ] ], "normalized": [] } ]

[ { "id": "PMID-9243748_E1", "type": "Binding", "trigger": { "text": [ "recognized" ], "offsets": [ [ 385, 395 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "PMID-9243748_T4" } ] }, { "id": "PMID-9243748_E2", "type": "Binding", "trigger": { "text": [ "recognized" ], "offsets": [ [ 385, 395 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "PMID-9243748_T1" } ] }, { "id": "PMID-9243748_E3", "type": "Binding", "trigger": { "text": [ "recognized" ], "offsets": [ [ 385, 395 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "PMID-9243748_T3" } ] }, { "id": "PMID-9243748_E4", "type": "Gene_expression", "trigger": { "text": [ "detectable" ], "offsets": [ [ 455, 465 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "PMID-9243748_T4" } ] }, { "id": "PMID-9243748_E5", "type": "Gene_expression", "trigger": { "text": [ "detectable" ], "offsets": [ [ 455, 465 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "PMID-9243748_T1" } ] }, { "id": "PMID-9243748_E6", "type": "Gene_expression", "trigger": { "text": [ "detectable" ], "offsets": [ [ 455, 465 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "PMID-9243748_T3" } ] }, { "id": "PMID-9243748_E7", "type": "Negative_regulation", "trigger": { "text": [ "inhibitor" ], "offsets": [ [ 760, 769 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "PMID-9243748_E8" } ] }, { "id": "PMID-9243748_E8", "type": "Protein_catabolism", "trigger": { "text": [ "degradation" ], "offsets": [ [ 789, 800 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "PMID-9243748_T5" } ] } ]

[ { "id": "PMID-9243748_1", "entity_ids": [ "PMID-9243748_T1", "PMID-9243748_T2" ] } ]

[]

[ { "id": "PMID-9247567__text", "type": "abstract", "text": [ "Cyclosporin A interferes with the inducible degradation of NF-kappa B inhibitors, but not with the processing of p105/NF-kappa B1 in T cells. \nThe transcription factor NF-kappa B controls the induction of numerous cytokine promoters during the activation of T lymphocytes. Inhibition of T cell activation by the immunosuppressants cyclosporin A (CsA) and FK506 exerts a suppressive effect on the induction of these NF-kappa B-controlled cytokine promoters. We show for human Jurkat T leukemia cells, as well as human and mouse primary T lymphocytes, that this inhibitory effect is accompanied by an impaired nuclear translocation of the Rel proteins c-Rel, RelA/p65 and NF-kappa B1/p50, whereas the nuclear appearance of RelB remains unaffected. CsA does not interfere with the synthesis of Rel proteins, but prevents the inducible degradation of cytosolic NF-kappa B inhibitors I kappa B alpha and I kappa B beta upon T cell activation. CsA neither inhibits the processing of the NF-kappa B1 precursor p105 to p50, nor does it \"stabilize\" the C-terminal portion of p105, I kappa B gamma, which is degraded during p105 processing to mature p50. These results indicate that CsA interferes with a specific event in the signal-induced degradation of I kappa B alpha and I kappa B beta, but does not affect the processing of NF-kappa B1/p105 to p50. " ], "offsets": [ [ 0, 1346 ] ] } ]

[ { "id": "PMID-9247567_T1", "type": "Protein", "text": [ "p105" ], "offsets": [ [ 113, 117 ] ], "normalized": [] }, { "id": "PMID-9247567_T2", "type": "Protein", "text": [ "NF-kappa B1" ], "offsets": [ [ 118, 129 ] ], "normalized": [] }, { "id": "PMID-9247567_T3", "type": "Protein", "text": [ "c-Rel" ], "offsets": [ [ 650, 655 ] ], "normalized": [] }, { "id": "PMID-9247567_T4", "type": "Protein", "text": [ "RelA" ], "offsets": [ [ 657, 661 ] ], "normalized": [] }, { "id": "PMID-9247567_T5", "type": "Protein", "text": [ "p65" ], "offsets": [ [ 662, 665 ] ], "normalized": [] }, { "id": "PMID-9247567_T6", "type": "Protein", "text": [ "NF-kappa B1" ], "offsets": [ [ 670, 681 ] ], "normalized": [] }, { "id": "PMID-9247567_T7", "type": "Protein", "text": [ "p50" ], "offsets": [ [ 682, 685 ] ], "normalized": [] }, { "id": "PMID-9247567_T8", "type": "Protein", "text": [ "RelB" ], "offsets": [ [ 721, 725 ] ], "normalized": [] }, { "id": "PMID-9247567_T9", "type": "Protein", "text": [ "I kappa B alpha" ], "offsets": [ [ 879, 894 ] ], "normalized": [] }, { "id": "PMID-9247567_T10", "type": "Protein", "text": [ "I kappa B beta" ], "offsets": [ [ 899, 913 ] ], "normalized": [] }, { "id": "PMID-9247567_T11", "type": "Protein", "text": [ "NF-kappa B1" ], "offsets": [ [ 981, 992 ] ], "normalized": [] }, { "id": "PMID-9247567_T12", "type": "Protein", "text": [ "p105" ], "offsets": [ [ 1003, 1007 ] ], "normalized": [] }, { "id": "PMID-9247567_T13", "type": "Protein", "text": [ "p50" ], "offsets": [ [ 1011, 1014 ] ], "normalized": [] }, { "id": "PMID-9247567_T14", "type": "Protein", "text": [ "p105" ], "offsets": [ [ 1066, 1070 ] ], "normalized": [] }, { "id": "PMID-9247567_T15", "type": "Protein", "text": [ "I kappa B gamma" ], "offsets": [ [ 1072, 1087 ] ], "normalized": [] }, { "id": "PMID-9247567_T16", "type": "Protein", "text": [ "p105" ], "offsets": [ [ 1114, 1118 ] ], "normalized": [] }, { "id": "PMID-9247567_T17", "type": "Protein", "text": [ "p50" ], "offsets": [ [ 1140, 1143 ] ], "normalized": [] }, { "id": "PMID-9247567_T18", "type": "Protein", "text": [ "I kappa B alpha" ], "offsets": [ [ 1247, 1262 ] ], "normalized": [] }, { "id": "PMID-9247567_T19", "type": "Protein", "text": [ "I kappa B beta" ], "offsets": [ [ 1267, 1281 ] ], "normalized": [] }, { "id": "PMID-9247567_T20", "type": "Protein", "text": [ "NF-kappa B1" ], "offsets": [ [ 1321, 1332 ] ], "normalized": [] }, { "id": "PMID-9247567_T21", "type": "Protein", "text": [ "p105" ], "offsets": [ [ 1333, 1337 ] ], "normalized": [] }, { "id": "PMID-9247567_T22", "type": "Protein", "text": [ "p50" ], "offsets": [ [ 1341, 1344 ] ], "normalized": [] }, { "id": "PMID-9247567_T24", "type": "Entity", "text": [ "nuclear" ], "offsets": [ [ 608, 615 ] ], "normalized": [] }, { "id": "PMID-9247567_T26", "type": "Entity", "text": [ "nuclear" ], "offsets": [ [ 699, 706 ] ], "normalized": [] } ]

[ { "id": "PMID-9247567_E1", "type": "Negative_regulation", "trigger": { "text": [ "impaired" ], "offsets": [ [ 599, 607 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "PMID-9247567_E5" } ] }, { "id": "PMID-9247567_E2", "type": "Negative_regulation", "trigger": { "text": [ "impaired" ], "offsets": [ [ 599, 607 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "PMID-9247567_E4" } ] }, { "id": "PMID-9247567_E3", "type": "Negative_regulation", "trigger": { "text": [ "impaired" ], "offsets": [ [ 599, 607 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "PMID-9247567_E6" } ] }, { "id": "PMID-9247567_E4", "type": "Localization", "trigger": { "text": [ "translocation" ], "offsets": [ [ 616, 629 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "PMID-9247567_T4" }, { "role": "ToLoc", "ref_id": "PMID-9247567_T24" } ] }, { "id": "PMID-9247567_E5", "type": "Localization", "trigger": { "text": [ "translocation" ], "offsets": [ [ 616, 629 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "PMID-9247567_T3" }, { "role": "ToLoc", "ref_id": "PMID-9247567_T24" } ] }, { "id": "PMID-9247567_E6", "type": "Localization", "trigger": { "text": [ "translocation" ], "offsets": [ [ 616, 629 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "PMID-9247567_T7" }, { "role": "ToLoc", "ref_id": "PMID-9247567_T24" } ] }, { "id": "PMID-9247567_E7", "type": "Localization", "trigger": { "text": [ "appearance" ], "offsets": [ [ 707, 717 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "PMID-9247567_T8" }, { "role": "AtLoc", "ref_id": "PMID-9247567_T26" } ] }, { "id": "PMID-9247567_E8", "type": "Negative_regulation", "trigger": { "text": [ "unaffected" ], "offsets": [ [ 734, 744 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "PMID-9247567_E7" } ] }, { "id": "PMID-9247567_E9", "type": "Negative_regulation", "trigger": { "text": [ "prevents" ], "offsets": [ [ 809, 817 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "PMID-9247567_E13" } ] }, { "id": "PMID-9247567_E10", "type": "Negative_regulation", "trigger": { "text": [ "prevents" ], "offsets": [ [ 809, 817 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "PMID-9247567_E14" } ] }, { "id": "PMID-9247567_E11", "type": "Positive_regulation", "trigger": { "text": [ "inducible" ], "offsets": [ [ 822, 831 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "PMID-9247567_E14" } ] }, { "id": "PMID-9247567_E12", "type": "Positive_regulation", "trigger": { "text": [ "inducible" ], "offsets": [ [ 822, 831 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "PMID-9247567_E13" } ] }, { "id": "PMID-9247567_E13", "type": "Protein_catabolism", "trigger": { "text": [ "degradation" ], "offsets": [ [ 832, 843 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "PMID-9247567_T9" } ] }, { "id": "PMID-9247567_E14", "type": "Protein_catabolism", "trigger": { "text": [ "degradation" ], "offsets": [ [ 832, 843 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "PMID-9247567_T10" } ] }, { "id": "PMID-9247567_E15", "type": "Negative_regulation", "trigger": { "text": [ "\"stabilize\"" ], "offsets": [ [ 1028, 1039 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "PMID-9247567_E16" } ] }, { "id": "PMID-9247567_E16", "type": "Protein_catabolism", "trigger": { "text": [ "degraded" ], "offsets": [ [ 1098, 1106 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "PMID-9247567_T15" } ] }, { "id": "PMID-9247567_E17", "type": "Negative_regulation", "trigger": { "text": [ "interferes" ], "offsets": [ [ 1177, 1187 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "PMID-9247567_E20" } ] }, { "id": "PMID-9247567_E18", "type": "Negative_regulation", "trigger": { "text": [ "interferes" ], "offsets": [ [ 1177, 1187 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "PMID-9247567_E19" } ] }, { "id": "PMID-9247567_E19", "type": "Protein_catabolism", "trigger": { "text": [ "degradation" ], "offsets": [ [ 1232, 1243 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "PMID-9247567_T18" } ] }, { "id": "PMID-9247567_E20", "type": "Protein_catabolism", "trigger": { "text": [ "degradation" ], "offsets": [ [ 1232, 1243 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "PMID-9247567_T19" } ] } ]

[ { "id": "PMID-9247567_1", "entity_ids": [ "PMID-9247567_T1", "PMID-9247567_T2" ] }, { "id": "PMID-9247567_2", "entity_ids": [ "PMID-9247567_T15", "PMID-9247567_T14" ] }, { "id": "PMID-9247567_3", "entity_ids": [ "PMID-9247567_T20", "PMID-9247567_T21" ] }, { "id": "PMID-9247567_4", "entity_ids": [ "PMID-9247567_T4", "PMID-9247567_T5" ] }, { "id": "PMID-9247567_5", "entity_ids": [ "PMID-9247567_T7", "PMID-9247567_T6" ] } ]

[]

[ { "id": "PMID-9252117__text", "type": "abstract", "text": [ "EBF and E47 collaborate to induce expression of the endogenous immunoglobulin surrogate light chain genes. \nEarly B cell factor (EBF) and E47 participate in the transcriptional control of early B lymphocyte differentiation. With the aim of identifying genetic targets for these transcription factors, we stably transfected cDNAs encoding EBF or a covalent homodimer of E47, individually or together, into immature hematopoietic Ba/F3 cells, which lack both factors. In combination, EBF and E47 induce efficient expression of the endogenous immunoglobulin surrogate light chain genes, lambda5 and VpreB, whereas other pre-B cell-specific genes remain silent. Multiple functionally important EBF and E47 binding sites were identified in the lambda5 promoter/enhancer region, indicating that lambda5 is a direct genetic target for these transcription factors. Taken together, these data suggest that EBF and E47 synergize to activate expression of a subset of genes that define an early stage of the B cell lineage. " ], "offsets": [ [ 0, 1013 ] ] } ]

[ { "id": "PMID-9252117_T1", "type": "Protein", "text": [ "EBF" ], "offsets": [ [ 0, 3 ] ], "normalized": [] }, { "id": "PMID-9252117_T2", "type": "Protein", "text": [ "E47" ], "offsets": [ [ 8, 11 ] ], "normalized": [] }, { "id": "PMID-9252117_T3", "type": "Protein", "text": [ "Early B cell factor" ], "offsets": [ [ 108, 127 ] ], "normalized": [] }, { "id": "PMID-9252117_T4", "type": "Protein", "text": [ "EBF" ], "offsets": [ [ 129, 132 ] ], "normalized": [] }, { "id": "PMID-9252117_T5", "type": "Protein", "text": [ "E47" ], "offsets": [ [ 138, 141 ] ], "normalized": [] }, { "id": "PMID-9252117_T6", "type": "Protein", "text": [ "EBF" ], "offsets": [ [ 338, 341 ] ], "normalized": [] }, { "id": "PMID-9252117_T7", "type": "Protein", "text": [ "E47" ], "offsets": [ [ 369, 372 ] ], "normalized": [] }, { "id": "PMID-9252117_T8", "type": "Protein", "text": [ "EBF" ], "offsets": [ [ 482, 485 ] ], "normalized": [] }, { "id": "PMID-9252117_T9", "type": "Protein", "text": [ "E47" ], "offsets": [ [ 490, 493 ] ], "normalized": [] }, { "id": "PMID-9252117_T10", "type": "Protein", "text": [ "lambda5" ], "offsets": [ [ 584, 591 ] ], "normalized": [] }, { "id": "PMID-9252117_T11", "type": "Protein", "text": [ "VpreB" ], "offsets": [ [ 596, 601 ] ], "normalized": [] }, { "id": "PMID-9252117_T12", "type": "Protein", "text": [ "EBF" ], "offsets": [ [ 690, 693 ] ], "normalized": [] }, { "id": "PMID-9252117_T13", "type": "Protein", "text": [ "E47" ], "offsets": [ [ 698, 701 ] ], "normalized": [] }, { "id": "PMID-9252117_T14", "type": "Protein", "text": [ "lambda5" ], "offsets": [ [ 739, 746 ] ], "normalized": [] }, { "id": "PMID-9252117_T15", "type": "Protein", "text": [ "lambda5" ], "offsets": [ [ 789, 796 ] ], "normalized": [] }, { "id": "PMID-9252117_T16", "type": "Protein", "text": [ "EBF" ], "offsets": [ [ 897, 900 ] ], "normalized": [] }, { "id": "PMID-9252117_T17", "type": "Protein", "text": [ "E47" ], "offsets": [ [ 905, 908 ] ], "normalized": [] } ]

[ { "id": "PMID-9252117_E1", "type": "Gene_expression", "trigger": { "text": [ "transfected" ], "offsets": [ [ 311, 322 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "PMID-9252117_T6" } ] }, { "id": "PMID-9252117_E2", "type": "Gene_expression", "trigger": { "text": [ "transfected" ], "offsets": [ [ 311, 322 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "PMID-9252117_T7" } ] }, { "id": "PMID-9252117_E3", "type": "Positive_regulation", "trigger": { "text": [ "transfected" ], "offsets": [ [ 311, 322 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "PMID-9252117_E2" } ] }, { "id": "PMID-9252117_E4", "type": "Positive_regulation", "trigger": { "text": [ "transfected" ], "offsets": [ [ 311, 322 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "PMID-9252117_E1" } ] }, { "id": "PMID-9252117_E5", "type": "Gene_expression", "trigger": { "text": [ "lack" ], "offsets": [ [ 447, 451 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "PMID-9252117_T7" } ] }, { "id": "PMID-9252117_E6", "type": "Gene_expression", "trigger": { "text": [ "lack" ], "offsets": [ [ 447, 451 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "PMID-9252117_T6" } ] }, { "id": "PMID-9252117_E7", "type": "Positive_regulation", "trigger": { "text": [ "induce" ], "offsets": [ [ 494, 500 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "PMID-9252117_E11" }, { "role": "Cause", "ref_id": "PMID-9252117_T8" } ] }, { "id": "PMID-9252117_E8", "type": "Positive_regulation", "trigger": { "text": [ "induce" ], "offsets": [ [ 494, 500 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "PMID-9252117_E12" }, { "role": "Cause", "ref_id": "PMID-9252117_T9" } ] }, { "id": "PMID-9252117_E9", "type": "Positive_regulation", "trigger": { "text": [ "induce" ], "offsets": [ [ 494, 500 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "PMID-9252117_E11" }, { "role": "Cause", "ref_id": "PMID-9252117_T9" } ] }, { "id": "PMID-9252117_E10", "type": "Positive_regulation", "trigger": { "text": [ "induce" ], "offsets": [ [ 494, 500 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "PMID-9252117_E12" }, { "role": "Cause", "ref_id": "PMID-9252117_T8" } ] }, { "id": "PMID-9252117_E11", "type": "Gene_expression", "trigger": { "text": [ "expression" ], "offsets": [ [ 511, 521 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "PMID-9252117_T10" } ] }, { "id": "PMID-9252117_E12", "type": "Gene_expression", "trigger": { "text": [ "expression" ], "offsets": [ [ 511, 521 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "PMID-9252117_T11" } ] }, { "id": "PMID-9252117_E13", "type": "Regulation", "trigger": { "text": [ "target" ], "offsets": [ [ 817, 823 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "PMID-9252117_T15" }, { "role": "Cause", "ref_id": "PMID-9252117_T8" } ] }, { "id": "PMID-9252117_E14", "type": "Regulation", "trigger": { "text": [ "target" ], "offsets": [ [ 817, 823 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "PMID-9252117_T15" }, { "role": "Cause", "ref_id": "PMID-9252117_T9" } ] } ]

[ { "id": "PMID-9252117_1", "entity_ids": [ "PMID-9252117_T3", "PMID-9252117_T4" ] } ]

[]

[ { "id": "PMID-9256234__text", "type": "abstract", "text": [ "Nuclear levels of NF-kappaB correlate with syncytium-forming capacity of 8e51 cells, expressing a defective HIV virus. \nThe double NF-kappaB site identified in the LTR of the human immunodeficiency virus-1 (HIV-1) has been demonstrated to be necessary for efficient viral transcription. In this report we present the characterisation of NF-kappaB subunits engaged in complexes binding to the HIV-1 NF-kappaB site in human 8e51 T-cells, that harbour a defective HIV-1. At least four different specific NF-kappaB complexes are present in the nucleus of these cells. With the use of specific antibodies we have determined the composition of each complex using electrophoretic mobility shift assays. The results show the presence of several NF-kappaB family members, with the transactivating RelA being engaged in multiple complexes. The importance of NF-kappaB complexes in viral functions has been established comparing the level of NF-kappaB DNA-binding complexes with syncytia-forming activity of 8e51 cells. In fact, 8e51 cells that had almost lost their syncytia-forming capacity were found to contain at least 10 times less active NF-kappaB DNA-binding complex than the actively fusing cells. The correlation is specific as the level of at least three other transcription factors did not change. " ], "offsets": [ [ 0, 1299 ] ] } ]

[ { "id": "PMID-9256234_T1", "type": "Protein", "text": [ "RelA" ], "offsets": [ [ 788, 792 ] ], "normalized": [] } ]

[]

[]

[]

[ { "id": "PMID-9257843__text", "type": "abstract", "text": [ "Differential interaction of nuclear factors with the leukocyte-specific pp52 promoter in B and T cells. \nThe leukocyte-specific, cytoskeleton-binding pp52 (LSP-1, WP-34) protein is widely expressed in multiple leukocyte lineages, including B and T lymphocytes, granulocytes, and macrophages. We previously detected a tissue-specific promoter preceding the exon encoding the N terminus of the pp52 leukocyte protein. Here we describe the functional characterization of this promoter and identification of the factors in B and T cells that regulate its activity. The pp52 promoter contains an initiator specifying the unique 5' terminus of pp52 mRNA, tandem pairs of Ets and SP1 motifs, and a lone C/EBP motif. All these motifs are essential and collectively control transcriptional activity. DNA binding studies and Ab supershift assays revealed that different combinations of factors interact with these motifs in B cells vs T cells. The Ets motifs are preferentially bound by PU-1 in B cell extracts from all stages of development, whereas a different Ets family member reacts with these motifs in T cell extracts. The C/EBP motif is bound by Ig/EBP-1 in pre-B cell and T cell extracts, but is replaced by nuclear factor-IL-6beta or a nuclear factor-IL-6beta-Ig/EBP-1 heterodimer in plasmacytoma cell extracts. Despite its reported role as a negative regulator of transcription, Ig/EBP-1 appears to exert a stimulatory effect on this promoter. These findings reveal the features controlling the pp52 promoter in B and T cells and provide the foundation for determining the regulation of this promoter in other leukocyte lineages. " ], "offsets": [ [ 0, 1631 ] ] } ]

[ { "id": "PMID-9257843_T1", "type": "Protein", "text": [ "pp52" ], "offsets": [ [ 72, 76 ] ], "normalized": [] }, { "id": "PMID-9257843_T2", "type": "Protein", "text": [ "pp52" ], "offsets": [ [ 150, 154 ] ], "normalized": [] }, { "id": "PMID-9257843_T3", "type": "Protein", "text": [ "LSP-1" ], "offsets": [ [ 156, 161 ] ], "normalized": [] }, { "id": "PMID-9257843_T4", "type": "Protein", "text": [ "WP-34" ], "offsets": [ [ 163, 168 ] ], "normalized": [] }, { "id": "PMID-9257843_T5", "type": "Protein", "text": [ "pp52 leukocyte protein" ], "offsets": [ [ 392, 414 ] ], "normalized": [] }, { "id": "PMID-9257843_T6", "type": "Protein", "text": [ "pp52" ], "offsets": [ [ 565, 569 ] ], "normalized": [] }, { "id": "PMID-9257843_T7", "type": "Protein", "text": [ "pp52" ], "offsets": [ [ 638, 642 ] ], "normalized": [] }, { "id": "PMID-9257843_T8", "type": "Protein", "text": [ "PU-1" ], "offsets": [ [ 977, 981 ] ], "normalized": [] }, { "id": "PMID-9257843_T9", "type": "Protein", "text": [ "Ig/EBP-1" ], "offsets": [ [ 1144, 1152 ] ], "normalized": [] }, { "id": "PMID-9257843_T10", "type": "Protein", "text": [ "nuclear factor-IL-6beta" ], "offsets": [ [ 1207, 1230 ] ], "normalized": [] }, { "id": "PMID-9257843_T11", "type": "Protein", "text": [ "nuclear factor-IL-6beta" ], "offsets": [ [ 1236, 1259 ] ], "normalized": [] }, { "id": "PMID-9257843_T12", "type": "Protein", "text": [ "Ig/EBP-1" ], "offsets": [ [ 1260, 1268 ] ], "normalized": [] }, { "id": "PMID-9257843_T13", "type": "Protein", "text": [ "Ig/EBP-1" ], "offsets": [ [ 1380, 1388 ] ], "normalized": [] }, { "id": "PMID-9257843_T14", "type": "Protein", "text": [ "pp52" ], "offsets": [ [ 1496, 1500 ] ], "normalized": [] }, { "id": "PMID-9257843_T16", "type": "Entity", "text": [ "promoter" ], "offsets": [ [ 570, 578 ] ], "normalized": [] }, { "id": "PMID-9257843_T17", "type": "Entity", "text": [ "initiator" ], "offsets": [ [ 591, 600 ] ], "normalized": [] }, { "id": "PMID-9257843_T19", "type": "Entity", "text": [ "5' terminus" ], "offsets": [ [ 623, 634 ] ], "normalized": [] }, { "id": "PMID-9257843_T20", "type": "Entity", "text": [ "C/EBP motif" ], "offsets": [ [ 696, 707 ] ], "normalized": [] }, { "id": "PMID-9257843_T27", "type": "Entity", "text": [ "promoter" ], "offsets": [ [ 1501, 1509 ] ], "normalized": [] } ]

[ { "id": "PMID-9257843_E1", "type": "Gene_expression", "trigger": { "text": [ "expressed" ], "offsets": [ [ 188, 197 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "PMID-9257843_T3" } ] }, { "id": "PMID-9257843_E2", "type": "Regulation", "trigger": { "text": [ "specifying" ], "offsets": [ [ 601, 611 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "PMID-9257843_T7" }, { "role": "Cause", "ref_id": "PMID-9257843_T6" }, { "role": "Site", "ref_id": "PMID-9257843_T19" }, { "role": "CSite", "ref_id": "PMID-9257843_T17" } ] }, { "id": "PMID-9257843_E3", "type": "Binding", "trigger": { "text": [ "interact" ], "offsets": [ [ 884, 892 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "PMID-9257843_T6" }, { "role": "Site", "ref_id": "PMID-9257843_T20" } ] }, { "id": "PMID-9257843_E4", "type": "Binding", "trigger": { "text": [ "interact" ], "offsets": [ [ 884, 892 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "PMID-9257843_T6" }, { "role": "Site", "ref_id": "PMID-9257843_T17" } ] }, { "id": "PMID-9257843_E5", "type": "Binding", "trigger": { "text": [ "bound" ], "offsets": [ [ 968, 973 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "PMID-9257843_T8" } ] }, { "id": "PMID-9257843_E6", "type": "Binding", "trigger": { "text": [ "bound" ], "offsets": [ [ 1135, 1140 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "PMID-9257843_T9" } ] }, { "id": "PMID-9257843_E7", "type": "Binding", "trigger": { "text": [ "replaced" ], "offsets": [ [ 1195, 1203 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "PMID-9257843_T10" } ] }, { "id": "PMID-9257843_E8", "type": "Binding", "trigger": { "text": [ "replaced" ], "offsets": [ [ 1195, 1203 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "PMID-9257843_T11" } ] }, { "id": "PMID-9257843_E9", "type": "Binding", "trigger": { "text": [ "replaced" ], "offsets": [ [ 1195, 1203 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "PMID-9257843_T12" } ] }, { "id": "PMID-9257843_E10", "type": "Positive_regulation", "trigger": { "text": [ "exert a stimulatory effect" ], "offsets": [ [ 1400, 1426 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "PMID-9257843_T6" }, { "role": "Cause", "ref_id": "PMID-9257843_T13" }, { "role": "Site", "ref_id": "PMID-9257843_T16" } ] }, { "id": "PMID-9257843_E11", "type": "Regulation", "trigger": { "text": [ "controlling" ], "offsets": [ [ 1480, 1491 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "PMID-9257843_T14" }, { "role": "Site", "ref_id": "PMID-9257843_T27" } ] }, { "id": "PMID-9257843_E12", "type": "Regulation", "trigger": { "text": [ "regulation" ], "offsets": [ [ 1574, 1584 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "PMID-9257843_T14" }, { "role": "Site", "ref_id": "PMID-9257843_T27" } ] } ]

[ { "id": "PMID-9257843_1", "entity_ids": [ "PMID-9257843_T3", "PMID-9257843_T2", "PMID-9257843_T4" ] } ]

[]

[ { "id": "PMID-9261181__text", "type": "abstract", "text": [ "Transcription factor GATA-3 is differentially expressed in murine Th1 and Th2 cells and controls Th2-specific expression of the interleukin-5 gene. \nInterleukin-5 (IL-5), which is produced by CD4(+) T helper 2 (Th2) cells, but not by Th1 cells, plays a key role in the development of eosinophilia in asthma. Despite increasing evidence that the outcome of many diseases is determined by the ratio of the two subsets of CD4(+) T helper cells, Th1 and Th2, the molecular basis for Th1- and Th2- specific gene expression remains to be elucidated. We previously established a critical role for the transcription factor GATA-3 in IL-5 promoter activation in EL-4 cells, which express both Th1- and Th2-type cytokines. Our studies reported here demonstrate that GATA-3 is critical for expression of the IL-5 gene in bona fide Th2 cells. Whereas mutations in the GATA-3 site abolished antigen- or cAMP- stimulated IL-5 promoter activation in Th2 cells, ectopic expression of GATA-3 in Th1 cells or in a non-lymphoid, non-IL-5-producing cell line activated the IL-5 promoter. During the differentiation of naive CD4(+) T cells isolated from T cell receptor transgenic mice, GATA-3 gene expression was up-regulated in developing Th2 cells, but was down-regulated in Th1 cells, and antigen- or cAMP-activated Th2 cells (but not Th1 cells) expressed the GATA-3 protein. Thus, GATA-3 may play an important role in the balance between Th1 and Th2 subsets in immune responses. Inhibition of GATA-3 activity has therapeutic potential in the treatment of asthma and other hypereosinophilic diseases. " ], "offsets": [ [ 0, 1584 ] ] } ]

[ { "id": "PMID-9261181_T1", "type": "Protein", "text": [ "GATA-3" ], "offsets": [ [ 21, 27 ] ], "normalized": [] }, { "id": "PMID-9261181_T2", "type": "Protein", "text": [ "interleukin-5" ], "offsets": [ [ 128, 141 ] ], "normalized": [] }, { "id": "PMID-9261181_T3", "type": "Protein", "text": [ "Interleukin-5" ], "offsets": [ [ 149, 162 ] ], "normalized": [] }, { "id": "PMID-9261181_T4", "type": "Protein", "text": [ "IL-5" ], "offsets": [ [ 164, 168 ] ], "normalized": [] }, { "id": "PMID-9261181_T5", "type": "Protein", "text": [ "CD4" ], "offsets": [ [ 192, 195 ] ], "normalized": [] }, { "id": "PMID-9261181_T6", "type": "Protein", "text": [ "CD4" ], "offsets": [ [ 419, 422 ] ], "normalized": [] }, { "id": "PMID-9261181_T7", "type": "Protein", "text": [ "GATA-3" ], "offsets": [ [ 615, 621 ] ], "normalized": [] }, { "id": "PMID-9261181_T8", "type": "Protein", "text": [ "IL-5" ], "offsets": [ [ 625, 629 ] ], "normalized": [] }, { "id": "PMID-9261181_T9", "type": "Protein", "text": [ "GATA-3" ], "offsets": [ [ 756, 762 ] ], "normalized": [] }, { "id": "PMID-9261181_T10", "type": "Protein", "text": [ "IL-5" ], "offsets": [ [ 797, 801 ] ], "normalized": [] }, { "id": "PMID-9261181_T11", "type": "Protein", "text": [ "GATA-3" ], "offsets": [ [ 856, 862 ] ], "normalized": [] }, { "id": "PMID-9261181_T12", "type": "Protein", "text": [ "IL-5" ], "offsets": [ [ 907, 911 ] ], "normalized": [] }, { "id": "PMID-9261181_T13", "type": "Protein", "text": [ "GATA-3" ], "offsets": [ [ 968, 974 ] ], "normalized": [] }, { "id": "PMID-9261181_T14", "type": "Protein", "text": [ "IL-5" ], "offsets": [ [ 1014, 1018 ] ], "normalized": [] }, { "id": "PMID-9261181_T15", "type": "Protein", "text": [ "IL-5" ], "offsets": [ [ 1053, 1057 ] ], "normalized": [] }, { "id": "PMID-9261181_T16", "type": "Protein", "text": [ "CD4" ], "offsets": [ [ 1104, 1107 ] ], "normalized": [] }, { "id": "PMID-9261181_T17", "type": "Protein", "text": [ "GATA-3" ], "offsets": [ [ 1166, 1172 ] ], "normalized": [] }, { "id": "PMID-9261181_T18", "type": "Protein", "text": [ "GATA-3" ], "offsets": [ [ 1343, 1349 ] ], "normalized": [] }, { "id": "PMID-9261181_T19", "type": "Protein", "text": [ "GATA-3" ], "offsets": [ [ 1365, 1371 ] ], "normalized": [] }, { "id": "PMID-9261181_T20", "type": "Protein", "text": [ "GATA-3" ], "offsets": [ [ 1477, 1483 ] ], "normalized": [] }, { "id": "PMID-9261181_T26", "type": "Entity", "text": [ "promoter" ], "offsets": [ [ 630, 638 ] ], "normalized": [] }, { "id": "PMID-9261181_T31", "type": "Entity", "text": [ "promoter" ], "offsets": [ [ 912, 920 ] ], "normalized": [] }, { "id": "PMID-9261181_T36", "type": "Entity", "text": [ "promoter" ], "offsets": [ [ 1058, 1066 ] ], "normalized": [] } ]

