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[ { "id": "PMID-8139041__text", "type": "abstract", "text": [ "A transcriptional regulatory element is associated with a nuclease-hypersensitive site in the pol gene of human immunodeficiency virus type 1. \nAnalysis of the chromatin organization of the integrated human immunodeficiency virus type 1 (HIV-1) genome has previously revealed a major constitutive DNase I-hypersensitive site associated with the pol gene (E. Verdin, J. Virol. 65:6790-6799, 1991). In the present report, high-resolution mapping of this site with DNase I and micrococcal nuclease identified a nucleosome-free region centered around nucleotides (nt) 4490 to 4766. A 500-bp fragment encompassing this hypersensitive site (nt 4481 to 4982) exhibited transcription-enhancing activity (two- to threefold) when it was cloned in its natural position with respect to the HIV-1 promoter after transient transfection in U937 and CEM cells. Using in vitro footprinting and gel shift assays, we have identified four distinct binding sites for nuclear proteins within this positive regulatory element. Site B (nt 4519 to 4545) specifically bound four distinct nuclear protein complexes: a ubiquitous factor, a T-cell-specific factor, a B-cell-specific factor, and the monocyte/macrophage- and B-cell-specific transcription factor PU.1/Spi-1. In most HIV-1 isolates in which this PU box was not conserved, it was replaced by a binding site for the related factor Ets1. Factors binding to site C (nt 4681 to 4701) had a DNA-binding specificity similar to that of factors binding to site B, except for PU.1/Spi-1. A GC box containing a binding site for Sp1 was identified (nt 4623 to 4631). Site D (nt 4816 to 4851) specifically bound a ubiquitously expressed factor. These results identify a transcriptional regulatory element associated with a nuclease-hypersensitive site in the pol gene of HIV-1 and suggest that its activity may be controlled by a complex interplay of cis-regulatory elements. " ], "offsets": [ [ 0, 1898 ] ] } ]

[ { "id": "PMID-8139041_T1", "type": "Protein", "text": [ "pol" ], "offsets": [ [ 94, 97 ] ], "normalized": [] }, { "id": "PMID-8139041_T2", "type": "Protein", "text": [ "pol" ], "offsets": [ [ 345, 348 ] ], "normalized": [] }, { "id": "PMID-8139041_T3", "type": "Protein", "text": [ "DNase I" ], "offsets": [ [ 462, 469 ] ], "normalized": [] }, { "id": "PMID-8139041_T4", "type": "Protein", "text": [ "micrococcal nuclease" ], "offsets": [ [ 474, 494 ] ], "normalized": [] }, { "id": "PMID-8139041_T5", "type": "Protein", "text": [ "PU.1" ], "offsets": [ [ 1232, 1236 ] ], "normalized": [] }, { "id": "PMID-8139041_T6", "type": "Protein", "text": [ "Spi-1" ], "offsets": [ [ 1237, 1242 ] ], "normalized": [] }, { "id": "PMID-8139041_T7", "type": "Protein", "text": [ "Ets1" ], "offsets": [ [ 1364, 1368 ] ], "normalized": [] }, { "id": "PMID-8139041_T8", "type": "Protein", "text": [ "PU.1" ], "offsets": [ [ 1501, 1505 ] ], "normalized": [] }, { "id": "PMID-8139041_T9", "type": "Protein", "text": [ "Spi-1" ], "offsets": [ [ 1506, 1511 ] ], "normalized": [] }, { "id": "PMID-8139041_T10", "type": "Protein", "text": [ "Sp1" ], "offsets": [ [ 1552, 1555 ] ], "normalized": [] }, { "id": "PMID-8139041_T11", "type": "Protein", "text": [ "pol" ], "offsets": [ [ 1781, 1784 ] ], "normalized": [] } ]

[ { "id": "PMID-8139041_E1", "type": "Binding", "trigger": { "text": [ "bound" ], "offsets": [ [ 1042, 1047 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "PMID-8139041_T5" } ] }, { "id": "PMID-8139041_E2", "type": "Binding", "trigger": { "text": [ "binding" ], "offsets": [ [ 1328, 1335 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "PMID-8139041_T7" } ] }, { "id": "PMID-8139041_E3", "type": "Binding", "trigger": { "text": [ "containing a binding site" ], "offsets": [ [ 1522, 1547 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "PMID-8139041_T10" } ] } ]

[ { "id": "PMID-8139041_1", "entity_ids": [ "PMID-8139041_T8", "PMID-8139041_T9" ] }, { "id": "PMID-8139041_2", "entity_ids": [ "PMID-8139041_T5", "PMID-8139041_T6" ] } ]

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[ { "id": "PMID-8144878__text", "type": "abstract", "text": [ "Expression of v-src in T cells correlates with nuclear expression of NF-kappa B. \nNF-kappa B is a rapidly inducible transcriptional activator that responds to a variety of signals and influences the expression of many genes involved in the immune response. Protein tyrosine kinases transmit signals from cytokine and immune receptors. Very little information exists linking these two important classes of signaling molecules. We now demonstrate that v-src expression correlates with nuclear expression of a kappa B binding complex similar to that induced by phorbol ester and ionomycin, as detected by electrophoretic mobility shift assay using a variety of kappa B sites. This complex was blocked by the tyrosine kinase inhibitor, herbimycin A. The v-src-induced complex comprised the p50 and p65 components of NF-kappa B, as determined by supershift and immunoblot analysis. As a functional correlate of this finding, transient co-transfection of HIV-1 LTR reporter constructs in a different T cell line demonstrated that v-src activated this promoter in a kappa B-dependent manner. We found that transactivation of the HIV-1 LTR by v-src was more sensitive to mutations of the proximal, rather than the distal, kappa B element. The implications for T cell receptor signaling and HIV-1 gene expression are considered. " ], "offsets": [ [ 0, 1320 ] ] } ]

[ { "id": "PMID-8144878_T1", "type": "Protein", "text": [ "v-src" ], "offsets": [ [ 14, 19 ] ], "normalized": [] }, { "id": "PMID-8144878_T2", "type": "Protein", "text": [ "v-src" ], "offsets": [ [ 450, 455 ] ], "normalized": [] }, { "id": "PMID-8144878_T3", "type": "Protein", "text": [ "v-src" ], "offsets": [ [ 750, 755 ] ], "normalized": [] }, { "id": "PMID-8144878_T4", "type": "Protein", "text": [ "p50" ], "offsets": [ [ 786, 789 ] ], "normalized": [] }, { "id": "PMID-8144878_T5", "type": "Protein", "text": [ "p65" ], "offsets": [ [ 794, 797 ] ], "normalized": [] }, { "id": "PMID-8144878_T6", "type": "Protein", "text": [ "v-src" ], "offsets": [ [ 1024, 1029 ] ], "normalized": [] }, { "id": "PMID-8144878_T7", "type": "Protein", "text": [ "v-src" ], "offsets": [ [ 1135, 1140 ] ], "normalized": [] } ]

[ { "id": "PMID-8144878_E1", "type": "Gene_expression", "trigger": { "text": [ "Expression" ], "offsets": [ [ 0, 10 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "PMID-8144878_T1" } ] }, { "id": "PMID-8144878_E2", "type": "Gene_expression", "trigger": { "text": [ "expression" ], "offsets": [ [ 456, 466 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "PMID-8144878_T2" } ] }, { "id": "PMID-8144878_E3", "type": "Binding", "trigger": { "text": [ "induced complex" ], "offsets": [ [ 756, 771 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "PMID-8144878_T4" }, { "role": "Theme", "ref_id": "PMID-8144878_T5" } ] }, { "id": "PMID-8144878_E4", "type": "Positive_regulation", "trigger": { "text": [ "induced" ], "offsets": [ [ 756, 763 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "PMID-8144878_E3" }, { "role": "Cause", "ref_id": "PMID-8144878_T3" } ] } ]

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[ { "id": "PMID-8151786__text", "type": "abstract", "text": [ "Human immunodeficiency virus type 1 Nef protein down-regulates transcription factors NF-kappa B and AP-1 in human T cells in vitro after T-cell receptor stimulation. \nHuman immunodeficiency virus type 1 (HIV-1) negative factor (Nef) has been shown to down-regulate the transcription factors NF-kappa B and AP-1 in vitro. To define the mechanism of action of the Nef protein, the signal transduction pathways which may be affected in T cells by constitutive expression of the nef gene were examined. Stimulation of T cells with tumor necrosis factor, interleukin-1, or lipopolysaccharide resulted in the recruitment of transcriptional factors to a similar level whether or not the cells expressed the nef gene. On the other hand, stimulation of T cells by mitogens or antibodies to the T-cell receptor (TCR)-CD3 complex resulted in the down-regulation of transcriptional factors NF-kappa B and AP-1 in cells expressing the nef gene compared with cells not expressing the nef gene. Because the Nef protein does not affect the surface expression of the CD3-TCR complex, we conclude that the Nef protein down-regulates the transcriptional factors NF-kappa B and AP-1 in T cells in vitro through an effect on the TCR-dependent signal transduction pathway. " ], "offsets": [ [ 0, 1251 ] ] } ]

[ { "id": "PMID-8151786_T1", "type": "Protein", "text": [ "Nef" ], "offsets": [ [ 36, 39 ] ], "normalized": [] }, { "id": "PMID-8151786_T2", "type": "Protein", "text": [ "negative factor" ], "offsets": [ [ 211, 226 ] ], "normalized": [] }, { "id": "PMID-8151786_T3", "type": "Protein", "text": [ "Nef" ], "offsets": [ [ 228, 231 ] ], "normalized": [] }, { "id": "PMID-8151786_T4", "type": "Protein", "text": [ "Nef" ], "offsets": [ [ 362, 365 ] ], "normalized": [] }, { "id": "PMID-8151786_T5", "type": "Protein", "text": [ "nef" ], "offsets": [ [ 475, 478 ] ], "normalized": [] }, { "id": "PMID-8151786_T6", "type": "Protein", "text": [ "nef" ], "offsets": [ [ 922, 925 ] ], "normalized": [] }, { "id": "PMID-8151786_T7", "type": "Protein", "text": [ "Nef" ], "offsets": [ [ 992, 995 ] ], "normalized": [] }, { "id": "PMID-8151786_T8", "type": "Protein", "text": [ "Nef" ], "offsets": [ [ 1088, 1091 ] ], "normalized": [] } ]

[ { "id": "PMID-8151786_E1", "type": "Gene_expression", "trigger": { "text": [ "expression" ], "offsets": [ [ 457, 467 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "PMID-8151786_T5" } ] }, { "id": "PMID-8151786_E2", "type": "Gene_expression", "trigger": { "text": [ "expressing" ], "offsets": [ [ 907, 917 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "PMID-8151786_T6" } ] } ]

[ { "id": "PMID-8151786_1", "entity_ids": [ "PMID-8151786_T2", "PMID-8151786_T3" ] } ]

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[ { "id": "PMID-8158122__text", "type": "abstract", "text": [ "Activation of nuclear factor kappa B in human neuroblastoma cell lines. \nThe nuclear factor kappa B (NF-kappa B) is a eukaryotic transcription factor. In B cells and macrophages it is constitutively present in cell nuclei, whereas in many other cell types, NF-kappa B translocates from cytosol to nucleus as a result of transduction by tumor necrosis factor alpha (TNF alpha), phorbol ester, and other polyclonal signals. Using neuroblastoma cell lines as models, we have shown that in neural cells NF-kappa B was present in the cytosol and translocated into nuclei as a result of TNF alpha treatment. The TNF alpha-activated NF-kappa B was transcriptionally functional. NF-kappa B activation by TNF alpha was not correlated with cell differentiation or proliferation. However, reagents such as nerve growth factor (NGF) and the phorbol ester phorbol 12-myristate 13-acetate (PMA), which induce phenotypical differentiation of the SH-SY5Y neuroblastoma cell line, activated NF-kappa B, but only in that particular cell line. In a NGF-responsive rat pheochromocytoma cell line, PC12, PMA activated NF-kappa B, whereas NGF did not. In other neuroblastoma cell lines, such as SK-N-Be(2), the lack of PMA induction of differentiation was correlated with the lack of NF-kappa B activation. We found, moreover, that in SK-N-Be(2) cells protein kinase C (PKC) enzymatic activity was much lower compared with that in a control cell line and that the low PKC enzymatic activity was due to low PKC protein expression. NF-kappa B was not activated by retinoic acid, which induced morphological differentiation of all the neuroblastoma cell lines used in the present study. Thus, NF-kappa B activation was not required for neuroblastoma cell differentiation. Furthermore, the results obtained with TNF alpha proved that NF-kappa B activation was not sufficient for induction of neuroblastoma differentiation. " ], "offsets": [ [ 0, 1897 ] ] } ]

[ { "id": "PMID-8158122_T1", "type": "Protein", "text": [ "tumor necrosis factor alpha" ], "offsets": [ [ 336, 363 ] ], "normalized": [] }, { "id": "PMID-8158122_T2", "type": "Protein", "text": [ "TNF alpha" ], "offsets": [ [ 365, 374 ] ], "normalized": [] }, { "id": "PMID-8158122_T3", "type": "Protein", "text": [ "TNF alpha" ], "offsets": [ [ 581, 590 ] ], "normalized": [] }, { "id": "PMID-8158122_T4", "type": "Protein", "text": [ "TNF alpha" ], "offsets": [ [ 606, 615 ] ], "normalized": [] }, { "id": "PMID-8158122_T5", "type": "Protein", "text": [ "TNF alpha" ], "offsets": [ [ 696, 705 ] ], "normalized": [] }, { "id": "PMID-8158122_T6", "type": "Protein", "text": [ "TNF alpha" ], "offsets": [ [ 1786, 1795 ] ], "normalized": [] } ]

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[ { "id": "PMID-8158122_1", "entity_ids": [ "PMID-8158122_T1", "PMID-8158122_T2" ] } ]

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[ { "id": "PMID-8162052__text", "type": "abstract", "text": [ "Genes encoding general initiation factors for RNA polymerase II transcription are dispersed in the human genome. \nGeneral transcription factors are required for accurate initiation of transcription by RNA polymerase II. Human cDNAs encoding subunits of these factors have been cloned and sequenced. Using fluorescence in situ hybridization (FISH), we show here that the genes encoding the TATA-box binding protein (TBP), TFIIB, TFIIE alpha, TFIIE beta, RAP30, RAP74 and the 62 kDa subunit, of TFIIH are located at the human chromosomal bands 6q26-27, 1p21-22, 3q21-24, 8p12, 13q14, 19p13.3 and 11p14-15.1, respectively. This dispersed localization of a group of functionally related gene provides insights into the molecular mechanism of human genome evolution and their possible involvement in human diseases. " ], "offsets": [ [ 0, 811 ] ] } ]

[ { "id": "PMID-8162052_T1", "type": "Protein", "text": [ "TATA-box binding protein" ], "offsets": [ [ 389, 413 ] ], "normalized": [] }, { "id": "PMID-8162052_T2", "type": "Protein", "text": [ "TBP" ], "offsets": [ [ 415, 418 ] ], "normalized": [] }, { "id": "PMID-8162052_T3", "type": "Protein", "text": [ "TFIIB" ], "offsets": [ [ 421, 426 ] ], "normalized": [] }, { "id": "PMID-8162052_T4", "type": "Protein", "text": [ "TFIIE alpha" ], "offsets": [ [ 428, 439 ] ], "normalized": [] }, { "id": "PMID-8162052_T5", "type": "Protein", "text": [ "TFIIE beta" ], "offsets": [ [ 441, 451 ] ], "normalized": [] }, { "id": "PMID-8162052_T6", "type": "Protein", "text": [ "RAP30" ], "offsets": [ [ 453, 458 ] ], "normalized": [] }, { "id": "PMID-8162052_T7", "type": "Protein", "text": [ "RAP74" ], "offsets": [ [ 460, 465 ] ], "normalized": [] } ]

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[ { "id": "PMID-8162052_1", "entity_ids": [ "PMID-8162052_T1", "PMID-8162052_T2" ] } ]

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[ { "id": "PMID-8163464__text", "type": "abstract", "text": [ "A novel heterodimerization partner for thyroid hormone receptor. Peroxisome proliferator-activated receptor. \nRetinoid-like receptors play a central role in hormonal responses by forming heterodimers with other nuclear hormone receptors. In this study we have identified the peroxisome proliferator-activated receptor (PPAR) as a new thyroid hormone receptor (THR) auxiliary nuclear protein, heterodimerizing with THR in solution. Although these heterodimers do not recognize a classical thyroid hormone response element (TRE) characterized by direct repeat separated by four nucleotides (DR+4), PPAR behaves as a dominant negative regulator of thyroid hormone (TH) action. However, a TH-dependent positive effect is elicited by selective interaction of the THR beta-PPAR but not the THR alpha-PPAR heterodimer with a novel TRE (DR+2). The critical region of THR beta was mapped to 3 amino acids in the distal box of the DNA binding domain. Hence, PPAR can positively or negatively influence TH action depending on TRE structure and THR isotype. " ], "offsets": [ [ 0, 1046 ] ] } ]

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[ { "id": "PMID-8163658__text", "type": "abstract", "text": [ "Hypoxic induction of interleukin-8 gene expression in human endothelial cells. \nBecause leukocyte-mediated tissue damage is an important component of the pathologic picture in ischemia/reperfusion, we have sought mechanisms by which PMNs are directed into hypoxic tissue. Incubation of human endothelial cells (ECs) in hypoxia, PO2 approximately 14-18 Torr, led to time-dependent release of IL-8 antigen into the conditioned medium; this was accompanied by increased chemotactic activity for PMNs, blocked by antibody to IL-8. Production of IL-8 by hypoxic ECs occurred concomitantly with both increased levels of IL-8 mRNA, based on polymerase chain reaction analysis, and increased IL-8 transcription, based on nuclear run-on assays. Northern analysis of mRNA from hypoxic ECs also demonstrated increased levels of mRNA for macrophage chemotactic protein-1, another member of the chemokine superfamily of proinflammatory cytokines. IL-8 gene induction was associated with the presence of increased binding activity in nuclear extracts from hypoxic ECs for the NF-kB site. Studies with human umbilical vein segments exposed to hypoxia also demonstrated increased elaboration of IL-8 antigen compared with normoxic controls. In mice exposed to hypoxia (PO2 approximately 30-40 Torr), there was increased pulmonary leukostasis, as evidenced by increased myeloperoxidase activity in tissue homogenates. In parallel, increased levels of transcripts for IP-10, a murine homologue in the chemokine family related to IL-8, were observed in hypoxic lung tissue. Taken together, these data suggest that hypoxia constitutes a stimulus for leukocyte chemotaxis and tissue leukostasis. " ], "offsets": [ [ 0, 1675 ] ] } ]

[ { "id": "PMID-8163658_T1", "type": "Protein", "text": [ "interleukin-8" ], "offsets": [ [ 21, 34 ] ], "normalized": [] }, { "id": "PMID-8163658_T2", "type": "Protein", "text": [ "IL-8" ], "offsets": [ [ 391, 395 ] ], "normalized": [] }, { "id": "PMID-8163658_T3", "type": "Protein", "text": [ "IL-8" ], "offsets": [ [ 521, 525 ] ], "normalized": [] }, { "id": "PMID-8163658_T4", "type": "Protein", "text": [ "IL-8" ], "offsets": [ [ 541, 545 ] ], "normalized": [] }, { "id": "PMID-8163658_T5", "type": "Protein", "text": [ "IL-8" ], "offsets": [ [ 614, 618 ] ], "normalized": [] }, { "id": "PMID-8163658_T6", "type": "Protein", "text": [ "IL-8" ], "offsets": [ [ 684, 688 ] ], "normalized": [] }, { "id": "PMID-8163658_T7", "type": "Protein", "text": [ "macrophage chemotactic protein-1" ], "offsets": [ [ 826, 858 ] ], "normalized": [] }, { "id": "PMID-8163658_T8", "type": "Protein", "text": [ "IL-8" ], "offsets": [ [ 934, 938 ] ], "normalized": [] }, { "id": "PMID-8163658_T9", "type": "Protein", "text": [ "IL-8" ], "offsets": [ [ 1179, 1183 ] ], "normalized": [] }, { "id": "PMID-8163658_T10", "type": "Protein", "text": [ "myeloperoxidase" ], "offsets": [ [ 1353, 1368 ] ], "normalized": [] }, { "id": "PMID-8163658_T11", "type": "Protein", "text": [ "IP-10" ], "offsets": [ [ 1450, 1455 ] ], "normalized": [] }, { "id": "PMID-8163658_T12", "type": "Protein", "text": [ "IL-8" ], "offsets": [ [ 1511, 1515 ] ], "normalized": [] } ]

[ { "id": "PMID-8163658_E1", "type": "Positive_regulation", "trigger": { "text": [ "induction" ], "offsets": [ [ 8, 17 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "PMID-8163658_E2" } ] }, { "id": "PMID-8163658_E2", "type": "Gene_expression", "trigger": { "text": [ "expression" ], "offsets": [ [ 40, 50 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "PMID-8163658_T1" } ] }, { "id": "PMID-8163658_E3", "type": "Positive_regulation", "trigger": { "text": [ "led" ], "offsets": [ [ 358, 361 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "PMID-8163658_E4" } ] }, { "id": "PMID-8163658_E4", "type": "Localization", "trigger": { "text": [ "release" ], "offsets": [ [ 380, 387 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "PMID-8163658_T2" } ] }, { "id": "PMID-8163658_E5", "type": "Positive_regulation", "trigger": { "text": [ "Production" ], "offsets": [ [ 527, 537 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "PMID-8163658_T4" } ] }, { "id": "PMID-8163658_E6", "type": "Positive_regulation", "trigger": { "text": [ "increased" ], "offsets": [ [ 594, 603 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "PMID-8163658_T5" } ] }, { "id": "PMID-8163658_E7", "type": "Positive_regulation", "trigger": { "text": [ "increased" ], "offsets": [ [ 674, 683 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "PMID-8163658_E8" } ] }, { "id": "PMID-8163658_E8", "type": "Transcription", "trigger": { "text": [ "transcription" ], "offsets": [ [ 689, 702 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "PMID-8163658_T6" } ] }, { "id": "PMID-8163658_E9", "type": "Positive_regulation", "trigger": { "text": [ "increased" ], "offsets": [ [ 797, 806 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "PMID-8163658_T7" } ] }, { "id": "PMID-8163658_E10", "type": "Positive_regulation", "trigger": { "text": [ "induction" ], "offsets": [ [ 944, 953 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "PMID-8163658_T8" } ] }, { "id": "PMID-8163658_E11", "type": "Positive_regulation", "trigger": { "text": [ "increased" ], "offsets": [ [ 1154, 1163 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "PMID-8163658_T9" } ] }, { "id": "PMID-8163658_E12", "type": "Positive_regulation", "trigger": { "text": [ "increased" ], "offsets": [ [ 1414, 1423 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "PMID-8163658_T11" } ] } ]

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[ { "id": "PMID-8164652__text", "type": "abstract", "text": [ "Function of NF-kappa B/Rel binding sites in the major histocompatibility complex class II invariant chain promoter is dependent on cell-specific binding of different NF-kappa B/Rel subunits. \nThe promoter of the human major histocompatibility complex class II-associated invariant-chain gene (Ii) contains two NF-kappa B/Rel binding sites located at -109 to -118 (Ii kappa B-1) and -163 to -172 (Ii kappa B-2) from the transcription start site. We report here that the differential function of each of these NF-kappa B/Rel sites in several distinct cell types depends on cell-specific binding of NF-kappa B/Rel transcription factors. Ii kappa B-1 is a positive regulatory element in B-cell lines and in the Ii-expressing T-cell line, H9, but acts as a negative regulatory element in myelomonocytic and glia cell lines. In vivo protein-DNA contacts are detectable at Ii kappa B-1 in cell lines in which this site is functional as either a positive or negative regulator. Electrophoretic mobility supershift assays determine that members of the NF-kappa B/Rel family of transcription factors can bind to this site in vitro and that DNA-binding complexes that contain p50, p52, p65, and cRel correlate with positive regulation whereas the presence of p50 correlates with negative regulation. Ii kappa B-2 is a site of positive regulation in B-cell lines and a site of negative regulation in H9 T cells, myelomonocytic, and glial cell lines. In vivo occupancy of this site is observed only in the H9 T-cell line. Again, in vitro supershift studies indicate that the presence of p50, p52, p65, and cRel correlates with positive function whereas the presence of only p50 and p52 correlates with negative function. This differential binding of specific NF-kappa B/Rel subunits is likely to mediate the disparate functions of these two NF-kappa B/Rel binding sites. " ], "offsets": [ [ 0, 1858 ] ] } ]

[ { "id": "PMID-8164652_T1", "type": "Protein", "text": [ "major histocompatibility complex class II invariant chain" ], "offsets": [ [ 48, 105 ] ], "normalized": [] }, { "id": "PMID-8164652_T2", "type": "Protein", "text": [ "histocompatibility complex class II-associated invariant-chain" ], "offsets": [ [ 224, 286 ] ], "normalized": [] }, { "id": "PMID-8164652_T3", "type": "Protein", "text": [ "p50" ], "offsets": [ [ 1165, 1168 ] ], "normalized": [] }, { "id": "PMID-8164652_T4", "type": "Protein", "text": [ "p52" ], "offsets": [ [ 1170, 1173 ] ], "normalized": [] }, { "id": "PMID-8164652_T5", "type": "Protein", "text": [ "p65" ], "offsets": [ [ 1175, 1178 ] ], "normalized": [] }, { "id": "PMID-8164652_T6", "type": "Protein", "text": [ "cRel" ], "offsets": [ [ 1184, 1188 ] ], "normalized": [] }, { "id": "PMID-8164652_T7", "type": "Protein", "text": [ "p50" ], "offsets": [ [ 1248, 1251 ] ], "normalized": [] }, { "id": "PMID-8164652_T8", "type": "Protein", "text": [ "p50" ], "offsets": [ [ 1574, 1577 ] ], "normalized": [] }, { "id": "PMID-8164652_T9", "type": "Protein", "text": [ "p52" ], "offsets": [ [ 1579, 1582 ] ], "normalized": [] }, { "id": "PMID-8164652_T10", "type": "Protein", "text": [ "p65" ], "offsets": [ [ 1584, 1587 ] ], "normalized": [] }, { "id": "PMID-8164652_T11", "type": "Protein", "text": [ "cRel" ], "offsets": [ [ 1593, 1597 ] ], "normalized": [] }, { "id": "PMID-8164652_T12", "type": "Protein", "text": [ "p50" ], "offsets": [ [ 1661, 1664 ] ], "normalized": [] }, { "id": "PMID-8164652_T13", "type": "Protein", "text": [ "p52" ], "offsets": [ [ 1669, 1672 ] ], "normalized": [] }, { "id": "PMID-8164652_T15", "type": "Entity", "text": [ "promoter" ], "offsets": [ [ 106, 114 ] ], "normalized": [] } ]

[ { "id": "PMID-8164652_E1", "type": "Regulation", "trigger": { "text": [ "Function" ], "offsets": [ [ 0, 8 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "PMID-8164652_T1" }, { "role": "Site", "ref_id": "PMID-8164652_T15" } ] }, { "id": "PMID-8164652_E2", "type": "Regulation", "trigger": { "text": [ "dependent" ], "offsets": [ [ 118, 127 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "PMID-8164652_E1" } ] }, { "id": "PMID-8164652_E3", "type": "Binding", "trigger": { "text": [ "binding complexes" ], "offsets": [ [ 1134, 1151 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "PMID-8164652_T3" }, { "role": "Theme", "ref_id": "PMID-8164652_T4" }, { "role": "Theme", "ref_id": "PMID-8164652_T5" }, { "role": "Theme", "ref_id": "PMID-8164652_T6" } ] }, { "id": "PMID-8164652_E4", "type": "Binding", "trigger": { "text": [ "presence" ], "offsets": [ [ 1236, 1244 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "PMID-8164652_T7" } ] }, { "id": "PMID-8164652_E5", "type": "Binding", "trigger": { "text": [ "presence" ], "offsets": [ [ 1562, 1570 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "PMID-8164652_T8" }, { "role": "Theme", "ref_id": "PMID-8164652_T9" }, { "role": "Theme", "ref_id": "PMID-8164652_T10" }, { "role": "Theme", "ref_id": "PMID-8164652_T11" } ] }, { "id": "PMID-8164652_E6", "type": "Binding", "trigger": { "text": [ "presence" ], "offsets": [ [ 1644, 1652 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "PMID-8164652_T12" }, { "role": "Theme", "ref_id": "PMID-8164652_T13" } ] } ]

[]

[]

[ { "id": "PMID-8164666__text", "type": "abstract", "text": [ "Positive regulators of the lineage-specific transcription factor GATA-1 in differentiating erythroid cells. \nThe zinc finger transcription factor GATA-1 is a major regulator of gene expression in erythroid, megakaryocyte, and mast cell lineages. GATA-1 binds to WGATAR consensus motifs in the regulatory regions of virtually all erythroid cell-specific genes. Analyses with cultured cells and cell-free systems have provided strong evidence that GATA-1 is involved in control of globin gene expression during erythroid differentiation. Targeted mutagenesis of the GATA-1 gene in embryonic stem cells has demonstrated its requirement in normal erythroid development. Efficient rescue of the defect requires an intact GATA element in the distal promoter, suggesting autoregulatory control of GATA-1 transcription. To examine whether GATA-1 expression involves additional regulatory factors or is maintained entirely by an autoregulatory loop, we have used a transient heterokaryon system to test the ability of erythroid factors to activate the GATA-1 gene in nonerythroid nuclei. We show here that proerythroblasts and mature erythroid cells contain a diffusible activity (TAG) capable of transcriptional activation of GATA-1 and that this activity decreases during the terminal differentiation of erythroid cells. Nuclei from GATA-1- mutant embryonic stem cells can still be reprogrammed to express their globin genes in erythroid heterokaryons, indicating that de novo induction of GATA-1 is not required for globin gene activation following cell fusion. " ], "offsets": [ [ 0, 1556 ] ] } ]

[ { "id": "PMID-8164666_T1", "type": "Protein", "text": [ "GATA-1" ], "offsets": [ [ 65, 71 ] ], "normalized": [] }, { "id": "PMID-8164666_T2", "type": "Protein", "text": [ "GATA-1" ], "offsets": [ [ 146, 152 ] ], "normalized": [] }, { "id": "PMID-8164666_T3", "type": "Protein", "text": [ "GATA-1" ], "offsets": [ [ 246, 252 ] ], "normalized": [] }, { "id": "PMID-8164666_T4", "type": "Protein", "text": [ "GATA-1" ], "offsets": [ [ 446, 452 ] ], "normalized": [] }, { "id": "PMID-8164666_T5", "type": "Protein", "text": [ "GATA-1" ], "offsets": [ [ 564, 570 ] ], "normalized": [] }, { "id": "PMID-8164666_T6", "type": "Protein", "text": [ "GATA-1" ], "offsets": [ [ 790, 796 ] ], "normalized": [] }, { "id": "PMID-8164666_T7", "type": "Protein", "text": [ "GATA-1" ], "offsets": [ [ 831, 837 ] ], "normalized": [] }, { "id": "PMID-8164666_T8", "type": "Protein", "text": [ "GATA-1" ], "offsets": [ [ 1043, 1049 ] ], "normalized": [] }, { "id": "PMID-8164666_T9", "type": "Protein", "text": [ "GATA-1" ], "offsets": [ [ 1218, 1224 ] ], "normalized": [] }, { "id": "PMID-8164666_T10", "type": "Protein", "text": [ "GATA-1" ], "offsets": [ [ 1326, 1332 ] ], "normalized": [] }, { "id": "PMID-8164666_T11", "type": "Protein", "text": [ "GATA-1" ], "offsets": [ [ 1483, 1489 ] ], "normalized": [] } ]