[ { "id": "PMID-9261181_E1", "type": "Gene_expression", "trigger": { "text": [ "expressed" ], "offsets": [ [ 46, 55 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "PMID-9261181_T1" } ] }, { "id": "PMID-9261181_E2", "type": "Regulation", "trigger": { "text": [ "controls" ], "offsets": [ [ 88, 96 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "PMID-9261181_E3" }, { "role": "Cause", "ref_id": "PMID-9261181_T1" } ] }, { "id": "PMID-9261181_E3", "type": "Gene_expression", "trigger": { "text": [ "expression" ], "offsets": [ [ 110, 120 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "PMID-9261181_T2" } ] }, { "id": "PMID-9261181_E4", "type": "Gene_expression", "trigger": { "text": [ "produced" ], "offsets": [ [ 180, 188 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "PMID-9261181_T4" } ] }, { "id": "PMID-9261181_E5", "type": "Positive_regulation", "trigger": { "text": [ "critical role" ], "offsets": [ [ 572, 585 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "PMID-9261181_E6" }, { "role": "Cause", "ref_id": "PMID-9261181_T7" } ] }, { "id": "PMID-9261181_E6", "type": "Positive_regulation", "trigger": { "text": [ "activation" ], "offsets": [ [ 639, 649 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "PMID-9261181_T8" }, { "role": "Site", "ref_id": "PMID-9261181_T26" } ] }, { "id": "PMID-9261181_E7", "type": "Positive_regulation", "trigger": { "text": [ "critical" ], "offsets": [ [ 766, 774 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "PMID-9261181_E8" }, { "role": "Cause", "ref_id": "PMID-9261181_T9" } ] }, { "id": "PMID-9261181_E8", "type": "Gene_expression", "trigger": { "text": [ "expression" ], "offsets": [ [ 779, 789 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "PMID-9261181_T10" } ] }, { "id": "PMID-9261181_E9", "type": "Negative_regulation", "trigger": { "text": [ "abolished" ], "offsets": [ [ 868, 877 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "PMID-9261181_E10" } ] }, { "id": "PMID-9261181_E10", "type": "Positive_regulation", "trigger": { "text": [ "activation" ], "offsets": [ [ 921, 931 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "PMID-9261181_T12" }, { "role": "Site", "ref_id": "PMID-9261181_T31" } ] }, { "id": "PMID-9261181_E11", "type": "Gene_expression", "trigger": { "text": [ "expression" ], "offsets": [ [ 954, 964 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "PMID-9261181_T13" } ] }, { "id": "PMID-9261181_E12", "type": "Gene_expression", "trigger": { "text": [ "producing" ], "offsets": [ [ 1019, 1028 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "PMID-9261181_T14" } ] }, { "id": "PMID-9261181_E13", "type": "Positive_regulation", "trigger": { "text": [ "activated" ], "offsets": [ [ 1039, 1048 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "PMID-9261181_T15" }, { "role": "Site", "ref_id": "PMID-9261181_T36" } ] }, { "id": "PMID-9261181_E14", "type": "Positive_regulation", "trigger": { "text": [ "activated" ], "offsets": [ [ 1039, 1048 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "PMID-9261181_T15" }, { "role": "Cause", "ref_id": "PMID-9261181_E11" }, { "role": "Site", "ref_id": "PMID-9261181_T36" } ] }, { "id": "PMID-9261181_E15", "type": "Gene_expression", "trigger": { "text": [ "expression" ], "offsets": [ [ 1178, 1188 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "PMID-9261181_T17" } ] }, { "id": "PMID-9261181_E16", "type": "Positive_regulation", "trigger": { "text": [ "up-regulated" ], "offsets": [ [ 1193, 1205 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "PMID-9261181_E15" } ] }, { "id": "PMID-9261181_E17", "type": "Negative_regulation", "trigger": { "text": [ "down-regulated" ], "offsets": [ [ 1239, 1253 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "PMID-9261181_E15" } ] }, { "id": "PMID-9261181_E18", "type": "Gene_expression", "trigger": { "text": [ "expressed" ], "offsets": [ [ 1329, 1338 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "PMID-9261181_T18" } ] }, { "id": "PMID-9261181_E19", "type": "Negative_regulation", "trigger": { "text": [ "Inhibition" ], "offsets": [ [ 1463, 1473 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "PMID-9261181_T20" } ] } ]

[ { "id": "PMID-9261181_1", "entity_ids": [ "PMID-9261181_T4", "PMID-9261181_T3" ] } ]

[]

[ { "id": "PMID-9261367__text", "type": "abstract", "text": [ "Inhibition of human immunodeficiency virus type 1 replication in vitro by a novel combination of anti-Tat single-chain intrabodies and NF-kappa B antagonists. \nHuman immunodeficiency virus type 1 (HIV-1) Tat, an early regulatory protein that is critical for viral gene expression and replication, transactivates the HIV-1 long terminal repeat (LTR) via its binding to the transactivation response element (TAR) and, along with other cellular factors, increases viral transcription initiation and elongation. Tat also superactivates the HIV-1 promoter through a TAR-independent mechanism, including tumor necrosis factor alpha-induced and protein kinase C (PKC)-dependent activation of NF-kappa B, and inhibitors of Tat and NF-kappa B cooperatively down-regulate this Tat-mediated LTR superactivation. In this study, a combined pharmacologic and genetic strategy using two PKC (NF-kappa B) inhibitors, pentoxifylline (PTX) and Go-6976, and a stably expressed anti-Tat single-chain intracellular antibody (sFv intrabody) was employed to obtain cooperative inhibition of both HIV-1 LTR-driven gene expression and HIV-1 replication. Treatment of cells with PTX and Go-6976 resulted in cooperative inhibition of both HIV-1 LTR-driven gene expression and HIV-1 replication. In addition, the combined use of anti-Tat sFv intrabodies and the two NF-kappa B inhibitors retained the virus in the latent state for as long as 45 days. The combined treatment resulted in more durable inhibition of HIV-1 replication than was seen with the NF-kappa B inhibitors alone or the anti-Tat sFv intrabodies alone. Together, these results suggest that in future clinical gene therapy trials, a combined pharmacologic and genetic strategy like the one reported here may improve the survival of transduced cells and prolong clinical benefit. " ], "offsets": [ [ 0, 1818 ] ] } ]

[ { "id": "PMID-9261367_T1", "type": "Protein", "text": [ "Tat" ], "offsets": [ [ 102, 105 ] ], "normalized": [] }, { "id": "PMID-9261367_T2", "type": "Protein", "text": [ "Tat" ], "offsets": [ [ 204, 207 ] ], "normalized": [] }, { "id": "PMID-9261367_T3", "type": "Protein", "text": [ "Tat" ], "offsets": [ [ 508, 511 ] ], "normalized": [] }, { "id": "PMID-9261367_T4", "type": "Protein", "text": [ "tumor necrosis factor alpha" ], "offsets": [ [ 598, 625 ] ], "normalized": [] }, { "id": "PMID-9261367_T5", "type": "Protein", "text": [ "Tat" ], "offsets": [ [ 715, 718 ] ], "normalized": [] }, { "id": "PMID-9261367_T6", "type": "Protein", "text": [ "Tat" ], "offsets": [ [ 767, 770 ] ], "normalized": [] }, { "id": "PMID-9261367_T7", "type": "Protein", "text": [ "Tat" ], "offsets": [ [ 963, 966 ] ], "normalized": [] }, { "id": "PMID-9261367_T8", "type": "Protein", "text": [ "Tat" ], "offsets": [ [ 1306, 1309 ] ], "normalized": [] }, { "id": "PMID-9261367_T9", "type": "Protein", "text": [ "Tat" ], "offsets": [ [ 1566, 1569 ] ], "normalized": [] } ]

[ { "id": "PMID-9261367_E1", "type": "Binding", "trigger": { "text": [ "binding" ], "offsets": [ [ 357, 364 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "PMID-9261367_T2" } ] } ]

[]

[]

[ { "id": "PMID-9265727__text", "type": "abstract", "text": [ "Transcription factors in immune-mediated disease. \nA large amount of detailed information about the intracellular proteins regulating NF-kappa B activation and the cellular response to NF-kappa B activation has emerged recently. Several small molecules, an antisense oligonucleotide, and gene therapeutic agents that inhibit NF-kappa b activation have been described. Despite this, there are still significant gaps in our understanding of this process and its consequences. In contrast, the characterization of transcription factors selectively regulating cytokine production by CD4+ T cell subsets is at a very early stage. Three interacting proteins have recently been shown to contribute to subset-restricted expression of the IL-4 gene. There are other elements regulating IL-4 gene expression, however, and the relative importance of these recently identified proteins has yet to be determined. " ], "offsets": [ [ 0, 900 ] ] } ]

[ { "id": "PMID-9265727_T1", "type": "Protein", "text": [ "CD4" ], "offsets": [ [ 579, 582 ] ], "normalized": [] }, { "id": "PMID-9265727_T2", "type": "Protein", "text": [ "IL-4" ], "offsets": [ [ 730, 734 ] ], "normalized": [] }, { "id": "PMID-9265727_T3", "type": "Protein", "text": [ "IL-4" ], "offsets": [ [ 777, 781 ] ], "normalized": [] } ]

[ { "id": "PMID-9265727_E1", "type": "Regulation", "trigger": { "text": [ "contribute" ], "offsets": [ [ 680, 690 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "PMID-9265727_E2" } ] }, { "id": "PMID-9265727_E2", "type": "Gene_expression", "trigger": { "text": [ "expression" ], "offsets": [ [ 712, 722 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "PMID-9265727_T2" } ] }, { "id": "PMID-9265727_E3", "type": "Regulation", "trigger": { "text": [ "regulating" ], "offsets": [ [ 766, 776 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "PMID-9265727_E4" } ] }, { "id": "PMID-9265727_E4", "type": "Gene_expression", "trigger": { "text": [ "expression" ], "offsets": [ [ 787, 797 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "PMID-9265727_T3" } ] } ]

[]

[]

[ { "id": "PMID-9271352__text", "type": "abstract", "text": [ "CholecystokininB receptor from human Jurkat lymphoblastic T cells is involved in activator protein-1-responsive gene activation. \nThe aim of this study was to analyze the role of cholecystokinin (CCK(B)) receptor in human lymphoblastic Jurkat T cells. We investigated the trophic effect resulting from activation of such a receptor by using the reporter gene strategy. For this purpose, we transiently transfected Jurkat T cells with the reporter plasmid p[(TRE)3-tk-Luc] and found that CCK-8 was able to dose-dependently induce luciferase expression related to activator protein-1 (AP-1) activation with a maximal response identical to that obtained with compounds known to activate AP-1 complex (quantitatively, the same level of induction was obtained with 1 nM 12-O-tetradecanoylphorbol-13-acetate, 100 microM diacylglycerol, or 4 nM epidermal growth factor). The involvement of the CCK(B) receptor in such a stimulation was demonstrated by the inhibiting effect of the selective CCK(B) receptor antagonist PD-135,158. This effect was confirmed in COS-7 cells transfected with the cDNA of CCK(B) receptor cloned from Jurkat T cells. To better understand the AP-1-dependent luciferase expression in Jurkat T cells, we tested two specific inhibitors of serine/threonine phosphatases-1 and -2A: okadaic acid and calyculin A. These compounds strongly increased the phorbol-12-myristate-13-acetate response, whereas we have not observed a contribution of phosphatase inhibitors on a CCK-8-induced luciferase activity. To confirm that CCK(B) receptors are involved in AP-1 response, we investigated the CCK-8 effect on interleukin-2 expression, a natural endogenous gene regulated by several factors, including AP-1. In Jurkat T cells activated by phorbol-12-myristate-13-acetate and phytohemagglutinin, CCK-8 induced IL-2 expression. This induction was abolished by PD-135,158. Our results indicate that CCK-8 exerts a trophic effect in Jurkat T cells through stimulation of CCK(B) receptors by modulation of expression of AP-1-regulated genes. " ], "offsets": [ [ 0, 2044 ] ] } ]

[ { "id": "PMID-9271352_T1", "type": "Protein", "text": [ "CholecystokininB receptor" ], "offsets": [ [ 0, 25 ] ], "normalized": [] }, { "id": "PMID-9271352_T2", "type": "Protein", "text": [ "(CCK(B)) receptor" ], "offsets": [ [ 195, 212 ] ], "normalized": [] }, { "id": "PMID-9271352_T3", "type": "Protein", "text": [ "luciferase" ], "offsets": [ [ 529, 539 ] ], "normalized": [] }, { "id": "PMID-9271352_T4", "type": "Protein", "text": [ "CCK(B) receptor" ], "offsets": [ [ 887, 902 ] ], "normalized": [] }, { "id": "PMID-9271352_T5", "type": "Protein", "text": [ "CCK(B) receptor" ], "offsets": [ [ 984, 999 ] ], "normalized": [] }, { "id": "PMID-9271352_T6", "type": "Protein", "text": [ "CCK(B) receptor" ], "offsets": [ [ 1093, 1108 ] ], "normalized": [] }, { "id": "PMID-9271352_T7", "type": "Protein", "text": [ "luciferase" ], "offsets": [ [ 1177, 1187 ] ], "normalized": [] }, { "id": "PMID-9271352_T8", "type": "Protein", "text": [ "serine/threonine phosphatases-1" ], "offsets": [ [ 1255, 1286 ] ], "normalized": [] }, { "id": "PMID-9271352_T9", "type": "Protein", "text": [ "-2A" ], "offsets": [ [ 1291, 1294 ] ], "normalized": [] }, { "id": "PMID-9271352_T10", "type": "Protein", "text": [ "luciferase" ], "offsets": [ [ 1496, 1506 ] ], "normalized": [] }, { "id": "PMID-9271352_T11", "type": "Protein", "text": [ "CCK(B) receptors" ], "offsets": [ [ 1533, 1549 ] ], "normalized": [] }, { "id": "PMID-9271352_T12", "type": "Protein", "text": [ "interleukin-2" ], "offsets": [ [ 1617, 1630 ] ], "normalized": [] }, { "id": "PMID-9271352_T13", "type": "Protein", "text": [ "phytohemagglutinin" ], "offsets": [ [ 1782, 1800 ] ], "normalized": [] }, { "id": "PMID-9271352_T14", "type": "Protein", "text": [ "IL-2" ], "offsets": [ [ 1816, 1820 ] ], "normalized": [] }, { "id": "PMID-9271352_T15", "type": "Protein", "text": [ "CCK(B) receptors" ], "offsets": [ [ 1974, 1990 ] ], "normalized": [] } ]

[ { "id": "PMID-9271352_E1", "type": "Positive_regulation", "trigger": { "text": [ "activation" ], "offsets": [ [ 302, 312 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "PMID-9271352_T2" } ] }, { "id": "PMID-9271352_E2", "type": "Positive_regulation", "trigger": { "text": [ "induce" ], "offsets": [ [ 522, 528 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "PMID-9271352_E3" } ] }, { "id": "PMID-9271352_E3", "type": "Gene_expression", "trigger": { "text": [ "expression" ], "offsets": [ [ 540, 550 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "PMID-9271352_T3" } ] }, { "id": "PMID-9271352_E4", "type": "Positive_regulation", "trigger": { "text": [ "induction was obtained" ], "offsets": [ [ 732, 754 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "PMID-9271352_E3" } ] }, { "id": "PMID-9271352_E5", "type": "Regulation", "trigger": { "text": [ "involvement" ], "offsets": [ [ 868, 879 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "PMID-9271352_E2" }, { "role": "Cause", "ref_id": "PMID-9271352_T4" } ] }, { "id": "PMID-9271352_E6", "type": "Negative_regulation", "trigger": { "text": [ "inhibiting effect" ], "offsets": [ [ 949, 966 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "PMID-9271352_E2" } ] }, { "id": "PMID-9271352_E7", "type": "Negative_regulation", "trigger": { "text": [ "antagonist" ], "offsets": [ [ 1000, 1010 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "PMID-9271352_T5" } ] }, { "id": "PMID-9271352_E8", "type": "Positive_regulation", "trigger": { "text": [ "dependent" ], "offsets": [ [ 1167, 1176 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "PMID-9271352_E9" } ] }, { "id": "PMID-9271352_E9", "type": "Gene_expression", "trigger": { "text": [ "expression" ], "offsets": [ [ 1188, 1198 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "PMID-9271352_T7" } ] }, { "id": "PMID-9271352_E10", "type": "Negative_regulation", "trigger": { "text": [ "inhibitors" ], "offsets": [ [ 1241, 1251 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "PMID-9271352_T8" } ] }, { "id": "PMID-9271352_E11", "type": "Negative_regulation", "trigger": { "text": [ "inhibitors" ], "offsets": [ [ 1241, 1251 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "PMID-9271352_T9" } ] }, { "id": "PMID-9271352_E12", "type": "Positive_regulation", "trigger": { "text": [ "induced" ], "offsets": [ [ 1488, 1495 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "PMID-9271352_T10" } ] }, { "id": "PMID-9271352_E13", "type": "Regulation", "trigger": { "text": [ "effect" ], "offsets": [ [ 1607, 1613 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "PMID-9271352_E14" } ] }, { "id": "PMID-9271352_E14", "type": "Gene_expression", "trigger": { "text": [ "expression" ], "offsets": [ [ 1631, 1641 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "PMID-9271352_T12" } ] }, { "id": "PMID-9271352_E15", "type": "Regulation", "trigger": { "text": [ "regulated" ], "offsets": [ [ 1669, 1678 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "PMID-9271352_T12" } ] }, { "id": "PMID-9271352_E16", "type": "Positive_regulation", "trigger": { "text": [ "induced" ], "offsets": [ [ 1808, 1815 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "PMID-9271352_E17" } ] }, { "id": "PMID-9271352_E17", "type": "Gene_expression", "trigger": { "text": [ "expression" ], "offsets": [ [ 1821, 1831 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "PMID-9271352_T14" } ] }, { "id": "PMID-9271352_E18", "type": "Negative_regulation", "trigger": { "text": [ "abolished" ], "offsets": [ [ 1852, 1861 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "PMID-9271352_E16" } ] }, { "id": "PMID-9271352_E19", "type": "Positive_regulation", "trigger": { "text": [ "stimulation" ], "offsets": [ [ 1959, 1970 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "PMID-9271352_T15" } ] } ]

[]

[]

[ { "id": "PMID-9271588__text", "type": "abstract", "text": [ "Epstein-Barr virus binding to CD21 activates the initial viral promoter via NF-kappaB induction. \nEpstein-Barr virus (EBV), an oncogenic human herpesvirus, binds to and infects normal human B lymphocytes via CD21, the CR2 complement receptor. Studies of the mechanisms that enable EBV to infect nonactivated, noncycling B cells provide compelling evidence for a sequence of events in which EBV binding to CD21 on purified resting human B cells rapidly activates the NF-kappaB transcription factor, which, in turn, binds to and mediates transcriptional activation of Wp, the initial viral latent gene promoter. Thus, EBV binding to its cellular receptor on resting B cells triggers an NF-kappaB-dependent intracellular signaling pathway which is required for infection. " ], "offsets": [ [ 0, 769 ] ] } ]

[ { "id": "PMID-9271588_T1", "type": "Protein", "text": [ "CD21" ], "offsets": [ [ 30, 34 ] ], "normalized": [] }, { "id": "PMID-9271588_T2", "type": "Protein", "text": [ "CD21" ], "offsets": [ [ 208, 212 ] ], "normalized": [] }, { "id": "PMID-9271588_T3", "type": "Protein", "text": [ "CR2" ], "offsets": [ [ 218, 221 ] ], "normalized": [] }, { "id": "PMID-9271588_T4", "type": "Protein", "text": [ "CD21" ], "offsets": [ [ 405, 409 ] ], "normalized": [] } ]

[]

[]

[]

[ { "id": "PMID-9276471__text", "type": "abstract", "text": [ "Activation of transcription factor NF-kappa B by phagocytic stimuli in human neutrophils. \nPhagocytosis represents an important physiological trigger for the inducible expression of several genes in human neutrophils. Here, we report that a DNA-binding activity primarily consisting of the classical NF-kappa B heterodimer, p50/RelA, is induced in phagocytosing neutrophils. Under these conditions, NF-kappa B activation was found to be a rapid and transient response, reaching a maximum by 10-15 min, and returning to near-basal levels by 30 min. In neutrophils undergoing the phagocytosis of opsonized yeasts, the onset of NF-kappa B activation was paralleled by a decline in immunoreactive I kappa B-alpha protein levels, and the cellular I kappa B-alpha pool was replenished by 30 min, in agreement with our gel shift data. We conclude that NF-kappa B activation could constitute one of the mechanisms whereby the expression of kappa B-responsive genes is enhanced in phagocytosing neutrophils. To our knowledge, this represents the first demonstration that phagocytic stimuli can induce NF-kappa B activation in human neutrophils. " ], "offsets": [ [ 0, 1136 ] ] } ]

[ { "id": "PMID-9276471_T1", "type": "Protein", "text": [ "p50" ], "offsets": [ [ 324, 327 ] ], "normalized": [] }, { "id": "PMID-9276471_T2", "type": "Protein", "text": [ "RelA" ], "offsets": [ [ 328, 332 ] ], "normalized": [] }, { "id": "PMID-9276471_T3", "type": "Protein", "text": [ "I kappa B-alpha" ], "offsets": [ [ 693, 708 ] ], "normalized": [] }, { "id": "PMID-9276471_T4", "type": "Protein", "text": [ "I kappa B-alpha" ], "offsets": [ [ 742, 757 ] ], "normalized": [] } ]

[ { "id": "PMID-9276471_E1", "type": "Binding", "trigger": { "text": [ "binding" ], "offsets": [ [ 245, 252 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "PMID-9276471_T2" } ] }, { "id": "PMID-9276471_E2", "type": "Binding", "trigger": { "text": [ "binding" ], "offsets": [ [ 245, 252 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "PMID-9276471_T1" } ] }, { "id": "PMID-9276471_E3", "type": "Positive_regulation", "trigger": { "text": [ "induced" ], "offsets": [ [ 337, 344 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "PMID-9276471_E2" } ] }, { "id": "PMID-9276471_E4", "type": "Positive_regulation", "trigger": { "text": [ "induced" ], "offsets": [ [ 337, 344 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "PMID-9276471_E1" } ] }, { "id": "PMID-9276471_E5", "type": "Negative_regulation", "trigger": { "text": [ "decline" ], "offsets": [ [ 667, 674 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "PMID-9276471_T3" } ] }, { "id": "PMID-9276471_E6", "type": "Negative_regulation", "trigger": { "text": [ "replenished" ], "offsets": [ [ 767, 778 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "PMID-9276471_T4" } ] } ]

[]

[]

[ { "id": "PMID-9277450__text", "type": "abstract", "text": [ "Surfactant protein A activates NF-kappa B in the THP-1 monocytic cell line. \nThe expression of many genes for which products are involved in inflammation is controlled by the transcriptional regulator nuclear factor (NF)-kappa B. Because surfactant protein (SP) A is involved in local host defense in the lung and alters immune cell function by modulating the expression of proinflammatory cytokines as well as surface proteins involved in inflammation, we hypothesized that SP-A exerts its action, at least in part, via activation of NF-kappa B. We used gel shift assays to determine whether SP-A activated NF-kappa B in the THP-1 cell line, a human monocytic cell line. Activation of NF-kappa B in THP-1 cells by SP-A doses as low as 1 microgram/ml occurred within 30 min of SP-A treatment, peaked at 60 min, and then declined. This activation is inhibited by known inhibitors of NF-kappa B or by simultaneous treatment of the cells with surfactant lipids. Moreover, the NF-kappa B inhibitors blocked SP-A-dependent increases in tumor necrosis factor-alpha mRNA levels. These observations suggest a mechanism by which SP-A plays a role in the pathogenesis of some lung conditions and point to potential therapeutic measures that could be used to prevent SP-A induced inflammation in the lung. " ], "offsets": [ [ 0, 1295 ] ] } ]

[ { "id": "PMID-9277450_T1", "type": "Protein", "text": [ "Surfactant protein A" ], "offsets": [ [ 0, 20 ] ], "normalized": [] }, { "id": "PMID-9277450_T2", "type": "Protein", "text": [ "tumor necrosis factor-alpha" ], "offsets": [ [ 1031, 1058 ] ], "normalized": [] } ]

[ { "id": "PMID-9277450_E1", "type": "Negative_regulation", "trigger": { "text": [ "blocked" ], "offsets": [ [ 995, 1002 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "PMID-9277450_E2" } ] }, { "id": "PMID-9277450_E2", "type": "Positive_regulation", "trigger": { "text": [ "increases" ], "offsets": [ [ 1018, 1027 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "PMID-9277450_T2" } ] } ]

[]

[]

[ { "id": "PMID-9277478__text", "type": "abstract", "text": [ "alpha-Tocopheryl succinate inhibits monocytic cell adhesion to endothelial cells by suppressing NF-kappa B mobilization. \nThe adherence of monocytes to activated endothelium is an early event in atherogenesis. Because antioxidants have been considered to be of antiatherosclerotic potential, we investigated the effects of alpha-tocopherol (TCP) and its acetate and succinate esters on monocyte adhesion to cytokine-stimulated human umbilical vein endothelial cells (HUVEC). Endothelial cells were treated with TCP, alpha-tocopherol acetate (TCP acetate), or alpha-tocopheryl succinate (TCP succinate) before stimulation with tumor necrosis factor-alpha (TNF-alpha; 10 U/ml, 6 h) or interleukin-1 beta (IL-1 beta; 10 U/ml, 6 h). Cytokine-stimulated cell surface expression of vascular cell adhesion molecule-1 (VCAM-1, CD106) and E-selectin (ELAM-1, CD62E), but not of intercellular adhesion molecule-1 (ICAM-1, CD54), was time- and dose-dependently inhibited by TCP succinate but not by TCP or TCP acetate. TCP succinate (200 microM, 24 h) reduced TNF-induced VCAM-1 and E-selectin expression from a specific mean fluorescence intensity of 151 +/- 28 to 12 +/- 4 channels and from 225 +/- 38 to 79 +/- 21 channels, respectively. Succinate alone had no effect. Decreased adhesion molecule expression was associated with a reduction of monocytic cell adhesion. TCP succinate (20 microM, 72 h), but not TCP (200 microM, 72 h), reduced U-937 cell adhesion to TNF-alpha-stimulated (10 U/ml, 6 h) HUVEC by 30% (P < 0.025) and to IL-1 beta-stimulated HUVEC by 56% (P < 0.010). Electrophoretic mobility-shift assays of HUVEC nuclear proteins revealed a decrease in TNF-alpha-stimulated nuclear factor-kappa B (NF-kappa B) activation after pretreatment of HUVEC with TCP succinate but not with TCP, TCP acetate, or succinate alone. In conclusion, we demonstrate that the vitamin E derivative TCP succinate prevents monocytic cell adhesion to cytokine-stimulated endothelial cells by inhibiting the activation of NF-kappa B, further emphasizing the antiatherosclerotic potential of lipid soluble antioxidants. " ], "offsets": [ [ 0, 2101 ] ] } ]

[ { "id": "PMID-9277478_T1", "type": "Protein", "text": [ "tumor necrosis factor-alpha" ], "offsets": [ [ 626, 653 ] ], "normalized": [] }, { "id": "PMID-9277478_T2", "type": "Protein", "text": [ "TNF-alpha" ], "offsets": [ [ 655, 664 ] ], "normalized": [] }, { "id": "PMID-9277478_T3", "type": "Protein", "text": [ "interleukin-1 beta" ], "offsets": [ [ 683, 701 ] ], "normalized": [] }, { "id": "PMID-9277478_T4", "type": "Protein", "text": [ "IL-1 beta" ], "offsets": [ [ 703, 712 ] ], "normalized": [] }, { "id": "PMID-9277478_T5", "type": "Protein", "text": [ "vascular cell adhesion molecule-1" ], "offsets": [ [ 776, 809 ] ], "normalized": [] }, { "id": "PMID-9277478_T6", "type": "Protein", "text": [ "VCAM-1" ], "offsets": [ [ 811, 817 ] ], "normalized": [] }, { "id": "PMID-9277478_T7", "type": "Protein", "text": [ "CD106" ], "offsets": [ [ 819, 824 ] ], "normalized": [] }, { "id": "PMID-9277478_T8", "type": "Protein", "text": [ "E-selectin" ], "offsets": [ [ 830, 840 ] ], "normalized": [] }, { "id": "PMID-9277478_T9", "type": "Protein", "text": [ "ELAM-1" ], "offsets": [ [ 842, 848 ] ], "normalized": [] }, { "id": "PMID-9277478_T10", "type": "Protein", "text": [ "CD62E" ], "offsets": [ [ 850, 855 ] ], "normalized": [] }, { "id": "PMID-9277478_T11", "type": "Protein", "text": [ "intercellular adhesion molecule-1" ], "offsets": [ [ 869, 902 ] ], "normalized": [] }, { "id": "PMID-9277478_T12", "type": "Protein", "text": [ "ICAM-1" ], "offsets": [ [ 904, 910 ] ], "normalized": [] }, { "id": "PMID-9277478_T13", "type": "Protein", "text": [ "CD54" ], "offsets": [ [ 912, 916 ] ], "normalized": [] }, { "id": "PMID-9277478_T14", "type": "Protein", "text": [ "VCAM-1" ], "offsets": [ [ 1061, 1067 ] ], "normalized": [] }, { "id": "PMID-9277478_T15", "type": "Protein", "text": [ "E-selectin" ], "offsets": [ [ 1072, 1082 ] ], "normalized": [] }, { "id": "PMID-9277478_T16", "type": "Protein", "text": [ "TNF-alpha" ], "offsets": [ [ 1456, 1465 ] ], "normalized": [] }, { "id": "PMID-9277478_T17", "type": "Protein", "text": [ "IL-1 beta" ], "offsets": [ [ 1524, 1533 ] ], "normalized": [] }, { "id": "PMID-9277478_T18", "type": "Protein", "text": [ "TNF-alpha" ], "offsets": [ [ 1658, 1667 ] ], "normalized": [] } ]

[ { "id": "PMID-9277478_E1", "type": "Positive_regulation", "trigger": { "text": [ "stimulated" ], "offsets": [ [ 738, 748 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "PMID-9277478_E3" } ] }, { "id": "PMID-9277478_E2", "type": "Gene_expression", "trigger": { "text": [ "expression" ], "offsets": [ [ 762, 772 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "PMID-9277478_T9" } ] }, { "id": "PMID-9277478_E3", "type": "Gene_expression", "trigger": { "text": [ "expression" ], "offsets": [ [ 762, 772 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "PMID-9277478_T6" } ] }, { "id": "PMID-9277478_E4", "type": "Gene_expression", "trigger": { "text": [ "expression" ], "offsets": [ [ 762, 772 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "PMID-9277478_T12" } ] }, { "id": "PMID-9277478_E5", "type": "Negative_regulation", "trigger": { "text": [ "inhibited" ], "offsets": [ [ 950, 959 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "PMID-9277478_E2" } ] }, { "id": "PMID-9277478_E6", "type": "Negative_regulation", "trigger": { "text": [ "inhibited" ], "offsets": [ [ 950, 959 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "PMID-9277478_E3" } ] }, { "id": "PMID-9277478_E7", "type": "Negative_regulation", "trigger": { "text": [ "inhibited" ], "offsets": [ [ 950, 959 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "PMID-9277478_E4" } ] }, { "id": "PMID-9277478_E8", "type": "Negative_regulation", "trigger": { "text": [ "reduced" ], "offsets": [ [ 1041, 1048 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "PMID-9277478_E10" } ] }, { "id": "PMID-9277478_E9", "type": "Negative_regulation", "trigger": { "text": [ "reduced" ], "offsets": [ [ 1041, 1048 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "PMID-9277478_E11" } ] }, { "id": "PMID-9277478_E10", "type": "Positive_regulation", "trigger": { "text": [ "induced" ], "offsets": [ [ 1053, 1060 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "PMID-9277478_E12" } ] }, { "id": "PMID-9277478_E11", "type": "Positive_regulation", "trigger": { "text": [ "induced" ], "offsets": [ [ 1053, 1060 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "PMID-9277478_E13" } ] }, { "id": "PMID-9277478_E12", "type": "Gene_expression", "trigger": { "text": [ "expression" ], "offsets": [ [ 1083, 1093 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "PMID-9277478_T14" } ] }, { "id": "PMID-9277478_E13", "type": "Gene_expression", "trigger": { "text": [ "expression" ], "offsets": [ [ 1083, 1093 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "PMID-9277478_T15" } ] }, { "id": "PMID-9277478_E14", "type": "Regulation", "trigger": { "text": [ "effect" ], "offsets": [ [ 1253, 1259 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "PMID-9277478_E13" } ] }, { "id": "PMID-9277478_E15", "type": "Regulation", "trigger": { "text": [ "effect" ], "offsets": [ [ 1253, 1259 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "PMID-9277478_E12" } ] }, { "id": "PMID-9277478_E16", "type": "Negative_regulation", "trigger": { "text": [ "Decreased" ], "offsets": [ [ 1261, 1270 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "PMID-9277478_E13" } ] }, { "id": "PMID-9277478_E17", "type": "Negative_regulation", "trigger": { "text": [ "Decreased" ], "offsets": [ [ 1261, 1270 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "PMID-9277478_E12" } ] } ]

[ { "id": "PMID-9277478_1", "entity_ids": [ "PMID-9277478_T12", "PMID-9277478_T11", "PMID-9277478_T13" ] }, { "id": "PMID-9277478_2", "entity_ids": [ "PMID-9277478_T9", "PMID-9277478_T8", "PMID-9277478_T10" ] }, { "id": "PMID-9277478_3", "entity_ids": [ "PMID-9277478_T6", "PMID-9277478_T5", "PMID-9277478_T7" ] } ]

[]

[ { "id": "PMID-9277499__text", "type": "abstract", "text": [ "Distinct mechanisms for N-acetylcysteine inhibition of cytokine-induced E-selectin and VCAM-1 expression. \nWe have examined the effects of N-acetyl-L-cysteine (NAC), a well-characterized, thiol-containing antioxidant, on agonist-induced monocytic cell adhesion to endothelial cells (EC). NAC inhibited interleukin-1 (IL-1 beta)-induced, but not basal, adhesion with 50% inhibition at approximately 20 mM. Monocytic cell adhesion to EC in response to tumor necrosis factor-alpha (TNF-alpha), lipopolysaccharide (LPS), alpha-thrombin, or phorbol 12-myristate 13-acetate (PMA) was similarly inhibited by NAC. Unlike published studies with pyrrolidinedithiocarbamate, which specifically inhibited vascular cell adhesion molecule 1 (VCAM-1), NAC inhibited IL-1 beta-induced mRNA and cell surface expression of both E-selectin and VCAM-1. NAC had no effect on the half-life of E-selectin or VCAM-1 mRNA. Although NAC reduced nuclear factor-kappa B (NF-kappa B) activation in EC as measured by gel-shift assays using an oligonucleotide probe corresponding to the consensus NF-kappa B binding sites of the VCAM-1 gene (VCAM-NF-kappa B), the antioxidant had no appreciable effect when an oligomer corresponding to the consensus NF-kappa B binding site of the E-selectin gene (E-selectin-NF-kappa B) was used. Because NF-kappa B has been reported to be redox sensitive, we studied the effects of NAC on the EC redox environment. NAC caused an expected dramatic increase in the reduced glutathione (GSH) levels in EC. In vitro studies demonstrated that whereas the binding affinity of NF-kappa B to the VCAM-NF-kappa B oligomer peaked at a GSH-to-oxidized glutathione (GSSG) ratio of approximately 200 and decreased at higher ratios, the binding to the E-selectin-NF-kappa B oligomer appeared relatively unaffected even at ratios > 400, i.e., those achieved in EC treated with 40 mM NAC. These results suggest that NF-kappa B binding to its consensus sequences in the VCAM-1 and E-selectin gene exhibits marked differences in redox sensitivity, allowing for differential gene expression regulated by the same transcription factor. Our data also demonstrate that NAC increases the GSH-to-GSSG ratio within the EC suggesting one possible mechanism through which this antioxidant inhibits agonist-induced monocyte adhesion to EC. " ], "offsets": [ [ 0, 2316 ] ] } ]

[ { "id": "PMID-9277499_T1", "type": "Protein", "text": [ "E-selectin" ], "offsets": [ [ 72, 82 ] ], "normalized": [] }, { "id": "PMID-9277499_T2", "type": "Protein", "text": [ "VCAM-1" ], "offsets": [ [ 87, 93 ] ], "normalized": [] }, { "id": "PMID-9277499_T3", "type": "Protein", "text": [ "IL-1 beta" ], "offsets": [ [ 317, 326 ] ], "normalized": [] }, { "id": "PMID-9277499_T4", "type": "Protein", "text": [ "tumor necrosis factor-alpha" ], "offsets": [ [ 450, 477 ] ], "normalized": [] }, { "id": "PMID-9277499_T5", "type": "Protein", "text": [ "TNF-alpha" ], "offsets": [ [ 479, 488 ] ], "normalized": [] }, { "id": "PMID-9277499_T6", "type": "Protein", "text": [ "alpha-thrombin" ], "offsets": [ [ 517, 531 ] ], "normalized": [] }, { "id": "PMID-9277499_T7", "type": "Protein", "text": [ "vascular cell adhesion molecule 1" ], "offsets": [ [ 693, 726 ] ], "normalized": [] }, { "id": "PMID-9277499_T8", "type": "Protein", "text": [ "VCAM-1" ], "offsets": [ [ 728, 734 ] ], "normalized": [] }, { "id": "PMID-9277499_T9", "type": "Protein", "text": [ "IL-1 beta" ], "offsets": [ [ 751, 760 ] ], "normalized": [] }, { "id": "PMID-9277499_T10", "type": "Protein", "text": [ "E-selectin" ], "offsets": [ [ 810, 820 ] ], "normalized": [] }, { "id": "PMID-9277499_T11", "type": "Protein", "text": [ "VCAM-1" ], "offsets": [ [ 825, 831 ] ], "normalized": [] }, { "id": "PMID-9277499_T12", "type": "Protein", "text": [ "E-selectin" ], "offsets": [ [ 871, 881 ] ], "normalized": [] }, { "id": "PMID-9277499_T13", "type": "Protein", "text": [ "VCAM-1" ], "offsets": [ [ 885, 891 ] ], "normalized": [] }, { "id": "PMID-9277499_T14", "type": "Protein", "text": [ "VCAM-1" ], "offsets": [ [ 1098, 1104 ] ], "normalized": [] }, { "id": "PMID-9277499_T15", "type": "Protein", "text": [ "E-selectin" ], "offsets": [ [ 1250, 1260 ] ], "normalized": [] }, { "id": "PMID-9277499_T16", "type": "Protein", "text": [ "E-selectin" ], "offsets": [ [ 1267, 1277 ] ], "normalized": [] }, { "id": "PMID-9277499_T17", "type": "Protein", "text": [ "E-selectin" ], "offsets": [ [ 1742, 1752 ] ], "normalized": [] }, { "id": "PMID-9277499_T18", "type": "Protein", "text": [ "VCAM-1" ], "offsets": [ [ 1957, 1963 ] ], "normalized": [] }, { "id": "PMID-9277499_T19", "type": "Protein", "text": [ "E-selectin" ], "offsets": [ [ 1968, 1978 ] ], "normalized": [] } ]

[ { "id": "PMID-9277499_E1", "type": "Negative_regulation", "trigger": { "text": [ "inhibition" ], "offsets": [ [ 41, 51 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "PMID-9277499_E3" } ] }, { "id": "PMID-9277499_E2", "type": "Negative_regulation", "trigger": { "text": [ "inhibition" ], "offsets": [ [ 41, 51 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "PMID-9277499_E4" } ] }, { "id": "PMID-9277499_E3", "type": "Positive_regulation", "trigger": { "text": [ "induced" ], "offsets": [ [ 64, 71 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "PMID-9277499_E5" } ] }, { "id": "PMID-9277499_E4", "type": "Positive_regulation", "trigger": { "text": [ "induced" ], "offsets": [ [ 64, 71 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "PMID-9277499_E6" } ] }, { "id": "PMID-9277499_E5", "type": "Gene_expression", "trigger": { "text": [ "expression" ], "offsets": [ [ 94, 104 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "PMID-9277499_T2" } ] }, { "id": "PMID-9277499_E6", "type": "Gene_expression", "trigger": { "text": [ "expression" ], "offsets": [ [ 94, 104 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "PMID-9277499_T1" } ] }, { "id": "PMID-9277499_E7", "type": "Negative_regulation", "trigger": { "text": [ "inhibited" ], "offsets": [ [ 683, 692 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "PMID-9277499_T8" } ] }, { "id": "PMID-9277499_E8", "type": "Negative_regulation", "trigger": { "text": [ "inhibited" ], "offsets": [ [ 741, 750 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "PMID-9277499_E9" } ] }, { "id": "PMID-9277499_E9", "type": "Positive_regulation", "trigger": { "text": [ "induced" ], "offsets": [ [ 761, 768 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "PMID-9277499_E11" }, { "role": "Cause", "ref_id": "PMID-9277499_T9" } ] }, { "id": "PMID-9277499_E10", "type": "Transcription", "trigger": { "text": [ "mRNA" ], "offsets": [ [ 769, 773 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "PMID-9277499_T11" } ] }, { "id": "PMID-9277499_E11", "type": "Transcription", "trigger": { "text": [ "mRNA" ], "offsets": [ [ 769, 773 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "PMID-9277499_T10" } ] }, { "id": "PMID-9277499_E12", "type": "Gene_expression", "trigger": { "text": [ "expression" ], "offsets": [ [ 791, 801 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "PMID-9277499_T10" } ] }, { "id": "PMID-9277499_E13", "type": "Gene_expression", "trigger": { "text": [ "expression" ], "offsets": [ [ 791, 801 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "PMID-9277499_T11" } ] }, { "id": "PMID-9277499_E14", "type": "Regulation", "trigger": { "text": [ "effect on the half-life" ], "offsets": [ [ 844, 867 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "PMID-9277499_T12" } ] }, { "id": "PMID-9277499_E15", "type": "Regulation", "trigger": { "text": [ "effect on the half-life" ], "offsets": [ [ 844, 867 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "PMID-9277499_T13" } ] }, { "id": "PMID-9277499_E16", "type": "Binding", "trigger": { "text": [ "binding" ], "offsets": [ [ 1915, 1922 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "PMID-9277499_T18" } ] }, { "id": "PMID-9277499_E17", "type": "Binding", "trigger": { "text": [ "binding" ], "offsets": [ [ 1915, 1922 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "PMID-9277499_T19" } ] }, { "id": "PMID-9277499_E18", "type": "Gene_expression", "trigger": { "text": [ "expression" ], "offsets": [ [ 2065, 2075 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "PMID-9277499_T19" } ] }, { "id": "PMID-9277499_E19", "type": "Gene_expression", "trigger": { "text": [ "expression" ], "offsets": [ [ 2065, 2075 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "PMID-9277499_T18" } ] }, { "id": "PMID-9277499_E20", "type": "Regulation", "trigger": { "text": [ "regulated" ], "offsets": [ [ 2076, 2085 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "PMID-9277499_E19" } ] }, { "id": "PMID-9277499_E21", "type": "Regulation", "trigger": { "text": [ "regulated" ], "offsets": [ [ 2076, 2085 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "PMID-9277499_E18" } ] } ]

[ { "id": "PMID-9277499_1", "entity_ids": [ "PMID-9277499_T8", "PMID-9277499_T7" ] }, { "id": "PMID-9277499_2", "entity_ids": [ "PMID-9277499_T4", "PMID-9277499_T5" ] } ]

[]

[ { "id": "PMID-9278334__text", "type": "abstract", "text": [ "Human monocyte binding to fibronectin enhances IFN-gamma-induced early signaling events. \nLeukocyte integrins are fundamentally important in modulating adhesion to extracellular matrix components and to other cells. This integrin-mediated adhesion controls leukocyte arrest and extravasation during the onset of inflammatory responses. Moreover, integrin-ligand interactions trigger signaling pathways that may influence leukocyte phenotype and function at sites of inflammation. In the current studies, we evaluated the combinatorial effects of monocyte adhesion and IFN-gamma on intracellular signaling pathways. IFN-gamma triggers a well-defined signal transduction pathway, which although not directly stimulated by monocyte adherence to fibronectin or arginine-glycine-aspartate (RGD)-coated substrata, was enhanced significantly in these matrix-adherent cells. Compared with monocytes in suspension or adherent on plastic surfaces, monocytes adherent to fibronectin or RGD exhibited a greater than threefold increase in steady state levels of IFN-gamma-induced mRNA for the high affinity Fc gammaRI receptor. By electrophoretic mobility shift assays, this increase in mRNA was associated with a 5- to 10-fold increase in the STAT1-containing DNA-binding complex that binds to Fc gammaRI promoter elements. Furthermore, the tyrosine phosphorylation of STAT1 and the tyrosine kinases JAK1 and JAK2 was enhanced significantly in RGD-adherent monocytes compared with control cells. These results suggest a novel mechanism by which integrin-mediated cell adhesion can modulate the magnitude of cytokine-induced signal transduction pathways, thereby amplifying cellular events leading to monocyte activation and inflammation. " ], "offsets": [ [ 0, 1726 ] ] } ]

[ { "id": "PMID-9278334_T1", "type": "Protein", "text": [ "fibronectin" ], "offsets": [ [ 26, 37 ] ], "normalized": [] }, { "id": "PMID-9278334_T2", "type": "Protein", "text": [ "IFN-gamma" ], "offsets": [ [ 47, 56 ] ], "normalized": [] }, { "id": "PMID-9278334_T3", "type": "Protein", "text": [ "IFN-gamma" ], "offsets": [ [ 568, 577 ] ], "normalized": [] }, { "id": "PMID-9278334_T4", "type": "Protein", "text": [ "IFN-gamma" ], "offsets": [ [ 615, 624 ] ], "normalized": [] }, { "id": "PMID-9278334_T5", "type": "Protein", "text": [ "fibronectin" ], "offsets": [ [ 742, 753 ] ], "normalized": [] }, { "id": "PMID-9278334_T6", "type": "Protein", "text": [ "fibronectin" ], "offsets": [ [ 960, 971 ] ], "normalized": [] }, { "id": "PMID-9278334_T7", "type": "Protein", "text": [ "IFN-gamma" ], "offsets": [ [ 1049, 1058 ] ], "normalized": [] }, { "id": "PMID-9278334_T8", "type": "Protein", "text": [ "high affinity Fc gammaRI receptor" ], "offsets": [ [ 1080, 1113 ] ], "normalized": [] }, { "id": "PMID-9278334_T9", "type": "Protein", "text": [ "STAT1" ], "offsets": [ [ 1231, 1236 ] ], "normalized": [] }, { "id": "PMID-9278334_T10", "type": "Protein", "text": [ "STAT1" ], "offsets": [ [ 1357, 1362 ] ], "normalized": [] }, { "id": "PMID-9278334_T11", "type": "Protein", "text": [ "JAK1" ], "offsets": [ [ 1388, 1392 ] ], "normalized": [] }, { "id": "PMID-9278334_T12", "type": "Protein", "text": [ "JAK2" ], "offsets": [ [ 1397, 1401 ] ], "normalized": [] }, { "id": "PMID-9278334_T20", "type": "Entity", "text": [ "tyrosine" ], "offsets": [ [ 1329, 1337 ] ], "normalized": [] } ]

[ { "id": "PMID-9278334_E1", "type": "Positive_regulation", "trigger": { "text": [ "increase" ], "offsets": [ [ 1014, 1022 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "PMID-9278334_E2" } ] }, { "id": "PMID-9278334_E2", "type": "Transcription", "trigger": { "text": [ "levels" ], "offsets": [ [ 1039, 1045 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "PMID-9278334_T8" } ] }, { "id": "PMID-9278334_E3", "type": "Positive_regulation", "trigger": { "text": [ "induced" ], "offsets": [ [ 1059, 1066 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "PMID-9278334_E2" }, { "role": "Cause", "ref_id": "PMID-9278334_T7" } ] }, { "id": "PMID-9278334_E4", "type": "Positive_regulation", "trigger": { "text": [ "increase" ], "offsets": [ [ 1162, 1170 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "PMID-9278334_T8" } ] }, { "id": "PMID-9278334_E5", "type": "Positive_regulation", "trigger": { "text": [ "increase" ], "offsets": [ [ 1215, 1223 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "PMID-9278334_T9" } ] }, { "id": "PMID-9278334_E6", "type": "Binding", "trigger": { "text": [ "binding complex" ], "offsets": [ [ 1252, 1267 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "PMID-9278334_T9" } ] }, { "id": "PMID-9278334_E7", "type": "Binding", "trigger": { "text": [ "binds" ], "offsets": [ [ 1273, 1278 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "PMID-9278334_T9" } ] }, { "id": "PMID-9278334_E8", "type": "Phosphorylation", "trigger": { "text": [ "phosphorylation" ], "offsets": [ [ 1338, 1353 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "PMID-9278334_T10" }, { "role": "Site", "ref_id": "PMID-9278334_T20" } ] }, { "id": "PMID-9278334_E9", "type": "Phosphorylation", "trigger": { "text": [ "phosphorylation" ], "offsets": [ [ 1338, 1353 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "PMID-9278334_T12" }, { "role": "Site", "ref_id": "PMID-9278334_T20" } ] }, { "id": "PMID-9278334_E10", "type": "Phosphorylation", "trigger": { "text": [ "phosphorylation" ], "offsets": [ [ 1338, 1353 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "PMID-9278334_T11" }, { "role": "Site", "ref_id": "PMID-9278334_T20" } ] }, { "id": "PMID-9278334_E11", "type": "Positive_regulation", "trigger": { "text": [ "enhanced" ], "offsets": [ [ 1406, 1414 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "PMID-9278334_E8" } ] }, { "id": "PMID-9278334_E12", "type": "Positive_regulation", "trigger": { "text": [ "enhanced" ], "offsets": [ [ 1406, 1414 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "PMID-9278334_E10" } ] }, { "id": "PMID-9278334_E13", "type": "Positive_regulation", "trigger": { "text": [ "enhanced" ], "offsets": [ [ 1406, 1414 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "PMID-9278334_E9" } ] } ]

[]

[]

[ { "id": "PMID-9285527__text", "type": "abstract", "text": [ "The carboxyl-terminal cytoplasmic domain of CD36 is required for oxidized low-density lipoprotein modulation of NF-kappaB activity by tumor necrosis factor-alpha. \nThe binding of oxidized low-density lipoprotein (Ox LDL) by monocyte-macrophages causes pleiotropic effects, including changes in gene expression, and is thought to represent an early event in atherogenesis. The integral membrane glycoprotein CD36 appears to play a physiological role in binding and uptake of Ox LDL by monocyte-macrophages, although the molecular events associated with CD36-Ox LDL interaction are unknown. To approach this issue, we used CD36 transfected Chinese hampster ovary (CHO) cells, exposed them to Ox LDL, and determined changes in the activity of the transcription factor NF-kappaB. We report here that Ox LDL enhanced DNA binding activity of nuclear extracts to an NF-kappaB sequence following activation of CD36-producing CHO cells with the proinflammatory cytokine tumor necrosis factor-alpha (TNF-alpha). This enhanced DNA binding activity was inhibited by coincubation of CD36 transfected cells with the human CD36-specific antibody OKM5. We also determined that activation of NF-kappaB DNA binding activity required an intact carboxyl-terminal cytoplasmic segment on CD36. Our results support the idea that human CD36 mediates signal transduction events in response to Ox LDL. " ], "offsets": [ [ 0, 1376 ] ] } ]

[ { "id": "PMID-9285527_T1", "type": "Protein", "text": [ "CD36" ], "offsets": [ [ 44, 48 ] ], "normalized": [] }, { "id": "PMID-9285527_T2", "type": "Protein", "text": [ "tumor necrosis factor-alpha" ], "offsets": [ [ 134, 161 ] ], "normalized": [] }, { "id": "PMID-9285527_T3", "type": "Protein", "text": [ "CD36" ], "offsets": [ [ 407, 411 ] ], "normalized": [] }, { "id": "PMID-9285527_T4", "type": "Protein", "text": [ "CD36" ], "offsets": [ [ 552, 556 ] ], "normalized": [] }, { "id": "PMID-9285527_T5", "type": "Protein", "text": [ "CD36" ], "offsets": [ [ 621, 625 ] ], "normalized": [] }, { "id": "PMID-9285527_T6", "type": "Protein", "text": [ "CD36" ], "offsets": [ [ 902, 906 ] ], "normalized": [] }, { "id": "PMID-9285527_T7", "type": "Protein", "text": [ "tumor necrosis factor-alpha" ], "offsets": [ [ 961, 988 ] ], "normalized": [] }, { "id": "PMID-9285527_T8", "type": "Protein", "text": [ "TNF-alpha" ], "offsets": [ [ 990, 999 ] ], "normalized": [] }, { "id": "PMID-9285527_T9", "type": "Protein", "text": [ "CD36" ], "offsets": [ [ 1070, 1074 ] ], "normalized": [] }, { "id": "PMID-9285527_T10", "type": "Protein", "text": [ "CD36" ], "offsets": [ [ 1108, 1112 ] ], "normalized": [] }, { "id": "PMID-9285527_T11", "type": "Protein", "text": [ "CD36" ], "offsets": [ [ 1266, 1270 ] ], "normalized": [] }, { "id": "PMID-9285527_T12", "type": "Protein", "text": [ "CD36" ], "offsets": [ [ 1312, 1316 ] ], "normalized": [] } ]

[ { "id": "PMID-9285527_E1", "type": "Binding", "trigger": { "text": [ "interaction" ], "offsets": [ [ 564, 575 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "PMID-9285527_T4" } ] }, { "id": "PMID-9285527_E2", "type": "Gene_expression", "trigger": { "text": [ "producing" ], "offsets": [ [ 907, 916 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "PMID-9285527_T6" } ] } ]

[ { "id": "PMID-9285527_1", "entity_ids": [ "PMID-9285527_T7", "PMID-9285527_T8" ] } ]

[]

[ { "id": "PMID-9291089__text", "type": "abstract", "text": [ "Transcriptional regulation during myelopoiesis. \nThe coordinated production of all blood cells from a common stem cell is a highly regulated process involving successive stages of commitment and differentiation. From analyses of mice deficient in transcription factor genes and from the characterizations of chromosome breakpoints in human leukemias, it has become evident that transcription factors are important regulators of hematopoiesis. During myelopoiesis, which includes the development of granulocytic and monocytic lineages, transcription factors from several families are active, including AML1/CBF beta, C/EBP, Ets, c-Myb, HOX, and MZF-1. Few of these factors are expressed exclusively in myeloid cells; instead it appears that they cooperatively regulate transcription of myeloid-specific genes. Here we discuss recent advances in transcriptional regulation during myelopoiesis. " ], "offsets": [ [ 0, 892 ] ] } ]

[ { "id": "PMID-9291089_T1", "type": "Protein", "text": [ "AML1" ], "offsets": [ [ 601, 605 ] ], "normalized": [] }, { "id": "PMID-9291089_T2", "type": "Protein", "text": [ "CBF beta" ], "offsets": [ [ 606, 614 ] ], "normalized": [] }, { "id": "PMID-9291089_T3", "type": "Protein", "text": [ "c-Myb" ], "offsets": [ [ 628, 633 ] ], "normalized": [] }, { "id": "PMID-9291089_T4", "type": "Protein", "text": [ "MZF-1" ], "offsets": [ [ 644, 649 ] ], "normalized": [] } ]

[ { "id": "PMID-9291089_E1", "type": "Positive_regulation", "trigger": { "text": [ "active" ], "offsets": [ [ 583, 589 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "PMID-9291089_T1" } ] }, { "id": "PMID-9291089_E2", "type": "Positive_regulation", "trigger": { "text": [ "active" ], "offsets": [ [ 583, 589 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "PMID-9291089_T2" } ] }, { "id": "PMID-9291089_E3", "type": "Positive_regulation", "trigger": { "text": [ "active" ], "offsets": [ [ 583, 589 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "PMID-9291089_T4" } ] }, { "id": "PMID-9291089_E4", "type": "Positive_regulation", "trigger": { "text": [ "active" ], "offsets": [ [ 583, 589 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "PMID-9291089_T3" } ] }, { "id": "PMID-9291089_E5", "type": "Gene_expression", "trigger": { "text": [ "expressed" ], "offsets": [ [ 676, 685 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "PMID-9291089_T1" } ] }, { "id": "PMID-9291089_E6", "type": "Gene_expression", "trigger": { "text": [ "expressed" ], "offsets": [ [ 676, 685 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "PMID-9291089_T4" } ] }, { "id": "PMID-9291089_E7", "type": "Gene_expression", "trigger": { "text": [ "expressed" ], "offsets": [ [ 676, 685 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "PMID-9291089_T2" } ] }, { "id": "PMID-9291089_E8", "type": "Gene_expression", "trigger": { "text": [ "expressed" ], "offsets": [ [ 676, 685 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "PMID-9291089_T3" } ] } ]

[]

[]

[ { "id": "PMID-9299589__text", "type": "abstract", "text": [ "Rel/NF-kappa B transcription factors and the control of apoptosis. \nThe process of apoptosis is used to eliminate unwanted cells from a wide variety of organisms. Various extracellular signals, often converging in common intracellular pathways, can induce apoptosis in a cell-type-specific fashion. Recent work from several laboratories has demonstrated that Rel/NF-kappa B transcription factors regulate apoptosis in many cell types. In most cells, Rel/NF-kappa B transcription factors appear to mediate survival signals that protect cells from apoptosis; however, under some circumstances, activation of these factors may also promote apoptosis. " ], "offsets": [ [ 0, 648 ] ] } ]

[]

[]

[]

[]

[ { "id": "PMID-9299590__text", "type": "abstract", "text": [ "The role of Rel/NF-kappa B proteins in viral oncogenesis and the regulation of viral transcription. \nRel/NF-kappa B is a ubiquitous transcription factor that consists of multiple polypeptide subunits, and is subject to complex regulatory mechanisms that involve protein-protein interactions, phosphorylation, ubiquitination, proteolytic degradation, and nucleocytoplasmic translocation. The sophisticated control of Rel/NF-kappa B activity is not surprising since this transcription factor is involved in a wide array of cellular responses to extracellular cues, associated with growth, development, apoptosis, and pathogen invasion. Thus, it is not unexpected that this versatile cellular homeostatic switch would be affected by a variety of viral pathogens, which have evolved mechanisms to utilize various aspects of Rel/NF-kappa B activity to facilitate their replication, cell survival and possibly evasion of immune responses. This review will cover the molecular mechanisms that are utilized by mammalian oncogenic viruses to affect the activity of Rel/NF-kappa B transcription factors and the role of Rel/NF-kappa B in the regulation of viral gene expression and replication. " ], "offsets": [ [ 0, 1184 ] ] } ]

[]

[]

[]

[]

[ { "id": "PMID-9306134__text", "type": "abstract", "text": [ "Abnormal apoptosis and cell cycle progression in humans exposed to methyl tertiary-butyl ether and benzene contaminating water. \n1. In this study we hypothesized that in individuals with certain genetic makeup, MTBE, benzene or their metabolites act as adducts and may induce programmed cell death. 2. Our study involved a group of 60 male and female subjects who were exposed to MTBE and benzene-contaminated water concentrations up to 76 PPB for MTBE and 14 PPB for benzene, for a period of 5 to 8 years. For comparison, we recruited a control group consisting of 32 healthy males and females with similar age distribution and without a history of exposure to MTBE or benzene. 3. Peripheral blood lymphocytes (PBL) of both groups were tested for the percentage of apoptotic cells and cell cycle progression using flow cytometry. 4. When apoptotic lymphocytes from exposed individuals were compared to apoptotic lymphocytes from the control group, statistically-significant differences between each mean group were detected (26.4 +/- 1.8 and 12.1 +/- 1.3, respectively), indicating an increased rate of apoptosis in 80.5% of exposed individuals (P < 0.0001, Mann-Whitney U-Test). MTBE and benzene-induced apoptosis is attributed to a discrete block within the cell cycle progression. Because cell cycle analysis showed that in PBL from chemically-exposed individuals, between 20-50% of cells were accumulated at the S-G2/M boundaries. 5. One of the signaling molecules which mediates programmed cell death is nuclear factor Kappa-B (NF-kappa B). NF-kappa B was examined as one of the many molecular mechanisms for mediating cell death by MTBE and benzene. Indeed, addition of inhibitors of NF-kappa B activation pyrrolidine dithiocarbamate (PDTC), to the lymphocytes of the chemically-exposed group was capable of inhibiting programmed cell death by 40%. This reversal of apoptosis almost to the control level by inhibitor of NF-kappa B activation may indicate involvement of this signaling molecule in MTBE and benzene induction of programmed cell death. " ], "offsets": [ [ 0, 2057 ] ] } ]

[]

[]

[]

[]

[ { "id": "PMID-9307271__text", "type": "abstract", "text": [ "Activation of a novel gene in 3q21 and identification of intergenic fusion transcripts with ecotropic viral insertion site I in leukemia. \nWe have identified a novel gene, GR6, located within the leukemia breakpoint region of 3q21, that is normally expressed in early fetal development but not in adult peripheral blood. GR6 is activated in the UCSD-AML1 cell line and in a leukemic sample, both of which carry a t(3;3)(q21;q26). In UCSD-AML1, we have also identified fusion transcripts between the ecotropic viral insertion site I (EVI1) gene in 3q26 and GR6 and between EVI1 and Ribophorin I that maps 30 kb telomeric to GR6 in 3q21. All fusions splice the 5' ends of the 3q21 genes into exon 2 of the EVI1 gene, an event that is similar to the normal intergenic splicing of MDS1-EVI1 and to those previously documented in leukemias with t(3;21) and t(3;12), in which acute myelogenous leukemia 1-EVI1 fusions and ETV6-EVI1 fusions, respectively, occur. The Ribophorin I-EVI1 fusion in particular may be a common occurrence in t(3;3). " ], "offsets": [ [ 0, 1037 ] ] } ]

[ { "id": "PMID-9307271_T1", "type": "Protein", "text": [ "GR6" ], "offsets": [ [ 172, 175 ] ], "normalized": [] }, { "id": "PMID-9307271_T2", "type": "Protein", "text": [ "GR6" ], "offsets": [ [ 321, 324 ] ], "normalized": [] }, { "id": "PMID-9307271_T3", "type": "Protein", "text": [ "ecotropic viral insertion site I" ], "offsets": [ [ 499, 531 ] ], "normalized": [] }, { "id": "PMID-9307271_T4", "type": "Protein", "text": [ "EVI1" ], "offsets": [ [ 533, 537 ] ], "normalized": [] }, { "id": "PMID-9307271_T5", "type": "Protein", "text": [ "GR6" ], "offsets": [ [ 556, 559 ] ], "normalized": [] }, { "id": "PMID-9307271_T6", "type": "Protein", "text": [ "EVI1" ], "offsets": [ [ 572, 576 ] ], "normalized": [] }, { "id": "PMID-9307271_T7", "type": "Protein", "text": [ "Ribophorin I" ], "offsets": [ [ 581, 593 ] ], "normalized": [] }, { "id": "PMID-9307271_T8", "type": "Protein", "text": [ "GR6" ], "offsets": [ [ 623, 626 ] ], "normalized": [] }, { "id": "PMID-9307271_T9", "type": "Protein", "text": [ "EVI1" ], "offsets": [ [ 704, 708 ] ], "normalized": [] }, { "id": "PMID-9307271_T10", "type": "Protein", "text": [ "MDS1" ], "offsets": [ [ 777, 781 ] ], "normalized": [] }, { "id": "PMID-9307271_T11", "type": "Protein", "text": [ "EVI1" ], "offsets": [ [ 782, 786 ] ], "normalized": [] }, { "id": "PMID-9307271_T12", "type": "Protein", "text": [ "acute myelogenous leukemia 1" ], "offsets": [ [ 870, 898 ] ], "normalized": [] }, { "id": "PMID-9307271_T13", "type": "Protein", "text": [ "EVI1" ], "offsets": [ [ 899, 903 ] ], "normalized": [] }, { "id": "PMID-9307271_T14", "type": "Protein", "text": [ "ETV6" ], "offsets": [ [ 916, 920 ] ], "normalized": [] }, { "id": "PMID-9307271_T15", "type": "Protein", "text": [ "EVI1" ], "offsets": [ [ 921, 925 ] ], "normalized": [] }, { "id": "PMID-9307271_T16", "type": "Protein", "text": [ "Ribophorin I" ], "offsets": [ [ 960, 972 ] ], "normalized": [] }, { "id": "PMID-9307271_T17", "type": "Protein", "text": [ "EVI1" ], "offsets": [ [ 973, 977 ] ], "normalized": [] } ]

[ { "id": "PMID-9307271_E1", "type": "Gene_expression", "trigger": { "text": [ "expressed" ], "offsets": [ [ 249, 258 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "PMID-9307271_T1" } ] }, { "id": "PMID-9307271_E2", "type": "Positive_regulation", "trigger": { "text": [ "activated" ], "offsets": [ [ 328, 337 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "PMID-9307271_T2" } ] } ]

[ { "id": "PMID-9307271_1", "entity_ids": [ "PMID-9307271_T3", "PMID-9307271_T4" ] } ]

[]

[ { "id": "PMID-9309306__text", "type": "abstract", "text": [ "Alcohol-induced regulation of nuclear regulatory factor-kappa beta in human monocytes. \nAcute ethanol exposure has the capacity to modulate immune functions, particularly, to down regulate monocyte production of inflammatory cytokines. However, the intracellular mechanisms for these effects of ethanol are yet to be understood. Considering that nuclear regulatory factor-kappa beta (NF-kappa B)/Rel is a common regulatory element of the promoter region of the inflammatory cytokine genes, herein, we tested the hypothesis that acute ethanol affects NF-kappa B activation in human monocytes. Adherence-isolated monocytes showed constitutive DNA binding activity of NF-kappa B. A clinically relevant dose (25 mM) of acute ethanol treatment in vitro increased NF-kappa B binding activity in monocytes with a preferential induction of the inhibitory, p50/p50, NF-kappa B/Rel homodimer, and resulted in no induction of the p65/p50 heterodimer. In contrast, lipopolysaccharide stimulation primarily induced the p65/p50 heterodimer that has been shown to result in gene activation. Thus, such unique activation of the inhibitory p50/p50 homodimer by acute ethanol treatment may result in inhibition rather than activation of NF-kappa B-regulated inflammatory cytokine genes. Consequently, these results suggest that physiologically relevant concentrations of ethanol may affect production of inflammatory cytokines, such as tumor necrosis factor-alpha, interleukin-1 beta, and interleukin-6 by disrupting NF-kappa B signaling in monocytes. " ], "offsets": [ [ 0, 1534 ] ] } ]

[ { "id": "PMID-9309306_T1", "type": "Protein", "text": [ "p50" ], "offsets": [ [ 848, 851 ] ], "normalized": [] }, { "id": "PMID-9309306_T2", "type": "Protein", "text": [ "p50" ], "offsets": [ [ 852, 855 ] ], "normalized": [] }, { "id": "PMID-9309306_T3", "type": "Protein", "text": [ "p65" ], "offsets": [ [ 919, 922 ] ], "normalized": [] }, { "id": "PMID-9309306_T4", "type": "Protein", "text": [ "p50" ], "offsets": [ [ 923, 926 ] ], "normalized": [] }, { "id": "PMID-9309306_T5", "type": "Protein", "text": [ "p65" ], "offsets": [ [ 1006, 1009 ] ], "normalized": [] }, { "id": "PMID-9309306_T6", "type": "Protein", "text": [ "p50" ], "offsets": [ [ 1010, 1013 ] ], "normalized": [] }, { "id": "PMID-9309306_T7", "type": "Protein", "text": [ "p50" ], "offsets": [ [ 1123, 1126 ] ], "normalized": [] }, { "id": "PMID-9309306_T8", "type": "Protein", "text": [ "p50" ], "offsets": [ [ 1127, 1130 ] ], "normalized": [] }, { "id": "PMID-9309306_T9", "type": "Protein", "text": [ "tumor necrosis factor-alpha" ], "offsets": [ [ 1418, 1445 ] ], "normalized": [] }, { "id": "PMID-9309306_T10", "type": "Protein", "text": [ "interleukin-1 beta" ], "offsets": [ [ 1447, 1465 ] ], "normalized": [] }, { "id": "PMID-9309306_T11", "type": "Protein", "text": [ "interleukin-6" ], "offsets": [ [ 1471, 1484 ] ], "normalized": [] } ]

[ { "id": "PMID-9309306_E1", "type": "Positive_regulation", "trigger": { "text": [ "induction" ], "offsets": [ [ 819, 828 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "PMID-9309306_T1" } ] }, { "id": "PMID-9309306_E2", "type": "Positive_regulation", "trigger": { "text": [ "induced" ], "offsets": [ [ 994, 1001 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "PMID-9309306_T6" } ] }, { "id": "PMID-9309306_E3", "type": "Positive_regulation", "trigger": { "text": [ "induced" ], "offsets": [ [ 994, 1001 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "PMID-9309306_T5" } ] }, { "id": "PMID-9309306_E4", "type": "Positive_regulation", "trigger": { "text": [ "activation" ], "offsets": [ [ 1094, 1104 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "PMID-9309306_T7" } ] }, { "id": "PMID-9309306_E5", "type": "Regulation", "trigger": { "text": [ "affect" ], "offsets": [ [ 1365, 1371 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "PMID-9309306_E9" } ] }, { "id": "PMID-9309306_E6", "type": "Regulation", "trigger": { "text": [ "affect" ], "offsets": [ [ 1365, 1371 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "PMID-9309306_E10" } ] }, { "id": "PMID-9309306_E7", "type": "Regulation", "trigger": { "text": [ "affect" ], "offsets": [ [ 1365, 1371 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "PMID-9309306_E8" } ] }, { "id": "PMID-9309306_E8", "type": "Gene_expression", "trigger": { "text": [ "production" ], "offsets": [ [ 1372, 1382 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "PMID-9309306_T11" } ] }, { "id": "PMID-9309306_E9", "type": "Gene_expression", "trigger": { "text": [ "production" ], "offsets": [ [ 1372, 1382 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "PMID-9309306_T10" } ] }, { "id": "PMID-9309306_E10", "type": "Gene_expression", "trigger": { "text": [ "production" ], "offsets": [ [ 1372, 1382 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "PMID-9309306_T9" } ] } ]