[ { "id": "PMID-8164666_E1", "type": "Positive_regulation", "trigger": { "text": [ "Positive regulators" ], "offsets": [ [ 0, 19 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "PMID-8164666_T1" } ] }, { "id": "PMID-8164666_E2", "type": "Binding", "trigger": { "text": [ "binds" ], "offsets": [ [ 253, 258 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "PMID-8164666_T3" } ] }, { "id": "PMID-8164666_E3", "type": "Regulation", "trigger": { "text": [ "autoregulatory control" ], "offsets": [ [ 764, 786 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "PMID-8164666_E4" } ] }, { "id": "PMID-8164666_E4", "type": "Transcription", "trigger": { "text": [ "transcription" ], "offsets": [ [ 797, 810 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "PMID-8164666_T6" } ] }, { "id": "PMID-8164666_E5", "type": "Gene_expression", "trigger": { "text": [ "expression" ], "offsets": [ [ 838, 848 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "PMID-8164666_T7" } ] }, { "id": "PMID-8164666_E6", "type": "Positive_regulation", "trigger": { "text": [ "maintained" ], "offsets": [ [ 894, 904 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "PMID-8164666_E5" } ] }, { "id": "PMID-8164666_E7", "type": "Positive_regulation", "trigger": { "text": [ "activate" ], "offsets": [ [ 1030, 1038 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "PMID-8164666_T8" } ] }, { "id": "PMID-8164666_E8", "type": "Positive_regulation", "trigger": { "text": [ "transcriptional activation" ], "offsets": [ [ 1188, 1214 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "PMID-8164666_T9" } ] }, { "id": "PMID-8164666_E9", "type": "Negative_regulation", "trigger": { "text": [ "decreases" ], "offsets": [ [ 1248, 1257 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "PMID-8164666_E8" } ] }, { "id": "PMID-8164666_E10", "type": "Positive_regulation", "trigger": { "text": [ "induction" ], "offsets": [ [ 1470, 1479 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "PMID-8164666_T11" } ] } ]

[]

[]

[ { "id": "PMID-8170476__text", "type": "abstract", "text": [ "Patterns of Pan expression and role of Pan proteins in endocrine cell type-specific complex formation. \nThe Pan gene encodes at least two distinct transcripts, Pan-1 and Pan-2 (also known as E47 and E12, respectively), by the mechanism of alternative RNA splicing. Northern blot analyses performed on rat and mouse tissues have detected ubiquitously expressed Pan transcripts, but the abundance, distribution, and form of Pan proteins have not been clearly defined. Studies of cell lines representing endocrine, fibroblast, and lymphoid lineages using polyclonal antisera to detect E2A proteins have suggested that significant E2A protein expression is restricted to B-lymphocytes. We have developed a monoclonal antibody, Yae, which is specific for Pan/E2A proteins, and have used the Yae antibody to examine a variety of endocrine and nonendocrine cell lineages for differences in Pan/E2A protein expression, subcellular localization, and heteromeric complex formation. In contrast to previous results obtained using polyclonal antiseras to detect Pan/E2A proteins, we report comparable levels of Pan proteins in GH/PRL- and insulin-producing, B- and T-lymphocyte cells. IEF-1, a pancreatic beta-cell type-specific complex believed to regulate insulin expression, is demonstrated to consist of at least two distinct species, one of which does not contain Pan molecules. Although it has been postulated that pituitary endocrine cells and pancreatic endocrine beta-cells share identical Pan/E2A complexes, native-Western analyses of pituitary and endocrine beta-cells detect Pan proteins in distinct cell type-specific complexes. " ], "offsets": [ [ 0, 1630 ] ] } ]

[ { "id": "PMID-8170476_T1", "type": "Protein", "text": [ "Pan" ], "offsets": [ [ 108, 111 ] ], "normalized": [] }, { "id": "PMID-8170476_T2", "type": "Protein", "text": [ "Pan-1" ], "offsets": [ [ 160, 165 ] ], "normalized": [] }, { "id": "PMID-8170476_T3", "type": "Protein", "text": [ "Pan-2" ], "offsets": [ [ 170, 175 ] ], "normalized": [] }, { "id": "PMID-8170476_T4", "type": "Protein", "text": [ "E47" ], "offsets": [ [ 191, 194 ] ], "normalized": [] }, { "id": "PMID-8170476_T5", "type": "Protein", "text": [ "E12" ], "offsets": [ [ 199, 202 ] ], "normalized": [] }, { "id": "PMID-8170476_T6", "type": "Protein", "text": [ "Pan" ], "offsets": [ [ 360, 363 ] ], "normalized": [] }, { "id": "PMID-8170476_T7", "type": "Protein", "text": [ "Pan" ], "offsets": [ [ 422, 425 ] ], "normalized": [] }, { "id": "PMID-8170476_T8", "type": "Protein", "text": [ "E2A" ], "offsets": [ [ 582, 585 ] ], "normalized": [] }, { "id": "PMID-8170476_T9", "type": "Protein", "text": [ "E2A" ], "offsets": [ [ 627, 630 ] ], "normalized": [] }, { "id": "PMID-8170476_T10", "type": "Protein", "text": [ "Pan" ], "offsets": [ [ 750, 753 ] ], "normalized": [] }, { "id": "PMID-8170476_T11", "type": "Protein", "text": [ "E2A" ], "offsets": [ [ 754, 757 ] ], "normalized": [] }, { "id": "PMID-8170476_T12", "type": "Protein", "text": [ "Pan" ], "offsets": [ [ 883, 886 ] ], "normalized": [] }, { "id": "PMID-8170476_T13", "type": "Protein", "text": [ "E2A" ], "offsets": [ [ 887, 890 ] ], "normalized": [] }, { "id": "PMID-8170476_T14", "type": "Protein", "text": [ "Pan" ], "offsets": [ [ 1050, 1053 ] ], "normalized": [] }, { "id": "PMID-8170476_T15", "type": "Protein", "text": [ "E2A" ], "offsets": [ [ 1054, 1057 ] ], "normalized": [] }, { "id": "PMID-8170476_T16", "type": "Protein", "text": [ "Pan" ], "offsets": [ [ 1099, 1102 ] ], "normalized": [] }, { "id": "PMID-8170476_T17", "type": "Protein", "text": [ "GH" ], "offsets": [ [ 1115, 1117 ] ], "normalized": [] }, { "id": "PMID-8170476_T18", "type": "Protein", "text": [ "insulin" ], "offsets": [ [ 1127, 1134 ] ], "normalized": [] }, { "id": "PMID-8170476_T19", "type": "Protein", "text": [ "insulin" ], "offsets": [ [ 1246, 1253 ] ], "normalized": [] }, { "id": "PMID-8170476_T20", "type": "Protein", "text": [ "Pan" ], "offsets": [ [ 1357, 1360 ] ], "normalized": [] }, { "id": "PMID-8170476_T21", "type": "Protein", "text": [ "Pan" ], "offsets": [ [ 1487, 1490 ] ], "normalized": [] }, { "id": "PMID-8170476_T22", "type": "Protein", "text": [ "E2A" ], "offsets": [ [ 1491, 1494 ] ], "normalized": [] }, { "id": "PMID-8170476_T23", "type": "Protein", "text": [ "Pan" ], "offsets": [ [ 1575, 1578 ] ], "normalized": [] } ]

[ { "id": "PMID-8170476_E1", "type": "Transcription", "trigger": { "text": [ "expressed" ], "offsets": [ [ 350, 359 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "PMID-8170476_T6" } ] }, { "id": "PMID-8170476_E2", "type": "Gene_expression", "trigger": { "text": [ "expression" ], "offsets": [ [ 639, 649 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "PMID-8170476_T9" } ] }, { "id": "PMID-8170476_E3", "type": "Gene_expression", "trigger": { "text": [ "expression" ], "offsets": [ [ 899, 909 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "PMID-8170476_T12" } ] }, { "id": "PMID-8170476_E4", "type": "Binding", "trigger": { "text": [ "heteromeric complex formation" ], "offsets": [ [ 941, 970 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "PMID-8170476_T12" } ] }, { "id": "PMID-8170476_E5", "type": "Gene_expression", "trigger": { "text": [ "comparable levels" ], "offsets": [ [ 1078, 1095 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "PMID-8170476_T16" } ] }, { "id": "PMID-8170476_E6", "type": "Gene_expression", "trigger": { "text": [ "producing" ], "offsets": [ [ 1135, 1144 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "PMID-8170476_T17" } ] }, { "id": "PMID-8170476_E7", "type": "Gene_expression", "trigger": { "text": [ "producing" ], "offsets": [ [ 1135, 1144 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "PMID-8170476_T18" } ] }, { "id": "PMID-8170476_E8", "type": "Regulation", "trigger": { "text": [ "regulate" ], "offsets": [ [ 1237, 1245 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "PMID-8170476_E9" } ] }, { "id": "PMID-8170476_E9", "type": "Gene_expression", "trigger": { "text": [ "expression" ], "offsets": [ [ 1254, 1264 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "PMID-8170476_T19" } ] }, { "id": "PMID-8170476_E10", "type": "Gene_expression", "trigger": { "text": [ "detect" ], "offsets": [ [ 1568, 1574 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "PMID-8170476_T23" } ] } ]

[ { "id": "PMID-8170476_1", "entity_ids": [ "PMID-8170476_T3", "PMID-8170476_T5" ] }, { "id": "PMID-8170476_2", "entity_ids": [ "PMID-8170476_T2", "PMID-8170476_T4" ] } ]

[]

[ { "id": "PMID-8175775__text", "type": "abstract", "text": [ "Functional block for 1 alpha,25-dihydroxyvitamin D3-mediated gene regulation in human B lymphocytes. \nElements necessary for the steroid hormone 1 alpha,25-dihydroxyvitamin D3 (1 alpha,25-(OH)2D3) to induce a biological response include the presence of specific intracellular receptors (vitamin D3 receptors (VDR)) and modulation of gene expression via hormone-activated receptor binding to regulatory regions of target genes. These parameters were examined in normal and Epstein-Barr virus-immortalized human B cells and compared with 1 alpha,25-(OH)2D3-responsive cells of the T and monocytic lineages. Although resting tonsillar B cells did not express VDR mRNA, activation of these cells with interleukin-4 induced VDR in the absence of exogenously supplemented 1 alpha,25-(OH)2D3. As indicators of hormone-mediated gene regulation we analyzed modulation of CD23, a common B cell/monocyte surface antigen, and 24-hydroxylase. 1 alpha,25-(OH)2D3 inhibited CD23 expression in U937 cells, yet failed to modulate CD23 expression in B cells. Furthermore, 1 alpha,25-(OH)2D3 induced 24-hydroxylase mRNA expression and metabolic activity in both U937 cells and lectin-activated T cells, yet failed to induce 24-hydroxylase mRNA or its metabolic activity in B cells. These findings suggest that although human B lymphocytes can express VDR mRNA and protein, they exhibit a functional block for vitamin D-dependent gene regulation. " ], "offsets": [ [ 0, 1427 ] ] } ]

[ { "id": "PMID-8175775_T1", "type": "Protein", "text": [ "vitamin D3 receptors" ], "offsets": [ [ 287, 307 ] ], "normalized": [] }, { "id": "PMID-8175775_T2", "type": "Protein", "text": [ "VDR" ], "offsets": [ [ 309, 312 ] ], "normalized": [] }, { "id": "PMID-8175775_T3", "type": "Protein", "text": [ "VDR" ], "offsets": [ [ 656, 659 ] ], "normalized": [] }, { "id": "PMID-8175775_T4", "type": "Protein", "text": [ "interleukin-4" ], "offsets": [ [ 697, 710 ] ], "normalized": [] }, { "id": "PMID-8175775_T5", "type": "Protein", "text": [ "VDR" ], "offsets": [ [ 719, 722 ] ], "normalized": [] }, { "id": "PMID-8175775_T6", "type": "Protein", "text": [ "CD23" ], "offsets": [ [ 862, 866 ] ], "normalized": [] }, { "id": "PMID-8175775_T7", "type": "Protein", "text": [ "24-hydroxylase" ], "offsets": [ [ 914, 928 ] ], "normalized": [] }, { "id": "PMID-8175775_T8", "type": "Protein", "text": [ "CD23" ], "offsets": [ [ 959, 963 ] ], "normalized": [] }, { "id": "PMID-8175775_T9", "type": "Protein", "text": [ "CD23" ], "offsets": [ [ 1013, 1017 ] ], "normalized": [] }, { "id": "PMID-8175775_T10", "type": "Protein", "text": [ "24-hydroxylase" ], "offsets": [ [ 1081, 1095 ] ], "normalized": [] }, { "id": "PMID-8175775_T11", "type": "Protein", "text": [ "24-hydroxylase" ], "offsets": [ [ 1205, 1219 ] ], "normalized": [] }, { "id": "PMID-8175775_T12", "type": "Protein", "text": [ "VDR" ], "offsets": [ [ 1332, 1335 ] ], "normalized": [] } ]

[ { "id": "PMID-8175775_E1", "type": "Positive_regulation", "trigger": { "text": [ "activated" ], "offsets": [ [ 361, 370 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "PMID-8175775_T2" } ] }, { "id": "PMID-8175775_E2", "type": "Transcription", "trigger": { "text": [ "express" ], "offsets": [ [ 648, 655 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "PMID-8175775_T3" } ] }, { "id": "PMID-8175775_E3", "type": "Positive_regulation", "trigger": { "text": [ "induced" ], "offsets": [ [ 711, 718 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "PMID-8175775_T5" } ] }, { "id": "PMID-8175775_E4", "type": "Regulation", "trigger": { "text": [ "modulation" ], "offsets": [ [ 848, 858 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "PMID-8175775_T6" } ] }, { "id": "PMID-8175775_E5", "type": "Regulation", "trigger": { "text": [ "modulation" ], "offsets": [ [ 848, 858 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "PMID-8175775_T7" } ] }, { "id": "PMID-8175775_E6", "type": "Negative_regulation", "trigger": { "text": [ "inhibited" ], "offsets": [ [ 949, 958 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "PMID-8175775_E7" } ] }, { "id": "PMID-8175775_E7", "type": "Gene_expression", "trigger": { "text": [ "expression" ], "offsets": [ [ 964, 974 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "PMID-8175775_T8" } ] }, { "id": "PMID-8175775_E8", "type": "Regulation", "trigger": { "text": [ "modulate" ], "offsets": [ [ 1004, 1012 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "PMID-8175775_E9" } ] }, { "id": "PMID-8175775_E9", "type": "Gene_expression", "trigger": { "text": [ "expression" ], "offsets": [ [ 1018, 1028 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "PMID-8175775_T9" } ] }, { "id": "PMID-8175775_E10", "type": "Positive_regulation", "trigger": { "text": [ "induced" ], "offsets": [ [ 1073, 1080 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "PMID-8175775_E11" } ] }, { "id": "PMID-8175775_E11", "type": "Transcription", "trigger": { "text": [ "expression" ], "offsets": [ [ 1101, 1111 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "PMID-8175775_T10" } ] }, { "id": "PMID-8175775_E12", "type": "Positive_regulation", "trigger": { "text": [ "induce" ], "offsets": [ [ 1198, 1204 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "PMID-8175775_T11" } ] }, { "id": "PMID-8175775_E13", "type": "Transcription", "trigger": { "text": [ "express" ], "offsets": [ [ 1324, 1331 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "PMID-8175775_T12" } ] }, { "id": "PMID-8175775_E14", "type": "Gene_expression", "trigger": { "text": [ "express" ], "offsets": [ [ 1324, 1331 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "PMID-8175775_T12" } ] } ]

[ { "id": "PMID-8175775_1", "entity_ids": [ "PMID-8175775_T2", "PMID-8175775_T1" ] } ]

[]

[ { "id": "PMID-8179594__text", "type": "abstract", "text": [ "Effects of alpha-lipoic acid and dihydrolipoic acid on expression of proto-oncogene c-fos. \nThe transcription factor AP-1 is an important human mediator of the cellular response to serum, growth factors, and phorbol esters such as 12-O-tetradecanoyl-phorbol-13 acetate (TPA). The AP-1 complex consists of distinct protein heterodimers encoded by the proto-oncogene c-fos and c-jun mRNA whose gene expression can be induced by TPA, cyclic AMP and growth factors. Recent findings suggest an involvement of reactive oxygen species in the pathway of TPA and protein kinase C leading to expression of c-fos and c-jun mRNA. To investigate the role of reactive oxygen species we studied the effects of alpha-lipoic acid and dihydrolipoic acid (natural thiol antioxidants) on the expression of c-fos mRNA in human Jurkat T cells. When cells were preincubated with dihydrolipoic acid (0.2 mM) the expression of c-fos mRNA was suppressed at 30 min after stimulation of TPA (0.5 microM) whereas in the case of preincubation of alpha-lipoic acid (0.2 microM), the expression was enhanced at 30 min. These studies support the idea that superoxide anion radical plays a role in the expression of c-fos mRNA. " ], "offsets": [ [ 0, 1194 ] ] } ]