[ { "id": "PMID-9309306_1", "entity_ids": [ "PMID-9309306_T1", "PMID-9309306_T2" ] }, { "id": "PMID-9309306_2", "entity_ids": [ "PMID-9309306_T7", "PMID-9309306_T8" ] } ]

[]

[ { "id": "PMID-9310836__text", "type": "abstract", "text": [ "Four P-like elements are required for optimal transcription of the mouse IL-4 gene: involvement of a distinct set of nuclear factor of activated T cells and activator protein-1 family proteins. \nWe previously identified the P sequence as a critical regulatory element of the human IL-4 promoter. In the mouse IL-4 promoter, there are five elements homologous to the human P sequence designated conserved lymphokine element 0 (CLE0), P, P2, P3 and P4. To characterize the role of these P-like elements and their binding factors in the native promoter, we did transient transfection and electrophoretic mobility shift assays (EMSA). Transfection of EL-4 cells with the IL-4 promoter-reporter constructs carrying mutated P-like elements showed that four P-like elements, CLE0, P, P2 and P4, but not P3, were required for optimal activation of the IL-4 promoter. EMSA showed that both constitutive and inducible complexes bound to CLE0, P, P2 and P4, whereas only a constitutive complex bound to P3. In competition and antibody supershift assays in EMSA, complexes formed with P or P2 proved to contain nuclear factor of activated T cells (NFAT) family proteins as major components. Activator protein (AP)-1 family proteins interacted with CLE0, P, P2 and P4. NFAT/AP-1 complex formed only with P and P2. Cross-competition assays among the P-like elements revealed element-specific and common complexes. Six tandem repeats of the P element linked to the SV40 promoter responded to phorbol 12-myristate 13-acetate, while that of other elements did not. It would thus appear that components of each P-like element-binding complexes are not identical and may coordinately contribute to transcriptional activity. " ], "offsets": [ [ 0, 1705 ] ] } ]

[ { "id": "PMID-9310836_T1", "type": "Protein", "text": [ "IL-4" ], "offsets": [ [ 73, 77 ] ], "normalized": [] }, { "id": "PMID-9310836_T2", "type": "Protein", "text": [ "IL-4" ], "offsets": [ [ 281, 285 ] ], "normalized": [] }, { "id": "PMID-9310836_T3", "type": "Protein", "text": [ "IL-4" ], "offsets": [ [ 309, 313 ] ], "normalized": [] }, { "id": "PMID-9310836_T4", "type": "Protein", "text": [ "IL-4" ], "offsets": [ [ 667, 671 ] ], "normalized": [] }, { "id": "PMID-9310836_T5", "type": "Protein", "text": [ "IL-4" ], "offsets": [ [ 844, 848 ] ], "normalized": [] }, { "id": "PMID-9310836_T9", "type": "Entity", "text": [ "promoter" ], "offsets": [ [ 849, 857 ] ], "normalized": [] } ]

[ { "id": "PMID-9310836_E1", "type": "Positive_regulation", "trigger": { "text": [ "required" ], "offsets": [ [ 25, 33 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "PMID-9310836_E2" } ] }, { "id": "PMID-9310836_E2", "type": "Transcription", "trigger": { "text": [ "transcription" ], "offsets": [ [ 46, 59 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "PMID-9310836_T1" } ] }, { "id": "PMID-9310836_E3", "type": "Positive_regulation", "trigger": { "text": [ "activation" ], "offsets": [ [ 826, 836 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "PMID-9310836_T5" }, { "role": "Site", "ref_id": "PMID-9310836_T9" } ] } ]

[]

[]

[ { "id": "PMID-9311830__text", "type": "abstract", "text": [ "The ability of BHRF1 to inhibit apoptosis is dependent on stimulus and cell type. \nThe development of resistance to host defense mechanisms such as tumor necrosis factor (TNF)- and Fas-mediated apoptosis of transformed or virus-infected cells may be a critical component in the development of disease. To find genes that protect cells from apoptosis, we used an expression cloning strategy and identified BHRF1, an Epstein-Barr virus (EBV) early-lytic-cycle protein with distant homology to Bcl-2, as an anti-apoptosis protein. Expression of BHRF1 in MCF-Fas cells conferred nearly complete resistance against both anti-Fas antibody and TNF-mediated apoptosis. In addition, BHRF1 protected these cells from monocyte-mediated killing but failed to protect them from killing mediated by lymphokine-activated killer cells. The ability of BHRF1 to protect MCF-Fas cells from apoptosis induced by various stimuli was identical to that of Bcl-2 and Bcl-xL. Moreover, the mechanism of action of BHRF1 resembled that of Bcl-2 and Bcl-xL as it inhibited TNF- and anti-Fas-induced activation of two enzymes participating in the apoptosis pathway, cytosolic phospholipase A2 and caspase-3/CPP32, but did not interfere with the activation of NF-kappaB-like transcription factors. A putative function of BHRF1 in EBV-infected epithelial cells may be to protect virus-infected cells from TNF- and/or anti-Fas- induced cell death in order to maximize virus production. Surprisingly, expression of neither BHRF1 nor Bcl-2 in a B-cell line, BJAB, protected the cells from anti-Fas-mediated apoptosis even though they increased the survival of serum-starved cells. Thus, the protective role of BHRF1 against apoptosis resembles that of Bcl-2 in being cell type specific and dependent on the apoptotic stimulus. " ], "offsets": [ [ 0, 1793 ] ] } ]

[ { "id": "PMID-9311830_T1", "type": "Protein", "text": [ "BHRF1" ], "offsets": [ [ 15, 20 ] ], "normalized": [] }, { "id": "PMID-9311830_T2", "type": "Protein", "text": [ "Fas" ], "offsets": [ [ 181, 184 ] ], "normalized": [] }, { "id": "PMID-9311830_T3", "type": "Protein", "text": [ "BHRF1" ], "offsets": [ [ 405, 410 ] ], "normalized": [] }, { "id": "PMID-9311830_T4", "type": "Protein", "text": [ "Bcl-2" ], "offsets": [ [ 491, 496 ] ], "normalized": [] }, { "id": "PMID-9311830_T5", "type": "Protein", "text": [ "BHRF1" ], "offsets": [ [ 542, 547 ] ], "normalized": [] }, { "id": "PMID-9311830_T6", "type": "Protein", "text": [ "Fas" ], "offsets": [ [ 620, 623 ] ], "normalized": [] }, { "id": "PMID-9311830_T7", "type": "Protein", "text": [ "BHRF1" ], "offsets": [ [ 674, 679 ] ], "normalized": [] }, { "id": "PMID-9311830_T8", "type": "Protein", "text": [ "BHRF1" ], "offsets": [ [ 835, 840 ] ], "normalized": [] }, { "id": "PMID-9311830_T9", "type": "Protein", "text": [ "Bcl-2" ], "offsets": [ [ 933, 938 ] ], "normalized": [] }, { "id": "PMID-9311830_T10", "type": "Protein", "text": [ "Bcl-xL" ], "offsets": [ [ 943, 949 ] ], "normalized": [] }, { "id": "PMID-9311830_T11", "type": "Protein", "text": [ "BHRF1" ], "offsets": [ [ 988, 993 ] ], "normalized": [] }, { "id": "PMID-9311830_T12", "type": "Protein", "text": [ "Bcl-2" ], "offsets": [ [ 1012, 1017 ] ], "normalized": [] }, { "id": "PMID-9311830_T13", "type": "Protein", "text": [ "Bcl-xL" ], "offsets": [ [ 1022, 1028 ] ], "normalized": [] }, { "id": "PMID-9311830_T14", "type": "Protein", "text": [ "Fas" ], "offsets": [ [ 1059, 1062 ] ], "normalized": [] }, { "id": "PMID-9311830_T15", "type": "Protein", "text": [ "cytosolic phospholipase A2" ], "offsets": [ [ 1137, 1163 ] ], "normalized": [] }, { "id": "PMID-9311830_T16", "type": "Protein", "text": [ "caspase-3" ], "offsets": [ [ 1168, 1177 ] ], "normalized": [] }, { "id": "PMID-9311830_T17", "type": "Protein", "text": [ "CPP32" ], "offsets": [ [ 1178, 1183 ] ], "normalized": [] }, { "id": "PMID-9311830_T18", "type": "Protein", "text": [ "BHRF1" ], "offsets": [ [ 1291, 1296 ] ], "normalized": [] }, { "id": "PMID-9311830_T19", "type": "Protein", "text": [ "Fas" ], "offsets": [ [ 1391, 1394 ] ], "normalized": [] }, { "id": "PMID-9311830_T20", "type": "Protein", "text": [ "BHRF1" ], "offsets": [ [ 1490, 1495 ] ], "normalized": [] }, { "id": "PMID-9311830_T21", "type": "Protein", "text": [ "Bcl-2" ], "offsets": [ [ 1500, 1505 ] ], "normalized": [] }, { "id": "PMID-9311830_T22", "type": "Protein", "text": [ "Fas" ], "offsets": [ [ 1560, 1563 ] ], "normalized": [] }, { "id": "PMID-9311830_T23", "type": "Protein", "text": [ "BHRF1" ], "offsets": [ [ 1676, 1681 ] ], "normalized": [] }, { "id": "PMID-9311830_T24", "type": "Protein", "text": [ "Bcl-2" ], "offsets": [ [ 1718, 1723 ] ], "normalized": [] } ]

[ { "id": "PMID-9311830_E1", "type": "Gene_expression", "trigger": { "text": [ "Expression" ], "offsets": [ [ 528, 538 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "PMID-9311830_T5" } ] }, { "id": "PMID-9311830_E2", "type": "Negative_regulation", "trigger": { "text": [ "inhibited" ], "offsets": [ [ 1035, 1044 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "PMID-9311830_E8" }, { "role": "Cause", "ref_id": "PMID-9311830_T13" } ] }, { "id": "PMID-9311830_E3", "type": "Negative_regulation", "trigger": { "text": [ "inhibited" ], "offsets": [ [ 1035, 1044 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "PMID-9311830_E9" }, { "role": "Cause", "ref_id": "PMID-9311830_T12" } ] }, { "id": "PMID-9311830_E4", "type": "Negative_regulation", "trigger": { "text": [ "inhibited" ], "offsets": [ [ 1035, 1044 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "PMID-9311830_E9" }, { "role": "Cause", "ref_id": "PMID-9311830_T13" } ] }, { "id": "PMID-9311830_E5", "type": "Negative_regulation", "trigger": { "text": [ "inhibited" ], "offsets": [ [ 1035, 1044 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "PMID-9311830_E8" }, { "role": "Cause", "ref_id": "PMID-9311830_T11" } ] }, { "id": "PMID-9311830_E6", "type": "Negative_regulation", "trigger": { "text": [ "inhibited" ], "offsets": [ [ 1035, 1044 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "PMID-9311830_E8" }, { "role": "Cause", "ref_id": "PMID-9311830_T12" } ] }, { "id": "PMID-9311830_E7", "type": "Negative_regulation", "trigger": { "text": [ "inhibited" ], "offsets": [ [ 1035, 1044 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "PMID-9311830_E9" }, { "role": "Cause", "ref_id": "PMID-9311830_T11" } ] }, { "id": "PMID-9311830_E8", "type": "Positive_regulation", "trigger": { "text": [ "activation" ], "offsets": [ [ 1071, 1081 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "PMID-9311830_T15" } ] }, { "id": "PMID-9311830_E9", "type": "Positive_regulation", "trigger": { "text": [ "activation" ], "offsets": [ [ 1071, 1081 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "PMID-9311830_T16" } ] }, { "id": "PMID-9311830_E10", "type": "Gene_expression", "trigger": { "text": [ "expression" ], "offsets": [ [ 1468, 1478 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "PMID-9311830_T21" } ] }, { "id": "PMID-9311830_E11", "type": "Gene_expression", "trigger": { "text": [ "expression" ], "offsets": [ [ 1468, 1478 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "PMID-9311830_T20" } ] } ]

[ { "id": "PMID-9311830_1", "entity_ids": [ "PMID-9311830_T16", "PMID-9311830_T17" ] } ]

[]

[ { "id": "PMID-9311921__text", "type": "abstract", "text": [ "NF-AT activation induced by a CAML-interacting member of the tumor necrosis factor receptor superfamily. \nActivation of the nuclear factor of activated T cells transcription factor (NF-AT) is a key event underlying lymphocyte action. The CAML (calcium-modulator and cyclophilin ligand) protein is a coinducer of NF-AT activation when overexpressed in Jurkat T cells. A member of the tumor necrosis factor receptor superfamily was isolated by virtue of its affinity for CAML. Cross-linking of this lymphocyte-specific protein, designated TACI (transmembrane activator and CAML-interactor), on the surface of transfected Jurkat cells with TACI-specific antibodies led to activation of the transcription factors NF-AT, AP-1, and NFkappaB. TACI-induced activation of NF-AT was specifically blocked by a dominant-negative CAML mutant, thus implicating CAML as a signaling intermediate. " ], "offsets": [ [ 0, 881 ] ] } ]

[ { "id": "PMID-9311921_T1", "type": "Protein", "text": [ "CAML" ], "offsets": [ [ 30, 34 ] ], "normalized": [] }, { "id": "PMID-9311921_T2", "type": "Protein", "text": [ "CAML" ], "offsets": [ [ 238, 242 ] ], "normalized": [] }, { "id": "PMID-9311921_T3", "type": "Protein", "text": [ "calcium-modulator and cyclophilin ligand" ], "offsets": [ [ 244, 284 ] ], "normalized": [] }, { "id": "PMID-9311921_T4", "type": "Protein", "text": [ "CAML" ], "offsets": [ [ 469, 473 ] ], "normalized": [] }, { "id": "PMID-9311921_T5", "type": "Protein", "text": [ "TACI" ], "offsets": [ [ 537, 541 ] ], "normalized": [] }, { "id": "PMID-9311921_T6", "type": "Protein", "text": [ "transmembrane activator and CAML-interactor" ], "offsets": [ [ 543, 586 ] ], "normalized": [] }, { "id": "PMID-9311921_T7", "type": "Protein", "text": [ "TACI" ], "offsets": [ [ 637, 641 ] ], "normalized": [] }, { "id": "PMID-9311921_T8", "type": "Protein", "text": [ "TACI" ], "offsets": [ [ 736, 740 ] ], "normalized": [] }, { "id": "PMID-9311921_T9", "type": "Protein", "text": [ "CAML" ], "offsets": [ [ 817, 821 ] ], "normalized": [] }, { "id": "PMID-9311921_T10", "type": "Protein", "text": [ "CAML" ], "offsets": [ [ 847, 851 ] ], "normalized": [] } ]

[ { "id": "PMID-9311921_E1", "type": "Gene_expression", "trigger": { "text": [ "overexpressed" ], "offsets": [ [ 334, 347 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "PMID-9311921_T2" } ] }, { "id": "PMID-9311921_E2", "type": "Positive_regulation", "trigger": { "text": [ "overexpressed" ], "offsets": [ [ 334, 347 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "PMID-9311921_E1" } ] }, { "id": "PMID-9311921_E3", "type": "Binding", "trigger": { "text": [ "affinity" ], "offsets": [ [ 456, 464 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "PMID-9311921_T4" } ] } ]

[ { "id": "PMID-9311921_1", "entity_ids": [ "PMID-9311921_T2", "PMID-9311921_T3" ] }, { "id": "PMID-9311921_2", "entity_ids": [ "PMID-9311921_T5", "PMID-9311921_T6" ] } ]

[]

[ { "id": "PMID-9312094__text", "type": "abstract", "text": [ "The DNA binding domain of the A-MYB transcription factor is responsible for its B cell-specific activity and binds to a B cell 110-kDa nuclear protein. \nExpression studies as well as the use of transgenic animals have demonstrated that the A-MYB transcription factor plays central and specific role in the regulation of mature B cell proliferation and/or differentiation. Furthermore, it is highly expressed in Burkitt's lymphoma cells and may participate in the pathogenesis of this disease. We have therefore investigated the transcriptional activity of A-MYB and its regulation in several human lymphoid cell lines using co-transfection assays and show that A-MYB is transcriptionally active in all the B cell lines studied, but not in T cells. In particular the best responder cell line was the Burkitt's cell line Namalwa. The activity of A-MYB in B and not T cells was observed when either an artificial construct or the c-MYC promoter was used as a reporter. Furthermore, the functional domains responsible for DNA binding, transactivation, and negative regulation, previously characterized in a fibroblast context, were found to have similar activity in B cells. The region of A-MYB responsible for the B cell specific activity was defined to be the N-terminal 218 amino acids containing the DNA binding domain. Finally, a 110-kDa protein has been identified in the nuclei of all the B, but not T, cell lines that specifically binds to this A-MYB N-terminal domain. We hypothesize that this 110-kDa protein may be a functionally important B cell-specific co-activator of A-MYB. " ], "offsets": [ [ 0, 1586 ] ] } ]

[ { "id": "PMID-9312094_T1", "type": "Protein", "text": [ "A-MYB" ], "offsets": [ [ 30, 35 ] ], "normalized": [] }, { "id": "PMID-9312094_T2", "type": "Protein", "text": [ "A-MYB" ], "offsets": [ [ 240, 245 ] ], "normalized": [] }, { "id": "PMID-9312094_T3", "type": "Protein", "text": [ "A-MYB" ], "offsets": [ [ 556, 561 ] ], "normalized": [] }, { "id": "PMID-9312094_T4", "type": "Protein", "text": [ "A-MYB" ], "offsets": [ [ 661, 666 ] ], "normalized": [] }, { "id": "PMID-9312094_T5", "type": "Protein", "text": [ "A-MYB" ], "offsets": [ [ 844, 849 ] ], "normalized": [] }, { "id": "PMID-9312094_T6", "type": "Protein", "text": [ "c-MYC" ], "offsets": [ [ 927, 932 ] ], "normalized": [] }, { "id": "PMID-9312094_T7", "type": "Protein", "text": [ "A-MYB" ], "offsets": [ [ 1185, 1190 ] ], "normalized": [] }, { "id": "PMID-9312094_T8", "type": "Protein", "text": [ "A-MYB" ], "offsets": [ [ 1449, 1454 ] ], "normalized": [] }, { "id": "PMID-9312094_T9", "type": "Protein", "text": [ "A-MYB" ], "offsets": [ [ 1579, 1584 ] ], "normalized": [] }, { "id": "PMID-9312094_T10", "type": "Entity", "text": [ "DNA binding domain" ], "offsets": [ [ 4, 22 ] ], "normalized": [] }, { "id": "PMID-9312094_T20", "type": "Entity", "text": [ "N-terminal domain" ], "offsets": [ [ 1455, 1472 ] ], "normalized": [] } ]

[ { "id": "PMID-9312094_E1", "type": "Binding", "trigger": { "text": [ "binds" ], "offsets": [ [ 109, 114 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "PMID-9312094_T1" }, { "role": "Site", "ref_id": "PMID-9312094_T10" } ] }, { "id": "PMID-9312094_E2", "type": "Gene_expression", "trigger": { "text": [ "expressed" ], "offsets": [ [ 398, 407 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "PMID-9312094_T2" } ] }, { "id": "PMID-9312094_E3", "type": "Regulation", "trigger": { "text": [ "regulation" ], "offsets": [ [ 570, 580 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "PMID-9312094_T3" } ] }, { "id": "PMID-9312094_E4", "type": "Positive_regulation", "trigger": { "text": [ "transcriptionally active" ], "offsets": [ [ 670, 694 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "PMID-9312094_T4" } ] }, { "id": "PMID-9312094_E5", "type": "Positive_regulation", "trigger": { "text": [ "responder" ], "offsets": [ [ 771, 780 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "PMID-9312094_T4" } ] }, { "id": "PMID-9312094_E6", "type": "Positive_regulation", "trigger": { "text": [ "observed" ], "offsets": [ [ 875, 883 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "PMID-9312094_T5" } ] }, { "id": "PMID-9312094_E7", "type": "Binding", "trigger": { "text": [ "binding" ], "offsets": [ [ 1022, 1029 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "PMID-9312094_T5" } ] }, { "id": "PMID-9312094_E8", "type": "Negative_regulation", "trigger": { "text": [ "negative regulation" ], "offsets": [ [ 1052, 1071 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "PMID-9312094_T5" } ] }, { "id": "PMID-9312094_E9", "type": "Binding", "trigger": { "text": [ "binds" ], "offsets": [ [ 1435, 1440 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "PMID-9312094_T8" }, { "role": "Site", "ref_id": "PMID-9312094_T20" } ] }, { "id": "PMID-9312094_E10", "type": "Positive_regulation", "trigger": { "text": [ "co-activator" ], "offsets": [ [ 1563, 1575 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "PMID-9312094_T9" } ] } ]

[]

[]

[ { "id": "PMID-9312192__text", "type": "abstract", "text": [ "Evidence that calcineurin is rate-limiting for primary human lymphocyte activation. \nCyclosporine (CsA) is both a clinical immunosuppressive drug and a probe to dissect intracellular signaling pathways. In vitro, CsA inhibits lymphocyte gene activation by inhibiting the phosphatase activity of calcineurin (CN). In clinical use, CsA treatment inhibits 50-75% of CN activity in circulating leukocytes. We modeled this degree of CN inhibition in primary human leukocytes in vitro in order to study the effect of partial CN inhibition on the downstream signaling events that lead to gene activation. In CsA-treated leukocytes stimulated by calcium ionophore, the degree of reduction in CN activity was accompanied by a similar degree of inhibition of each event tested: dephosphorylation of nuclear factor of activated T cell proteins, nuclear DNA binding, activation of a transfected reporter gene construct, IFN-gamma and IL-2 mRNA accumulation, and IFN-gamma production. Furthermore, the degree of CN inhibition was reflected by a similar degree of reduction in lymphocyte proliferation and IFN-gamma production in the allogeneic mixed lymphocyte cultures. These data support the conclusion that CN activity is rate-limiting for the activation of primary human T lymphocytes. Thus, the reduction of CN activity observed in CsA-treated patients is accompanied by a similar degree of reduction in lymphocyte gene activation, and accounts for the immunosuppression observed. " ], "offsets": [ [ 0, 1473 ] ] } ]

[ { "id": "PMID-9312192_T1", "type": "Protein", "text": [ "IFN-gamma" ], "offsets": [ [ 908, 917 ] ], "normalized": [] }, { "id": "PMID-9312192_T2", "type": "Protein", "text": [ "IL-2" ], "offsets": [ [ 922, 926 ] ], "normalized": [] }, { "id": "PMID-9312192_T3", "type": "Protein", "text": [ "IFN-gamma" ], "offsets": [ [ 950, 959 ] ], "normalized": [] }, { "id": "PMID-9312192_T4", "type": "Protein", "text": [ "IFN-gamma" ], "offsets": [ [ 1092, 1101 ] ], "normalized": [] } ]

[ { "id": "PMID-9312192_E1", "type": "Negative_regulation", "trigger": { "text": [ "inhibition" ], "offsets": [ [ 735, 745 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "PMID-9312192_E4" } ] }, { "id": "PMID-9312192_E2", "type": "Negative_regulation", "trigger": { "text": [ "inhibition" ], "offsets": [ [ 735, 745 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "PMID-9312192_E5" } ] }, { "id": "PMID-9312192_E3", "type": "Negative_regulation", "trigger": { "text": [ "inhibition" ], "offsets": [ [ 735, 745 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "PMID-9312192_E6" } ] }, { "id": "PMID-9312192_E4", "type": "Positive_regulation", "trigger": { "text": [ "accumulation" ], "offsets": [ [ 932, 944 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "PMID-9312192_T2" } ] }, { "id": "PMID-9312192_E5", "type": "Positive_regulation", "trigger": { "text": [ "accumulation" ], "offsets": [ [ 932, 944 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "PMID-9312192_T1" } ] }, { "id": "PMID-9312192_E6", "type": "Gene_expression", "trigger": { "text": [ "production" ], "offsets": [ [ 960, 970 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "PMID-9312192_T3" } ] }, { "id": "PMID-9312192_E7", "type": "Negative_regulation", "trigger": { "text": [ "reduction" ], "offsets": [ [ 1050, 1059 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "PMID-9312192_E8" } ] }, { "id": "PMID-9312192_E8", "type": "Gene_expression", "trigger": { "text": [ "production" ], "offsets": [ [ 1102, 1112 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "PMID-9312192_T4" } ] } ]

[]

[]

[ { "id": "PMID-9317131__text", "type": "abstract", "text": [ "Cooperation of binding sites for STAT6 and NF kappa B/rel in the IL-4-induced up-regulation of the human IgE germline promoter. \nIg heavy chain class switching is directed by cytokines inducing transcription from unrearranged CH genes. Subsequently, such primed cells can undergo switch recombination to express the selected new isotype. In the case of IgE class switching, IL-4 activates the IgE germline promoter by inducing the interaction of the transcription factor STAT6 (IL-4STAT) with a responsive DNA element in the proximal region of the promoter. This study describes the characterization of two additional cis-acting elements that interact with members of the NF kappa B/rel transcription factor family in an IL-4-independent fashion. Electrophoretic mobility shift assays show that the nucleoprotein complex formed on the upstream site (NF kappa B1) contains the classical p50/p65 heterodimer. The complex on the proximal site (NF kappa B2) appears to be composed of p50 and relB. IgE germline promoter reporter gene constructs carrying point mutations in the NF kappa B2 site were largely unresponsive to IL-4 stimulation in transient transfection experiments, while plasmids with similar mutations in the NF kappa B1 site responded to cytokine stimulation better than the wild-type promoter. The NF kappa B2 effect was dependent on the presence of the STAT6 binding site, demonstrating that the NF kappa B2 motif is necessary but not sufficient for mediating cytokine up-regulation. In addition, the combination of a NF kappa B/rel binding site and the STAT6 response element conferred IL-4 inducibility to a heterologous minimal promoter, while the individual sites had no effect. The available data suggest that the NF kappa B2 nucleoprotein complex may cooperate with DNA-bound STAT6 to achieve IL-4-dependent activation of the human IgE germline gene. " ], "offsets": [ [ 0, 1871 ] ] } ]

[ { "id": "PMID-9317131_T1", "type": "Protein", "text": [ "STAT6" ], "offsets": [ [ 33, 38 ] ], "normalized": [] }, { "id": "PMID-9317131_T2", "type": "Protein", "text": [ "IL-4" ], "offsets": [ [ 65, 69 ] ], "normalized": [] }, { "id": "PMID-9317131_T3", "type": "Protein", "text": [ "IgE" ], "offsets": [ [ 105, 108 ] ], "normalized": [] }, { "id": "PMID-9317131_T4", "type": "Protein", "text": [ "IL-4" ], "offsets": [ [ 374, 378 ] ], "normalized": [] }, { "id": "PMID-9317131_T5", "type": "Protein", "text": [ "STAT6" ], "offsets": [ [ 471, 476 ] ], "normalized": [] }, { "id": "PMID-9317131_T6", "type": "Protein", "text": [ "IL-4STAT" ], "offsets": [ [ 478, 486 ] ], "normalized": [] }, { "id": "PMID-9317131_T7", "type": "Protein", "text": [ "IL-4" ], "offsets": [ [ 721, 725 ] ], "normalized": [] }, { "id": "PMID-9317131_T8", "type": "Protein", "text": [ "NF kappa B1" ], "offsets": [ [ 850, 861 ] ], "normalized": [] }, { "id": "PMID-9317131_T9", "type": "Protein", "text": [ "p50" ], "offsets": [ [ 886, 889 ] ], "normalized": [] }, { "id": "PMID-9317131_T10", "type": "Protein", "text": [ "p65" ], "offsets": [ [ 890, 893 ] ], "normalized": [] }, { "id": "PMID-9317131_T11", "type": "Protein", "text": [ "NF kappa B2" ], "offsets": [ [ 941, 952 ] ], "normalized": [] }, { "id": "PMID-9317131_T12", "type": "Protein", "text": [ "p50" ], "offsets": [ [ 980, 983 ] ], "normalized": [] }, { "id": "PMID-9317131_T13", "type": "Protein", "text": [ "relB" ], "offsets": [ [ 988, 992 ] ], "normalized": [] }, { "id": "PMID-9317131_T14", "type": "Protein", "text": [ "NF kappa B2" ], "offsets": [ [ 1073, 1084 ] ], "normalized": [] }, { "id": "PMID-9317131_T15", "type": "Protein", "text": [ "IL-4" ], "offsets": [ [ 1119, 1123 ] ], "normalized": [] }, { "id": "PMID-9317131_T16", "type": "Protein", "text": [ "NF kappa B1" ], "offsets": [ [ 1220, 1231 ] ], "normalized": [] }, { "id": "PMID-9317131_T17", "type": "Protein", "text": [ "NF kappa B2" ], "offsets": [ [ 1311, 1322 ] ], "normalized": [] }, { "id": "PMID-9317131_T18", "type": "Protein", "text": [ "STAT6" ], "offsets": [ [ 1367, 1372 ] ], "normalized": [] }, { "id": "PMID-9317131_T19", "type": "Protein", "text": [ "NF kappa B2" ], "offsets": [ [ 1410, 1421 ] ], "normalized": [] }, { "id": "PMID-9317131_T20", "type": "Protein", "text": [ "STAT6" ], "offsets": [ [ 1568, 1573 ] ], "normalized": [] }, { "id": "PMID-9317131_T21", "type": "Protein", "text": [ "IL-4" ], "offsets": [ [ 1601, 1605 ] ], "normalized": [] }, { "id": "PMID-9317131_T22", "type": "Protein", "text": [ "NF kappa B2" ], "offsets": [ [ 1733, 1744 ] ], "normalized": [] }, { "id": "PMID-9317131_T23", "type": "Protein", "text": [ "STAT6" ], "offsets": [ [ 1796, 1801 ] ], "normalized": [] }, { "id": "PMID-9317131_T24", "type": "Protein", "text": [ "IL-4" ], "offsets": [ [ 1813, 1817 ] ], "normalized": [] }, { "id": "PMID-9317131_T26", "type": "Entity", "text": [ "binding sites" ], "offsets": [ [ 15, 28 ] ], "normalized": [] }, { "id": "PMID-9317131_T28", "type": "Entity", "text": [ "germline promoter" ], "offsets": [ [ 109, 126 ] ], "normalized": [] } ]

[ { "id": "PMID-9317131_E1", "type": "Positive_regulation", "trigger": { "text": [ "Cooperation" ], "offsets": [ [ 0, 11 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "PMID-9317131_E2" }, { "role": "Cause", "ref_id": "PMID-9317131_T1" }, { "role": "CSite", "ref_id": "PMID-9317131_T26" } ] }, { "id": "PMID-9317131_E2", "type": "Positive_regulation", "trigger": { "text": [ "up-regulation" ], "offsets": [ [ 78, 91 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "PMID-9317131_T3" }, { "role": "Cause", "ref_id": "PMID-9317131_T2" }, { "role": "Site", "ref_id": "PMID-9317131_T28" } ] }, { "id": "PMID-9317131_E3", "type": "Positive_regulation", "trigger": { "text": [ "inducing" ], "offsets": [ [ 418, 426 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "PMID-9317131_E4" }, { "role": "Cause", "ref_id": "PMID-9317131_T4" } ] }, { "id": "PMID-9317131_E4", "type": "Binding", "trigger": { "text": [ "interaction" ], "offsets": [ [ 431, 442 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "PMID-9317131_T5" } ] }, { "id": "PMID-9317131_E5", "type": "Binding", "trigger": { "text": [ "complex formed" ], "offsets": [ [ 813, 827 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "PMID-9317131_T9" }, { "role": "Theme", "ref_id": "PMID-9317131_T10" } ] }, { "id": "PMID-9317131_E6", "type": "Regulation", "trigger": { "text": [ "dependent" ], "offsets": [ [ 1334, 1343 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "PMID-9317131_T17" } ] }, { "id": "PMID-9317131_E7", "type": "Positive_regulation", "trigger": { "text": [ "conferred" ], "offsets": [ [ 1591, 1600 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "PMID-9317131_E8" } ] }, { "id": "PMID-9317131_E8", "type": "Positive_regulation", "trigger": { "text": [ "inducibility" ], "offsets": [ [ 1606, 1618 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "PMID-9317131_T21" } ] }, { "id": "PMID-9317131_E9", "type": "Positive_regulation", "trigger": { "text": [ "effect" ], "offsets": [ [ 1689, 1695 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "PMID-9317131_E8" } ] }, { "id": "PMID-9317131_E10", "type": "Binding", "trigger": { "text": [ "bound" ], "offsets": [ [ 1790, 1795 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "PMID-9317131_T23" } ] } ]

[ { "id": "PMID-9317131_1", "entity_ids": [ "PMID-9317131_T5", "PMID-9317131_T6" ] } ]

[]

[ { "id": "PMID-9317151__text", "type": "abstract", "text": [ "Dual effects of LPS antibodies on cellular uptake of LPS and LPS-induced proinflammatory functions. \nHuman phagocytes recognize bacterial LPS (endotoxin) through membrane CD14 (mCD14), a proinflammatory LPS receptor. This study tested the hypothesis that anti-LPS Abs neutralize endotoxin by blocking cellular uptake through mCD14. Ab-associated changes in the uptake and cellular distribution of FITC-LPS were assessed by flow cytometry and laser scanning confocal microscopy in human CD14-transfected Chinese hamster ovary fibroblasts (CHO-CD14 cells) and human peripheral blood monocytes. LPS core- and O-side chain-specific mAbs inhibited mCD14-mediated LPS uptake by both cell types in the presence of serum. O-side chain-specific mAb concurrently enhanced complement-dependent LPS uptake by monocytes through complement receptor-1 (CR1) and uptake by CHO-CD14 cells involving another heat-labile serum factor(s) and cell-associated recognition molecule(s). Core-specific mAb inhibited mCD14-mediated uptake of homologous and heterologous LPS, while producing less concurrent enhancement of non-mCD14-mediated LPS uptake. The modulation by anti-LPS mAbs of mCD14-mediated LPS uptake was associated with inhibition of LPS-induced nuclear factor-kappaB (NF-kappaB) translocation and TNF-alpha secretion in CHO-CD14 cells and monocytes, respectively, while mAb enhancement of non-mCD14-mediated LPS uptake stimulated these activities. LPS-specific Abs thus mediate anti-inflammatory and proinflammatory functions, respectively, by preventing target cell uptake of LPS through mCD14 and augmenting uptake through CR1 or other cell receptors. " ], "offsets": [ [ 0, 1643 ] ] } ]