[ { "id": "PMID-8179594_T1", "type": "Protein", "text": [ "c-fos" ], "offsets": [ [ 84, 89 ] ], "normalized": [] }, { "id": "PMID-8179594_T2", "type": "Protein", "text": [ "c-fos" ], "offsets": [ [ 365, 370 ] ], "normalized": [] }, { "id": "PMID-8179594_T3", "type": "Protein", "text": [ "c-jun" ], "offsets": [ [ 375, 380 ] ], "normalized": [] }, { "id": "PMID-8179594_T4", "type": "Protein", "text": [ "c-fos" ], "offsets": [ [ 596, 601 ] ], "normalized": [] }, { "id": "PMID-8179594_T5", "type": "Protein", "text": [ "c-jun" ], "offsets": [ [ 606, 611 ] ], "normalized": [] }, { "id": "PMID-8179594_T6", "type": "Protein", "text": [ "c-fos" ], "offsets": [ [ 786, 791 ] ], "normalized": [] }, { "id": "PMID-8179594_T7", "type": "Protein", "text": [ "c-fos" ], "offsets": [ [ 902, 907 ] ], "normalized": [] }, { "id": "PMID-8179594_T8", "type": "Protein", "text": [ "c-fos" ], "offsets": [ [ 1182, 1187 ] ], "normalized": [] } ]

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[ { "id": "PMID-8183915__text", "type": "abstract", "text": [ "Alternative splicing of RNA transcripts encoded by the murine p105 NF-kappa B gene generates I kappa B gamma isoforms with different inhibitory activities. \nThe gene encoding the 105-kDa protein (p105) precursor of the p50 subunit of transcription factor NF-kappa B also encodes a p70 I kappa B protein, I kappa B gamma, which is identical to the C-terminal 607 amino acids of p105. Here we show that alternative RNA splicing generates I kappa B gamma isoforms with properties different from those of p70. One 63-kDa isoform, termed I kappa B gamma-1, which lacks 59 amino acids C-terminal to ankyrin repeat 7, has a novel 35-amino acid C terminus encoded by an alternative reading frame of the p105 gene. A 55-kDa isoform, I kappa B gamma-2, lacks the 190 C-terminal amino acids of p70I kappa B gamma. In contrast to p70I kappa B gamma, which is a cytoplasmic protein, I kappa B gamma-1 is found in both the cytoplasm and nucleus, whereas I kappa B gamma-2 is predominantly nuclear. The I kappa B gamma isoforms also display differences in specificity and affinity for Rel/NF-kappa B proteins. While p70I kappa B gamma inhibits p50-, p65-, and c-Rel-mediated transactivation and/or DNA binding, both I kappa B gamma-1 and I kappa B gamma-2 are specific for p50 and have different affinities for this subunit. The absence in I kappa B gamma-1 and I kappa B gamma-2 of a protein kinase A site whose phosphorylation modulates p70I kappa B gamma inhibitory activity suggests that alternative RNA splicing may be used to generate I kappa B gamma isoforms that respond differently to intracellular signals. " ], "offsets": [ [ 0, 1602 ] ] } ]

[ { "id": "PMID-8183915_T1", "type": "Protein", "text": [ "p105 NF-kappa B" ], "offsets": [ [ 62, 77 ] ], "normalized": [] }, { "id": "PMID-8183915_T2", "type": "Protein", "text": [ "I kappa B gamma" ], "offsets": [ [ 93, 108 ] ], "normalized": [] }, { "id": "PMID-8183915_T3", "type": "Protein", "text": [ "p105" ], "offsets": [ [ 196, 200 ] ], "normalized": [] }, { "id": "PMID-8183915_T4", "type": "Protein", "text": [ "p50" ], "offsets": [ [ 219, 222 ] ], "normalized": [] }, { "id": "PMID-8183915_T5", "type": "Protein", "text": [ "p70 I kappa B" ], "offsets": [ [ 281, 294 ] ], "normalized": [] }, { "id": "PMID-8183915_T6", "type": "Protein", "text": [ "I kappa B gamma" ], "offsets": [ [ 304, 319 ] ], "normalized": [] }, { "id": "PMID-8183915_T7", "type": "Protein", "text": [ "I kappa B gamma" ], "offsets": [ [ 436, 451 ] ], "normalized": [] }, { "id": "PMID-8183915_T8", "type": "Protein", "text": [ "I kappa B gamma-1" ], "offsets": [ [ 533, 550 ] ], "normalized": [] }, { "id": "PMID-8183915_T9", "type": "Protein", "text": [ "p105" ], "offsets": [ [ 695, 699 ] ], "normalized": [] }, { "id": "PMID-8183915_T10", "type": "Protein", "text": [ "I kappa B gamma-2" ], "offsets": [ [ 724, 741 ] ], "normalized": [] }, { "id": "PMID-8183915_T11", "type": "Protein", "text": [ "p70I kappa B gamma" ], "offsets": [ [ 783, 801 ] ], "normalized": [] }, { "id": "PMID-8183915_T12", "type": "Protein", "text": [ "p70I kappa B gamma" ], "offsets": [ [ 818, 836 ] ], "normalized": [] }, { "id": "PMID-8183915_T13", "type": "Protein", "text": [ "I kappa B gamma-1" ], "offsets": [ [ 870, 887 ] ], "normalized": [] }, { "id": "PMID-8183915_T14", "type": "Protein", "text": [ "I kappa B gamma-2" ], "offsets": [ [ 940, 957 ] ], "normalized": [] }, { "id": "PMID-8183915_T15", "type": "Protein", "text": [ "I kappa B gamma" ], "offsets": [ [ 988, 1003 ] ], "normalized": [] }, { "id": "PMID-8183915_T16", "type": "Protein", "text": [ "p70I kappa B gamma" ], "offsets": [ [ 1101, 1119 ] ], "normalized": [] }, { "id": "PMID-8183915_T17", "type": "Protein", "text": [ "p50" ], "offsets": [ [ 1129, 1132 ] ], "normalized": [] }, { "id": "PMID-8183915_T18", "type": "Protein", "text": [ "p65" ], "offsets": [ [ 1135, 1138 ] ], "normalized": [] }, { "id": "PMID-8183915_T19", "type": "Protein", "text": [ "c-Rel" ], "offsets": [ [ 1145, 1150 ] ], "normalized": [] }, { "id": "PMID-8183915_T20", "type": "Protein", "text": [ "I kappa B gamma-1" ], "offsets": [ [ 1201, 1218 ] ], "normalized": [] }, { "id": "PMID-8183915_T21", "type": "Protein", "text": [ "I kappa B gamma-2" ], "offsets": [ [ 1223, 1240 ] ], "normalized": [] }, { "id": "PMID-8183915_T22", "type": "Protein", "text": [ "p50" ], "offsets": [ [ 1258, 1261 ] ], "normalized": [] }, { "id": "PMID-8183915_T23", "type": "Protein", "text": [ "I kappa B gamma-1" ], "offsets": [ [ 1325, 1342 ] ], "normalized": [] }, { "id": "PMID-8183915_T24", "type": "Protein", "text": [ "I kappa B gamma-2" ], "offsets": [ [ 1347, 1364 ] ], "normalized": [] }, { "id": "PMID-8183915_T25", "type": "Protein", "text": [ "p70I kappa B gamma" ], "offsets": [ [ 1424, 1442 ] ], "normalized": [] }, { "id": "PMID-8183915_T26", "type": "Protein", "text": [ "I kappa B gamma" ], "offsets": [ [ 1526, 1541 ] ], "normalized": [] }, { "id": "PMID-8183915_T32", "type": "Entity", "text": [ "cytoplasm" ], "offsets": [ [ 909, 918 ] ], "normalized": [] }, { "id": "PMID-8183915_T33", "type": "Entity", "text": [ "nucleus" ], "offsets": [ [ 923, 930 ] ], "normalized": [] }, { "id": "PMID-8183915_T34", "type": "Entity", "text": [ "nuclear" ], "offsets": [ [ 975, 982 ] ], "normalized": [] } ]

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[ { "id": "PMID-8184011__text", "type": "abstract", "text": [ "Activation of nuclear factor kappa B in human lymphoblastoid cells by low-dose ionizing radiation. \nNuclear factor kappa B (NF-kappa B) is a pleiotropic transcription factor which is involved in the transcriptional regulation of several specific genes. Recent reports demonstrated that ionizing radiation in the dose range of 2-50 Gy results in expression of NF-kappa B in human KG-1 myeloid leukemia cells and human B-lymphocyte precursor cells; the precise mechanism involved and the significance are not yet known. The present report demonstrates that even lower doses of ionizing radiation, 0.25-2.0 Gy, are capable of inducing expression of NF-kappa B in EBV-transformed 244B human lymphoblastoid cells. These results are in a dose range where the viability of the cells remains very high. After exposure to 137Cs gamma rays at a dose rate of 1.17 Gy/min, a maximum in expression of NF-kappa B was seen at 8 h after a 0.5-Gy exposure. Time-course studies revealed a biphasic time-dependent expression after 0.5-, 1- and 2-Gy exposures. However, for each time examined, the expression of NF-kappa B was maximum after the 0.5-Gy exposure. The expression of the p50 and p65 NF-kappa B subunits was also shown to be regulated differentially after exposures to 1.0 and 2.0 Gy. " ], "offsets": [ [ 0, 1277 ] ] } ]

[ { "id": "PMID-8184011_T1", "type": "Protein", "text": [ "p50" ], "offsets": [ [ 1164, 1167 ] ], "normalized": [] }, { "id": "PMID-8184011_T2", "type": "Protein", "text": [ "p65" ], "offsets": [ [ 1172, 1175 ] ], "normalized": [] } ]

[ { "id": "PMID-8184011_E1", "type": "Gene_expression", "trigger": { "text": [ "expression" ], "offsets": [ [ 1146, 1156 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "PMID-8184011_T2" } ] }, { "id": "PMID-8184011_E2", "type": "Gene_expression", "trigger": { "text": [ "expression" ], "offsets": [ [ 1146, 1156 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "PMID-8184011_T1" } ] }, { "id": "PMID-8184011_E3", "type": "Regulation", "trigger": { "text": [ "regulated" ], "offsets": [ [ 1217, 1226 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "PMID-8184011_E1" } ] }, { "id": "PMID-8184011_E4", "type": "Regulation", "trigger": { "text": [ "regulated" ], "offsets": [ [ 1217, 1226 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "PMID-8184011_E2" } ] } ]

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[ { "id": "PMID-8186192__text", "type": "abstract", "text": [ "Some antioxidants inhibit, in a co-ordinate fashion, the production of tumor necrosis factor-alpha, IL-beta, and IL-6 by human peripheral blood mononuclear cells. \nSome antioxidants, including butylated hydroxyanisole (BHA), tetrahydropapaveroline (THP), nordihydroguiauretic acid, and 10,11-dihydroxyaporphine (DHA), were found to be potent inhibitors of the production of tumor necrosis factor (TNF)-alpha, IL-1 beta, and IL-6 by human peripheral blood mononuclear cells (PBMC) stimulated by lipopolysaccharide (LPS) (IC50s in the low micromolar range). Inhibition of cytokine production was gene selective and not due to general effects on protein synthesis. Inhibition of cytokine production by PBMC was observed also when other inducers were used (staphylococci, silica, zymosan). Much higher concentrations of other antioxidants--including ascorbic acid, trolox, alpha-tocopherol, butylated hydroxytoluene, and the 5-lipoxygenase inhibitor zileuton--did not affect the production of these cytokines. The active compounds did not inhibit IL-1-induced production of IL-6 in fibroblasts, showing the cell selectivity of the effect. Antioxidant-mediated inhibition of cytokine production was correlated with low levels of the corresponding messenger RNAs. Nuclear run-on experiments showed that THP inhibited transcription of the IL-1 beta gene. THP decreased the concentration of the transcription factors NF-kappa B and AP-1 detected in nuclear extracts of PBMC cultured in the presence or absence of LPS. THP and DHA markedly decreased the levels of TNF-alpha and IL-1 beta in the circulation of mice following LPS injection. Thus antioxidants vary widely in potency as inhibitors of the activation of transcription factors and of the transcription of genes for pro-inflammatory cytokines. Coordinate inhibition of the transcription of genes for inflammatory cytokines could provide a strategy for therapy of diseases with inflammatory pathogenesis and for septic shock. " ], "offsets": [ [ 0, 1976 ] ] } ]

[ { "id": "PMID-8186192_T1", "type": "Protein", "text": [ "tumor necrosis factor-alpha" ], "offsets": [ [ 71, 98 ] ], "normalized": [] }, { "id": "PMID-8186192_T2", "type": "Protein", "text": [ "IL-beta" ], "offsets": [ [ 100, 107 ] ], "normalized": [] }, { "id": "PMID-8186192_T3", "type": "Protein", "text": [ "IL-6" ], "offsets": [ [ 113, 117 ] ], "normalized": [] }, { "id": "PMID-8186192_T4", "type": "Protein", "text": [ "tumor necrosis factor (TNF)-alpha" ], "offsets": [ [ 374, 407 ] ], "normalized": [] }, { "id": "PMID-8186192_T5", "type": "Protein", "text": [ "IL-1 beta" ], "offsets": [ [ 409, 418 ] ], "normalized": [] }, { "id": "PMID-8186192_T6", "type": "Protein", "text": [ "IL-6" ], "offsets": [ [ 424, 428 ] ], "normalized": [] }, { "id": "PMID-8186192_T7", "type": "Protein", "text": [ "IL-6" ], "offsets": [ [ 1070, 1074 ] ], "normalized": [] }, { "id": "PMID-8186192_T8", "type": "Protein", "text": [ "IL-1 beta" ], "offsets": [ [ 1332, 1341 ] ], "normalized": [] }, { "id": "PMID-8186192_T9", "type": "Protein", "text": [ "TNF-alpha" ], "offsets": [ [ 1555, 1564 ] ], "normalized": [] }, { "id": "PMID-8186192_T10", "type": "Protein", "text": [ "IL-1 beta" ], "offsets": [ [ 1569, 1578 ] ], "normalized": [] } ]