[ { "id": "PMID-9317151_T1", "type": "Protein", "text": [ "CD14" ], "offsets": [ [ 171, 175 ] ], "normalized": [] }, { "id": "PMID-9317151_T2", "type": "Protein", "text": [ "mCD14" ], "offsets": [ [ 177, 182 ] ], "normalized": [] }, { "id": "PMID-9317151_T3", "type": "Protein", "text": [ "mCD14" ], "offsets": [ [ 325, 330 ] ], "normalized": [] }, { "id": "PMID-9317151_T4", "type": "Protein", "text": [ "CD14" ], "offsets": [ [ 486, 490 ] ], "normalized": [] }, { "id": "PMID-9317151_T5", "type": "Protein", "text": [ "CD14" ], "offsets": [ [ 542, 546 ] ], "normalized": [] }, { "id": "PMID-9317151_T6", "type": "Protein", "text": [ "mCD14" ], "offsets": [ [ 643, 648 ] ], "normalized": [] }, { "id": "PMID-9317151_T7", "type": "Protein", "text": [ "complement receptor-1" ], "offsets": [ [ 815, 836 ] ], "normalized": [] }, { "id": "PMID-9317151_T8", "type": "Protein", "text": [ "CR1" ], "offsets": [ [ 838, 841 ] ], "normalized": [] }, { "id": "PMID-9317151_T9", "type": "Protein", "text": [ "CD14" ], "offsets": [ [ 861, 865 ] ], "normalized": [] }, { "id": "PMID-9317151_T10", "type": "Protein", "text": [ "mCD14" ], "offsets": [ [ 991, 996 ] ], "normalized": [] }, { "id": "PMID-9317151_T11", "type": "Protein", "text": [ "mCD14" ], "offsets": [ [ 1100, 1105 ] ], "normalized": [] }, { "id": "PMID-9317151_T12", "type": "Protein", "text": [ "mCD14" ], "offsets": [ [ 1162, 1167 ] ], "normalized": [] }, { "id": "PMID-9317151_T13", "type": "Protein", "text": [ "TNF-alpha" ], "offsets": [ [ 1286, 1295 ] ], "normalized": [] }, { "id": "PMID-9317151_T14", "type": "Protein", "text": [ "CD14" ], "offsets": [ [ 1313, 1317 ] ], "normalized": [] }, { "id": "PMID-9317151_T15", "type": "Protein", "text": [ "mCD14" ], "offsets": [ [ 1382, 1387 ] ], "normalized": [] }, { "id": "PMID-9317151_T16", "type": "Protein", "text": [ "mCD14" ], "offsets": [ [ 1578, 1583 ] ], "normalized": [] }, { "id": "PMID-9317151_T17", "type": "Protein", "text": [ "CR1" ], "offsets": [ [ 1614, 1617 ] ], "normalized": [] } ]

[ { "id": "PMID-9317151_E1", "type": "Negative_regulation", "trigger": { "text": [ "inhibition" ], "offsets": [ [ 1208, 1218 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "PMID-9317151_E3" } ] }, { "id": "PMID-9317151_E2", "type": "Positive_regulation", "trigger": { "text": [ "induced" ], "offsets": [ [ 1226, 1233 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "PMID-9317151_E3" } ] }, { "id": "PMID-9317151_E3", "type": "Localization", "trigger": { "text": [ "secretion" ], "offsets": [ [ 1296, 1305 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "PMID-9317151_T13" } ] }, { "id": "PMID-9317151_E4", "type": "Positive_regulation", "trigger": { "text": [ "stimulated" ], "offsets": [ [ 1408, 1418 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "PMID-9317151_E2" } ] } ]

[ { "id": "PMID-9317151_1", "entity_ids": [ "PMID-9317151_T1", "PMID-9317151_T2" ] }, { "id": "PMID-9317151_2", "entity_ids": [ "PMID-9317151_T7", "PMID-9317151_T8" ] } ]

[]

[ { "id": "PMID-9322967__text", "type": "abstract", "text": [ "Human neutrophils express GH-N gene transcripts and the pituitary transcription factor Pit-1b. \nSince GH stimulates the development and function of granulocytes, we investigated the expression of GH in granulocyte subsets. By immunocytochemistry, 25 +/- 7% of the human neutrophils were shown to express immunoreactive GH, whereas eosinophils were negative. Reversed transcription (RT)-PCR analysis demonstrated GH mRNA in neutrophils. Restriction analysis revealed that neutrophils express the GH-N gene but not the GH-V gene. Furthermore, we demonstrated by western blot analysis that neutrophils express an alternatively spliced variant of the pituitary transcription factor Pit-1, designated Pit-1b. " ], "offsets": [ [ 0, 704 ] ] } ]

[ { "id": "PMID-9322967_T1", "type": "Protein", "text": [ "GH-N" ], "offsets": [ [ 26, 30 ] ], "normalized": [] }, { "id": "PMID-9322967_T2", "type": "Protein", "text": [ "Pit-1b" ], "offsets": [ [ 87, 93 ] ], "normalized": [] }, { "id": "PMID-9322967_T3", "type": "Protein", "text": [ "GH" ], "offsets": [ [ 102, 104 ] ], "normalized": [] }, { "id": "PMID-9322967_T4", "type": "Protein", "text": [ "GH" ], "offsets": [ [ 196, 198 ] ], "normalized": [] }, { "id": "PMID-9322967_T5", "type": "Protein", "text": [ "GH" ], "offsets": [ [ 319, 321 ] ], "normalized": [] }, { "id": "PMID-9322967_T6", "type": "Protein", "text": [ "GH" ], "offsets": [ [ 412, 414 ] ], "normalized": [] }, { "id": "PMID-9322967_T7", "type": "Protein", "text": [ "GH-N" ], "offsets": [ [ 495, 499 ] ], "normalized": [] }, { "id": "PMID-9322967_T8", "type": "Protein", "text": [ "GH-V" ], "offsets": [ [ 517, 521 ] ], "normalized": [] }, { "id": "PMID-9322967_T9", "type": "Protein", "text": [ "Pit-1" ], "offsets": [ [ 678, 683 ] ], "normalized": [] }, { "id": "PMID-9322967_T10", "type": "Protein", "text": [ "Pit-1b" ], "offsets": [ [ 696, 702 ] ], "normalized": [] } ]

[ { "id": "PMID-9322967_E1", "type": "Gene_expression", "trigger": { "text": [ "express" ], "offsets": [ [ 18, 25 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "PMID-9322967_T2" } ] }, { "id": "PMID-9322967_E2", "type": "Transcription", "trigger": { "text": [ "express" ], "offsets": [ [ 18, 25 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "PMID-9322967_T1" } ] }, { "id": "PMID-9322967_E3", "type": "Gene_expression", "trigger": { "text": [ "expression" ], "offsets": [ [ 182, 192 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "PMID-9322967_T4" } ] }, { "id": "PMID-9322967_E4", "type": "Gene_expression", "trigger": { "text": [ "express" ], "offsets": [ [ 296, 303 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "PMID-9322967_T5" } ] }, { "id": "PMID-9322967_E5", "type": "Gene_expression", "trigger": { "text": [ "negative" ], "offsets": [ [ 348, 356 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "PMID-9322967_T5" } ] }, { "id": "PMID-9322967_E6", "type": "Transcription", "trigger": { "text": [ "demonstrated" ], "offsets": [ [ 399, 411 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "PMID-9322967_T6" } ] }, { "id": "PMID-9322967_E7", "type": "Gene_expression", "trigger": { "text": [ "express" ], "offsets": [ [ 483, 490 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "PMID-9322967_T7" } ] }, { "id": "PMID-9322967_E8", "type": "Gene_expression", "trigger": { "text": [ "express" ], "offsets": [ [ 483, 490 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "PMID-9322967_T8" } ] }, { "id": "PMID-9322967_E9", "type": "Gene_expression", "trigger": { "text": [ "express" ], "offsets": [ [ 599, 606 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "PMID-9322967_T10" } ] } ]

[]

[]

[ { "id": "PMID-9326236__text", "type": "abstract", "text": [ "Interleukin-7 upregulates the interleukin-2-gene expression in activated human T lymphocytes at the transcriptional level by enhancing the DNA binding activities of both nuclear factor of activated T cells and activator protein-1. \nIn the present report, we studied the role of the stromal-derived cytokine interleukin-7 (IL-7) in the IL-2-gene regulation in activated T lymphocytes. Production of IL-2 requires the formation of transcription factors involved in the IL-2-gene regulation. T-cell receptor (TCR)/CD3 engagement results in the activation of nuclear factor of activated T cells (NFAT), activator protein-1 (AP-1), and nuclear factor kappaB (NFkappaB), whereas the CD28 responsive complex (CD28RC) is activated in response to the CD28 signal. Costimulation of phytohemagglutinin/anti-CD28 activated T lymphocytes with IL-7 induces a fivefold enhanced IL-2-mRNA accumulation and a 2.5-fold enhanced protein secretion. The IL-2-gene transcription rate is increased 3.4-fold, indicating that the effect of IL-7 is in part mediated at the transcriptional level. The molecular mechanisms underlying the IL-7 effect involve the upregulation of the DNA binding activity of NFAT (60%) and AP-1 (120%), without affecting the activities of NFkappaB and CD28RC, which was confirmed by transfection assays. We also show that the IL-7-induced enhancement of the AP-1-DNA binding activity is not cyclosporin A-sensitive. Since AP-1 is part of the NFAT complex, we conclude that the IL-7-signaling pathway is involved in the activation of the fos and jun proteins of which AP-1 consists. " ], "offsets": [ [ 0, 1585 ] ] } ]

[ { "id": "PMID-9326236_T1", "type": "Protein", "text": [ "Interleukin-7" ], "offsets": [ [ 0, 13 ] ], "normalized": [] }, { "id": "PMID-9326236_T2", "type": "Protein", "text": [ "interleukin-2" ], "offsets": [ [ 30, 43 ] ], "normalized": [] }, { "id": "PMID-9326236_T3", "type": "Protein", "text": [ "interleukin-7" ], "offsets": [ [ 307, 320 ] ], "normalized": [] }, { "id": "PMID-9326236_T4", "type": "Protein", "text": [ "IL-7" ], "offsets": [ [ 322, 326 ] ], "normalized": [] }, { "id": "PMID-9326236_T5", "type": "Protein", "text": [ "IL-2" ], "offsets": [ [ 335, 339 ] ], "normalized": [] }, { "id": "PMID-9326236_T6", "type": "Protein", "text": [ "IL-2" ], "offsets": [ [ 398, 402 ] ], "normalized": [] }, { "id": "PMID-9326236_T7", "type": "Protein", "text": [ "IL-2" ], "offsets": [ [ 467, 471 ] ], "normalized": [] }, { "id": "PMID-9326236_T8", "type": "Protein", "text": [ "CD28" ], "offsets": [ [ 742, 746 ] ], "normalized": [] }, { "id": "PMID-9326236_T9", "type": "Protein", "text": [ "phytohemagglutinin" ], "offsets": [ [ 772, 790 ] ], "normalized": [] }, { "id": "PMID-9326236_T10", "type": "Protein", "text": [ "CD28" ], "offsets": [ [ 796, 800 ] ], "normalized": [] }, { "id": "PMID-9326236_T11", "type": "Protein", "text": [ "IL-7" ], "offsets": [ [ 830, 834 ] ], "normalized": [] }, { "id": "PMID-9326236_T12", "type": "Protein", "text": [ "IL-2" ], "offsets": [ [ 863, 867 ] ], "normalized": [] }, { "id": "PMID-9326236_T13", "type": "Protein", "text": [ "IL-2" ], "offsets": [ [ 933, 937 ] ], "normalized": [] }, { "id": "PMID-9326236_T14", "type": "Protein", "text": [ "IL-7" ], "offsets": [ [ 1015, 1019 ] ], "normalized": [] }, { "id": "PMID-9326236_T15", "type": "Protein", "text": [ "IL-7" ], "offsets": [ [ 1110, 1114 ] ], "normalized": [] }, { "id": "PMID-9326236_T16", "type": "Protein", "text": [ "IL-7" ], "offsets": [ [ 1329, 1333 ] ], "normalized": [] }, { "id": "PMID-9326236_T17", "type": "Protein", "text": [ "IL-7" ], "offsets": [ [ 1480, 1484 ] ], "normalized": [] }, { "id": "PMID-9326236_T18", "type": "Protein", "text": [ "fos" ], "offsets": [ [ 1540, 1543 ] ], "normalized": [] }, { "id": "PMID-9326236_T19", "type": "Protein", "text": [ "jun" ], "offsets": [ [ 1548, 1551 ] ], "normalized": [] } ]

[ { "id": "PMID-9326236_E1", "type": "Positive_regulation", "trigger": { "text": [ "upregulates" ], "offsets": [ [ 14, 25 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "PMID-9326236_E2" } ] }, { "id": "PMID-9326236_E2", "type": "Transcription", "trigger": { "text": [ "at the transcriptional level" ], "offsets": [ [ 93, 121 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "PMID-9326236_T2" } ] }, { "id": "PMID-9326236_E3", "type": "Regulation", "trigger": { "text": [ "role" ], "offsets": [ [ 270, 274 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "PMID-9326236_E4" }, { "role": "Cause", "ref_id": "PMID-9326236_T4" } ] }, { "id": "PMID-9326236_E4", "type": "Regulation", "trigger": { "text": [ "regulation" ], "offsets": [ [ 345, 355 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "PMID-9326236_T5" } ] }, { "id": "PMID-9326236_E5", "type": "Gene_expression", "trigger": { "text": [ "Production" ], "offsets": [ [ 384, 394 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "PMID-9326236_T6" } ] }, { "id": "PMID-9326236_E6", "type": "Regulation", "trigger": { "text": [ "requires" ], "offsets": [ [ 403, 411 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "PMID-9326236_E5" } ] }, { "id": "PMID-9326236_E7", "type": "Regulation", "trigger": { "text": [ "involved" ], "offsets": [ [ 451, 459 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "PMID-9326236_E8" } ] }, { "id": "PMID-9326236_E8", "type": "Regulation", "trigger": { "text": [ "regulation" ], "offsets": [ [ 477, 487 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "PMID-9326236_T7" } ] }, { "id": "PMID-9326236_E9", "type": "Positive_regulation", "trigger": { "text": [ "enhanced" ], "offsets": [ [ 854, 862 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "PMID-9326236_E10" } ] }, { "id": "PMID-9326236_E10", "type": "Positive_regulation", "trigger": { "text": [ "accumulation" ], "offsets": [ [ 873, 885 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "PMID-9326236_T12" } ] }, { "id": "PMID-9326236_E11", "type": "Transcription", "trigger": { "text": [ "transcription" ], "offsets": [ [ 943, 956 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "PMID-9326236_T13" } ] }, { "id": "PMID-9326236_E12", "type": "Positive_regulation", "trigger": { "text": [ "increased" ], "offsets": [ [ 965, 974 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "PMID-9326236_E11" } ] }, { "id": "PMID-9326236_E13", "type": "Positive_regulation", "trigger": { "text": [ "mediated" ], "offsets": [ [ 1031, 1039 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "PMID-9326236_E11" }, { "role": "Cause", "ref_id": "PMID-9326236_T14" } ] }, { "id": "PMID-9326236_E14", "type": "Regulation", "trigger": { "text": [ "involved" ], "offsets": [ [ 1506, 1514 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "PMID-9326236_E15" } ] }, { "id": "PMID-9326236_E15", "type": "Positive_regulation", "trigger": { "text": [ "activation" ], "offsets": [ [ 1522, 1532 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "PMID-9326236_T18" } ] } ]

[ { "id": "PMID-9326236_1", "entity_ids": [ "PMID-9326236_T4", "PMID-9326236_T3" ] } ]

[]

[ { "id": "PMID-9334193__text", "type": "abstract", "text": [ "Monochloramine inhibits phorbol ester-inducible neutrophil respiratory burst activation and T cell interleukin-2 receptor expression by inhibiting inducible protein kinase C activity. \nMonochloramine derivatives are long lived physiological oxidants produced by neutrophils during the respiratory burst. The effects of chemically prepared monochloramine (NH2Cl) on protein kinase C (PKC) and PKC-mediated cellular responses were studied in elicited rat peritoneal neutrophils and human Jurkat T cells. Neutrophils pretreated with NH2Cl (30-50 microM) showed a marked decrease in the respiratory burst activity induced by phorbol 12-myristate 13-acetate (PMA), which is a potent PKC activator. These cells, however, were viable and showed a complete respiratory burst upon arachidonic acid stimulation, which induces the respiratory burst by a PKC-independent mechanism. The NH2Cl-treated neutrophils showed a decrease in both PKC activity and PMA-induced phosphorylation of a 47-kDa protein, which corresponds to the cytosolic factor of NADPH oxidase, p47(phox). Jurkat T cells pretreated with NH2Cl (20-70 microM) showed a decrease in the expression of the interleukin-2 receptor alpha chain following PMA stimulation. This was also accompanied by a decrease in both PKC activity and nuclear transcription factor-kappaB activation, also without loss of cell viability. These results show that NH2Cl inhibits PKC-mediated cellular responses through inhibition of the inducible PKC activity. " ], "offsets": [ [ 0, 1491 ] ] } ]

[ { "id": "PMID-9334193_T1", "type": "Protein", "text": [ "p47(phox)" ], "offsets": [ [ 1052, 1061 ] ], "normalized": [] }, { "id": "PMID-9334193_T2", "type": "Protein", "text": [ "interleukin-2 receptor alpha chain" ], "offsets": [ [ 1158, 1192 ] ], "normalized": [] } ]

[ { "id": "PMID-9334193_E1", "type": "Negative_regulation", "trigger": { "text": [ "decrease" ], "offsets": [ [ 909, 917 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "PMID-9334193_E3" } ] }, { "id": "PMID-9334193_E2", "type": "Positive_regulation", "trigger": { "text": [ "induced" ], "offsets": [ [ 947, 954 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "PMID-9334193_E3" } ] }, { "id": "PMID-9334193_E3", "type": "Phosphorylation", "trigger": { "text": [ "phosphorylation" ], "offsets": [ [ 955, 970 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "PMID-9334193_T1" } ] }, { "id": "PMID-9334193_E4", "type": "Negative_regulation", "trigger": { "text": [ "decrease" ], "offsets": [ [ 1124, 1132 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "PMID-9334193_E5" } ] }, { "id": "PMID-9334193_E5", "type": "Gene_expression", "trigger": { "text": [ "expression" ], "offsets": [ [ 1140, 1150 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "PMID-9334193_T2" } ] } ]

[]

[]

[ { "id": "PMID-9334723__text", "type": "abstract", "text": [ "HIV-1 Vpr suppresses immune activation and apoptosis through regulation of nuclear factor kappa B [see comments] \nThe HIV-1 accessory gene product Vpr can influence viral pathogenesis by affecting viral replication as well as host cell transcription and proliferation. We have investigated the effects of Vpr on host cell activation and confirm that it influences cellular proliferation. However, we have also found that Vpr modulates T-cell receptor (TCR)-triggered apoptosis in a manner similar to that of glucocorticoids. In the absence of TCR-mediated activation, Vpr induces apoptosis whereas in its presence, Vpr interrupts the expected induction of apoptosis. This regulation of apoptosis is linked to Vpr suppression of NF-kappa B activity via the induction of I kappa B, an inhibitor of NF-kappa B. Further, Vpr suppresses expression of IL-2, IL-10, IL-12, TNF alpha and IL-4, all of which are NF-kappa B-dependent. The effects of Vpr could be reversed by RU486. Our finding that Vpr can regulate NF-kappa B supports the hypothesis that some aspects of viral pathogenesis are the consequence of cell dysregulation by Vpr. " ], "offsets": [ [ 0, 1131 ] ] } ]

[ { "id": "PMID-9334723_T1", "type": "Protein", "text": [ "Vpr" ], "offsets": [ [ 6, 9 ] ], "normalized": [] }, { "id": "PMID-9334723_T2", "type": "Protein", "text": [ "Vpr" ], "offsets": [ [ 147, 150 ] ], "normalized": [] }, { "id": "PMID-9334723_T3", "type": "Protein", "text": [ "Vpr" ], "offsets": [ [ 305, 308 ] ], "normalized": [] }, { "id": "PMID-9334723_T4", "type": "Protein", "text": [ "Vpr" ], "offsets": [ [ 421, 424 ] ], "normalized": [] }, { "id": "PMID-9334723_T5", "type": "Protein", "text": [ "Vpr" ], "offsets": [ [ 568, 571 ] ], "normalized": [] }, { "id": "PMID-9334723_T6", "type": "Protein", "text": [ "Vpr" ], "offsets": [ [ 615, 618 ] ], "normalized": [] }, { "id": "PMID-9334723_T7", "type": "Protein", "text": [ "Vpr" ], "offsets": [ [ 709, 712 ] ], "normalized": [] }, { "id": "PMID-9334723_T8", "type": "Protein", "text": [ "Vpr" ], "offsets": [ [ 817, 820 ] ], "normalized": [] }, { "id": "PMID-9334723_T9", "type": "Protein", "text": [ "IL-2" ], "offsets": [ [ 846, 850 ] ], "normalized": [] }, { "id": "PMID-9334723_T10", "type": "Protein", "text": [ "IL-10" ], "offsets": [ [ 852, 857 ] ], "normalized": [] }, { "id": "PMID-9334723_T11", "type": "Protein", "text": [ "TNF alpha" ], "offsets": [ [ 866, 875 ] ], "normalized": [] }, { "id": "PMID-9334723_T12", "type": "Protein", "text": [ "IL-4" ], "offsets": [ [ 880, 884 ] ], "normalized": [] }, { "id": "PMID-9334723_T13", "type": "Protein", "text": [ "Vpr" ], "offsets": [ [ 940, 943 ] ], "normalized": [] }, { "id": "PMID-9334723_T14", "type": "Protein", "text": [ "Vpr" ], "offsets": [ [ 989, 992 ] ], "normalized": [] }, { "id": "PMID-9334723_T15", "type": "Protein", "text": [ "Vpr" ], "offsets": [ [ 1126, 1129 ] ], "normalized": [] } ]

[ { "id": "PMID-9334723_E1", "type": "Negative_regulation", "trigger": { "text": [ "suppresses" ], "offsets": [ [ 821, 831 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "PMID-9334723_E5" }, { "role": "Cause", "ref_id": "PMID-9334723_T8" } ] }, { "id": "PMID-9334723_E2", "type": "Negative_regulation", "trigger": { "text": [ "suppresses" ], "offsets": [ [ 821, 831 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "PMID-9334723_E8" }, { "role": "Cause", "ref_id": "PMID-9334723_T8" } ] }, { "id": "PMID-9334723_E3", "type": "Negative_regulation", "trigger": { "text": [ "suppresses" ], "offsets": [ [ 821, 831 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "PMID-9334723_E6" }, { "role": "Cause", "ref_id": "PMID-9334723_T8" } ] }, { "id": "PMID-9334723_E4", "type": "Negative_regulation", "trigger": { "text": [ "suppresses" ], "offsets": [ [ 821, 831 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "PMID-9334723_E7" }, { "role": "Cause", "ref_id": "PMID-9334723_T8" } ] }, { "id": "PMID-9334723_E5", "type": "Gene_expression", "trigger": { "text": [ "expression" ], "offsets": [ [ 832, 842 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "PMID-9334723_T10" } ] }, { "id": "PMID-9334723_E6", "type": "Gene_expression", "trigger": { "text": [ "expression" ], "offsets": [ [ 832, 842 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "PMID-9334723_T11" } ] }, { "id": "PMID-9334723_E7", "type": "Gene_expression", "trigger": { "text": [ "expression" ], "offsets": [ [ 832, 842 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "PMID-9334723_T12" } ] }, { "id": "PMID-9334723_E8", "type": "Gene_expression", "trigger": { "text": [ "expression" ], "offsets": [ [ 832, 842 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "PMID-9334723_T9" } ] }, { "id": "PMID-9334723_E9", "type": "Regulation", "trigger": { "text": [ "dependent" ], "offsets": [ [ 914, 923 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "PMID-9334723_E7" } ] }, { "id": "PMID-9334723_E10", "type": "Regulation", "trigger": { "text": [ "dependent" ], "offsets": [ [ 914, 923 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "PMID-9334723_E6" } ] }, { "id": "PMID-9334723_E11", "type": "Regulation", "trigger": { "text": [ "dependent" ], "offsets": [ [ 914, 923 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "PMID-9334723_E8" } ] }, { "id": "PMID-9334723_E12", "type": "Regulation", "trigger": { "text": [ "dependent" ], "offsets": [ [ 914, 923 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "PMID-9334723_E5" } ] }, { "id": "PMID-9334723_E13", "type": "Negative_regulation", "trigger": { "text": [ "reversed" ], "offsets": [ [ 953, 961 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "PMID-9334723_T13" } ] } ]

[]

[]

[ { "id": "PMID-9341193__text", "type": "abstract", "text": [ "The tax protein of human T-cell leukemia virus type 1 mediates the transactivation of the c-sis/platelet-derived growth factor-B promoter through interactions with the zinc finger transcription factors Sp1 and NGFI-A/Egr-1. \nTranscriptional up-regulation of the c-sis/platelet-derived growth factor-B (PDGF-B) proto-oncogene by the Tax protein of human T-cell leukemia virus type 1 has been implicated as one possible mechanism of cellular transformation by human T-cell leukemia virus type 1. In previous work, we identified an essential site in the c-sis/PDGF-B promoter, Tax-responsive element 1 (TRE1), necessary for transactivation by Tax. We also identified Sp1, Sp3, and NGFI-A/Egr-1 as the primary nuclear transcription factors binding to TRE1 which mediate Tax responsiveness. In the present work, we have investigated the mechanism(s) whereby Tax transactivates the c-sis/PDGF-B proto-oncogene. In vitro transcription assays showed that Tax was able to significantly increase the transcriptional activity of a template containing the -257 to +74 region of the c-sis/PDGF-B promoter. Electrophoretic mobility shift assay analysis showed that Tax increased the DNA binding activity of both Sp1 and NGFI-A/Egr-1 using a TRE1 probe. Analysis of Tax mutants showed that two mutants, IEXC29S and IEXL320G, were unable to significantly transactivate the c-sis/PDGF-B promoter. Finally, co-immunoprecipitation analysis revealed that Tax is able to stably bind to both Sp1 and NGFI-A/Egr-1. Interestingly, co-immunoprecipitation analysis also revealed that Tax mutant IEXC29S is unable to interact with NGFI-A/Egr-1, whereas Tax mutant IEXL320G is able to interact with NGFI-A/Egr-1. " ], "offsets": [ [ 0, 1685 ] ] } ]

[ { "id": "PMID-9341193_T1", "type": "Protein", "text": [ "tax" ], "offsets": [ [ 4, 7 ] ], "normalized": [] }, { "id": "PMID-9341193_T2", "type": "Protein", "text": [ "c-sis" ], "offsets": [ [ 90, 95 ] ], "normalized": [] }, { "id": "PMID-9341193_T3", "type": "Protein", "text": [ "platelet-derived growth factor-B" ], "offsets": [ [ 96, 128 ] ], "normalized": [] }, { "id": "PMID-9341193_T4", "type": "Protein", "text": [ "Sp1" ], "offsets": [ [ 202, 205 ] ], "normalized": [] }, { "id": "PMID-9341193_T5", "type": "Protein", "text": [ "NGFI-A" ], "offsets": [ [ 210, 216 ] ], "normalized": [] }, { "id": "PMID-9341193_T6", "type": "Protein", "text": [ "Egr-1" ], "offsets": [ [ 217, 222 ] ], "normalized": [] }, { "id": "PMID-9341193_T7", "type": "Protein", "text": [ "c-sis" ], "offsets": [ [ 262, 267 ] ], "normalized": [] }, { "id": "PMID-9341193_T8", "type": "Protein", "text": [ "platelet-derived growth factor-B" ], "offsets": [ [ 268, 300 ] ], "normalized": [] }, { "id": "PMID-9341193_T9", "type": "Protein", "text": [ "PDGF-B" ], "offsets": [ [ 302, 308 ] ], "normalized": [] }, { "id": "PMID-9341193_T10", "type": "Protein", "text": [ "Tax" ], "offsets": [ [ 332, 335 ] ], "normalized": [] }, { "id": "PMID-9341193_T11", "type": "Protein", "text": [ "c-sis" ], "offsets": [ [ 551, 556 ] ], "normalized": [] }, { "id": "PMID-9341193_T12", "type": "Protein", "text": [ "PDGF-B" ], "offsets": [ [ 557, 563 ] ], "normalized": [] }, { "id": "PMID-9341193_T13", "type": "Protein", "text": [ "Tax" ], "offsets": [ [ 574, 577 ] ], "normalized": [] }, { "id": "PMID-9341193_T14", "type": "Protein", "text": [ "Tax" ], "offsets": [ [ 640, 643 ] ], "normalized": [] }, { "id": "PMID-9341193_T15", "type": "Protein", "text": [ "Sp1" ], "offsets": [ [ 664, 667 ] ], "normalized": [] }, { "id": "PMID-9341193_T16", "type": "Protein", "text": [ "Sp3" ], "offsets": [ [ 669, 672 ] ], "normalized": [] }, { "id": "PMID-9341193_T17", "type": "Protein", "text": [ "NGFI-A" ], "offsets": [ [ 678, 684 ] ], "normalized": [] }, { "id": "PMID-9341193_T18", "type": "Protein", "text": [ "Egr-1" ], "offsets": [ [ 685, 690 ] ], "normalized": [] }, { "id": "PMID-9341193_T19", "type": "Protein", "text": [ "Tax" ], "offsets": [ [ 766, 769 ] ], "normalized": [] }, { "id": "PMID-9341193_T20", "type": "Protein", "text": [ "Tax" ], "offsets": [ [ 853, 856 ] ], "normalized": [] }, { "id": "PMID-9341193_T21", "type": "Protein", "text": [ "c-sis" ], "offsets": [ [ 876, 881 ] ], "normalized": [] }, { "id": "PMID-9341193_T22", "type": "Protein", "text": [ "PDGF-B" ], "offsets": [ [ 882, 888 ] ], "normalized": [] }, { "id": "PMID-9341193_T23", "type": "Protein", "text": [ "Tax" ], "offsets": [ [ 947, 950 ] ], "normalized": [] }, { "id": "PMID-9341193_T24", "type": "Protein", "text": [ "c-sis" ], "offsets": [ [ 1070, 1075 ] ], "normalized": [] }, { "id": "PMID-9341193_T25", "type": "Protein", "text": [ "PDGF-B" ], "offsets": [ [ 1076, 1082 ] ], "normalized": [] }, { "id": "PMID-9341193_T26", "type": "Protein", "text": [ "Tax" ], "offsets": [ [ 1151, 1154 ] ], "normalized": [] }, { "id": "PMID-9341193_T27", "type": "Protein", "text": [ "Sp1" ], "offsets": [ [ 1198, 1201 ] ], "normalized": [] }, { "id": "PMID-9341193_T28", "type": "Protein", "text": [ "NGFI-A" ], "offsets": [ [ 1206, 1212 ] ], "normalized": [] }, { "id": "PMID-9341193_T29", "type": "Protein", "text": [ "Egr-1" ], "offsets": [ [ 1213, 1218 ] ], "normalized": [] }, { "id": "PMID-9341193_T30", "type": "Protein", "text": [ "Tax" ], "offsets": [ [ 1251, 1254 ] ], "normalized": [] }, { "id": "PMID-9341193_T31", "type": "Protein", "text": [ "c-sis" ], "offsets": [ [ 1357, 1362 ] ], "normalized": [] }, { "id": "PMID-9341193_T32", "type": "Protein", "text": [ "PDGF-B" ], "offsets": [ [ 1363, 1369 ] ], "normalized": [] }, { "id": "PMID-9341193_T33", "type": "Protein", "text": [ "Tax" ], "offsets": [ [ 1435, 1438 ] ], "normalized": [] }, { "id": "PMID-9341193_T34", "type": "Protein", "text": [ "Sp1" ], "offsets": [ [ 1470, 1473 ] ], "normalized": [] }, { "id": "PMID-9341193_T35", "type": "Protein", "text": [ "NGFI-A" ], "offsets": [ [ 1478, 1484 ] ], "normalized": [] }, { "id": "PMID-9341193_T36", "type": "Protein", "text": [ "Egr-1" ], "offsets": [ [ 1485, 1490 ] ], "normalized": [] }, { "id": "PMID-9341193_T37", "type": "Protein", "text": [ "Tax" ], "offsets": [ [ 1558, 1561 ] ], "normalized": [] }, { "id": "PMID-9341193_T38", "type": "Protein", "text": [ "NGFI-A" ], "offsets": [ [ 1604, 1610 ] ], "normalized": [] }, { "id": "PMID-9341193_T39", "type": "Protein", "text": [ "Egr-1" ], "offsets": [ [ 1611, 1616 ] ], "normalized": [] }, { "id": "PMID-9341193_T40", "type": "Protein", "text": [ "Tax" ], "offsets": [ [ 1626, 1629 ] ], "normalized": [] }, { "id": "PMID-9341193_T41", "type": "Protein", "text": [ "NGFI-A" ], "offsets": [ [ 1671, 1677 ] ], "normalized": [] }, { "id": "PMID-9341193_T42", "type": "Protein", "text": [ "Egr-1" ], "offsets": [ [ 1678, 1683 ] ], "normalized": [] }, { "id": "PMID-9341193_T44", "type": "Entity", "text": [ "promoter" ], "offsets": [ [ 129, 137 ] ], "normalized": [] }, { "id": "PMID-9341193_T54", "type": "Entity", "text": [ "promoter" ], "offsets": [ [ 1370, 1378 ] ], "normalized": [] } ]