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975, 985 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "PMID-8186192_T4" } ] }, { "id": "PMID-8186192_E17", "type": "Gene_expression", "trigger": { "text": [ "production" ], "offsets": [ [ 975, 985 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "PMID-8186192_T6" } ] }, { "id": "PMID-8186192_E18", "type": "Gene_expression", "trigger": { "text": [ "production" ], "offsets": [ [ 975, 985 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "PMID-8186192_T5" } ] }, { "id": "PMID-8186192_E19", "type": "Negative_regulation", "trigger": { "text": [ "inhibit" ], "offsets": [ [ 1035, 1042 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "PMID-8186192_E20" } ] }, { "id": "PMID-8186192_E20", "type": "Positive_regulation", "trigger": { "text": [ "induced" ], "offsets": [ [ 1048, 1055 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "PMID-8186192_E21" } ] }, { "id": "PMID-8186192_E21", "type": "Gene_expression", "trigger": { "text": [ "production" ], "offsets": [ [ 1056, 1066 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "PMID-8186192_T7" } ] }, { "id": "PMID-8186192_E22", "type": "Negative_regulation", "trigger": { "text": [ "inhibited" ], "offsets": [ [ 1301, 1310 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "PMID-8186192_E23" } ] }, { "id": "PMID-8186192_E23", "type": "Transcription", "trigger": { "text": [ "transcription" ], "offsets": [ [ 1311, 1324 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "PMID-8186192_T8" } ] }, { "id": "PMID-8186192_E24", "type": "Negative_regulation", "trigger": { "text": [ "decreased" ], "offsets": [ [ 1531, 1540 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "PMID-8186192_E27" } ] }, { "id": "PMID-8186192_E25", "type": "Negative_regulation", "trigger": { "text": [ "decreased" ], "offsets": [ [ 1531, 1540 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "PMID-8186192_E26" } ] }, { "id": "PMID-8186192_E26", "type": "Gene_expression", "trigger": { "text": [ "levels" ], "offsets": [ [ 1545, 1551 ] ] }, 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[ { "id": "PMID-8186461__text", "type": "abstract", "text": [ "Calcineurin potentiates activation of the granulocyte-macrophage colony-stimulating factor gene in T cells: involvement of the conserved lymphokine element 0. \nGranulocyte-macrophage colony-stimulating factor (GM-CSF) and interleukin-2 (IL-2) are produced by stimulation with phorbol-12-myristate acetate (PMA) and calcium ionophore (A23187) in human T cell leukemia Jurkat cells. The expression of GM-CSF and IL-2 is inhibited by immunosuppressive drugs such as cyclosporin A (CsA) and FK506. Earlier studies on the IL-2 gene expression showed that overexpression of calcineurin (CN), a Ca2+/calmodulin-dependent protein phosphatase, can stimulate transcription from the IL-2 promoter through the NF-AT-binding site. In this study, we obtained evidence that transfection of the cDNAs for CN A (catalytic) and CN B (regulatory) subunits also augments transcription from the GM-CSF promoter and recovers the transcription inhibited by CsA. The constitutively active type of the CN A subunit, which lacks the auto-inhibitory and calmodulin-binding domains, acts in synergy with PMA to activate transcription from the GM-CSF promoter. We also found that the active CN partially replaces calcium ionophore in synergy with PMA to induce expression of endogenous GM-CSF and IL-2. By multimerizing the regulatory elements of the GM-CSF promoter, we found that one of the target sites for the CN action is the conserved lymphokine element 0 (CLE0), located at positions between -54 and -40. Mobility shift assays showed that the CLE0 sequence has an AP1-binding site and is associated with an NF-AT-like factor, termed NF-CLE0 gamma. NF-CLE0 gamma binding is induced by PMA/A23187 and is inhibited by treatment with CsA. These results suggest that CN is involved in the coordinated induction of the GM-CSF and IL-2 genes and that the CLE0 sequence of the GM-CSF gene is a functional analogue of the NF-AT-binding site in the IL-2 promoter, which mediates signals downstream of T cell activation. " ], "offsets": [ [ 0, 1988 ] ] } ]

[ { "id": "PMID-8186461_T1", "type": "Protein", "text": [ "granulocyte-macrophage colony-stimulating factor" ], "offsets": [ [ 42, 90 ] ], "normalized": [] }, { "id": "PMID-8186461_T2", "type": "Protein", "text": [ "Granulocyte-macrophage colony-stimulating factor" ], "offsets": [ [ 160, 208 ] ], "normalized": [] }, { "id": "PMID-8186461_T3", "type": "Protein", "text": [ "GM-CSF" ], "offsets": [ [ 210, 216 ] ], "normalized": [] }, { "id": "PMID-8186461_T4", "type": "Protein", "text": [ "interleukin-2" ], "offsets": [ [ 222, 235 ] ], "normalized": [] }, { "id": "PMID-8186461_T5", "type": "Protein", "text": [ "IL-2" ], "offsets": [ [ 237, 241 ] ], "normalized": [] }, { "id": "PMID-8186461_T6", "type": "Protein", "text": [ "GM-CSF" ], "offsets": [ [ 399, 405 ] ], "normalized": [] }, { "id": "PMID-8186461_T7", "type": "Protein", "text": [ "IL-2" ], "offsets": [ [ 410, 414 ] ], "normalized": [] }, { "id": "PMID-8186461_T8", "type": "Protein", "text": [ "IL-2" ], "offsets": [ [ 517, 521 ] ], "normalized": [] }, { "id": "PMID-8186461_T9", "type": "Protein", "text": [ "calmodulin" ], "offsets": [ [ 593, 603 ] ], "normalized": [] }, { "id": "PMID-8186461_T10", "type": "Protein", "text": [ "IL-2" ], "offsets": [ [ 672, 676 ] ], "normalized": [] }, { "id": "PMID-8186461_T11", "type": "Protein", "text": [ "CN A" ], "offsets": [ [ 789, 793 ] ], "normalized": [] }, { "id": "PMID-8186461_T12", "type": "Protein", "text": [ "CN B" ], "offsets": [ [ 810, 814 ] ], "normalized": [] }, { "id": "PMID-8186461_T13", "type": "Protein", "text": [ "GM-CSF" ], "offsets": [ [ 874, 880 ] ], "normalized": [] }, { "id": "PMID-8186461_T14", "type": "Protein", "text": [ "CN A" ], "offsets": [ [ 977, 981 ] ], "normalized": [] }, { "id": "PMID-8186461_T15", "type": "Protein", "text": [ "GM-CSF" ], "offsets": [ [ 1115, 1121 ] ], "normalized": [] }, { "id": "PMID-8186461_T16", "type": "Protein", "text": [ "GM-CSF" ], "offsets": [ [ 1257, 1263 ] ], "normalized": [] }, { "id": "PMID-8186461_T17", "type": "Protein", "text": [ "IL-2" ], "offsets": [ [ 1268, 1272 ] ], "normalized": [] }, { "id": "PMID-8186461_T18", "type": "Protein", "text": [ "GM-CSF" ], "offsets": [ [ 1322, 1328 ] ], "normalized": [] }, { "id": "PMID-8186461_T19", "type": "Protein", "text": [ "NF-CLE0 gamma" ], "offsets": [ [ 1611, 1624 ] ], "normalized": [] }, { "id": "PMID-8186461_T20", "type": "Protein", "text": [ "NF-CLE0 gamma" ], "offsets": [ [ 1626, 1639 ] ], "normalized": [] }, { "id": "PMID-8186461_T21", "type": "Protein", "text": [ "GM-CSF" ], "offsets": [ [ 1791, 1797 ] ], "normalized": [] }, { "id": "PMID-8186461_T22", "type": "Protein", "text": [ "IL-2" ], "offsets": [ [ 1802, 1806 ] ], "normalized": [] }, { "id": "PMID-8186461_T23", "type": "Protein", "text": [ "GM-CSF" ], "offsets": [ [ 1847, 1853 ] ], "normalized": [] }, { "id": "PMID-8186461_T24", "type": "Protein", "text": [ "IL-2" ], "offsets": [ [ 1917, 1921 ] ], "normalized": [] } ]

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"PMID-8186461_E6", "type": "Positive_regulation", "trigger": { "text": [ "by stimulation with" ], "offsets": [ [ 256, 275 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "PMID-8186461_E4" } ] }, { "id": "PMID-8186461_E7", "type": "Gene_expression", "trigger": { "text": [ "expression" ], "offsets": [ [ 385, 395 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "PMID-8186461_T7" } ] }, { "id": "PMID-8186461_E8", "type": "Gene_expression", "trigger": { "text": [ "expression" ], "offsets": [ [ 385, 395 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "PMID-8186461_T6" } ] }, { "id": "PMID-8186461_E9", "type": "Negative_regulation", "trigger": { "text": [ "inhibited" ], "offsets": [ [ 418, 427 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "PMID-8186461_E8" } ] }, { "id": "PMID-8186461_E10", "type": "Negative_regulation", "trigger": { "text": [ "inhibited" ], "offsets": [ [ 418, 427 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "PMID-8186461_E7" } ] }, { "id": "PMID-8186461_E11", "type": "Gene_expression", "trigger": { "text": [ "expression" ], "offsets": [ [ 527, 537 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "PMID-8186461_T8" } ] }, { "id": "PMID-8186461_E12", "type": "Positive_regulation", "trigger": { "text": [ "stimulate" ], "offsets": [ [ 639, 648 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "PMID-8186461_E13" } ] }, { "id": "PMID-8186461_E13", "type": "Transcription", "trigger": { "text": [ "transcription" ], "offsets": [ [ 649, 662 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "PMID-8186461_T10" } ] }, { "id": "PMID-8186461_E14", "type": "Positive_regulation", "trigger": { "text": [ "transfection" ], "offsets": [ [ 759, 771 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "PMID-8186461_E15" } ] }, { "id": "PMID-8186461_E15", "type": "Gene_expression", "trigger": { "text": [ "transfection" ], "offsets": [ [ 759, 771 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "PMID-8186461_T12" } ] }, { "id": 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864 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "PMID-8186461_T13" } ] }, { "id": "PMID-8186461_E21", "type": "Negative_regulation", "trigger": { "text": [ "recovers" ], "offsets": [ [ 894, 902 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "PMID-8186461_E23" }, { "role": "Cause", "ref_id": "PMID-8186461_E16" } ] }, { "id": "PMID-8186461_E22", "type": "Negative_regulation", "trigger": { "text": [ "recovers" ], "offsets": [ [ 894, 902 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "PMID-8186461_E23" }, { "role": "Cause", "ref_id": "PMID-8186461_E14" } ] }, { "id": "PMID-8186461_E23", "type": "Negative_regulation", "trigger": { "text": [ "inhibited" ], "offsets": [ [ 921, 930 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "PMID-8186461_E20" } ] }, { "id": "PMID-8186461_E24", "type": "Positive_regulation", "trigger": { "text": [ "activate" ], "offsets": [ [ 1083, 1091 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "PMID-8186461_E25" } ] }, { "id": "PMID-8186461_E25", "type": "Transcription", "trigger": { "text": [ "transcription" ], "offsets": [ [ 1092, 1105 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "PMID-8186461_T15" } ] }, { "id": "PMID-8186461_E26", "type": "Positive_regulation", "trigger": { "text": [ "to induce" ], "offsets": [ [ 1222, 1231 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "PMID-8186461_E28" } ] }, { "id": "PMID-8186461_E27", "type": "Positive_regulation", "trigger": { "text": [ "to induce" ], "offsets": [ [ 1222, 1231 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "PMID-8186461_E29" } ] }, { "id": "PMID-8186461_E28", "type": "Gene_expression", "trigger": { "text": [ "expression" ], "offsets": [ [ 1232, 1242 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "PMID-8186461_T17" } ] }, { "id": "PMID-8186461_E29", "type": "Gene_expression", "trigger": { "text": [ "expression" ], "offsets": [ [ 1232, 1242 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "PMID-8186461_T16" } ] }, { "id": "PMID-8186461_E30", "type": "Binding", "trigger": { "text": [ "associated" ], "offsets": [ [ 1566, 1576 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "PMID-8186461_T19" } ] }, { "id": "PMID-8186461_E31", "type": "Binding", "trigger": { "text": [ "binding" ], "offsets": [ [ 1640, 1647 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "PMID-8186461_T20" } ] }, { "id": "PMID-8186461_E32", "type": "Positive_regulation", "trigger": { "text": [ "induced" ], "offsets": [ [ 1651, 1658 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "PMID-8186461_E31" } ] }, { "id": "PMID-8186461_E33", "type": "Negative_regulation", "trigger": { "text": [ "inhibited" ], "offsets": [ [ 1680, 1689 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "PMID-8186461_E31" } ] }, { "id": "PMID-8186461_E34", "type": "Positive_regulation", "trigger": { "text": [ "induction" ], "offsets": [ [ 1774, 1783 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "PMID-8186461_T22" } ] }, { "id": "PMID-8186461_E35", "type": "Positive_regulation", "trigger": { "text": [ "induction" ], "offsets": [ [ 1774, 1783 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "PMID-8186461_T21" } ] } ]

[ { "id": "PMID-8186461_1", "entity_ids": [ "PMID-8186461_T3", "PMID-8186461_T2" ] }, { "id": "PMID-8186461_2", "entity_ids": [ "PMID-8186461_T5", "PMID-8186461_T4" ] } ]

[]

[ { "id": "PMID-8189531__text", "type": "abstract", "text": [ "Central nervous system-derived cells express a kappa B-binding activity that enhances human immunodeficiency virus type 1 transcription in vitro and facilitates TAR-independent transactivation by Tat. \nThe Tat protein of human immunodeficiency virus type 1 (HIV-1) is a potent activator of long terminal repeat-directed transcription. While in most cell types, activation requires interaction of Tat with the unusual transcription element TAR, astrocytic glial cells support TAR-independent transactivation of HIV-1 transcription by Tat. This alternative pathway of Tat activation is mediated by the viral enhancer, a kappa B domain capable of binding the prototypical form of the transcription factor nuclear factor kappa B (NF-kappa B) present in many cell types, including T lymphocytes. Tat transactivation mediated by the kappa B domain is sufficient to allow replication of TAR-deleted mutant HIV-1 in astrocytes. The present study demonstrates the existence of kappa B-specific binding factors present in human glial astrocytes that differ from prototypical NF-kappa B. The novel astrocyte-derived kappa B-binding activity is retained on an HIV-1 Tat affinity column, while prototypical NF-kappa B from Jurkat T cells is not. In vitro transcription studies demonstrate that astrocyte-derived kappa B-binding factors activate transcription of the HIV-1 long terminal repeat and that this activation is dependent on the kappa B domain. Moreover, TAR-independent transactivation of HIV-1 transcription is reproduced in vitro in an astrocyte factor-dependent manner which correlates with kappa B-binding activity. The importance of the central nervous system-enriched kappa B transcription factor in the regulation of HIV-1 expression is discussed. " ], "offsets": [ [ 0, 1752 ] ] } ]

[ { "id": "PMID-8189531_T1", "type": "Protein", "text": [ "Tat" ], "offsets": [ [ 196, 199 ] ], "normalized": [] }, { "id": "PMID-8189531_T2", "type": "Protein", "text": [ "Tat" ], "offsets": [ [ 206, 209 ] ], "normalized": [] }, { "id": "PMID-8189531_T3", "type": "Protein", "text": [ "Tat" ], "offsets": [ [ 396, 399 ] ], "normalized": [] }, { "id": "PMID-8189531_T4", "type": "Protein", "text": [ "Tat" ], "offsets": [ [ 533, 536 ] ], "normalized": [] }, { "id": "PMID-8189531_T5", "type": "Protein", "text": [ "Tat" ], "offsets": [ [ 566, 569 ] ], "normalized": [] }, { "id": "PMID-8189531_T6", "type": "Protein", "text": [ "Tat" ], "offsets": [ [ 791, 794 ] ], "normalized": [] }, { "id": "PMID-8189531_T7", "type": "Protein", "text": [ "Tat" ], "offsets": [ [ 1154, 1157 ] ], "normalized": [] } ]

[ { "id": "PMID-8189531_E1", "type": "Binding", "trigger": { "text": [ "interaction" ], "offsets": [ [ 381, 392 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "PMID-8189531_T3" } ] } ]

[]

[]

[ { "id": "PMID-8195215__text", "type": "abstract", "text": [ "An intricate arrangement of binding sites for the Ets family of transcription factors regulates activity of the alpha 4 integrin gene promoter. \nalpha 4 integrins mediate cell-cell and cell-extracellular matrix interactions that are critical for maturation and function of the immune system as well as differentiation of skeletal muscle. Here we examine molecular mechanisms controlling the pattern of alpha 4 expression. The activity of constructs containing 5' deletion mutants of the alpha 4 gene promoter was compared in transfection assays into cell lines that express alpha 4 and cell lines that do not. The sequence between position -42 and -76 base pairs (bp) was required for efficient transcription in cells that express alpha 4, but it showed no activity in HeLa cells, which do not express alpha 4. Three binding sites for the Ets family of transcription factors are found in this region: two adjacent sites at positions -50 and -54 bp and a more 5' site at position -67 bp. Using a series of constructs containing deletions and mutations in this region, we found that the 3'-most site alone was sufficient for binding GA-binding protein alpha (GABP alpha)/GABP beta and for a low level of transcriptional activation. When all three sites were present, a second complex \"a\" was detected, which contains an unknown member of the Ets family. Formation of complex a was cell-type specific and correlated with a high level of transcription. Deletion of the 5'-most Ets site had no effect on binding to GABP alpha/GABP beta, but it eliminated a. Concomitant with this loss of a, a new Ets-1-containing complex \"c\" appeared. Complex c substituted efficiently for complex a in transcriptional activation. We conclude that although neither of the two 5'-most Ets sites alone binds nuclear protein, they appear to act as modulators which control the pattern of Ets proteins that bind the alpha 4 gene promoter. This arrangement of Ets sites, coupled with the tissue- and developmental-specific expression of Ets members, likely play a key role in defining the pattern of alpha 4 integrin. " ], "offsets": [ [ 0, 2092 ] ] } ]

[ { "id": "PMID-8195215_T1", "type": "Protein", "text": [ "alpha 4 integrin" ], "offsets": [ [ 112, 128 ] ], "normalized": [] }, { "id": "PMID-8195215_T2", "type": "Protein", "text": [ "alpha 4 integrins" ], "offsets": [ [ 145, 162 ] ], "normalized": [] }, { "id": "PMID-8195215_T3", "type": "Protein", "text": [ "alpha 4" ], "offsets": [ [ 402, 409 ] ], "normalized": [] }, { "id": "PMID-8195215_T4", "type": "Protein", "text": [ "alpha 4" ], "offsets": [ [ 487, 494 ] ], "normalized": [] }, { "id": "PMID-8195215_T5", "type": "Protein", "text": [ "alpha 4" ], "offsets": [ [ 574, 581 ] ], "normalized": [] }, { "id": "PMID-8195215_T6", "type": "Protein", "text": [ "alpha 4" ], "offsets": [ [ 731, 738 ] ], "normalized": [] }, { "id": "PMID-8195215_T7", "type": "Protein", "text": [ "alpha 4" ], "offsets": [ [ 802, 809 ] ], "normalized": [] }, { "id": "PMID-8195215_T8", "type": "Protein", "text": [ "GA-binding protein alpha" ], "offsets": [ [ 1131, 1155 ] ], "normalized": [] }, { "id": "PMID-8195215_T9", "type": "Protein", "text": [ "GABP alpha" ], "offsets": [ [ 1157, 1167 ] ], "normalized": [] }, { "id": "PMID-8195215_T10", "type": "Protein", "text": [ "GABP alpha" ], "offsets": [ [ 1510, 1520 ] ], "normalized": [] }, { "id": "PMID-8195215_T11", "type": "Protein", "text": [ "alpha 4" ], "offsets": [ [ 1891, 1898 ] ], "normalized": [] }, { "id": "PMID-8195215_T12", "type": "Protein", "text": [ "alpha 4 integrin" ], "offsets": [ [ 2074, 2090 ] ], "normalized": [] }, { "id": "PMID-8195215_T14", "type": "Entity", "text": [ "promoter" ], "offsets": [ [ 134, 142 ] ], "normalized": [] }, { "id": "PMID-8195215_T17", "type": "Entity", "text": [ "promoter" ], "offsets": [ [ 500, 508 ] ], "normalized": [] }, { "id": "PMID-8195215_T33", "type": "Entity", "text": [ "promoter" ], "offsets": [ [ 1904, 1912 ] ], "normalized": [] } ]

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[]

[ { "id": "PMID-8196620__text", "type": "abstract", "text": [ "Lipopolysaccharide induction of tissue factor gene expression in monocytic cells is mediated by binding of c-Rel/p65 heterodimers to a kappa B-like site. \nExposure of monocytic cells to bacterial lipopolysaccharide (LPS) activates the NF-kappa B/Rel family of proteins and leads to the rapid induction of inflammatory gene products, including tissue factor (TF). TF is the primary cellular initiator of the coagulation protease cascades. Here we report the characterization of a nuclear complex from human monocytic cells that bound to a kappa B-like site, 5'-CGGAGTTTCC-3', in the 5'-flanking region of the human TF gene. This nuclear complex was activated by LPS with kinetics that preceded induction of the TF gene. In vitro binding studies demonstrated that the TF site bound translated c-Rel and p65 homodimers but not p50/p65 heterodimers or p50 homodimers. Base-pair substitutions in the TF site indicated that the presence of a cytosine at position 1 precluded binding of NF-kappa B. In fact, under low-ionic-strength conditions, the TF complex did not migrate with translated p50/p65 dimers but instead comigrated with c-Rel/p65 dimers. Antibodies against the NF-kappa B and Rel proteins and UV cross-linking studies revealed the presence of c-Rel and p65 and the absence of p50 in the TF complex and further showed that c-Rel/p65 heterodimers selectively bound to the TF kappa B-like site. Functional studies indicated that the TF site conferred LPS inducibility on a heterologous promoter and was transactivated by c-Rel or p65. Taken together, our results demonstrated that binding of c-Rel/p65 heterodimers to a novel kappa B-like site mediated LPS induction of TF gene expression in monocytic cells. " ], "offsets": [ [ 0, 1714 ] ] } ]

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"ref_id": "PMID-8196620_T20" }, { "role": "Theme", "ref_id": "PMID-8196620_T23" } ] }, { "id": "PMID-8196620_E16", "type": "Binding", "trigger": { "text": [ "presence" ], "offsets": [ [ 1239, 1247 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "PMID-8196620_T21" }, { "role": "Theme", "ref_id": "PMID-8196620_T23" } ] }, { "id": "PMID-8196620_E17", "type": "Binding", "trigger": { "text": [ "absence" ], "offsets": [ [ 1273, 1280 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "PMID-8196620_T22" }, { "role": "Theme", "ref_id": "PMID-8196620_T23" } ] }, { "id": "PMID-8196620_E18", "type": "Binding", "trigger": { "text": [ "bound" ], "offsets": [ [ 1365, 1370 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "PMID-8196620_T24" } ] }, { "id": "PMID-8196620_E19", "type": "Binding", "trigger": { "text": [ "bound" ], "offsets": [ [ 1365, 1370 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "PMID-8196620_T25" } ] }, { "id": "PMID-8196620_E20", "type": "Binding", "trigger": { "text": [ "binding" ], "offsets": [ [ 1586, 1593 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "PMID-8196620_T31" } ] }, { "id": "PMID-8196620_E21", "type": "Binding", "trigger": { "text": [ "binding" ], "offsets": [ [ 1586, 1593 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "PMID-8196620_T30" } ] }, { "id": "PMID-8196620_E22", "type": "Positive_regulation", "trigger": { "text": [ "mediated" ], "offsets": [ [ 1649, 1657 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "PMID-8196620_E24" }, { "role": "Cause", "ref_id": "PMID-8196620_E21" } ] }, { "id": "PMID-8196620_E23", "type": "Positive_regulation", "trigger": { "text": [ "mediated" ], "offsets": [ [ 1649, 1657 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "PMID-8196620_E24" }, { "role": "Cause", "ref_id": "PMID-8196620_E20" } ] }, { "id": "PMID-8196620_E24", "type": "Positive_regulation", "trigger": { "text": [ "induction" ], "offsets": [ [ 1662, 1671 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "PMID-8196620_E25" } ] 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[]

[ { "id": "PMID-8207643__text", "type": "abstract", "text": [ "Stimulation of HIV replication in mononuclear phagocytes by leukemia inhibitory factor. \nThis study examined the effects of leukemia inhibitory factor (LIF) on human immunodeficiency virus (HIV) replication in mononuclear phagocytes (MNP). LIF induced a dose-dependent increase in p24 antigen production in the chronically infected promonocytic cell line U1. The magnitude and time kinetics of the LIF effects were similar to interleukin 1 (IL-1), IL-6, and tumor necrosis factor (TNF), other cytokines known to induce HIV replication in this cell line. To characterize mechanisms responsible for these LIF effects, levels of HIV mRNA, activation of the DNA binding protein nuclear factor (NF)-kB, signal transduction pathways, and potential interactions with other cytokines were analyzed. LIF increased steady-state levels of HIV mRNA at 2.0, 4.3, and 9.2 kB. This was detectable by 24 h and persisted until 72 h. The DNA binding protein NF-kB is a central mediator in cytokine activation of HIV transcription. NF-kB levels were higher in unstimulated U1 cells as compared to the parent cell line U937. In both cell lines LIF increased NF-kB activity. Induction of NF-kB and HIV replication by cytokines are at least in part dependent on reactive oxygen intermediates. The oxygen radical scavenger N-acetyl-L-cysteine, but not an inhibitor of nitric oxide synthase, inhibited LIF-induced HIV replication. LIF induces the production of other cytokines in monocytes but its effects on HIV replication were not inhibited by antibodies to IL-1, TNF, or IL-6. These results identify LIF as a stimulus of HIV replication. (ABSTRACT TRUNCATED AT 250 WORDS) " ], "offsets": [ [ 0, 1652 ] ] } ]

[ { "id": "PMID-8207643_T1", "type": "Protein", "text": [ "leukemia inhibitory factor" ], "offsets": [ [ 60, 86 ] ], "normalized": [] }, { "id": "PMID-8207643_T2", "type": "Protein", "text": [ "leukemia inhibitory factor" ], "offsets": [ [ 124, 150 ] ], "normalized": [] }, { "id": "PMID-8207643_T3", "type": "Protein", "text": [ "LIF" ], "offsets": [ [ 152, 155 ] ], "normalized": [] }, { "id": "PMID-8207643_T4", "type": "Protein", "text": [ "LIF" ], "offsets": [ [ 240, 243 ] ], "normalized": [] }, { "id": "PMID-8207643_T5", "type": "Protein", "text": [ "p24 antigen" ], "offsets": [ [ 281, 292 ] ], "normalized": [] }, { "id": "PMID-8207643_T6", "type": "Protein", "text": [ "LIF" ], "offsets": [ [ 398, 401 ] ], "normalized": [] }, { "id": "PMID-8207643_T7", "type": "Protein", "text": [ "IL-6" ], "offsets": [ [ 448, 452 ] ], "normalized": [] }, { "id": "PMID-8207643_T8", "type": "Protein", "text": [ "LIF" ], "offsets": [ [ 603, 606 ] ], "normalized": [] }, { "id": "PMID-8207643_T9", "type": "Protein", "text": [ "LIF" ], "offsets": [ [ 791, 794 ] ], "normalized": [] }, { "id": "PMID-8207643_T10", "type": "Protein", "text": [ "LIF" ], "offsets": [ [ 1124, 1127 ] ], "normalized": [] }, { "id": "PMID-8207643_T11", "type": "Protein", "text": [ "LIF" ], "offsets": [ [ 1378, 1381 ] ], "normalized": [] }, { "id": "PMID-8207643_T12", "type": "Protein", "text": [ "LIF" ], "offsets": [ [ 1407, 1410 ] ], "normalized": [] }, { "id": "PMID-8207643_T13", "type": "Protein", "text": [ "IL-6" ], "offsets": [ [ 1551, 1555 ] ], "normalized": [] }, { "id": "PMID-8207643_T14", "type": "Protein", "text": [ "LIF" ], "offsets": [ [ 1580, 1583 ] ], "normalized": [] } ]

[ { "id": "PMID-8207643_E1", "type": "Positive_regulation", "trigger": { "text": [ "increase" ], "offsets": [ [ 269, 277 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "PMID-8207643_E2" }, { "role": "Cause", "ref_id": "PMID-8207643_T4" } ] }, { "id": "PMID-8207643_E2", "type": "Gene_expression", "trigger": { "text": [ "production" ], "offsets": [ [ 293, 303 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "PMID-8207643_T5" } ] } ]

[ { "id": "PMID-8207643_1", "entity_ids": [ "PMID-8207643_T2", "PMID-8207643_T3" ] } ]

[]

[ { "id": "PMID-8207793__text", "type": "abstract", "text": [ "Human immunodeficiency virus type 1 Tat upregulates interleukin-2 secretion in activated T cells. \nDysregulation of cytokines secreted by T cells may play an important role in the pathogenesis of AIDS. To investigate the effects of human immunodeficiency virus type 1 (HIV-1) Tat on interleukin-2 (IL-2) expression, we used IL-2 promoter-chloramphenicol acetyltransferase constructs and IL-2-secreting Jurkat T cells as a model system. Transient expression of HIV-1 Tat induced a five- to eightfold increase in IL-2 promoter activity in Jurkat T cells stimulated with phytohemagglutinin and phorbol myristate acetate. IL-2 secretion was increased more than twofold in both Jurkat T cells and primary T cells stimulated by extracellular HIV-1 Tat protein. Analysis of mRNA suggested that Tat exerts its effect on IL-2 primarily at the transcriptional level. The NF-kappa B site at positions -206 to -195 of the IL-2 promoter was required but not sufficient for the Tat effect. The Tat-mediated increase in IL-2 promoter activity could selectively be blocked by antisense tat or-unlike the analogous effect of human T-cell lymphotropic virus type 1 Tax-by cyclosporin A. The observed increase in IL-2 levels might facilitate virus spread from or to T cells. Furthermore, it might contribute to the hypergammaglobulinemia or, together with other cytokines found to be dysregulated, the T-helper cell dysfunctions observed in AIDS patients. " ], "offsets": [ [ 0, 1437 ] ] } ]

[ { "id": "PMID-8207793_T1", "type": "Protein", "text": [ "Tat" ], "offsets": [ [ 36, 39 ] ], "normalized": [] }, { "id": "PMID-8207793_T2", "type": "Protein", "text": [ "interleukin-2" ], "offsets": [ [ 52, 65 ] ], "normalized": [] }, { "id": "PMID-8207793_T3", "type": "Protein", "text": [ "Tat" ], "offsets": [ [ 276, 279 ] ], "normalized": [] }, { "id": "PMID-8207793_T4", "type": "Protein", "text": [ "interleukin-2" ], "offsets": [ [ 283, 296 ] ], "normalized": [] }, { "id": "PMID-8207793_T5", "type": "Protein", "text": [ "IL-2" ], "offsets": [ [ 298, 302 ] ], "normalized": [] }, { "id": "PMID-8207793_T6", "type": "Protein", "text": [ "IL-2" ], "offsets": [ [ 324, 328 ] ], "normalized": [] }, { "id": "PMID-8207793_T7", "type": "Protein", "text": [ "chloramphenicol acetyltransferase" ], "offsets": [ [ 338, 371 ] ], "normalized": [] }, { "id": "PMID-8207793_T8", "type": "Protein", "text": [ "IL-2" ], "offsets": [ [ 387, 391 ] ], "normalized": [] }, { "id": "PMID-8207793_T9", "type": "Protein", "text": [ "Tat" ], "offsets": [ [ 466, 469 ] ], "normalized": [] }, { "id": "PMID-8207793_T10", "type": "Protein", "text": [ "IL-2" ], "offsets": [ [ 511, 515 ] ], "normalized": [] }, { "id": "PMID-8207793_T11", "type": "Protein", "text": [ "phytohemagglutinin" ], "offsets": [ [ 568, 586 ] ], "normalized": [] }, { "id": "PMID-8207793_T12", "type": "Protein", "text": [ "IL-2" ], "offsets": [ [ 618, 622 ] ], "normalized": [] }, { "id": "PMID-8207793_T13", "type": "Protein", "text": [ "Tat" ], "offsets": [ [ 742, 745 ] ], "normalized": [] }, { "id": "PMID-8207793_T14", "type": "Protein", "text": [ "Tat" ], "offsets": [ [ 787, 790 ] ], "normalized": [] }, { "id": "PMID-8207793_T15", "type": "Protein", "text": [ "IL-2" ], "offsets": [ [ 812, 816 ] ], "normalized": [] }, { "id": "PMID-8207793_T16", "type": "Protein", "text": [ "IL-2" ], "offsets": [ [ 910, 914 ] ], "normalized": [] }, { "id": "PMID-8207793_T17", "type": "Protein", "text": [ "Tat" ], "offsets": [ [ 964, 967 ] ], "normalized": [] }, { "id": "PMID-8207793_T18", "type": "Protein", "text": [ "Tat" ], "offsets": [ [ 980, 983 ] ], "normalized": [] }, { "id": "PMID-8207793_T19", "type": "Protein", "text": [ "IL-2" ], "offsets": [ [ 1005, 1009 ] ], "normalized": [] }, { "id": "PMID-8207793_T20", "type": "Protein", "text": [ "tat" ], "offsets": [ [ 1070, 1073 ] ], "normalized": [] }, { "id": "PMID-8207793_T21", "type": "Protein", "text": [ "Tax" ], "offsets": [ [ 1147, 1150 ] ], "normalized": [] }, { "id": "PMID-8207793_T22", "type": "Protein", "text": [ "IL-2" ], "offsets": [ [ 1194, 1198 ] ], "normalized": [] } ]