[ { "id": "PMID-9341193_E1", "type": "Positive_regulation", "trigger": { "text": [ "transactivation" ], "offsets": [ [ 67, 82 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "PMID-9341193_T2" }, { "role": "Cause", "ref_id": "PMID-9341193_E4" }, { "role": "Site", "ref_id": "PMID-9341193_T44" } ] }, { "id": "PMID-9341193_E2", "type": "Positive_regulation", "trigger": { "text": [ "transactivation" ], "offsets": [ [ 67, 82 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "PMID-9341193_T2" }, { "role": "Cause", "ref_id": "PMID-9341193_E3" }, { "role": "Site", "ref_id": "PMID-9341193_T44" } ] }, { "id": "PMID-9341193_E3", "type": "Binding", "trigger": { "text": [ "interactions" ], "offsets": [ [ 146, 158 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "PMID-9341193_T1" }, { "role": "Theme", "ref_id": "PMID-9341193_T4" } ] }, { "id": "PMID-9341193_E4", "type": "Binding", "trigger": { "text": [ "interactions" ], "offsets": [ [ 146, 158 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "PMID-9341193_T1" }, { "role": "Theme", "ref_id": "PMID-9341193_T5" } ] }, { "id": "PMID-9341193_E5", "type": "Positive_regulation", "trigger": { "text": [ "Transcriptional up-regulation" ], "offsets": [ [ 225, 254 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "PMID-9341193_T7" }, { "role": "Cause", "ref_id": "PMID-9341193_T10" } ] }, { "id": "PMID-9341193_E6", "type": "Binding", "trigger": { "text": [ "binding" ], "offsets": [ [ 736, 743 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "PMID-9341193_T15" } ] }, { "id": "PMID-9341193_E7", "type": "Binding", "trigger": { "text": [ "binding" ], "offsets": [ [ 736, 743 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "PMID-9341193_T16" } ] }, { "id": "PMID-9341193_E8", "type": "Binding", "trigger": { "text": [ "binding" ], "offsets": [ [ 736, 743 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "PMID-9341193_T17" } ] }, { "id": "PMID-9341193_E9", "type": "Positive_regulation", "trigger": { "text": [ "transactivates" ], "offsets": [ [ 857, 871 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "PMID-9341193_T21" }, { "role": "Cause", "ref_id": "PMID-9341193_T20" } ] }, { "id": "PMID-9341193_E10", "type": "Positive_regulation", "trigger": { "text": [ "increase" ], "offsets": [ [ 977, 985 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "PMID-9341193_E11" }, { "role": "Cause", "ref_id": "PMID-9341193_T23" } ] }, { "id": "PMID-9341193_E11", "type": "Transcription", "trigger": { "text": [ "transcriptional activity" ], "offsets": [ [ 990, 1014 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "PMID-9341193_T24" } ] }, { "id": "PMID-9341193_E12", "type": "Positive_regulation", "trigger": { "text": [ "increased" ], "offsets": [ [ 1155, 1164 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "PMID-9341193_E15" }, { "role": "Cause", "ref_id": "PMID-9341193_T26" } ] }, { "id": "PMID-9341193_E13", "type": "Positive_regulation", "trigger": { "text": [ "increased" ], "offsets": [ [ 1155, 1164 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "PMID-9341193_E14" }, { "role": "Cause", "ref_id": "PMID-9341193_T26" } ] }, { "id": "PMID-9341193_E14", "type": "Binding", "trigger": { "text": [ "binding activity" ], "offsets": [ [ 1173, 1189 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "PMID-9341193_T28" } ] }, { "id": "PMID-9341193_E15", "type": "Binding", "trigger": { "text": [ "binding activity" ], "offsets": [ [ 1173, 1189 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "PMID-9341193_T27" } ] }, { "id": "PMID-9341193_E16", "type": "Positive_regulation", "trigger": { "text": [ "transactivate" ], "offsets": [ [ 1339, 1352 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "PMID-9341193_T31" }, { "role": "Site", "ref_id": "PMID-9341193_T54" } ] }, { "id": "PMID-9341193_E17", "type": "Binding", "trigger": { "text": [ "bind" ], "offsets": [ [ 1457, 1461 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "PMID-9341193_T33" }, { "role": "Theme", "ref_id": "PMID-9341193_T34" } ] }, { "id": "PMID-9341193_E18", "type": "Binding", "trigger": { "text": [ "bind" ], "offsets": [ [ 1457, 1461 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "PMID-9341193_T33" }, { "role": "Theme", "ref_id": "PMID-9341193_T35" } ] }, { "id": "PMID-9341193_E19", "type": "Binding", "trigger": { "text": [ "interact" ], "offsets": [ [ 1590, 1598 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "PMID-9341193_T38" } ] }, { "id": "PMID-9341193_E20", "type": "Binding", "trigger": { "text": [ "interact" ], "offsets": [ [ 1657, 1665 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "PMID-9341193_T42" } ] } ]

[ { "id": "PMID-9341193_1", "entity_ids": [ "PMID-9341193_T28", "PMID-9341193_T29" ] }, { "id": "PMID-9341193_2", "entity_ids": [ "PMID-9341193_T11", "PMID-9341193_T12" ] }, { "id": "PMID-9341193_3", "entity_ids": [ "PMID-9341193_T35", "PMID-9341193_T36" ] }, { "id": "PMID-9341193_4", "entity_ids": [ "PMID-9341193_T2", "PMID-9341193_T3" ] }, { "id": "PMID-9341193_5", "entity_ids": [ "PMID-9341193_T17", "PMID-9341193_T18" ] }, { "id": "PMID-9341193_6", "entity_ids": [ "PMID-9341193_T38", "PMID-9341193_T39" ] }, { "id": "PMID-9341193_7", "entity_ids": [ "PMID-9341193_T24", "PMID-9341193_T25" ] }, { "id": "PMID-9341193_8", "entity_ids": [ "PMID-9341193_T31", "PMID-9341193_T32" ] }, { "id": "PMID-9341193_9", "entity_ids": [ "PMID-9341193_T21", "PMID-9341193_T22" ] }, { "id": "PMID-9341193_10", "entity_ids": [ "PMID-9341193_T5", "PMID-9341193_T6" ] }, { "id": "PMID-9341193_11", "entity_ids": [ "PMID-9341193_T42", "PMID-9341193_T41" ] }, { "id": "PMID-9341193_12", "entity_ids": [ "PMID-9341193_T7", "PMID-9341193_T8", "PMID-9341193_T9" ] } ]

[]

[ { "id": "PMID-9341756__text", "type": "abstract", "text": [ "Induction of endothelial cell surface adhesion molecules by tumor necrosis factor is blocked by protein tyrosine phosphatase inhibitors: role of the nuclear transcription factor NF-kappa B. \nRecent studies from our laboratory have indicated that protein tyrosine phosphatase (PTPase) inhibitors can down-modulate the tumor necrosis factor (TNF)-mediated activation of the nuclear transcription factor NF-kappa B in ML-1a, a monocytic cell line (Singh and Aggarwal, J. Biol. Chem. 1995: 270: 10631). Since TNF is one of the major inducers of various adhesion molecules in human endothelial cells and their expression is known to require the activation of NF-kappa B, we examined the effect of PTPase inhibitors on the TNF-mediated induction of intracellular adhesion molecule (ICAM)-1, vascular cell adhesion molecule (VCAM)-1 and endothelial leukocyte adhesion molecule (ELAM)-1. Like ML-1a, human dermal microvessel endothelial cells (MVEC) treated with TNF rapidly activated (within 30 min) NF-kappa B; this effect was completely abolished by co-treatment with phenylarsine oxide (PAO), a specific inhibitor of PTPase. The induction of ICAM-1, VCAM-1, and ELAM-1 by TNF in MVEC occurred within 6 h and was also completely down-regulated by PAO in a dose-dependent manner. PAO was found to be effective even when added 3 h after TNF, suggesting a rapid mode of action of this inhibitor. Besides PAO, other inhibitors of PTPase, including pervanadate and diamide, also blocked TNF-dependent NF-kappa B activation and induction of all the three adhesion proteins. Consistent with these results, the attachment of monocytes to MVEC was also blocked by the PTPase inhibitors. Thus, overall, our results demonstrate that a PTPase is involved either directly or indirectly in the pathway leading to the induction of endothelial cell adhesion molecules by TNF. Because of their role in cell adhesion, PTPase may provide a novel target of drug development for treatment of inflammation, atherogenesis, and tumor metastasis. " ], "offsets": [ [ 0, 2017 ] ] } ]

[ { "id": "PMID-9341756_T1", "type": "Protein", "text": [ "intracellular adhesion molecule (ICAM)-1" ], "offsets": [ [ 743, 783 ] ], "normalized": [] }, { "id": "PMID-9341756_T2", "type": "Protein", "text": [ "vascular cell adhesion molecule (VCAM)-1" ], "offsets": [ [ 785, 825 ] ], "normalized": [] }, { "id": "PMID-9341756_T3", "type": "Protein", "text": [ "endothelial leukocyte adhesion molecule (ELAM)-1" ], "offsets": [ [ 830, 878 ] ], "normalized": [] }, { "id": "PMID-9341756_T4", "type": "Protein", "text": [ "ICAM-1" ], "offsets": [ [ 1138, 1144 ] ], "normalized": [] }, { "id": "PMID-9341756_T5", "type": "Protein", "text": [ "VCAM-1" ], "offsets": [ [ 1146, 1152 ] ], "normalized": [] }, { "id": "PMID-9341756_T6", "type": "Protein", "text": [ "ELAM-1" ], "offsets": [ [ 1158, 1164 ] ], "normalized": [] } ]

[ { "id": "PMID-9341756_E1", "type": "Regulation", "trigger": { "text": [ "effect" ], "offsets": [ [ 682, 688 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "PMID-9341756_E5" } ] }, { "id": "PMID-9341756_E2", "type": "Regulation", "trigger": { "text": [ "effect" ], "offsets": [ [ 682, 688 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "PMID-9341756_E6" } ] }, { "id": "PMID-9341756_E3", "type": "Regulation", "trigger": { "text": [ "effect" ], "offsets": [ [ 682, 688 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "PMID-9341756_E4" } ] }, { "id": "PMID-9341756_E4", "type": "Positive_regulation", "trigger": { "text": [ "induction" ], "offsets": [ [ 730, 739 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "PMID-9341756_T1" } ] }, { "id": "PMID-9341756_E5", "type": "Positive_regulation", "trigger": { "text": [ "induction" ], "offsets": [ [ 730, 739 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "PMID-9341756_T3" } ] }, { "id": "PMID-9341756_E6", "type": "Positive_regulation", "trigger": { "text": [ "induction" ], "offsets": [ [ 730, 739 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "PMID-9341756_T2" } ] }, { "id": "PMID-9341756_E7", "type": "Positive_regulation", "trigger": { "text": [ "induction" ], "offsets": [ [ 1125, 1134 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "PMID-9341756_T6" } ] }, { "id": "PMID-9341756_E8", "type": "Positive_regulation", "trigger": { "text": [ "induction" ], "offsets": [ [ 1125, 1134 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "PMID-9341756_T5" } ] }, { "id": "PMID-9341756_E9", "type": "Positive_regulation", "trigger": { "text": [ "induction" ], "offsets": [ [ 1125, 1134 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "PMID-9341756_T4" } ] }, { "id": "PMID-9341756_E10", "type": "Negative_regulation", "trigger": { "text": [ "down-regulated" ], "offsets": [ [ 1224, 1238 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "PMID-9341756_E7" } ] }, { "id": "PMID-9341756_E11", "type": "Negative_regulation", "trigger": { "text": [ "down-regulated" ], "offsets": [ [ 1224, 1238 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "PMID-9341756_E9" } ] }, { "id": "PMID-9341756_E12", "type": "Negative_regulation", "trigger": { "text": [ "down-regulated" ], "offsets": [ [ 1224, 1238 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "PMID-9341756_E8" } ] }, { "id": "PMID-9341756_E13", "type": "Negative_regulation", "trigger": { "text": [ "blocked" ], "offsets": [ [ 1469, 1476 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "PMID-9341756_E18" } ] }, { "id": "PMID-9341756_E14", "type": "Negative_regulation", "trigger": { "text": [ "blocked" ], "offsets": [ [ 1469, 1476 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "PMID-9341756_E17" } ] }, { "id": "PMID-9341756_E15", "type": "Negative_regulation", "trigger": { "text": [ "blocked" ], "offsets": [ [ 1469, 1476 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "PMID-9341756_E16" } ] }, { "id": "PMID-9341756_E16", "type": "Positive_regulation", "trigger": { "text": [ "induction" ], "offsets": [ [ 1517, 1526 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "PMID-9341756_T4" } ] }, { "id": "PMID-9341756_E17", "type": "Positive_regulation", "trigger": { "text": [ "induction" ], "offsets": [ [ 1517, 1526 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "PMID-9341756_T5" } ] }, { "id": "PMID-9341756_E18", "type": "Positive_regulation", "trigger": { "text": [ "induction" ], "offsets": [ [ 1517, 1526 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "PMID-9341756_T6" } ] } ]

[]

[]

[ { "id": "PMID-9341877__text", "type": "abstract", "text": [ "The spatial distribution of human immunoglobulin genes within the nucleus: evidence for gene topography independent of cell type and transcriptional activity. \nThe three-dimensional positioning of immunoglobulin (Ig) genes within the nucleus of human cells was investigated using in situ hybridization and confocal microscopy. The visualization of heavy and light chain genes in B-lymphoid cells showed that the three Ig genes are differentially and nonrandomly distributed in different nuclear subvolumes: the kappa genes were found to be preferentially confined to an outer nuclear volume, whereas the gamma and lambda genes consistently occupied more central positions within the nucleus, the lambda genes being more interior when compared with the gamma genes. The data further show that these overall topographical distributions are independent of gene transcriptional activity and are conserved in different cell types. Although subtle gene movements within those defined topographical regions cannot be excluded by this study, the results indicate that tissue specificity of gene expression is not accompanied by drastic changes in gene nuclear topography, rather suggesting that gene organization within the nucleus may be primarily dependent on structural constraints imposed on the respective chromosomes. " ], "offsets": [ [ 0, 1316 ] ] } ]

[]

[]

[]

[]

[ { "id": "PMID-9343210__text", "type": "abstract", "text": [ "Transcriptional activation of the vascular cell adhesion molecule-1 gene in T lymphocytes expressing human T-cell leukemia virus type 1 Tax protein. \nRecruitment and extravasation of T cells through the blood-brain barrier are favored by adhesion molecule-mediated interactions of circulating T cells with endothelial cells. Since a common pathological finding in human T-cell leukemia virus type 1 (HTLV-1)-associated diseases is the infiltration of HTLV-1-infected T lymphocytes into various organs, we have looked for the profile of adhesion molecules expressed by HTLV-1-transformed T cells. Flow cytometry analysis indicated that these cells were expressing high levels of vascular cell adhesion molecule 1 (VCAM-1 [CD106]), a 110-kDa member of the immunoglobulin gene superfamily, first identified on endothelial cells stimulated with inflammatory cytokines. This adhesion molecule was also expressed by T cells obtained from one patient with HTLV-1-associated myelopathy/tropical spastic paraparesis but not by activated T cells isolated from one normal blood donor. The role of the viral trans-activator Tax protein in the induction of VCAM-1 was first indicated by the detection of this adhesion molecule on Jurkat T-cell clones stably expressing the tax gene. The effect of Tax on VCAM-1 gene transcription was next confirmed in JPX-9 cells, a subclone of Jurkat cells, carrying the tax sequences under the control of an inducible promoter. Furthermore, deletion and mutation analyses of the VCAM-1 promoter performed with chloramphenicol acetyltransferase constructs revealed that Tax was trans activating the VCAM-1 promoter via two NF-kappaB sites present at bp -72 and -57 in the VCAM-1 gene promoter, with both of them being required for the Tax-induced expression of this adhesion molecule. Finally, gel mobility shift assays demonstrated the nuclear translocation of proteins specifically bound to these two NF-kappaB motifs, confirming that VCAM-1 was induced on Tax-expressing cells in a kappaB-dependent manner. Collectively, these results therefore suggest that the exclusive Tax-induced expression of VCAM-1 on T cells may represent a pivotal event in the progression of HTLV-1-associated diseases. " ], "offsets": [ [ 0, 2221 ] ] } ]

[ { "id": "PMID-9343210_T1", "type": "Protein", "text": [ "vascular cell adhesion molecule-1" ], "offsets": [ [ 34, 67 ] ], "normalized": [] }, { "id": "PMID-9343210_T2", "type": "Protein", "text": [ "Tax" ], "offsets": [ [ 136, 139 ] ], "normalized": [] }, { "id": "PMID-9343210_T3", "type": "Protein", "text": [ "vascular cell adhesion molecule 1" ], "offsets": [ [ 678, 711 ] ], "normalized": [] }, { "id": "PMID-9343210_T4", "type": "Protein", "text": [ "VCAM-1" ], "offsets": [ [ 713, 719 ] ], "normalized": [] }, { "id": "PMID-9343210_T5", "type": "Protein", "text": [ "CD106" ], "offsets": [ [ 721, 726 ] ], "normalized": [] }, { "id": "PMID-9343210_T6", "type": "Protein", "text": [ "Tax" ], "offsets": [ [ 1112, 1115 ] ], "normalized": [] }, { "id": "PMID-9343210_T7", "type": "Protein", "text": [ "VCAM-1" ], "offsets": [ [ 1144, 1150 ] ], "normalized": [] }, { "id": "PMID-9343210_T8", "type": "Protein", "text": [ "tax" ], "offsets": [ [ 1260, 1263 ] ], "normalized": [] }, { "id": "PMID-9343210_T9", "type": "Protein", "text": [ "Tax" ], "offsets": [ [ 1284, 1287 ] ], "normalized": [] }, { "id": "PMID-9343210_T10", "type": "Protein", "text": [ "VCAM-1" ], "offsets": [ [ 1291, 1297 ] ], "normalized": [] }, { "id": "PMID-9343210_T11", "type": "Protein", "text": [ "tax" ], "offsets": [ [ 1393, 1396 ] ], "normalized": [] }, { "id": "PMID-9343210_T12", "type": "Protein", "text": [ "VCAM-1" ], "offsets": [ [ 1502, 1508 ] ], "normalized": [] }, { "id": "PMID-9343210_T13", "type": "Protein", "text": [ "chloramphenicol acetyltransferase" ], "offsets": [ [ 1533, 1566 ] ], "normalized": [] }, { "id": "PMID-9343210_T14", "type": "Protein", "text": [ "Tax" ], "offsets": [ [ 1592, 1595 ] ], "normalized": [] }, { "id": "PMID-9343210_T15", "type": "Protein", "text": [ "VCAM-1" ], "offsets": [ [ 1621, 1627 ] ], "normalized": [] }, { "id": "PMID-9343210_T16", "type": "Protein", "text": [ "VCAM-1" ], "offsets": [ [ 1694, 1700 ] ], "normalized": [] }, { "id": "PMID-9343210_T17", "type": "Protein", "text": [ "Tax" ], "offsets": [ [ 1757, 1760 ] ], "normalized": [] }, { "id": "PMID-9343210_T18", "type": "Protein", "text": [ "VCAM-1" ], "offsets": [ [ 1959, 1965 ] ], "normalized": [] }, { "id": "PMID-9343210_T19", "type": "Protein", "text": [ "Tax" ], "offsets": [ [ 1981, 1984 ] ], "normalized": [] }, { "id": "PMID-9343210_T20", "type": "Protein", "text": [ "Tax" ], "offsets": [ [ 2097, 2100 ] ], "normalized": [] }, { "id": "PMID-9343210_T21", "type": "Protein", "text": [ "VCAM-1" ], "offsets": [ [ 2123, 2129 ] ], "normalized": [] }, { "id": "PMID-9343210_T35", "type": "Entity", "text": [ "promoter" ], "offsets": [ [ 1628, 1636 ] ], "normalized": [] }, { "id": "PMID-9343210_T37", "type": "Entity", "text": [ "NF-kappaB sites" ], "offsets": [ [ 1645, 1660 ] ], "normalized": [] } ]

[ { "id": "PMID-9343210_E1", "type": "Positive_regulation", "trigger": { "text": [ "Transcriptional activation" ], "offsets": [ [ 0, 26 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "PMID-9343210_T1" } ] }, { "id": "PMID-9343210_E2", "type": "Gene_expression", "trigger": { "text": [ "expressing" ], "offsets": [ [ 90, 100 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "PMID-9343210_T2" } ] }, { "id": "PMID-9343210_E3", "type": "Gene_expression", "trigger": { "text": [ "expressing" ], "offsets": [ [ 652, 662 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "PMID-9343210_T4" } ] }, { "id": "PMID-9343210_E4", "type": "Positive_regulation", "trigger": { "text": [ "high levels" ], "offsets": [ [ 663, 674 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "PMID-9343210_E3" } ] }, { "id": "PMID-9343210_E5", "type": "Gene_expression", "trigger": { "text": [ "identified" ], "offsets": [ [ 793, 803 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "PMID-9343210_T4" } ] }, { "id": "PMID-9343210_E6", "type": "Gene_expression", "trigger": { "text": [ "expressed" ], "offsets": [ [ 897, 906 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "PMID-9343210_T4" } ] }, { "id": "PMID-9343210_E7", "type": "Regulation", "trigger": { "text": [ "role" ], "offsets": [ [ 1078, 1082 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "PMID-9343210_E8" }, { "role": "Cause", "ref_id": "PMID-9343210_T6" } ] }, { "id": "PMID-9343210_E8", "type": "Positive_regulation", "trigger": { "text": [ "induction" ], "offsets": [ [ 1131, 1140 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "PMID-9343210_T7" } ] }, { "id": "PMID-9343210_E9", "type": "Gene_expression", "trigger": { "text": [ "detection" ], "offsets": [ [ 1178, 1187 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "PMID-9343210_T7" } ] }, { "id": "PMID-9343210_E10", "type": "Gene_expression", "trigger": { "text": [ "expressing" ], "offsets": [ [ 1245, 1255 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "PMID-9343210_T8" } ] }, { "id": "PMID-9343210_E11", "type": "Regulation", "trigger": { "text": [ "effect" ], "offsets": [ [ 1274, 1280 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "PMID-9343210_E12" }, { "role": "Cause", "ref_id": "PMID-9343210_T9" } ] }, { "id": "PMID-9343210_E12", "type": "Transcription", "trigger": { "text": [ "transcription" ], "offsets": [ [ 1303, 1316 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "PMID-9343210_T10" } ] }, { "id": "PMID-9343210_E13", "type": "Positive_regulation", "trigger": { "text": [ "trans activating" ], "offsets": [ [ 1600, 1616 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "PMID-9343210_T15" }, { "role": "Cause", "ref_id": "PMID-9343210_E14" }, { "role": "Site", "ref_id": "PMID-9343210_T35" } ] }, { "id": "PMID-9343210_E14", "type": "Binding", "trigger": { "text": [ "via" ], "offsets": [ [ 1637, 1640 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "PMID-9343210_T14" }, { "role": "Theme", "ref_id": "PMID-9343210_T16" }, { "role": "Site", "ref_id": "PMID-9343210_T37" } ] }, { "id": "PMID-9343210_E15", "type": "Positive_regulation", "trigger": { "text": [ "required" ], "offsets": [ [ 1740, 1748 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "PMID-9343210_E16" }, { "role": "Cause", "ref_id": "PMID-9343210_T16" }, { "role": "CSite", "ref_id": "PMID-9343210_T37" } ] }, { "id": "PMID-9343210_E16", "type": "Positive_regulation", "trigger": { "text": [ "induced" ], "offsets": [ [ 1761, 1768 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "PMID-9343210_E17" }, { "role": "Cause", "ref_id": "PMID-9343210_T17" } ] }, { "id": "PMID-9343210_E17", "type": "Gene_expression", "trigger": { "text": [ "expression" ], "offsets": [ [ 1769, 1779 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "PMID-9343210_T16" } ] }, { "id": "PMID-9343210_E18", "type": "Positive_regulation", "trigger": { "text": [ "induced" ], "offsets": [ [ 1970, 1977 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "PMID-9343210_T18" } ] }, { "id": "PMID-9343210_E19", "type": "Gene_expression", "trigger": { "text": [ "expressing" ], "offsets": [ [ 1985, 1995 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "PMID-9343210_T19" } ] }, { "id": "PMID-9343210_E20", "type": "Regulation", "trigger": { "text": [ "dependent" ], "offsets": [ [ 2014, 2023 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "PMID-9343210_E18" } ] }, { "id": "PMID-9343210_E21", "type": "Positive_regulation", "trigger": { "text": [ "induced" ], "offsets": [ [ 2101, 2108 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "PMID-9343210_E22" }, { "role": "Cause", "ref_id": "PMID-9343210_T20" } ] }, { "id": "PMID-9343210_E22", "type": "Gene_expression", "trigger": { "text": [ "expression" ], "offsets": [ [ 2109, 2119 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "PMID-9343210_T21" } ] } ]

[]

[]

[ { "id": "PMID-9343406__text", "type": "abstract", "text": [ "Blockade of T-cell activation by dithiocarbamates involves novel mechanisms of inhibition of nuclear factor of activated T cells. \nDithiocarbamates (DTCs) have recently been reported as powerful inhibitors of NF-kappaB activation in a number of cell types. Given the role of this transcription factor in the regulation of gene expression in the inflammatory response, NF-kappaB inhibitors have been suggested as potential therapeutic drugs for inflammatory diseases. We show here that DTCs inhibited both interleukin 2 (IL-2) synthesis and membrane expression of antigens which are induced during T-cell activation. This inhibition, which occurred with a parallel activation of c-Jun transactivating functions and expression, was reflected by transfection experiments at the IL-2 promoter level, and involved not only the inhibition of NF-kappaB-driven reporter activation but also that of nuclear factor of activated T cells (NFAT). Accordingly, electrophoretic mobility shift assays (EMSAs) indicated that pyrrolidine DTC (PDTC) prevented NF-kappaB, and NFAT DNA-binding activity in T cells stimulated with either phorbol myristate acetate plus ionophore or antibodies against the CD3-T-cell receptor complex and simultaneously activated the binding of AP-1. Furthermore, PDTC differentially targeted both NFATp and NFATc family members, inhibiting the transactivation functions of NFATp and mRNA induction of NFATc. Strikingly, Western blotting and immunocytochemical experiments indicated that PDTC promoted a transient and rapid shuttling of NFATp and NFATc, leading to their accelerated export from the nucleus of activated T cells. We propose that the activation of an NFAT kinase by PDTC could be responsible for the rapid shuttling of the NFAT, therefore transiently converting the sustained transactivation of this transcription factor that occurs during lymphocyte activation, and show that c-Jun NH2-terminal kinase (JNK) can act by directly phosphorylating NFATp. In addition, the combined inhibitory effects on NFAT and NF-KB support a potential use of DTCs as immunosuppressants. " ], "offsets": [ [ 0, 2095 ] ] } ]

[ { "id": "PMID-9343406_T1", "type": "Protein", "text": [ "interleukin 2" ], "offsets": [ [ 505, 518 ] ], "normalized": [] }, { "id": "PMID-9343406_T2", "type": "Protein", "text": [ "IL-2" ], "offsets": [ [ 520, 524 ] ], "normalized": [] }, { "id": "PMID-9343406_T3", "type": "Protein", "text": [ "c-Jun" ], "offsets": [ [ 678, 683 ] ], "normalized": [] }, { "id": "PMID-9343406_T4", "type": "Protein", "text": [ "IL-2" ], "offsets": [ [ 775, 779 ] ], "normalized": [] }, { "id": "PMID-9343406_T5", "type": "Protein", "text": [ "NFATp" ], "offsets": [ [ 1308, 1313 ] ], "normalized": [] }, { "id": "PMID-9343406_T6", "type": "Protein", "text": [ "NFATp" ], "offsets": [ [ 1384, 1389 ] ], "normalized": [] }, { "id": "PMID-9343406_T7", "type": "Protein", "text": [ "NFATp" ], "offsets": [ [ 1547, 1552 ] ], "normalized": [] }, { "id": "PMID-9343406_T8", "type": "Protein", "text": [ "c-Jun NH2-terminal kinase" ], "offsets": [ [ 1902, 1927 ] ], "normalized": [] }, { "id": "PMID-9343406_T9", "type": "Protein", "text": [ "JNK" ], "offsets": [ [ 1929, 1932 ] ], "normalized": [] }, { "id": "PMID-9343406_T10", "type": "Protein", "text": [ "NFATp" ], "offsets": [ [ 1970, 1975 ] ], "normalized": [] } ]

[ { "id": "PMID-9343406_E1", "type": "Negative_regulation", "trigger": { "text": [ "inhibited" ], "offsets": [ [ 490, 499 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "PMID-9343406_E2" } ] }, { "id": "PMID-9343406_E2", "type": "Gene_expression", "trigger": { "text": [ "synthesis" ], "offsets": [ [ 526, 535 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "PMID-9343406_T2" } ] }, { "id": "PMID-9343406_E3", "type": "Positive_regulation", "trigger": { "text": [ "activation" ], "offsets": [ [ 664, 674 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "PMID-9343406_E4" } ] }, { "id": "PMID-9343406_E4", "type": "Gene_expression", "trigger": { "text": [ "expression" ], "offsets": [ [ 714, 724 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "PMID-9343406_T3" } ] }, { "id": "PMID-9343406_E5", "type": "Regulation", "trigger": { "text": [ "targeted" ], "offsets": [ [ 1294, 1302 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "PMID-9343406_T5" } ] }, { "id": "PMID-9343406_E6", "type": "Positive_regulation", "trigger": { "text": [ "promoted" ], "offsets": [ [ 1503, 1511 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "PMID-9343406_E7" } ] }, { "id": "PMID-9343406_E7", "type": "Localization", "trigger": { "text": [ "shuttling" ], "offsets": [ [ 1534, 1543 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "PMID-9343406_T7" } ] }, { "id": "PMID-9343406_E8", "type": "Positive_regulation", "trigger": { "text": [ "leading to their accelerated" ], "offsets": [ [ 1564, 1592 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "PMID-9343406_E9" }, { "role": "Cause", "ref_id": "PMID-9343406_E6" } ] }, { "id": "PMID-9343406_E9", "type": "Localization", "trigger": { "text": [ "export" ], "offsets": [ [ 1593, 1599 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "PMID-9343406_T7" } ] }, { "id": "PMID-9343406_E10", "type": "Phosphorylation", "trigger": { "text": [ "phosphorylating" ], "offsets": [ [ 1954, 1969 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "PMID-9343406_T10" } ] }, { "id": "PMID-9343406_E11", "type": "Positive_regulation", "trigger": { "text": [ "phosphorylating" ], "offsets": [ [ 1954, 1969 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "PMID-9343406_E10" }, { "role": "Cause", "ref_id": "PMID-9343406_T9" } ] } ]

[ { "id": "PMID-9343406_1", "entity_ids": [ "PMID-9343406_T2", "PMID-9343406_T1" ] }, { "id": "PMID-9343406_2", "entity_ids": [ "PMID-9343406_T9", "PMID-9343406_T8" ] } ]

[]

[ { "id": "PMID-9344365__text", "type": "abstract", "text": [ "Suppression of nuclear factor kappa B and CD18-mediated leukocyte adhesion to the corneal endothelium by dexamethasone. \nPURPOSE: To demonstrate that leukocyte adhesion to cultured corneal endothelial cells is mediated by the CD18 antigen, and to determine whether dexamethasone directly suppresses adhesion by inhibiting activation of nuclear factor kappa B (NFkappaB). METHODS: Cultured bovine corneal endothelium was stimulated for 6 hours by 40 micron/ml tumor necrosis factor alpha (TNFalpha). Dexamethasone was added 1 hour before TNFalpha stimulation in the dexamethasone group. After stimulation, neutrophils separated from a healthy human volunteer were added with or without anti-CD18 antibody. The culture plate was settled for 15 minutes at 37 degrees C, and then neutrophils were activated by N-formyl-methionyl-leucyl-phenylalanine for 5 minutes. Nonadherent neutrophils were removed by sealing and inverting the culture well. The intracellular localization of NFkappaB after TNFalpha simulation was determined by confocal immunocytochemistry using an anti-p65 antibody. RESULTS: Neutrophil adhesion to cultured corneal endothelial cells increased significantly on exposure to TNFalpha (451.4+/-45.4 cells/mm2, n = 16) compared to control (156.7+/-27.3 cells/mm2, n = 16, P < 0.01). This increased adhesion was suppressed by the addition of anti-CD18 antibody (157.6+/-25.1 cells/mm2, n = 8, P < 0.01) and by pretreatment with 10(-7) M dexamethasone (207.9+/-31.5 cells/mm2, n = 10, P < 0.01). Immunocytochemistry 60 minutes after stimulation revealed that NFkappaB was located in the cytoplasm in unstimulated cells; however, the addition of TNFalpha caused NFkappaB to translocate into the nucleus. Pretreatment with dexamethasone tapered NFkappaB translocation into the nucleus. CONCLUSIONS: Leukocyte adhesion to the corneal endothelium was shown to be mediated by CD18 expressed on activated leukocytes. Pretreatment of the endothelium with dexamethasone inhibited leukocyte adhesion; this may be due in part to the suppression of NFkappaB entry into the nucleus. " ], "offsets": [ [ 0, 2083 ] ] } ]

[ { "id": "PMID-9344365_T1", "type": "Protein", "text": [ "CD18" ], "offsets": [ [ 42, 46 ] ], "normalized": [] }, { "id": "PMID-9344365_T2", "type": "Protein", "text": [ "CD18" ], "offsets": [ [ 226, 230 ] ], "normalized": [] }, { "id": "PMID-9344365_T3", "type": "Protein", "text": [ "tumor necrosis factor alpha" ], "offsets": [ [ 459, 486 ] ], "normalized": [] }, { "id": "PMID-9344365_T4", "type": "Protein", "text": [ "TNFalpha" ], "offsets": [ [ 488, 496 ] ], "normalized": [] }, { "id": "PMID-9344365_T5", "type": "Protein", "text": [ "TNFalpha" ], "offsets": [ [ 537, 545 ] ], "normalized": [] }, { "id": "PMID-9344365_T6", "type": "Protein", "text": [ "CD18" ], "offsets": [ [ 690, 694 ] ], "normalized": [] }, { "id": "PMID-9344365_T7", "type": "Protein", "text": [ "TNFalpha" ], "offsets": [ [ 990, 998 ] ], "normalized": [] }, { "id": "PMID-9344365_T8", "type": "Protein", "text": [ "p65" ], "offsets": [ [ 1071, 1074 ] ], "normalized": [] }, { "id": "PMID-9344365_T9", "type": "Protein", "text": [ "TNFalpha" ], "offsets": [ [ 1191, 1199 ] ], "normalized": [] }, { "id": "PMID-9344365_T10", "type": "Protein", "text": [ "CD18" ], "offsets": [ [ 1360, 1364 ] ], "normalized": [] }, { "id": "PMID-9344365_T11", "type": "Protein", "text": [ "TNFalpha" ], "offsets": [ [ 1657, 1665 ] ], "normalized": [] }, { "id": "PMID-9344365_T12", "type": "Protein", "text": [ "CD18" ], "offsets": [ [ 1883, 1887 ] ], "normalized": [] } ]

[ { "id": "PMID-9344365_E1", "type": "Gene_expression", "trigger": { "text": [ "expressed" ], "offsets": [ [ 1888, 1897 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "PMID-9344365_T12" } ] } ]