[ { "id": "PMID-8207793_E1", "type": "Positive_regulation", "trigger": { "text": [ "upregulates" ], "offsets": [ [ 40, 51 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "PMID-8207793_E2" }, { "role": "Cause", "ref_id": "PMID-8207793_T1" } ] }, { "id": "PMID-8207793_E2", "type": "Localization", "trigger": { "text": [ "secretion" ], "offsets": [ [ 66, 75 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "PMID-8207793_T2" } ] }, { "id": "PMID-8207793_E3", "type": "Regulation", "trigger": { "text": [ "effects" ], "offsets": [ [ 221, 228 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "PMID-8207793_E4" }, { "role": "Cause", "ref_id": "PMID-8207793_T3" } ] }, { "id": "PMID-8207793_E4", "type": "Gene_expression", "trigger": { "text": [ "expression" ], "offsets": [ [ 304, 314 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "PMID-8207793_T5" } ] }, { "id": "PMID-8207793_E5", "type": "Localization", "trigger": { "text": [ "secreting" ], "offsets": [ [ 392, 401 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "PMID-8207793_T8" } ] }, { "id": "PMID-8207793_E6", "type": "Gene_expression", "trigger": { "text": [ "expression" ], "offsets": [ [ 446, 456 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "PMID-8207793_T9" } ] }, { "id": "PMID-8207793_E7", "type": "Localization", "trigger": { "text": [ "secretion" ], "offsets": [ [ 623, 632 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "PMID-8207793_T12" } ] }, { "id": "PMID-8207793_E8", "type": "Positive_regulation", "trigger": { "text": [ "increased" ], "offsets": [ [ 637, 646 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "PMID-8207793_E7" } ] }, { "id": "PMID-8207793_E9", "type": "Regulation", "trigger": { "text": [ "effect" ], "offsets": [ [ 802, 808 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "PMID-8207793_E10" }, { "role": "Cause", "ref_id": "PMID-8207793_T14" } ] }, { "id": "PMID-8207793_E10", "type": "Transcription", "trigger": { "text": [ "transcriptional" ], "offsets": [ [ 834, 849 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "PMID-8207793_T15" } ] } ]

[ { "id": "PMID-8207793_1", "entity_ids": [ "PMID-8207793_T5", "PMID-8207793_T4" ] } ]

[]

[ { "id": "PMID-8264604__text", "type": "abstract", "text": [ "The macrophage transcription factor PU.1 directs tissue-specific expression of the macrophage colony-stimulating factor receptor. \nThe macrophage colony-stimulating factor (M-CSF) receptor is expressed in a tissue-specific fashion from two distinct promoters in monocytes/macrophages and the placenta. In order to further understand the transcription factors which play a role in the commitment of multipotential progenitors to the monocyte/macrophage lineage, we have initiated an investigation of the factors which activate the M-CSF receptor very early during the monocyte differentiation process. Here we demonstrate that the human monocytic M-CSF receptor promoter directs reporter gene activity in a tissue-specific fashion. Since one of the few transcription factors which have been implicated in the regulation of monocyte genes is the macrophage- and B-cell-specific PU.1 transcription factor, we investigated whether PU.1 binds and activates the M-CSF receptor promoter. Here we demonstrate that both in vitro-translated PU.1 and PU.1 from nuclear extracts bind to a specific site in the M-CSF receptor promoter just upstream from the major transcription initiation site. Mutations in this site which eliminate PU.1 binding decrease M-CSF receptor promoter activity significantly in macrophage cell lines only. Furthermore, PU.1 transactivates the M-CSF receptor promoter in nonmacrophage cells. These results suggest that PU.1 plays a major role in macrophage gene regulation and development by directing the expression of a receptor for a key macrophage growth factor. " ], "offsets": [ [ 0, 1581 ] ] } ]

[ { "id": "PMID-8264604_T1", "type": "Protein", "text": [ "PU.1" ], "offsets": [ [ 36, 40 ] ], "normalized": [] }, { "id": "PMID-8264604_T2", "type": "Protein", "text": [ "macrophage colony-stimulating factor receptor" ], "offsets": [ [ 83, 128 ] ], "normalized": [] }, { "id": "PMID-8264604_T3", "type": "Protein", "text": [ "macrophage colony-stimulating factor (M-CSF) receptor" ], "offsets": [ [ 135, 188 ] ], "normalized": [] }, { "id": "PMID-8264604_T4", "type": "Protein", "text": [ "M-CSF receptor" ], "offsets": [ [ 530, 544 ] ], "normalized": [] }, { "id": "PMID-8264604_T5", "type": "Protein", "text": [ "M-CSF receptor" ], "offsets": [ [ 646, 660 ] ], "normalized": [] }, { "id": "PMID-8264604_T6", "type": "Protein", "text": [ "PU.1" ], "offsets": [ [ 876, 880 ] ], "normalized": [] }, { "id": "PMID-8264604_T7", "type": "Protein", "text": [ "PU.1" ], "offsets": [ [ 927, 931 ] ], "normalized": [] }, { "id": "PMID-8264604_T8", "type": "Protein", "text": [ "M-CSF receptor" ], "offsets": [ [ 956, 970 ] ], "normalized": [] }, { "id": "PMID-8264604_T9", "type": "Protein", "text": [ "PU.1" ], "offsets": [ [ 1031, 1035 ] ], "normalized": [] }, { "id": "PMID-8264604_T10", "type": "Protein", "text": [ "PU.1" ], "offsets": [ [ 1040, 1044 ] ], "normalized": [] }, { "id": "PMID-8264604_T11", "type": "Protein", "text": [ "M-CSF receptor" ], "offsets": [ [ 1098, 1112 ] ], "normalized": [] }, { "id": "PMID-8264604_T12", "type": "Protein", "text": [ "PU.1" ], "offsets": [ [ 1221, 1225 ] ], "normalized": [] }, { "id": "PMID-8264604_T13", "type": "Protein", "text": [ "M-CSF receptor" ], "offsets": [ [ 1243, 1257 ] ], "normalized": [] }, { "id": "PMID-8264604_T14", "type": "Protein", "text": [ "PU.1" ], "offsets": [ [ 1334, 1338 ] ], "normalized": [] }, { "id": "PMID-8264604_T15", "type": "Protein", "text": [ "M-CSF receptor" ], "offsets": [ [ 1358, 1372 ] ], "normalized": [] }, { "id": "PMID-8264604_T16", "type": "Protein", "text": [ "PU.1" ], "offsets": [ [ 1433, 1437 ] ], "normalized": [] }, { "id": "PMID-8264604_T24", "type": "Entity", "text": [ "promoter" ], "offsets": [ [ 971, 979 ] ], "normalized": [] }, { "id": "PMID-8264604_T26", "type": "Entity", "text": [ "specific site" ], "offsets": [ [ 1077, 1090 ] ], "normalized": [] }, { "id": "PMID-8264604_T27", "type": "Entity", "text": [ "promoter" ], "offsets": [ [ 1113, 1121 ] ], "normalized": [] }, { "id": "PMID-8264604_T31", "type": "Entity", "text": [ "promoter" ], "offsets": [ [ 1258, 1266 ] ], "normalized": [] }, { "id": "PMID-8264604_T33", "type": "Entity", "text": [ "promoter" ], "offsets": [ [ 1373, 1381 ] ], "normalized": [] } ]

[ { "id": "PMID-8264604_E1", "type": "Positive_regulation", "trigger": { "text": [ "directs" ], "offsets": [ [ 41, 48 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "PMID-8264604_E2" }, { "role": "Cause", "ref_id": "PMID-8264604_T1" } ] }, { "id": "PMID-8264604_E2", "type": "Gene_expression", "trigger": { "text": [ "expression" ], "offsets": [ [ 65, 75 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "PMID-8264604_T2" } ] }, { "id": "PMID-8264604_E3", "type": "Gene_expression", "trigger": { "text": [ "expressed" ], "offsets": [ [ 192, 201 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "PMID-8264604_T3" } ] }, { "id": "PMID-8264604_E4", "type": "Regulation", "trigger": { "text": [ "from" ], "offsets": [ [ 231, 235 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "PMID-8264604_E3" } ] }, { "id": "PMID-8264604_E5", "type": "Positive_regulation", "trigger": { "text": [ "activate" ], "offsets": [ [ 517, 525 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "PMID-8264604_T4" } ] }, { "id": "PMID-8264604_E6", "type": "Binding", "trigger": { "text": [ "binds" ], "offsets": [ [ 932, 937 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "PMID-8264604_T7" }, { "role": "Theme", "ref_id": "PMID-8264604_T8" }, { "role": "Site", "ref_id": "PMID-8264604_T24" } ] }, { "id": "PMID-8264604_E7", "type": "Positive_regulation", "trigger": { "text": [ "activates" ], "offsets": [ [ 942, 951 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "PMID-8264604_T8" }, { "role": "Cause", "ref_id": "PMID-8264604_T7" }, { "role": "Site", "ref_id": "PMID-8264604_T24" } ] }, { "id": "PMID-8264604_E8", "type": "Binding", "trigger": { "text": [ "bind" ], "offsets": [ [ 1067, 1071 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "PMID-8264604_T10" }, { "role": "Theme", "ref_id": "PMID-8264604_T11" }, { "role": "Site", "ref_id": "PMID-8264604_T27" } ] }, { "id": "PMID-8264604_E9", "type": "Binding", "trigger": { "text": [ "bind" ], "offsets": [ [ 1067, 1071 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "PMID-8264604_T9" }, { "role": "Theme", "ref_id": "PMID-8264604_T11" }, { "role": "Site", "ref_id": "PMID-8264604_T27" } ] }, { "id": "PMID-8264604_E10", "type": "Negative_regulation", "trigger": { "text": [ "eliminate" ], "offsets": [ [ 1211, 1220 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "PMID-8264604_E11" } ] }, { "id": "PMID-8264604_E11", "type": "Binding", "trigger": { "text": [ "binding" ], "offsets": [ [ 1226, 1233 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "PMID-8264604_T11" }, { "role": "Theme", "ref_id": "PMID-8264604_T12" }, { "role": "Site", "ref_id": "PMID-8264604_T26" } ] }, { "id": "PMID-8264604_E12", "type": "Negative_regulation", "trigger": { "text": [ "decrease" ], "offsets": [ [ 1234, 1242 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "PMID-8264604_T13" }, { "role": "Cause", "ref_id": "PMID-8264604_E10" }, { "role": "Site", "ref_id": "PMID-8264604_T31" } ] }, { "id": "PMID-8264604_E13", "type": "Positive_regulation", "trigger": { "text": [ "transactivates" ], "offsets": [ [ 1339, 1353 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "PMID-8264604_T15" }, { "role": "Cause", "ref_id": "PMID-8264604_T14" }, { "role": "Site", "ref_id": "PMID-8264604_T33" } ] } ]

[]

[]

[ { "id": "PMID-8298127__text", "type": "abstract", "text": [ "Retinoic acid downmodulates erythroid differentiation and GATA1 expression in purified adult-progenitor culture. \nAll-trans retinoic acid (RA) is an important morphogen in vertebrate development, a normal constituent in human adult blood and is also involved in the control of cell growth and differentiation in acute promyelocytic leukemia. We have examined the effects of RA on normal hematopoiesis by using early hematopoietic progenitor cells (HPC) stringently purified from adult peripheral blood. In clonogenetic fetal calf serum-supplemented (FCS+) or -nonsupplemented (FCS-) culture treated with saturating levels of interleukin-3 (IL-3) granulocyte-macrophage colony-stimulating factor (GM-CSF) and erythropoietin (Ep) (combined with c-kit ligand in FCS(-)-culture conditions), RA induces a dramatic dose-dependent shift from erythroid to granulomonocytic colony formation, the latter colonies being essentially represented by granulocytic clones. This shift is apparently not caused by a recruitment phenomenon, because in FCS+ culture, the total number of colonies is not significantly modified by RA addition. In FCS- liquid-suspension culture supplemented with saturating Ep level and low-dose IL-3/GM-CSF, adult HPC undergo unilineage erythropoietic differentiation: Here again, treatment with high-dose RA induces a shift from the erythroid to granulocytic differentiation pathway. Studies on RA time-response or pulse treatment in semisolid or liquid culture show that early RA addition is most effective, thus indicating that early but not late HPC are sensitive to its action. We then analyzed the expression of the master GATA1 gene, which encodes a finger transcription factor required for normal erythroid development; addition of RA to HPC stimulated into unilineage erythropoietic differentiation in liquid culture caused a virtually complete inhibition of GATA1 mRNA induction. These results indicate that RA directly inhibits the erythroid differentiation program at the level of early adult HPC, and may lead to a shift from the erythroid to granulocytic differentiation pathway. This phenomenon is correlated with inhibition of GATA1 induction in the early stages of erythropoietic differentiation. " ], "offsets": [ [ 0, 2226 ] ] } ]

[ { "id": "PMID-8298127_T1", "type": "Protein", "text": [ "GATA1" ], "offsets": [ [ 58, 63 ] ], "normalized": [] }, { "id": "PMID-8298127_T2", "type": "Protein", "text": [ "interleukin-3" ], "offsets": [ [ 625, 638 ] ], "normalized": [] }, { "id": "PMID-8298127_T3", "type": "Protein", "text": [ "IL-3" ], "offsets": [ [ 640, 644 ] ], "normalized": [] }, { "id": "PMID-8298127_T4", "type": "Protein", "text": [ "granulocyte-macrophage colony-stimulating factor" ], "offsets": [ [ 646, 694 ] ], "normalized": [] }, { "id": "PMID-8298127_T5", "type": "Protein", "text": [ "GM-CSF" ], "offsets": [ [ 696, 702 ] ], "normalized": [] }, { "id": "PMID-8298127_T6", "type": "Protein", "text": [ "erythropoietin" ], "offsets": [ [ 708, 722 ] ], "normalized": [] }, { "id": "PMID-8298127_T7", "type": "Protein", "text": [ "Ep" ], "offsets": [ [ 724, 726 ] ], "normalized": [] }, { "id": "PMID-8298127_T8", "type": "Protein", "text": [ "c-kit ligand" ], "offsets": [ [ 743, 755 ] ], "normalized": [] }, { "id": "PMID-8298127_T9", "type": "Protein", "text": [ "Ep" ], "offsets": [ [ 1185, 1187 ] ], "normalized": [] }, { "id": "PMID-8298127_T10", "type": "Protein", "text": [ "IL-3" ], "offsets": [ [ 1207, 1211 ] ], "normalized": [] }, { "id": "PMID-8298127_T11", "type": "Protein", "text": [ "GM-CSF" ], "offsets": [ [ 1212, 1218 ] ], "normalized": [] }, { "id": "PMID-8298127_T12", "type": "Protein", "text": [ "GATA1" ], "offsets": [ [ 1641, 1646 ] ], "normalized": [] }, { "id": "PMID-8298127_T13", "type": "Protein", "text": [ "GATA1" ], "offsets": [ [ 1880, 1885 ] ], "normalized": [] }, { "id": "PMID-8298127_T14", "type": "Protein", "text": [ "GATA1" ], "offsets": [ [ 2155, 2160 ] ], "normalized": [] } ]

[ { "id": "PMID-8298127_E1", "type": "Gene_expression", "trigger": { "text": [ "expression" ], "offsets": [ [ 64, 74 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "PMID-8298127_T1" } ] }, { "id": "PMID-8298127_E2", "type": "Gene_expression", "trigger": { "text": [ "expression" ], "offsets": [ [ 1616, 1626 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "PMID-8298127_T12" } ] }, { "id": "PMID-8298127_E3", "type": "Negative_regulation", "trigger": { "text": [ "inhibition" ], "offsets": [ [ 1866, 1876 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "PMID-8298127_E4" } ] }, { "id": "PMID-8298127_E4", "type": "Positive_regulation", "trigger": { "text": [ "induction" ], "offsets": [ [ 1891, 1900 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "PMID-8298127_T13" } ] }, { "id": "PMID-8298127_E5", "type": "Negative_regulation", "trigger": { "text": [ "inhibition" ], "offsets": [ [ 2141, 2151 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "PMID-8298127_E6" } ] }, { "id": "PMID-8298127_E6", "type": "Positive_regulation", "trigger": { "text": [ "induction" ], "offsets": [ [ 2161, 2170 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "PMID-8298127_T14" } ] } ]