[ { "id": "PMID-9344365_1", "entity_ids": [ "PMID-9344365_T3", "PMID-9344365_T4" ] } ]

[]

[ { "id": "PMID-9348104__text", "type": "abstract", "text": [ "Helenalin, an anti-inflammatory sesquiterpene lactone from Arnica, selectively inhibits transcription factor NF-kappaB [see comments] \nAlcoholic extracts prepared form Arnicae flos, the collective name for flowerheads from Arnica montana and A. chamissonis ssp. foliosa, are used therapeutically as anti-inflammatory remedies. The active ingredients mediating the pharmacological effect are mainly sesquiterpene lactones, such as helenalin, 11alpha,13-dihydrohelenalin, chamissonolid and their ester derivatives. While these compounds affect various cellular processes, current data do not fully explain how sesquiterpene lactones exert their anti-inflammatory effect. We show here that helenalin, and, to a much lesser degree, 11alpha,13-dihydrohelenalin and chamissonolid, inhibit activation of transcription factor NF-kappaB. This difference in efficacy, which correlates with the compounds' anti-inflammatory potency in vivo, may be explained by differences in structure and conformation. NF-kappaB, which resides in an inactive, cytoplasmic complex in unstimulated cells, is activated by phosphorylation and degradation of its inhibitory subunit, IkappaB. Helenalin inhibits NF-kappaB activation in response to four different stimuli in T-cells, B-cells and epithelial cells and abrogates kappaB-driven gene expression. This inhibition is selective, as the activity of four other transcription factors, Oct-1, TBP, Sp1 and STAT 5 was not affected. We show that inhibition is not due to a direct modification of the active NF-kappaB heterodimer. Rather, helenalin modifies the NF-kappaB/IkappaB complex, preventing the release of IkappaB. These data suggest a molecular mechanism for the anti-inflammatory effect of sesquiterpene lactones, which differs from that of other nonsteroidal anti-inflammatory drugs (NSAIDs), indomethacin and acetyl salicylic acid. " ], "offsets": [ [ 0, 1864 ] ] } ]

[ { "id": "PMID-9348104_T1", "type": "Protein", "text": [ "Oct-1" ], "offsets": [ [ 1408, 1413 ] ], "normalized": [] }, { "id": "PMID-9348104_T2", "type": "Protein", "text": [ "TBP" ], "offsets": [ [ 1415, 1418 ] ], "normalized": [] }, { "id": "PMID-9348104_T3", "type": "Protein", "text": [ "Sp1" ], "offsets": [ [ 1420, 1423 ] ], "normalized": [] } ]

[ { "id": "PMID-9348104_E1", "type": "Regulation", "trigger": { "text": [ "affected" ], "offsets": [ [ 1443, 1451 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "PMID-9348104_T3" } ] }, { "id": "PMID-9348104_E2", "type": "Regulation", "trigger": { "text": [ "affected" ], "offsets": [ [ 1443, 1451 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "PMID-9348104_T2" } ] }, { "id": "PMID-9348104_E3", "type": "Regulation", "trigger": { "text": [ "affected" ], "offsets": [ [ 1443, 1451 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "PMID-9348104_T1" } ] } ]

[]

[]

[ { "id": "PMID-9374467__text", "type": "abstract", "text": [ "Nuclear accumulation of NFAT4 opposed by the JNK signal transduction pathway. \nThe nuclear factor of activated T cells (NFAT) group of transcription factors is retained in the cytoplasm of quiescent cells. NFAT activation is mediated in part by induced nuclear import. This process requires calcium-dependent dephosphorylation of NFAT caused by the phosphatase calcineurin. The c-Jun amino-terminal kinase (JNK) phosphorylates NFAT4 on two sites. Mutational removal of the JNK phosphorylation sites caused constitutive nuclear localization of NFAT4. In contrast, JNK activation in calcineurin-stimulated cells caused nuclear exclusion of NFAT4. These findings show that the nuclear accumulation of NFAT4 promoted by calcineurin is opposed by the JNK signal transduction pathway. " ], "offsets": [ [ 0, 779 ] ] } ]

[ { "id": "PMID-9374467_T1", "type": "Protein", "text": [ "NFAT4" ], "offsets": [ [ 24, 29 ] ], "normalized": [] }, { "id": "PMID-9374467_T2", "type": "Protein", "text": [ "NFAT4" ], "offsets": [ [ 427, 432 ] ], "normalized": [] }, { "id": "PMID-9374467_T3", "type": "Protein", "text": [ "NFAT4" ], "offsets": [ [ 543, 548 ] ], "normalized": [] }, { "id": "PMID-9374467_T4", "type": "Protein", "text": [ "NFAT4" ], "offsets": [ [ 638, 643 ] ], "normalized": [] }, { "id": "PMID-9374467_T5", "type": "Protein", "text": [ "NFAT4" ], "offsets": [ [ 698, 703 ] ], "normalized": [] }, { "id": "PMID-9374467_T6", "type": "Entity", "text": [ "Nuclear" ], "offsets": [ [ 0, 7 ] ], "normalized": [] }, { "id": "PMID-9374467_T11", "type": "Entity", "text": [ "nuclear" ], "offsets": [ [ 519, 526 ] ], "normalized": [] }, { "id": "PMID-9374467_T14", "type": "Entity", "text": [ "nuclear" ], "offsets": [ [ 617, 624 ] ], "normalized": [] }, { "id": "PMID-9374467_T16", "type": "Entity", "text": [ "nuclear" ], "offsets": [ [ 674, 681 ] ], "normalized": [] } ]

[ { "id": "PMID-9374467_E1", "type": "Localization", "trigger": { "text": [ "accumulation" ], "offsets": [ [ 8, 20 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "PMID-9374467_T1" }, { "role": "AtLoc", "ref_id": "PMID-9374467_T6" } ] }, { "id": "PMID-9374467_E2", "type": "Negative_regulation", "trigger": { "text": [ "opposed" ], "offsets": [ [ 30, 37 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "PMID-9374467_E1" } ] }, { "id": "PMID-9374467_E3", "type": "Phosphorylation", "trigger": { "text": [ "phosphorylates" ], "offsets": [ [ 412, 426 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "PMID-9374467_T2" } ] }, { "id": "PMID-9374467_E4", "type": "Positive_regulation", "trigger": { "text": [ "caused" ], "offsets": [ [ 499, 505 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "PMID-9374467_E5" } ] }, { "id": "PMID-9374467_E5", "type": "Localization", "trigger": { "text": [ "localization" ], "offsets": [ [ 527, 539 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "PMID-9374467_T3" }, { "role": "AtLoc", "ref_id": "PMID-9374467_T11" } ] }, { "id": "PMID-9374467_E6", "type": "Positive_regulation", "trigger": { "text": [ "caused" ], "offsets": [ [ 610, 616 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "PMID-9374467_E7" } ] }, { "id": "PMID-9374467_E7", "type": "Localization", "trigger": { "text": [ "exclusion" ], "offsets": [ [ 625, 634 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "PMID-9374467_T4" }, { "role": "AtLoc", "ref_id": "PMID-9374467_T14" } ] }, { "id": "PMID-9374467_E8", "type": "Localization", "trigger": { "text": [ "accumulation" ], "offsets": [ [ 682, 694 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "PMID-9374467_T5" }, { "role": "AtLoc", "ref_id": "PMID-9374467_T16" } ] }, { "id": "PMID-9374467_E9", "type": "Positive_regulation", "trigger": { "text": [ "promoted" ], "offsets": [ [ 704, 712 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "PMID-9374467_E8" } ] }, { "id": "PMID-9374467_E10", "type": "Negative_regulation", "trigger": { "text": [ "opposed" ], "offsets": [ [ 731, 738 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "PMID-9374467_E9" } ] } ]

[]

[]

[ { "id": "PMID-9374642__text", "type": "abstract", "text": [ "Hypoxia enhances induction of endothelial ICAM-1: role for metabolic acidosis and proteasomes. \nIntercellular adhesion molecule 1 (ICAM-1) is an important molecule in promotion of polymorphonuclear neutrophil transendothelial migration during inflammation. Coincident with many inflammatory diseases is tissue hypoxia. Thus we hypothesized that combinations of hypoxia and inflammatory stimuli may differentially regulate expression of endothelial ICAM-1. Human endothelial cells were exposed to hypoxia in the presence or absence of added lipopolysaccharide (LPS) and examined for expression of functional ICAM-1. Although hypoxia alone did not induce ICAM-1, the combination of LPS and hypoxia enhanced (3 +/- 0.4-fold over normoxia) ICAM-1 expression. Combinations of hypoxia and LPS significantly increased lymphocyte binding, and such increases were inhibited by addition of anti-ICAM-1 antibodies or antisense oligonucleotides. Hypoxic endothelia showed a > 10-fold increase in sensitivity to inhibitors of proteasome activation, and combinations of hypoxia and LPS enhanced proteasome-dependent cytoplasmic-to-nuclear localization of the nuclear transcription factor-kappa B p65 (Rel A) subunit. Such proteasome activation correlated with hypoxia-evoked decreases in both extracellular and intracellular pH. We conclude from these studies that endothelial hypoxia provides a novel, proteasome-dependent stimulus for ICAM-1 induction. " ], "offsets": [ [ 0, 1441 ] ] } ]

[ { "id": "PMID-9374642_T1", "type": "Protein", "text": [ "ICAM-1" ], "offsets": [ [ 42, 48 ] ], "normalized": [] }, { "id": "PMID-9374642_T2", "type": "Protein", "text": [ "Intercellular adhesion molecule 1" ], "offsets": [ [ 96, 129 ] ], "normalized": [] }, { "id": "PMID-9374642_T3", "type": "Protein", "text": [ "ICAM-1" ], "offsets": [ [ 131, 137 ] ], "normalized": [] }, { "id": "PMID-9374642_T4", "type": "Protein", "text": [ "ICAM-1" ], "offsets": [ [ 448, 454 ] ], "normalized": [] }, { "id": "PMID-9374642_T5", "type": "Protein", "text": [ "ICAM-1" ], "offsets": [ [ 607, 613 ] ], "normalized": [] }, { "id": "PMID-9374642_T6", "type": "Protein", "text": [ "ICAM-1" ], "offsets": [ [ 653, 659 ] ], "normalized": [] }, { "id": "PMID-9374642_T7", "type": "Protein", "text": [ "ICAM-1" ], "offsets": [ [ 736, 742 ] ], "normalized": [] }, { "id": "PMID-9374642_T8", "type": "Protein", "text": [ "ICAM-1" ], "offsets": [ [ 885, 891 ] ], "normalized": [] }, { "id": "PMID-9374642_T9", "type": "Protein", "text": [ "p65" ], "offsets": [ [ 1182, 1185 ] ], "normalized": [] }, { "id": "PMID-9374642_T10", "type": "Protein", "text": [ "Rel A" ], "offsets": [ [ 1187, 1192 ] ], "normalized": [] }, { "id": "PMID-9374642_T11", "type": "Protein", "text": [ "ICAM-1" ], "offsets": [ [ 1423, 1429 ] ], "normalized": [] }, { "id": "PMID-9374642_T22", "type": "Entity", "text": [ "nuclear" ], "offsets": [ [ 1117, 1124 ] ], "normalized": [] } ]

[ { "id": "PMID-9374642_E1", "type": "Positive_regulation", "trigger": { "text": [ "enhances" ], "offsets": [ [ 8, 16 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "PMID-9374642_E2" } ] }, { "id": "PMID-9374642_E2", "type": "Positive_regulation", "trigger": { "text": [ "induction" ], "offsets": [ [ 17, 26 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "PMID-9374642_T1" } ] }, { "id": "PMID-9374642_E3", "type": "Regulation", "trigger": { "text": [ "regulate" ], "offsets": [ [ 413, 421 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "PMID-9374642_E4" } ] }, { "id": "PMID-9374642_E4", "type": "Gene_expression", "trigger": { "text": [ "expression" ], "offsets": [ [ 422, 432 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "PMID-9374642_T4" } ] }, { "id": "PMID-9374642_E5", "type": "Gene_expression", "trigger": { "text": [ "expression" ], "offsets": [ [ 582, 592 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "PMID-9374642_T5" } ] }, { "id": "PMID-9374642_E6", "type": "Positive_regulation", "trigger": { "text": [ "induce" ], "offsets": [ [ 646, 652 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "PMID-9374642_T6" } ] }, { "id": "PMID-9374642_E7", "type": "Positive_regulation", "trigger": { "text": [ "enhanced" ], "offsets": [ [ 696, 704 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "PMID-9374642_E8" } ] }, { "id": "PMID-9374642_E8", "type": "Gene_expression", "trigger": { "text": [ "expression" ], "offsets": [ [ 743, 753 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "PMID-9374642_T7" } ] }, { "id": "PMID-9374642_E9", "type": "Positive_regulation", "trigger": { "text": [ "enhanced" ], "offsets": [ [ 1072, 1080 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "PMID-9374642_E11" } ] }, { "id": "PMID-9374642_E10", "type": "Regulation", "trigger": { "text": [ "dependent" ], "offsets": [ [ 1092, 1101 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "PMID-9374642_E11" } ] }, { "id": "PMID-9374642_E11", "type": "Localization", "trigger": { "text": [ "localization" ], "offsets": [ [ 1125, 1137 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "PMID-9374642_T10" }, { "role": "ToLoc", "ref_id": "PMID-9374642_T22" } ] }, { "id": "PMID-9374642_E12", "type": "Regulation", "trigger": { "text": [ "dependent" ], "offsets": [ [ 1400, 1409 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "PMID-9374642_E13" } ] }, { "id": "PMID-9374642_E13", "type": "Positive_regulation", "trigger": { "text": [ "stimulus" ], "offsets": [ [ 1410, 1418 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "PMID-9374642_E14" } ] }, { "id": "PMID-9374642_E14", "type": "Positive_regulation", "trigger": { "text": [ "induction" ], "offsets": [ [ 1430, 1439 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "PMID-9374642_T11" } ] } ]

[ { "id": "PMID-9374642_1", "entity_ids": [ "PMID-9374642_T10", "PMID-9374642_T9" ] }, { "id": "PMID-9374642_2", "entity_ids": [ "PMID-9374642_T2", "PMID-9374642_T3" ] } ]

[]

[ { "id": "PMID-9376579__text", "type": "abstract", "text": [ "Modulation of mRNA expression of a novel human myeloid-selective CCAAT/enhancer binding protein gene (C/EBP epsilon). \nHuman C/EBP epsilon is a newly cloned gene coding for a CCAAT/enhancer binding protein that may be involved in the regulation of myeloid differentiation. Our studies showed that levels of C/EBP epsilon mRNA were markedly increased in NB4 cells (promyelocytic leukemia line), because they were induced by 9-cis retinoic acid (9-cis RA) to differentiate towards granulocytes. Accumulation of C/EBP epsilon mRNA occurred as early as 1 hour after exposure of NB4 cells to 9-cis RA (5 x 10(-7) mol/L); and at 48 hours, levels were increased by 5.1-fold. Dose-response studies showed that 10(-7) to 10(-6) mol/L 9-cis RA (12 hours) resulted in peak levels of C/EBP epsilon mRNA; but even 10(-10) mol/L 9-cis RA increased levels of these transcripts. NB4 cells pulse-exposed (30 minutes) to all-trans retinoic acid (ATRA), washed, and cultured (3 days) with either dimethylsulfoxide (DMSO) or hexamethylene bisacetamide (HMBA) had a prominent increase in levels of C/EBP epsilon mRNA and an increase in granulocytic differentiation, but exposure to either DMSO or HMBA alone had no effect on base levels of C/EBP epsilon and did not induce differentiation. Macrophage-differentiation of NB4 reduced levels of C/EBP epsilon mRNA. Nuclear run-off assays and half-life studies showed that accumulation of C/EBP epsilon mRNA by 9-cis RA was due to enhanced transcription. Furthermore, this C/EBP epsilon mRNA accumulation did not require synthesis of new protein factors because 9-cis RA induced C/EBP epsilon mRNA accumulation in the absence of new protein synthesis. ATRA also induced expression of C/EBP epsilon protein in NB4 cells, as shown by Western blotting. In contrast to the increase of C/EBP epsilon in 9-cis RA-mediated granulocytic differentiation, the DMSO-induced differentiation of HL-60 cells down the granulocytic pathway was associated with an initial reduction of C/EBP epsilon mRNA levels. In summary, we have discovered that expression of C/EBP epsilon mRNA is markedly enhanced as the NB4 promyelocytes are induced by retinoids to differentiate towards granulocytes. This induction of C/EBP epsilon mRNA expression is transcriptionally mediated and occurs in the absence of synthesis of additional protein factors. We suspect that the C/EBP epsilon promoter/enhancer contains a retinoic acid-response element that is directly stimulated by retinoids. " ], "offsets": [ [ 0, 2483 ] ] } ]

[ { "id": "PMID-9376579_T1", "type": "Protein", "text": [ "CCAAT/enhancer binding protein" ], "offsets": [ [ 65, 95 ] ], "normalized": [] }, { "id": "PMID-9376579_T2", "type": "Protein", "text": [ "C/EBP epsilon" ], "offsets": [ [ 102, 115 ] ], "normalized": [] }, { "id": "PMID-9376579_T3", "type": "Protein", "text": [ "C/EBP epsilon" ], "offsets": [ [ 125, 138 ] ], "normalized": [] }, { "id": "PMID-9376579_T4", "type": "Protein", "text": [ "CCAAT/enhancer binding protein" ], "offsets": [ [ 175, 205 ] ], "normalized": [] }, { "id": "PMID-9376579_T5", "type": "Protein", "text": [ "C/EBP epsilon" ], "offsets": [ [ 307, 320 ] ], "normalized": [] }, { "id": "PMID-9376579_T6", "type": "Protein", "text": [ "C/EBP epsilon" ], "offsets": [ [ 509, 522 ] ], "normalized": [] }, { "id": "PMID-9376579_T7", "type": "Protein", "text": [ "C/EBP epsilon" ], "offsets": [ [ 772, 785 ] ], "normalized": [] }, { "id": "PMID-9376579_T8", "type": "Protein", "text": [ "C/EBP epsilon" ], "offsets": [ [ 1077, 1090 ] ], "normalized": [] }, { "id": "PMID-9376579_T9", "type": "Protein", "text": [ "C/EBP epsilon" ], "offsets": [ [ 1219, 1232 ] ], "normalized": [] }, { "id": "PMID-9376579_T10", "type": "Protein", "text": [ "C/EBP epsilon" ], "offsets": [ [ 1321, 1334 ] ], "normalized": [] }, { "id": "PMID-9376579_T11", "type": "Protein", "text": [ "C/EBP epsilon" ], "offsets": [ [ 1414, 1427 ] ], "normalized": [] }, { "id": "PMID-9376579_T12", "type": "Protein", "text": [ "C/EBP epsilon" ], "offsets": [ [ 1498, 1511 ] ], "normalized": [] }, { "id": "PMID-9376579_T13", "type": "Protein", "text": [ "C/EBP epsilon" ], "offsets": [ [ 1604, 1617 ] ], "normalized": [] }, { "id": "PMID-9376579_T14", "type": "Protein", "text": [ "C/EBP epsilon" ], "offsets": [ [ 1709, 1722 ] ], "normalized": [] }, { "id": "PMID-9376579_T15", "type": "Protein", "text": [ "C/EBP epsilon" ], "offsets": [ [ 1806, 1819 ] ], "normalized": [] }, { "id": "PMID-9376579_T16", "type": "Protein", "text": [ "C/EBP epsilon" ], "offsets": [ [ 1993, 2006 ] ], "normalized": [] }, { "id": "PMID-9376579_T17", "type": "Protein", "text": [ "C/EBP epsilon" ], "offsets": [ [ 2070, 2083 ] ], "normalized": [] }, { "id": "PMID-9376579_T18", "type": "Protein", "text": [ "C/EBP epsilon" ], "offsets": [ [ 2217, 2230 ] ], "normalized": [] }, { "id": "PMID-9376579_T19", "type": "Protein", "text": [ "C/EBP epsilon" ], "offsets": [ [ 2367, 2380 ] ], "normalized": [] }, { "id": "PMID-9376579_T48", "type": "Entity", "text": [ "retinoic acid-response element" ], "offsets": [ [ 2410, 2440 ] ], "normalized": [] } ]

[ { "id": "PMID-9376579_E1", "type": "Regulation", "trigger": { "text": [ "Modulation" ], "offsets": [ [ 0, 10 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "PMID-9376579_E2" } ] }, { "id": "PMID-9376579_E2", "type": "Transcription", "trigger": { "text": [ "mRNA expression" ], "offsets": [ [ 14, 29 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "PMID-9376579_T2" } ] }, { "id": "PMID-9376579_E3", "type": "Positive_regulation", "trigger": { "text": [ "increased" ], "offsets": [ [ 340, 349 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "PMID-9376579_T5" } ] }, { "id": "PMID-9376579_E4", "type": "Positive_regulation", "trigger": { "text": [ "induced" ], "offsets": [ [ 412, 419 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "PMID-9376579_T5" } ] }, { "id": "PMID-9376579_E5", "type": "Positive_regulation", "trigger": { "text": [ "occurred" ], "offsets": [ [ 528, 536 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "PMID-9376579_T6" } ] }, { "id": "PMID-9376579_E6", "type": "Positive_regulation", "trigger": { "text": [ "increased" ], "offsets": [ [ 645, 654 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "PMID-9376579_T6" } ] }, { "id": "PMID-9376579_E7", "type": "Positive_regulation", "trigger": { "text": [ "resulted in peak levels" ], "offsets": [ [ 745, 768 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "PMID-9376579_T7" } ] }, { "id": "PMID-9376579_E8", "type": "Positive_regulation", "trigger": { "text": [ "increased levels" ], "offsets": [ [ 824, 840 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "PMID-9376579_T7" } ] }, { "id": "PMID-9376579_E9", "type": "Positive_regulation", "trigger": { "text": [ "had a prominent increase" ], "offsets": [ [ 1039, 1063 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "PMID-9376579_T8" } ] }, { "id": "PMID-9376579_E10", "type": "Regulation", "trigger": { "text": [ "had no effect" ], "offsets": [ [ 1187, 1200 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "PMID-9376579_T9" } ] }, { "id": "PMID-9376579_E11", "type": "Negative_regulation", "trigger": { "text": [ "reduced" ], "offsets": [ [ 1303, 1310 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "PMID-9376579_T10" } ] }, { "id": "PMID-9376579_E12", "type": "Positive_regulation", "trigger": { "text": [ "accumulation" ], "offsets": [ [ 1398, 1410 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "PMID-9376579_T11" } ] }, { "id": "PMID-9376579_E13", "type": "Positive_regulation", "trigger": { "text": [ "due to" ], "offsets": [ [ 1449, 1455 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "PMID-9376579_E12" }, { "role": "Cause", "ref_id": "PMID-9376579_E14" } ] }, { "id": "PMID-9376579_E14", "type": "Positive_regulation", "trigger": { "text": [ "enhanced" ], "offsets": [ [ 1456, 1464 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "PMID-9376579_E15" } ] }, { "id": "PMID-9376579_E15", "type": "Transcription", "trigger": { "text": [ "transcription" ], "offsets": [ [ 1465, 1478 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "PMID-9376579_T11" } ] }, { "id": "PMID-9376579_E16", "type": "Positive_regulation", "trigger": { "text": [ "accumulation" ], "offsets": [ [ 1517, 1529 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "PMID-9376579_T12" } ] }, { "id": "PMID-9376579_E17", "type": "Positive_regulation", "trigger": { "text": [ "not require" ], "offsets": [ [ 1534, 1545 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "PMID-9376579_E16" } ] }, { "id": "PMID-9376579_E18", "type": "Positive_regulation", "trigger": { "text": [ "induced" ], "offsets": [ [ 1596, 1603 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "PMID-9376579_E19" } ] }, { "id": "PMID-9376579_E19", "type": "Positive_regulation", "trigger": { "text": [ "accumulation" ], "offsets": [ [ 1623, 1635 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "PMID-9376579_T13" } ] }, { "id": "PMID-9376579_E20", "type": "Positive_regulation", "trigger": { "text": [ "induced" ], "offsets": [ [ 1687, 1694 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "PMID-9376579_E21" } ] }, { "id": "PMID-9376579_E21", "type": "Gene_expression", "trigger": { "text": [ "expression" ], "offsets": [ [ 1695, 1705 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "PMID-9376579_T14" } ] }, { "id": "PMID-9376579_E22", "type": "Positive_regulation", "trigger": { "text": [ "increase" ], "offsets": [ [ 1794, 1802 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "PMID-9376579_T15" } ] }, { "id": "PMID-9376579_E23", "type": "Negative_regulation", "trigger": { "text": [ "reduction" ], "offsets": [ [ 1980, 1989 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "PMID-9376579_T16" } ] }, { "id": "PMID-9376579_E24", "type": "Transcription", "trigger": { "text": [ "expression" ], "offsets": [ [ 2056, 2066 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "PMID-9376579_T17" } ] }, { "id": "PMID-9376579_E25", "type": "Positive_regulation", "trigger": { "text": [ "enhanced" ], "offsets": [ [ 2101, 2109 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "PMID-9376579_E24" } ] }, { "id": "PMID-9376579_E26", "type": "Positive_regulation", "trigger": { "text": [ "induction" ], "offsets": [ [ 2204, 2213 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "PMID-9376579_E27" } ] }, { "id": "PMID-9376579_E27", "type": "Transcription", "trigger": { "text": [ "expression" ], "offsets": [ [ 2236, 2246 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "PMID-9376579_T18" } ] }, { "id": "PMID-9376579_E28", "type": "Positive_regulation", "trigger": { "text": [ "transcriptionally mediated" ], "offsets": [ [ 2250, 2276 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "PMID-9376579_E26" } ] }, { "id": "PMID-9376579_E29", "type": "Positive_regulation", "trigger": { "text": [ "stimulated" ], "offsets": [ [ 2458, 2468 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "PMID-9376579_T19" }, { "role": "Site", "ref_id": "PMID-9376579_T48" } ] } ]

[]

[]

[ { "id": "PMID-9379002__text", "type": "abstract", "text": [ "Regulation of nuclear factor-kappa B and its inhibitor I kappa B-alpha/MAD-3 in monocytes by Mycobacterium tuberculosis and during human tuberculosis. \nBlood monocytes from patients with active tuberculosis are activated in vivo, as evidenced by an increase in the stimulated release of proinflammatory cytokines, such as TNF-alpha, and the spontaneous expression of IL-2R. Further, monocytes from patients demonstrate an augmented susceptibility to a productive infection with HIV-1 in vitro. Mycobacterium tuberculosis and its components are strong signals to activate monocytes to production of cytokines. In this study we examined the basis of activation of monocytes during active tuberculosis and by M. tuberculosis. We found a constitutive degradation of I kappa B-alpha, the major cytoplasmic inhibitor of nuclear factor kappa B (NF-kappa B), in freshly isolated PBMC and monocytes from patients with tuberculosis. In contrast, I kappa B-alpha levels in PBMC and monocytes from healthy subjects or from patients with nontuberculous pulmonary conditions were intact. Further, by electrophoretic mobility shift assay, NF-kappa B was activated in monocytes from tuberculous patients. The expression of I kappa B-alpha gene, which is responsive to activation by NF-kappa B, was up-regulated in PBMC and monocytes from patients, but not in mononuclear cells from healthy subjects or those with nontuberculous lung diseases. By contrast, the expression of other adherence-associated early genes, such as IL-8 and IL-1 beta, was not up-regulated in PBMC of tuberculous patients. Further, M. tuberculosis and its tuberculin, purified protein derivative, induced the degradation of I kappa B-alpha and the expression of I kappa B-alpha mRNA, and purified protein derivative induced the activation of NF-kappa B in monocytes. " ], "offsets": [ [ 0, 1824 ] ] } ]

[ { "id": "PMID-9379002_T1", "type": "Protein", "text": [ "I kappa B-alpha" ], "offsets": [ [ 55, 70 ] ], "normalized": [] }, { "id": "PMID-9379002_T2", "type": "Protein", "text": [ "MAD-3" ], "offsets": [ [ 71, 76 ] ], "normalized": [] }, { "id": "PMID-9379002_T3", "type": "Protein", "text": [ "TNF-alpha" ], "offsets": [ [ 322, 331 ] ], "normalized": [] }, { "id": "PMID-9379002_T4", "type": "Protein", "text": [ "IL-2R" ], "offsets": [ [ 367, 372 ] ], "normalized": [] }, { "id": "PMID-9379002_T5", "type": "Protein", "text": [ "I kappa B-alpha" ], "offsets": [ [ 762, 777 ] ], "normalized": [] }, { "id": "PMID-9379002_T6", "type": "Protein", "text": [ "I kappa B-alpha" ], "offsets": [ [ 936, 951 ] ], "normalized": [] }, { "id": "PMID-9379002_T7", "type": "Protein", "text": [ "I kappa B-alpha" ], "offsets": [ [ 1207, 1222 ] ], "normalized": [] }, { "id": "PMID-9379002_T8", "type": "Protein", "text": [ "IL-8" ], "offsets": [ [ 1506, 1510 ] ], "normalized": [] }, { "id": "PMID-9379002_T9", "type": "Protein", "text": [ "IL-1 beta" ], "offsets": [ [ 1515, 1524 ] ], "normalized": [] }, { "id": "PMID-9379002_T10", "type": "Protein", "text": [ "tuberculin" ], "offsets": [ [ 1613, 1623 ] ], "normalized": [] }, { "id": "PMID-9379002_T11", "type": "Protein", "text": [ "I kappa B-alpha" ], "offsets": [ [ 1681, 1696 ] ], "normalized": [] }, { "id": "PMID-9379002_T12", "type": "Protein", "text": [ "I kappa B-alpha" ], "offsets": [ [ 1719, 1734 ] ], "normalized": [] } ]

[ { "id": "PMID-9379002_E1", "type": "Regulation", "trigger": { "text": [ "Regulation" ], "offsets": [ [ 0, 10 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "PMID-9379002_T1" } ] }, { "id": "PMID-9379002_E2", "type": "Positive_regulation", "trigger": { "text": [ "increase" ], "offsets": [ [ 249, 257 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "PMID-9379002_E5" } ] }, { "id": "PMID-9379002_E3", "type": "Positive_regulation", "trigger": { "text": [ "increase" ], "offsets": [ [ 249, 257 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "PMID-9379002_E6" } ] }, { "id": "PMID-9379002_E4", "type": "Positive_regulation", "trigger": { "text": [ "stimulated" ], "offsets": [ [ 265, 275 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "PMID-9379002_E5" } ] }, { "id": "PMID-9379002_E5", "type": "Localization", "trigger": { "text": [ "release" ], "offsets": [ [ 276, 283 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "PMID-9379002_T3" } ] }, { "id": "PMID-9379002_E6", "type": "Gene_expression", "trigger": { "text": [ "spontaneous expression" ], "offsets": [ [ 341, 363 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "PMID-9379002_T4" } ] }, { "id": "PMID-9379002_E7", "type": "Protein_catabolism", "trigger": { "text": [ "degradation" ], "offsets": [ [ 747, 758 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "PMID-9379002_T5" } ] }, { "id": "PMID-9379002_E8", "type": "Protein_catabolism", "trigger": { "text": [ "intact" ], "offsets": [ [ 1066, 1072 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "PMID-9379002_T6" } ] }, { "id": "PMID-9379002_E9", "type": "Gene_expression", "trigger": { "text": [ "expression" ], "offsets": [ [ 1193, 1203 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "PMID-9379002_T7" } ] }, { "id": "PMID-9379002_E10", "type": "Positive_regulation", "trigger": { "text": [ "activation" ], "offsets": [ [ 1252, 1262 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "PMID-9379002_E9" } ] }, { "id": "PMID-9379002_E11", "type": "Positive_regulation", "trigger": { "text": [ "up-regulated" ], "offsets": [ [ 1282, 1294 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "PMID-9379002_E9" } ] }, { "id": "PMID-9379002_E12", "type": "Gene_expression", "trigger": { "text": [ "expression" ], "offsets": [ [ 1444, 1454 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "PMID-9379002_T9" } ] }, { "id": "PMID-9379002_E13", "type": "Gene_expression", "trigger": { "text": [ "expression" ], "offsets": [ [ 1444, 1454 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "PMID-9379002_T8" } ] }, { "id": "PMID-9379002_E14", "type": "Positive_regulation", "trigger": { "text": [ "up-regulated" ], "offsets": [ [ 1534, 1546 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "PMID-9379002_E13" } ] }, { "id": "PMID-9379002_E15", "type": "Positive_regulation", "trigger": { "text": [ "up-regulated" ], "offsets": [ [ 1534, 1546 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "PMID-9379002_E12" } ] }, { "id": "PMID-9379002_E16", "type": "Positive_regulation", "trigger": { "text": [ "induced" ], "offsets": [ [ 1654, 1661 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "PMID-9379002_E20" }, { "role": "Cause", "ref_id": "PMID-9379002_T10" } ] }, { "id": "PMID-9379002_E17", "type": "Positive_regulation", "trigger": { "text": [ "induced" ], "offsets": [ [ 1654, 1661 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "PMID-9379002_E21" }, { "role": "Cause", "ref_id": "PMID-9379002_T10" } ] }, { "id": "PMID-9379002_E18", "type": "Positive_regulation", "trigger": { "text": [ "induced" ], "offsets": [ [ 1654, 1661 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "PMID-9379002_E21" } ] }, { "id": "PMID-9379002_E19", "type": "Positive_regulation", "trigger": { "text": [ "induced" ], "offsets": [ [ 1654, 1661 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "PMID-9379002_E20" } ] }, { "id": "PMID-9379002_E20", "type": "Protein_catabolism", "trigger": { "text": [ "degradation" ], "offsets": [ [ 1666, 1677 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "PMID-9379002_T11" } ] }, { "id": "PMID-9379002_E21", "type": "Transcription", "trigger": { "text": [ "expression" ], "offsets": [ [ 1705, 1715 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "PMID-9379002_T12" } ] } ]

[ { "id": "PMID-9379002_1", "entity_ids": [ "PMID-9379002_T1", "PMID-9379002_T2" ] } ]

[]

[ { "id": "PMID-9384661__text", "type": "abstract", "text": [ "Expression of c-fos correlates with IFN-alpha responsiveness in Philadelphia chromosome positive chronic myelogenous leukemia. \nThis study evaluates (i) constitutive levels of oncogene and p53 transcripts in chronic phase CML patients and (ii) their modulations subsequent to in vivo therapy with rIFN-alpha 2c. Peripheral blood mononuclear cells (pbmc) and bone marrow cells of 26 patients were examined for c-fos, c-myc, p53 and the hybrid bcr/abl mRNA levels. Results indicated that (i) constitutive c-fos transcript levels are significantly higher in patients subsequently responding to IFN-alpha therapy (p < 0.01) and positively correlated with the proportion of lymphocytes (r = 0.6895, p < 0.01) and negatively with the proportion of immature cells (r = -0.568, p < 0.01) contained in the pbmc preparations tested, (ii) constitutive mRNA levels of the hybrid bcr/abl, c-myc and p53 are positively correlated with each other, but failed to relate to disease parameters, and (iii) acute and chronic in vivo exposure to IFN-alpha is accompanied by upregulation of c-fos and downregulation of c-myc mRNA levels in responder patients. " ], "offsets": [ [ 0, 1138 ] ] } ]

[ { "id": "PMID-9384661_T1", "type": "Protein", "text": [ "c-fos" ], "offsets": [ [ 14, 19 ] ], "normalized": [] }, { "id": "PMID-9384661_T2", "type": "Protein", "text": [ "p53" ], "offsets": [ [ 189, 192 ] ], "normalized": [] }, { "id": "PMID-9384661_T3", "type": "Protein", "text": [ "c-fos" ], "offsets": [ [ 409, 414 ] ], "normalized": [] }, { "id": "PMID-9384661_T4", "type": "Protein", "text": [ "c-myc" ], "offsets": [ [ 416, 421 ] ], "normalized": [] }, { "id": "PMID-9384661_T5", "type": "Protein", "text": [ "p53" ], "offsets": [ [ 423, 426 ] ], "normalized": [] }, { "id": "PMID-9384661_T6", "type": "Protein", "text": [ "c-myc" ], "offsets": [ [ 876, 881 ] ], "normalized": [] }, { "id": "PMID-9384661_T7", "type": "Protein", "text": [ "p53" ], "offsets": [ [ 886, 889 ] ], "normalized": [] }, { "id": "PMID-9384661_T8", "type": "Protein", "text": [ "c-fos" ], "offsets": [ [ 1069, 1074 ] ], "normalized": [] }, { "id": "PMID-9384661_T9", "type": "Protein", "text": [ "c-myc" ], "offsets": [ [ 1097, 1102 ] ], "normalized": [] } ]

[ { "id": "PMID-9384661_E1", "type": "Gene_expression", "trigger": { "text": [ "Expression" ], "offsets": [ [ 0, 10 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "PMID-9384661_T1" } ] }, { "id": "PMID-9384661_E2", "type": "Transcription", "trigger": { "text": [ "levels" ], "offsets": [ [ 166, 172 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "PMID-9384661_T2" } ] }, { "id": "PMID-9384661_E3", "type": "Transcription", "trigger": { "text": [ "levels" ], "offsets": [ [ 455, 461 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "PMID-9384661_T5" } ] }, { "id": "PMID-9384661_E4", "type": "Transcription", "trigger": { "text": [ "levels" ], "offsets": [ [ 455, 461 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "PMID-9384661_T4" } ] }, { "id": "PMID-9384661_E5", "type": "Transcription", "trigger": { "text": [ "levels" ], "offsets": [ [ 455, 461 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "PMID-9384661_T3" } ] }, { "id": "PMID-9384661_E6", "type": "Positive_regulation", "trigger": { "text": [ "accompanied by upregulation" ], "offsets": [ [ 1038, 1065 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "PMID-9384661_T8" } ] }, { "id": "PMID-9384661_E7", "type": "Negative_regulation", "trigger": { "text": [ "downregulation" ], "offsets": [ [ 1079, 1093 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "PMID-9384661_T9" } ] } ]

[]

[]

[ { "id": "PMID-9388475__text", "type": "abstract", "text": [ "Molecular cloning and functional characterization of murine cDNA encoding transcription factor NFATc. \nTranscription factors of the NFAT (nuclear factor of activated T cells) family play important roles in immune and inflammatory responses by regulating the expression of genes encoding cytokines and immunoregulatory proteins. Here we describe cloning and characterization of full-length cDNA encoding murine (m) NFATc which predicts that the protein has all the conserved structural motifs of NFAT family members, including the rel homology domain, the NFAT homology domain and the nuclear translocation signals. mNFATc complexed with AP-1 bound specifically to the murine IL-2 NFAT recognition sequence and activated transcription from the co-transfected IL-2 promoter in COS-7 cells. Northern blot analysis showed that the cDNA probe hybridized with a 4.5 kb transcript which is highly inducible in murine T cells. By Northern and in situ hybridization, mNFATc transcript was detected from the early stage of development. In the mouse embryo, mNFATc transcript was strongly expressed in thymus, lung and submandibular gland and weakly in skeletal muscle and heart suggesting that mNFATc may have a role both in embryogenesis and in mature T cells. " ], "offsets": [ [ 0, 1252 ] ] } ]

[ { "id": "PMID-9388475_T1", "type": "Protein", "text": [ "NFATc" ], "offsets": [ [ 95, 100 ] ], "normalized": [] }, { "id": "PMID-9388475_T2", "type": "Protein", "text": [ "murine (m) NFATc" ], "offsets": [ [ 403, 419 ] ], "normalized": [] }, { "id": "PMID-9388475_T3", "type": "Protein", "text": [ "mNFATc" ], "offsets": [ [ 615, 621 ] ], "normalized": [] }, { "id": "PMID-9388475_T4", "type": "Protein", "text": [ "AP-1" ], "offsets": [ [ 637, 641 ] ], "normalized": [] }, { "id": "PMID-9388475_T5", "type": "Protein", "text": [ "IL-2" ], "offsets": [ [ 675, 679 ] ], "normalized": [] }, { "id": "PMID-9388475_T6", "type": "Protein", "text": [ "IL-2" ], "offsets": [ [ 758, 762 ] ], "normalized": [] }, { "id": "PMID-9388475_T7", "type": "Protein", "text": [ "mNFATc" ], "offsets": [ [ 958, 964 ] ], "normalized": [] }, { "id": "PMID-9388475_T8", "type": "Protein", "text": [ "mNFATc" ], "offsets": [ [ 1047, 1053 ] ], "normalized": [] }, { "id": "PMID-9388475_T9", "type": "Protein", "text": [ "mNFATc" ], "offsets": [ [ 1184, 1190 ] ], "normalized": [] } ]

[ { "id": "PMID-9388475_E1", "type": "Binding", "trigger": { "text": [ "complexed" ], "offsets": [ [ 622, 631 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "PMID-9388475_T3" }, { "role": "Theme", "ref_id": "PMID-9388475_T4" } ] }, { "id": "PMID-9388475_E2", "type": "Binding", "trigger": { "text": [ "bound" ], "offsets": [ [ 642, 647 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "PMID-9388475_T3" } ] }, { "id": "PMID-9388475_E3", "type": "Positive_regulation", "trigger": { "text": [ "activated" ], "offsets": [ [ 710, 719 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "PMID-9388475_E4" }, { "role": "Cause", "ref_id": "PMID-9388475_E2" } ] }, { "id": "PMID-9388475_E4", "type": "Transcription", "trigger": { "text": [ "transcription" ], "offsets": [ [ 720, 733 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "PMID-9388475_T6" } ] }, { "id": "PMID-9388475_E5", "type": "Transcription", "trigger": { "text": [ "detected" ], "offsets": [ [ 980, 988 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "PMID-9388475_T7" } ] }, { "id": "PMID-9388475_E6", "type": "Transcription", "trigger": { "text": [ "expressed" ], "offsets": [ [ 1078, 1087 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "PMID-9388475_T8" } ] } ]

[]

[]

[ { "id": "PMID-9390691__text", "type": "abstract", "text": [ "Phosphatidylinositol 3-kinase couples the interleukin-2 receptor to the cell cycle regulator E2F. \nCell cycle progression initiated by interleukin-2 (IL-2) in T cells is critical for lymphoproliferation and an immune response. Phosphatidyl inositol 3-kinase (PI3K) is activated by IL-2. However, nuclear targets for PI3K are not known. Here we identify the cell cycle regulator E2F as an IL-2 target in T lymphocytes and PI3K as the critical signaling pathway. We eliminate both Stat5 and Raf/MEK pathways from E2F regulation. Protein kinase B (PKB) is activated by IL-2 via PI3K. The expression of an active PKB is sufficient to induce E2F activity. Inhibition of PI3K inhibits phosphorylation of Rb, induction of cyclin D3, and degradation of p27kip1. These results establish a crucial PI3K/PKB-mediated link between the IL-2 teceptor and the cell cycle machinery. " ], "offsets": [ [ 0, 867 ] ] } ]

[ { "id": "PMID-9390691_T1", "type": "Protein", "text": [ "interleukin-2" ], "offsets": [ [ 42, 55 ] ], "normalized": [] }, { "id": "PMID-9390691_T2", "type": "Protein", "text": [ "interleukin-2" ], "offsets": [ [ 135, 148 ] ], "normalized": [] }, { "id": "PMID-9390691_T3", "type": "Protein", "text": [ "IL-2" ], "offsets": [ [ 150, 154 ] ], "normalized": [] }, { "id": "PMID-9390691_T4", "type": "Protein", "text": [ "IL-2" ], "offsets": [ [ 281, 285 ] ], "normalized": [] }, { "id": "PMID-9390691_T5", "type": "Protein", "text": [ "IL-2" ], "offsets": [ [ 388, 392 ] ], "normalized": [] }, { "id": "PMID-9390691_T6", "type": "Protein", "text": [ "Stat5" ], "offsets": [ [ 479, 484 ] ], "normalized": [] }, { "id": "PMID-9390691_T7", "type": "Protein", "text": [ "Protein kinase B" ], "offsets": [ [ 527, 543 ] ], "normalized": [] }, { "id": "PMID-9390691_T8", "type": "Protein", "text": [ "PKB" ], "offsets": [ [ 545, 548 ] ], "normalized": [] }, { "id": "PMID-9390691_T9", "type": "Protein", "text": [ "IL-2" ], "offsets": [ [ 566, 570 ] ], "normalized": [] }, { "id": "PMID-9390691_T10", "type": "Protein", "text": [ "PKB" ], "offsets": [ [ 609, 612 ] ], "normalized": [] }, { "id": "PMID-9390691_T11", "type": "Protein", "text": [ "Rb" ], "offsets": [ [ 698, 700 ] ], "normalized": [] }, { "id": "PMID-9390691_T12", "type": "Protein", "text": [ "p27kip1" ], "offsets": [ [ 745, 752 ] ], "normalized": [] }, { "id": "PMID-9390691_T13", "type": "Protein", "text": [ "PKB" ], "offsets": [ [ 793, 796 ] ], "normalized": [] }, { "id": "PMID-9390691_T14", "type": "Protein", "text": [ "IL-2" ], "offsets": [ [ 823, 827 ] ], "normalized": [] }, { "id": "PMID-9390691_T16", "type": "Entity", "text": [ "PI3K" ], "offsets": [ [ 575, 579 ] ], "normalized": [] } ]

[ { "id": "PMID-9390691_E1", "type": "Positive_regulation", "trigger": { "text": [ "activated" ], "offsets": [ [ 553, 562 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "PMID-9390691_T8" }, { "role": "Cause", "ref_id": "PMID-9390691_T9" }, { "role": "CSite", "ref_id": "PMID-9390691_T16" } ] }, { "id": "PMID-9390691_E2", "type": "Gene_expression", "trigger": { "text": [ "expression" ], "offsets": [ [ 585, 595 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "PMID-9390691_T10" } ] }, { "id": "PMID-9390691_E3", "type": "Negative_regulation", "trigger": { "text": [ "inhibits" ], "offsets": [ [ 670, 678 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "PMID-9390691_E5" } ] }, { "id": "PMID-9390691_E4", "type": "Negative_regulation", "trigger": { "text": [ "inhibits" ], "offsets": [ [ 670, 678 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "PMID-9390691_E6" } ] }, { "id": "PMID-9390691_E5", "type": "Phosphorylation", "trigger": { "text": [ "phosphorylation" ], "offsets": [ [ 679, 694 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "PMID-9390691_T11" } ] }, { "id": "PMID-9390691_E6", "type": "Protein_catabolism", "trigger": { "text": [ "degradation" ], "offsets": [ [ 730, 741 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "PMID-9390691_T12" } ] } ]

[ { "id": "PMID-9390691_1", "entity_ids": [ "PMID-9390691_T2", "PMID-9390691_T3" ] }, { "id": "PMID-9390691_2", "entity_ids": [ "PMID-9390691_T8", "PMID-9390691_T7" ] } ]

[]

[ { "id": "PMID-9394832__text", "type": "abstract", "text": [ "Thiol modulation inhibits the interleukin (IL)-1-mediated activation of an IL-1 receptor-associated protein kinase and NF-kappa B. \nThe interleukin-1 receptor type I (IL-1RI) is associated with other proteins thus forming a complex system by which IL-1 exerts its various signals. The initiating event is still uncertain, but activation of a recently described receptor-associated protein kinase is one of the earliest events detectable (Martin et al., Eur.J.Immunol.1994.24: 1566). IL-1 signaling is commonly accompanied by oxidative processes and is thought to be subject to redox regulation. We therefore investigated whether the activation of the IL-1RI-associated protein kinase could be a target for redox regulation and whether an altered activity of the kinase could influence IL-1-mediated NF-kappa B activation. A murine T cell line, EL4, was stimulated with IL-1 with and without pretreatment with different compounds known to influence the cellular redox status. Thiol modifying agents like diamide, menadione, pyrrolidine dithiocarbamate (PDTC), diethyl dithiocarbamate or phenylarsine oxide inhibited the IL-1-induced activation of the IL-1RI-associated protein kinase. N-Acetylcysteine, alpha,alpha'-dipyridyl, aminotriazole or nitrofurantoin did not show any effect. The inhibition by PDTC was reversible unless glutathione synthesis was blocked by buthionine sulfoximine. The described conditions which inhibited or prevented the activation of the IL-1RI-associated kinase similarly impaired the activation of NF-kappa B in EL4 cells. From these observations we conclude that free thiols in the IL-1RI complex are essential for the activation of the IL-1RI-associated protein kinase and that this process is mandatory for IL-1 signaling leading to NF-kappa B activation. " ], "offsets": [ [ 0, 1788 ] ] } ]

[ { "id": "PMID-9394832_T1", "type": "Protein", "text": [ "IL-1 receptor" ], "offsets": [ [ 75, 88 ] ], "normalized": [] }, { "id": "PMID-9394832_T2", "type": "Protein", "text": [ "interleukin-1 receptor type I" ], "offsets": [ [ 136, 165 ] ], "normalized": [] }, { "id": "PMID-9394832_T3", "type": "Protein", "text": [ "IL-1RI" ], "offsets": [ [ 167, 173 ] ], "normalized": [] }, { "id": "PMID-9394832_T4", "type": "Protein", "text": [ "IL-1RI" ], "offsets": [ [ 651, 657 ] ], "normalized": [] }, { "id": "PMID-9394832_T5", "type": "Protein", "text": [ "IL-1RI" ], "offsets": [ [ 1150, 1156 ] ], "normalized": [] }, { "id": "PMID-9394832_T6", "type": "Protein", "text": [ "IL-1RI" ], "offsets": [ [ 1465, 1471 ] ], "normalized": [] }, { "id": "PMID-9394832_T7", "type": "Protein", "text": [ "IL-1RI" ], "offsets": [ [ 1612, 1618 ] ], "normalized": [] }, { "id": "PMID-9394832_T8", "type": "Protein", "text": [ "IL-1RI" ], "offsets": [ [ 1667, 1673 ] ], "normalized": [] } ]

[ { "id": "PMID-9394832_E1", "type": "Binding", "trigger": { "text": [ "associated" ], "offsets": [ [ 178, 188 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "PMID-9394832_T3" } ] } ]

[ { "id": "PMID-9394832_1", "entity_ids": [ "PMID-9394832_T3", "PMID-9394832_T2" ] } ]

[]

[ { "id": "PMID-9398163__text", "type": "abstract", "text": [ "ATF1 and CREB trans-activate a cell cycle regulated histone H4 gene at a distal nuclear matrix associated promoter element. \nProteins of the ATF/CREB class of transcription factors stimulate gene expression of several cell growth-related genes through protein kinase A-related cAMP response elements. The promoter activity of cell cycle regulated histone H4 genes is regulated by at least four principal cis-acting elements which mediate G1/S phase control and/or enhancement of transcription during the cell cycle. Using protein-DNA interaction assays we show that the H4 promoter contains two ATF/CREB recognition motifs which interact with CREB, ATF1, and ATF2 but not with ATF4/CREB2. One ATF/CRE motif is located in the distal promoter at the nuclear matrix-associated Site IV, and the second motif is present in the proximal promoter at Site I. Both ATF/CRE motifs overlap binding sequences for the multifunctional YY1 transcription factor, which has previously been shown to be nuclear matrix associated. Subnuclear fractionation reveals that there are two ATF1 isoforms which appear to differ with respect to DNA binding activity and partition selectively between nuclear matrix and nonmatrix compartments, consistent with the role of the nuclear matrix in regulating gene expression. Site-directed mutational studies demonstrate that Site I and Site IV together support ATF1- and CREB-induced trans-activation of the H4 promoter. Thus, our data establish that ATF/CREB factors functionally modulate histone H4 gene transcription at distal and proximal promoter elements. " ], "offsets": [ [ 0, 1580 ] ] } ]

[ { "id": "PMID-9398163_T1", "type": "Protein", "text": [ "ATF1" ], "offsets": [ [ 0, 4 ] ], "normalized": [] }, { "id": "PMID-9398163_T2", "type": "Protein", "text": [ "histone H4" ], "offsets": [ [ 52, 62 ] ], "normalized": [] }, { "id": "PMID-9398163_T3", "type": "Protein", "text": [ "histone H4" ], "offsets": [ [ 347, 357 ] ], "normalized": [] }, { "id": "PMID-9398163_T4", "type": "Protein", "text": [ "ATF1" ], "offsets": [ [ 649, 653 ] ], "normalized": [] }, { "id": "PMID-9398163_T5", "type": "Protein", "text": [ "ATF2" ], "offsets": [ [ 659, 663 ] ], "normalized": [] }, { "id": "PMID-9398163_T6", "type": "Protein", "text": [ "ATF4" ], "offsets": [ [ 677, 681 ] ], "normalized": [] }, { "id": "PMID-9398163_T7", "type": "Protein", "text": [ "CREB2" ], "offsets": [ [ 682, 687 ] ], "normalized": [] }, { "id": "PMID-9398163_T8", "type": "Protein", "text": [ "ATF1" ], "offsets": [ [ 1064, 1068 ] ], "normalized": [] }, { "id": "PMID-9398163_T9", "type": "Protein", "text": [ "ATF1" ], "offsets": [ [ 1379, 1383 ] ], "normalized": [] }, { "id": "PMID-9398163_T10", "type": "Protein", "text": [ "H4" ], "offsets": [ [ 1426, 1428 ] ], "normalized": [] }, { "id": "PMID-9398163_T11", "type": "Protein", "text": [ "histone H4" ], "offsets": [ [ 1508, 1518 ] ], "normalized": [] }, { "id": "PMID-9398163_T23", "type": "Entity", "text": [ "promoter" ], "offsets": [ [ 1429, 1437 ] ], "normalized": [] } ]

[ { "id": "PMID-9398163_E1", "type": "Positive_regulation", "trigger": { "text": [ "trans-activate" ], "offsets": [ [ 14, 28 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "PMID-9398163_E3" } ] }, { "id": "PMID-9398163_E2", "type": "Positive_regulation", "trigger": { "text": [ "trans-activate" ], "offsets": [ [ 14, 28 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "PMID-9398163_E3" }, { "role": "Cause", "ref_id": "PMID-9398163_T1" } ] }, { "id": "PMID-9398163_E3", "type": "Regulation", "trigger": { "text": [ "regulated" ], "offsets": [ [ 42, 51 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "PMID-9398163_T2" } ] }, { "id": "PMID-9398163_E4", "type": "Regulation", "trigger": { "text": [ "regulated" ], "offsets": [ [ 337, 346 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "PMID-9398163_T3" } ] }, { "id": "PMID-9398163_E5", "type": "Regulation", "trigger": { "text": [ "regulated" ], "offsets": [ [ 367, 376 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "PMID-9398163_E4" } ] }, { "id": "PMID-9398163_E6", "type": "Positive_regulation", "trigger": { "text": [ "mediate" ], "offsets": [ [ 430, 437 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "PMID-9398163_E7" } ] }, { "id": "PMID-9398163_E7", "type": "Positive_regulation", "trigger": { "text": [ "enhancement" ], "offsets": [ [ 464, 475 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "PMID-9398163_E8" } ] }, { "id": "PMID-9398163_E8", "type": "Transcription", "trigger": { "text": [ "transcription" ], "offsets": [ [ 479, 492 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "PMID-9398163_T3" } ] }, { "id": "PMID-9398163_E9", "type": "Binding", "trigger": { "text": [ "interact" ], "offsets": [ [ 629, 637 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "PMID-9398163_T5" } ] }, { "id": "PMID-9398163_E10", "type": "Binding", "trigger": { "text": [ "interact" ], "offsets": [ [ 629, 637 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "PMID-9398163_T4" } ] }, { "id": "PMID-9398163_E11", "type": "Binding", "trigger": { "text": [ "interact" ], "offsets": [ [ 629, 637 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "PMID-9398163_T6" } ] }, { "id": "PMID-9398163_E12", "type": "Binding", "trigger": { "text": [ "binding" ], "offsets": [ [ 1121, 1128 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "PMID-9398163_T8" } ] }, { "id": "PMID-9398163_E13", "type": "Positive_regulation", "trigger": { "text": [ "support" ], "offsets": [ [ 1371, 1378 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "PMID-9398163_E15" } ] }, { "id": "PMID-9398163_E14", "type": "Positive_regulation", "trigger": { "text": [ "support" ], "offsets": [ [ 1371, 1378 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "PMID-9398163_E16" } ] }, { "id": "PMID-9398163_E15", "type": "Positive_regulation", "trigger": { "text": [ "trans-activation" ], "offsets": [ [ 1402, 1418 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "PMID-9398163_T10" }, { "role": "Cause", "ref_id": "PMID-9398163_T9" }, { "role": "Site", "ref_id": "PMID-9398163_T23" } ] }, { "id": "PMID-9398163_E16", "type": "Positive_regulation", "trigger": { "text": [ "trans-activation" ], "offsets": [ [ 1402, 1418 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "PMID-9398163_T10" }, { "role": "Site", "ref_id": "PMID-9398163_T23" } ] }, { "id": "PMID-9398163_E17", "type": "Regulation", "trigger": { "text": [ "modulate" ], "offsets": [ [ 1499, 1507 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "PMID-9398163_E18" } ] }, { "id": "PMID-9398163_E18", "type": "Transcription", "trigger": { "text": [ "transcription" ], "offsets": [ [ 1524, 1537 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "PMID-9398163_T11" } ] }, { "id": "PMID-9398163_E19", "type": "Positive_regulation", "trigger": { "text": [ "at" ], "offsets": [ [ 1538, 1540 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "PMID-9398163_E17" } ] } ]

[ { "id": "PMID-9398163_1", "entity_ids": [ "PMID-9398163_T6", "PMID-9398163_T7" ] } ]

[]

[ { "id": "PMID-9398404__text", "type": "abstract", "text": [ "IL-2 and IL-7 induce heterodimerization of STAT5 isoforms in human peripheral blood T lymphoblasts. \nDespite differences in T cell responses induced by interleukin (IL)-2 and IL-7, both cytokines modulate T cell functions by activation of signal transducers and activators of transcription (STAT) proteins. We examined the contribution of the two isoforms of STAT5, STAT5A and STAT5B, to IL-2- and IL-7-induced activation of human peripheral blood T lymphoblasts. Both cytokines induced assembly of STAT5A and STAT5B containing complexes capable of binding to the interferon-gamma activation sequence (GAS), and these complexes rapidly translocated (within 1 min) into the nucleus of IL-2- or IL-7-treated cells. The kinetics of this translocation were delayed in IL-7-treated as compared to IL-2-treated cells. IL-2 and IL-7 were equivalent in their ability to induce tyrosine phosphorylation of STAT5A and STAT5B and to facilitate binding of these STATs to an immobilized GAS element. Both IL-2 and IL-7 induced substantial amounts of STAT5A/STAT5B heterodimerization. Moreover, we observed constitutive association of STAT3 with each STAT5 isomer. These data suggest that IL-2 and IL-7 induce assembly of STAT heterodimers in a similar manner and that subsequent cellular responses may be driven by induction of similar sets of genes. " ], "offsets": [ [ 0, 1338 ] ] } ]

[ { "id": "PMID-9398404_T1", "type": "Protein", "text": [ "IL-2" ], "offsets": [ [ 0, 4 ] ], "normalized": [] }, { "id": "PMID-9398404_T2", "type": "Protein", "text": [ "IL-7" ], "offsets": [ [ 9, 13 ] ], "normalized": [] }, { "id": "PMID-9398404_T3", "type": "Protein", "text": [ "interleukin (IL)-2" ], "offsets": [ [ 152, 170 ] ], "normalized": [] }, { "id": "PMID-9398404_T4", "type": "Protein", "text": [ "IL-7" ], "offsets": [ [ 175, 179 ] ], "normalized": [] }, { "id": "PMID-9398404_T5", "type": "Protein", "text": [ "STAT5A" ], "offsets": [ [ 366, 372 ] ], "normalized": [] }, { "id": "PMID-9398404_T6", "type": "Protein", "text": [ "STAT5B" ], "offsets": [ [ 377, 383 ] ], "normalized": [] }, { "id": "PMID-9398404_T7", "type": "Protein", "text": [ "IL-2" ], "offsets": [ [ 388, 392 ] ], "normalized": [] }, { "id": "PMID-9398404_T8", "type": "Protein", "text": [ "IL-7" ], "offsets": [ [ 398, 402 ] ], "normalized": [] }, { "id": "PMID-9398404_T9", "type": "Protein", "text": [ "STAT5A" ], "offsets": [ [ 499, 505 ] ], "normalized": [] }, { "id": "PMID-9398404_T10", "type": "Protein", "text": [ "STAT5B" ], "offsets": [ [ 510, 516 ] ], "normalized": [] }, { "id": "PMID-9398404_T11", "type": "Protein", "text": [ "IL-2" ], "offsets": [ [ 684, 688 ] ], "normalized": [] }, { "id": "PMID-9398404_T12", "type": "Protein", "text": [ "L-7" ], "offsets": [ [ 694, 697 ] ], "normalized": [] }, { "id": "PMID-9398404_T13", "type": "Protein", "text": [ "IL-7" ], "offsets": [ [ 764, 768 ] ], "normalized": [] }, { "id": "PMID-9398404_T14", "type": "Protein", "text": [ "IL-2" ], "offsets": [ [ 792, 796 ] ], "normalized": [] }, { "id": "PMID-9398404_T15", "type": "Protein", "text": [ "IL-2" ], "offsets": [ [ 812, 816 ] ], "normalized": [] }, { "id": "PMID-9398404_T16", "type": "Protein", "text": [ "IL-7" ], "offsets": [ [ 821, 825 ] ], "normalized": [] }, { "id": "PMID-9398404_T17", "type": "Protein", "text": [ "STAT5A" ], "offsets": [ [ 897, 903 ] ], "normalized": [] }, { "id": "PMID-9398404_T18", "type": "Protein", "text": [ "STAT5B" ], "offsets": [ [ 908, 914 ] ], "normalized": [] }, { "id": "PMID-9398404_T19", "type": "Protein", "text": [ "IL-2" ], "offsets": [ [ 992, 996 ] ], "normalized": [] }, { "id": "PMID-9398404_T20", "type": "Protein", "text": [ "IL-7" ], "offsets": [ [ 1001, 1005 ] ], "normalized": [] }, { "id": "PMID-9398404_T21", "type": "Protein", "text": [ "STAT5A" ], "offsets": [ [ 1037, 1043 ] ], "normalized": [] }, { "id": "PMID-9398404_T22", "type": "Protein", "text": [ "STAT5B" ], "offsets": [ [ 1044, 1050 ] ], "normalized": [] }, { "id": "PMID-9398404_T23", "type": "Protein", "text": [ "IL-2" ], "offsets": [ [ 1175, 1179 ] ], "normalized": [] }, { "id": "PMID-9398404_T24", "type": "Protein", "text": [ "IL-7" ], "offsets": [ [ 1184, 1188 ] ], "normalized": [] }, { "id": "PMID-9398404_T29", "type": "Entity", "text": [ "nucleus" ], "offsets": [ [ 673, 680 ] ], "normalized": [] }, { "id": "PMID-9398404_T32", "type": "Entity", "text": [ "tyrosine" ], "offsets": [ [ 869, 877 ] ], "normalized": [] } ]

[ { "id": "PMID-9398404_E1", "type": "Positive_regulation", "trigger": { "text": [ "induced" ], "offsets": [ [ 479, 486 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "PMID-9398404_E3" }, { "role": "Cause", "ref_id": "PMID-9398404_T7" } ] }, { "id": "PMID-9398404_E2", "type": "Positive_regulation", "trigger": { "text": [ "induced" ], "offsets": [ [ 479, 486 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "PMID-9398404_E3" }, { "role": "Cause", "ref_id": "PMID-9398404_T8" } ] }, { "id": "PMID-9398404_E3", "type": "Binding", "trigger": { "text": [ "complexes" ], "offsets": [ [ 528, 537 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "PMID-9398404_T9" }, { "role": "Theme", "ref_id": "PMID-9398404_T10" } ] }, { "id": "PMID-9398404_E4", "type": "Binding", "trigger": { "text": [ "binding" ], "offsets": [ [ 549, 556 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "PMID-9398404_T10" } ] }, { "id": "PMID-9398404_E5", "type": "Binding", "trigger": { "text": [ "binding" ], "offsets": [ [ 549, 556 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "PMID-9398404_T9" } ] }, { "id": "PMID-9398404_E6", "type": "Localization", "trigger": { "text": [ "translocated" ], "offsets": [ [ 636, 648 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "PMID-9398404_T10" }, { "role": "ToLoc", "ref_id": "PMID-9398404_T29" } ] }, { "id": "PMID-9398404_E7", "type": "Localization", "trigger": { "text": [ "translocated" ], "offsets": [ [ 636, 648 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "PMID-9398404_T9" }, { "role": "ToLoc", "ref_id": "PMID-9398404_T29" } ] }, { "id": "PMID-9398404_E8", "type": "Positive_regulation", "trigger": { "text": [ "treated" ], "offsets": [ [ 698, 705 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "PMID-9398404_E6" }, { "role": "Cause", "ref_id": "PMID-9398404_T11" } ] }, { "id": "PMID-9398404_E9", "type": "Positive_regulation", "trigger": { "text": [ "treated" ], "offsets": [ [ 698, 705 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "PMID-9398404_E7" }, { "role": "Cause", "ref_id": "PMID-9398404_T11" } ] }, { "id": "PMID-9398404_E10", "type": "Positive_regulation", "trigger": { "text": [ "induce" ], "offsets": [ [ 862, 868 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "PMID-9398404_E14" }, { "role": "Cause", "ref_id": "PMID-9398404_T15" } ] }, { "id": "PMID-9398404_E11", "type": "Positive_regulation", "trigger": { "text": [ "induce" ], "offsets": [ [ 862, 868 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "PMID-9398404_E14" }, { "role": "Cause", "ref_id": "PMID-9398404_T16" } ] }, { "id": "PMID-9398404_E12", "type": "Positive_regulation", "trigger": { "text": [ "induce" ], "offsets": [ [ 862, 868 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "PMID-9398404_E15" }, { "role": "Cause", "ref_id": "PMID-9398404_T16" } ] }, { "id": "PMID-9398404_E13", "type": "Positive_regulation", "trigger": { "text": [ "induce" ], "offsets": [ [ 862, 868 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "PMID-9398404_E15" }, { "role": "Cause", "ref_id": "PMID-9398404_T15" } ] }, { "id": "PMID-9398404_E14", "type": "Phosphorylation", "trigger": { "text": [ "phosphorylation" ], "offsets": [ [ 878, 893 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "PMID-9398404_T17" }, { "role": "Site", "ref_id": "PMID-9398404_T32" } ] }, { "id": "PMID-9398404_E15", "type": "Phosphorylation", "trigger": { "text": [ "phosphorylation" ], "offsets": [ [ 878, 893 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "PMID-9398404_T18" }, { "role": "Site", "ref_id": "PMID-9398404_T32" } ] }, { "id": "PMID-9398404_E16", "type": "Positive_regulation", "trigger": { "text": [ "facilitate" ], "offsets": [ [ 922, 932 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "PMID-9398404_E21" }, { "role": "Cause", "ref_id": "PMID-9398404_T15" } ] }, { "id": "PMID-9398404_E17", "type": "Positive_regulation", "trigger": { "text": [ "facilitate" ], "offsets": [ [ 922, 932 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "PMID-9398404_E20" }, { "role": "Cause", "ref_id": "PMID-9398404_T15" } ] }, { "id": "PMID-9398404_E18", "type": "Positive_regulation", "trigger": { "text": [ "facilitate" ], "offsets": [ [ 922, 932 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "PMID-9398404_E20" }, { "role": "Cause", "ref_id": "PMID-9398404_T16" } ] }, { "id": "PMID-9398404_E19", "type": "Positive_regulation", "trigger": { "text": [ "facilitate" ], "offsets": [ [ 922, 932 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "PMID-9398404_E21" }, { "role": "Cause", "ref_id": "PMID-9398404_T16" } ] }, { "id": "PMID-9398404_E20", "type": "Binding", "trigger": { "text": [ "binding" ], "offsets": [ [ 933, 940 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "PMID-9398404_T17" } ] }, { "id": "PMID-9398404_E21", "type": "Binding", "trigger": { "text": [ "binding" ], "offsets": [ [ 933, 940 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "PMID-9398404_T18" } ] }, { "id": "PMID-9398404_E22", "type": "Binding", "trigger": { "text": [ "heterodimerization" ], "offsets": [ [ 1051, 1069 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "PMID-9398404_T21" }, { "role": "Theme", "ref_id": "PMID-9398404_T22" } ] }, { "id": "PMID-9398404_E23", "type": "Binding", "trigger": { "text": [ "association" ], "offsets": [ [ 1106, 1117 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "PMID-9398404_T21" } ] }, { "id": "PMID-9398404_E24", "type": "Binding", "trigger": { "text": [ "association" ], "offsets": [ [ 1106, 1117 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "PMID-9398404_T22" } ] } ]

[]

[]