[ { "id": "PMID-8298127_1", "entity_ids": [ "PMID-8298127_T2", "PMID-8298127_T3" ] }, { "id": "PMID-8298127_2", "entity_ids": [ "PMID-8298127_T4", "PMID-8298127_T5" ] }, { "id": "PMID-8298127_3", "entity_ids": [ "PMID-8298127_T6", "PMID-8298127_T7" ] } ]

[]

[ { "id": "PMID-8314792__text", "type": "abstract", "text": [ "Comparative analysis of NFAT (nuclear factor of activated T cells) complex in human T and B lymphocytes. \nNuclear factor of activated T cells (NFAT) is a transcriptional activator that binds to sequences in the interleukin-2 (IL-2) promoter and is thought to be largely responsible for the T cell-specific inducibility of IL-2 expression. Electrophoretic mobility shift assays (EMSA) showed that specific NFAT binding activity could also be induced in human B cells. The B cell NFAT complex, however, was not functional, since it failed to activate transcription from an NFAT-driven chloramphenicol acetyltransferase (CAT) construct. Competition with an AP-1 motif or with anti-Jun and anti-Fos antibodies abolished binding to the NFAT motif in both T and B cells, indicating that Jun and Fos are critical for NFAT complex formation in both cell types. Purified recombinant Jun and Fos proteins failed to bind directly to the NFAT motif. However, when combined with unstimulated B or T cell extracts, full-length, but not truncated, Jun/Fos heterodimers were able to form an NFAT complex, indicating the presence of a constitutively expressed nuclear factor(s) in B and T cells necessary for the formation of the NFAT complex in both cell types. An NFAT oligonucleotide carrying mutations in the 5' purine-rich part of the NFAT sequence failed to form a complex and to compete with the wild type motif for NFAT complex formation in both T and B cells. We therefore propose a model whereby a core NFAT complex consisting of Jun, Fos, and a constitutive nuclear factor is formed in both T and B cells, but an additional factor and/or post-translational modification of a factor, missing in B cells, might be required for transactivation by NFAT. " ], "offsets": [ [ 0, 1744 ] ] } ]

[ { "id": "PMID-8314792_T1", "type": "Protein", "text": [ "interleukin-2" ], "offsets": [ [ 211, 224 ] ], "normalized": [] }, { "id": "PMID-8314792_T2", "type": "Protein", "text": [ "IL-2" ], "offsets": [ [ 226, 230 ] ], "normalized": [] }, { "id": "PMID-8314792_T3", "type": "Protein", "text": [ "IL-2" ], "offsets": [ [ 322, 326 ] ], "normalized": [] }, { "id": "PMID-8314792_T4", "type": "Protein", "text": [ "chloramphenicol acetyltransferase" ], "offsets": [ [ 583, 616 ] ], "normalized": [] }, { "id": "PMID-8314792_T5", "type": "Protein", "text": [ "CAT" ], "offsets": [ [ 618, 621 ] ], "normalized": [] }, { "id": "PMID-8314792_T7", "type": "Entity", "text": [ "promoter" ], "offsets": [ [ 232, 240 ] ], "normalized": [] } ]

[ { "id": "PMID-8314792_E1", "type": "Binding", "trigger": { "text": [ "binds" ], "offsets": [ [ 185, 190 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "PMID-8314792_T1" }, { "role": "Site", "ref_id": "PMID-8314792_T7" } ] }, { "id": "PMID-8314792_E2", "type": "Positive_regulation", "trigger": { "text": [ "responsible" ], "offsets": [ [ 270, 281 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "PMID-8314792_E3" } ] }, { "id": "PMID-8314792_E3", "type": "Positive_regulation", "trigger": { "text": [ "inducibility" ], "offsets": [ [ 306, 318 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "PMID-8314792_E4" } ] }, { "id": "PMID-8314792_E4", "type": "Gene_expression", "trigger": { "text": [ "expression" ], "offsets": [ [ 327, 337 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "PMID-8314792_T3" } ] }, { "id": "PMID-8314792_E5", "type": "Binding", "trigger": { "text": [ "binding activity" ], "offsets": [ [ 410, 426 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "PMID-8314792_T1" }, { "role": "Site", "ref_id": "PMID-8314792_T7" } ] }, { "id": "PMID-8314792_E6", "type": "Positive_regulation", "trigger": { "text": [ "induced" ], "offsets": [ [ 441, 448 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "PMID-8314792_E5" } ] }, { "id": "PMID-8314792_E7", "type": "Positive_regulation", "trigger": { "text": [ "activate" ], "offsets": [ [ 540, 548 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "PMID-8314792_E8" } ] }, { "id": "PMID-8314792_E8", "type": "Transcription", "trigger": { "text": [ "transcription" ], "offsets": [ [ 549, 562 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "PMID-8314792_T4" } ] } ]

[ { "id": "PMID-8314792_1", "entity_ids": [ "PMID-8314792_T1", "PMID-8314792_T2" ] }, { "id": "PMID-8314792_2", "entity_ids": [ "PMID-8314792_T4", "PMID-8314792_T5" ] } ]

[]

[ { "id": "PMID-8319574__text", "type": "abstract", "text": [ "Differential autoregulation of glucocorticoid receptor expression in human T- and B-cell lines. \nRegulation of glucocorticoid receptor (GR) expression by its cognate ligand was examined in the glucocorticoid-sensitive human leukemic T-cell line 6TG1.1 and in the human B-cell line IM-9. In contrast to the decrease in GR mRNA seen in IM-9 cells after treatment with 1 microM dexamethasone for 16-18 h, treatment of 6TG1.1 cells resulted in an 8-fold increase in GR mRNA, as determined by Northern blot and RNase protection analysis, with a corresponding 3- to 4-fold increase in GR protein. Half-maximal induction of GR mRNA and protein in 6TG1.1 cells was observed between 10-100 nM dexamethasone, and inclusion of 1 microM RU 38486 completely blocked the effects of 100 nM dexamethasone, demonstrating that positive autoregulation of GR expression in 6TG1.1 cells is a receptor-mediated response. Positive autoregulation of GR expression was also observed in glucocorticoid-resistant CEM-C1 cells, which contain functional GR, but whose growth is unaffected by glucocorticoids. Thus, positive autoregulation is neither a consequence nor the sole cause of growth arrest. The degree of negative autoregulation in IM-9 cells and positive autoregulation in 6TG1.1 cells was unaffected by inhibition of protein synthesis with cycloheximide. Measurement of GR mRNA turnover in 6TG1.1 cells treated with actinomycin-D revealed a half-life of 2.5 h, which was unaffected by dexamethasone treatment. A similar half-life was determined in IM-9 cells and was also unaffected by steroid treatment. These results are consistent with the interpretation that glucocorticoid-mediated autoregulation of GR expression is a tissue-specific primary transcriptional response. " ], "offsets": [ [ 0, 1757 ] ] } ]

[ { "id": "PMID-8319574_T1", "type": "Protein", "text": [ "glucocorticoid receptor" ], "offsets": [ [ 31, 54 ] ], "normalized": [] }, { "id": "PMID-8319574_T2", "type": "Protein", "text": [ "glucocorticoid receptor" ], "offsets": [ [ 111, 134 ] ], "normalized": [] }, { "id": "PMID-8319574_T3", "type": "Protein", "text": [ "GR" ], "offsets": [ [ 136, 138 ] ], "normalized": [] }, { "id": "PMID-8319574_T4", "type": "Protein", "text": [ "GR" ], "offsets": [ [ 318, 320 ] ], "normalized": [] }, { "id": "PMID-8319574_T5", "type": "Protein", "text": [ "GR" ], "offsets": [ [ 462, 464 ] ], "normalized": [] }, { "id": "PMID-8319574_T6", "type": "Protein", "text": [ "GR" ], "offsets": [ [ 579, 581 ] ], "normalized": [] }, { "id": "PMID-8319574_T7", "type": "Protein", "text": [ "GR" ], "offsets": [ [ 617, 619 ] ], "normalized": [] }, { "id": "PMID-8319574_T8", "type": "Protein", "text": [ "GR" ], "offsets": [ [ 836, 838 ] ], "normalized": [] }, { "id": "PMID-8319574_T9", "type": "Protein", "text": [ "GR" ], "offsets": [ [ 926, 928 ] ], "normalized": [] }, { "id": "PMID-8319574_T10", "type": "Protein", "text": [ "GR" ], "offsets": [ [ 1025, 1027 ] ], "normalized": [] }, { "id": "PMID-8319574_T11", "type": "Protein", "text": [ "GR" ], "offsets": [ [ 1353, 1355 ] ], "normalized": [] }, { "id": "PMID-8319574_T12", "type": "Protein", "text": [ "GR" ], "offsets": [ [ 1688, 1690 ] ], "normalized": [] } ]

[ { "id": "PMID-8319574_E1", "type": "Regulation", "trigger": { "text": [ "autoregulation" ], "offsets": [ [ 13, 27 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "PMID-8319574_E2" } ] }, { "id": "PMID-8319574_E2", "type": "Gene_expression", "trigger": { "text": [ "expression" ], "offsets": [ [ 55, 65 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "PMID-8319574_T1" } ] }, { "id": "PMID-8319574_E3", "type": "Regulation", "trigger": { "text": [ "Regulation" ], "offsets": [ [ 97, 107 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "PMID-8319574_E4" } ] }, { "id": "PMID-8319574_E4", "type": "Gene_expression", "trigger": { "text": [ "expression" ], "offsets": [ [ 140, 150 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "PMID-8319574_T3" } ] }, { "id": "PMID-8319574_E5", "type": "Negative_regulation", "trigger": { "text": [ "decrease" ], "offsets": [ [ 306, 314 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "PMID-8319574_T4" } ] }, { "id": "PMID-8319574_E6", "type": "Positive_regulation", "trigger": { "text": [ "increase" ], "offsets": [ [ 450, 458 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "PMID-8319574_T5" } ] }, { "id": "PMID-8319574_E7", "type": "Positive_regulation", "trigger": { "text": [ "increase" ], "offsets": [ [ 567, 575 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "PMID-8319574_T6" } ] }, { "id": "PMID-8319574_E8", "type": "Transcription", "trigger": { "text": [ "induction" ], "offsets": [ [ 604, 613 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "PMID-8319574_T7" } ] }, { "id": "PMID-8319574_E9", "type": "Negative_regulation", "trigger": { "text": [ "blocked" ], "offsets": [ [ 745, 752 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "PMID-8319574_E8" } ] }, { "id": "PMID-8319574_E10", "type": "Positive_regulation", "trigger": { "text": [ "positive autoregulation" ], "offsets": [ [ 809, 832 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "PMID-8319574_E11" }, { "role": "Cause", "ref_id": "PMID-8319574_T8" } ] }, { "id": "PMID-8319574_E11", "type": "Gene_expression", "trigger": { "text": [ "expression" ], "offsets": [ [ 839, 849 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "PMID-8319574_T8" } ] }, { "id": "PMID-8319574_E12", "type": "Regulation", "trigger": { "text": [ "Positive autoregulation" ], "offsets": [ [ 899, 922 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "PMID-8319574_E13" } ] }, { "id": "PMID-8319574_E13", "type": "Gene_expression", "trigger": { "text": [ "expression" ], "offsets": [ [ 929, 939 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "PMID-8319574_T9" } ] }, { "id": "PMID-8319574_E14", "type": "Positive_regulation", "trigger": { "text": [ "consequence" ], "offsets": [ [ 1123, 1134 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "PMID-8319574_E12" } ] }, { "id": "PMID-8319574_E15", "type": "Negative_regulation", "trigger": { "text": [ "negative autoregulation" ], "offsets": [ [ 1186, 1209 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "PMID-8319574_E13" } ] }, { "id": "PMID-8319574_E16", "type": "Positive_regulation", "trigger": { "text": [ "positive autoregulation" ], "offsets": [ [ 1228, 1251 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "PMID-8319574_E13" } ] }, { "id": "PMID-8319574_E17", "type": "Regulation", "trigger": { "text": [ "unaffected" ], "offsets": [ [ 1272, 1282 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "PMID-8319574_E15" } ] }, { "id": "PMID-8319574_E18", "type": "Regulation", "trigger": { "text": [ "unaffected" ], "offsets": [ [ 1272, 1282 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "PMID-8319574_E16" } ] }, { "id": "PMID-8319574_E19", "type": "Regulation", "trigger": { "text": [ "unaffected" ], "offsets": [ [ 1454, 1464 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "PMID-8319574_T11" } ] }, { "id": "PMID-8319574_E20", "type": "Regulation", "trigger": { "text": [ "unaffected" ], "offsets": [ [ 1555, 1565 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "PMID-8319574_T11" } ] }, { "id": "PMID-8319574_E21", "type": "Regulation", "trigger": { "text": [ "autoregulation" ], "offsets": [ [ 1670, 1684 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "PMID-8319574_E22" } ] }, { "id": "PMID-8319574_E22", "type": "Transcription", "trigger": { "text": [ "transcriptional" ], "offsets": [ [ 1731, 1746 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "PMID-8319574_T12" } ] } ]

[ { "id": "PMID-8319574_1", "entity_ids": [ "PMID-8319574_T3", "PMID-8319574_T2" ] } ]

[]

[ { "id": "PMID-8325322__text", "type": "abstract", "text": [ "Occurrence of a silencer of the interleukin-2 gene in naive but not in memory resting T helper lymphocytes. \nIn the immune system the first activation of a naive T cell by antigen is a key step in the shaping of the peripheral T cell specificity repertoire and maintenance of self-tolerance. In the present study, analysis of the interleukin-2 (IL-2) gene activation shows that naive human helper T cells (cord blood CD4+ T cells, adult CD4+CD45RO- T cells) regulate IL-2 transcription by a mechanism involving both a silencer and an activator acting on the purine-rich IL-2 promoter elements (NF-AT binding sites). By contrast, memory cells, either in vitro activated helper T cells reverting to a resting state, or CD4+ T (memory) clones, or CD4+CD45RO+ T cells isolated ex vivo, no longer have a silencer. Their IL-2 transcription seems to be controlled solely by the transition from inactive to active functional state of a positive transcription factor binding to these promoter elements as well as its cytoplasmic or nuclear location: in resting memory T cells the activator is located in the cytoplasm and is inactive, whereas in stimulated cells it is functional in promoting transcription and now resides in the nucleus. Thus, the regulation of the gene coding for the main T cell growth factor changes irreversibly after the first encounter of T cells with antigen. It is most likely that the presence of a silencer contributes to the more stringent activation requirements of naive CD4+ T cells. " ], "offsets": [ [ 0, 1507 ] ] } ]

[ { "id": "PMID-8325322_T1", "type": "Protein", "text": [ "interleukin-2" ], "offsets": [ [ 32, 45 ] ], "normalized": [] }, { "id": "PMID-8325322_T2", "type": "Protein", "text": [ "interleukin-2" ], "offsets": [ [ 330, 343 ] ], "normalized": [] }, { "id": "PMID-8325322_T3", "type": "Protein", "text": [ "IL-2" ], "offsets": [ [ 345, 349 ] ], "normalized": [] }, { "id": "PMID-8325322_T4", "type": "Protein", "text": [ "CD4" ], "offsets": [ [ 417, 420 ] ], "normalized": [] }, { "id": "PMID-8325322_T5", "type": "Protein", "text": [ "CD4" ], "offsets": [ [ 437, 440 ] ], "normalized": [] }, { "id": "PMID-8325322_T6", "type": "Protein", "text": [ "CD45" ], "offsets": [ [ 441, 445 ] ], "normalized": [] }, { "id": "PMID-8325322_T7", "type": "Protein", "text": [ "IL-2" ], "offsets": [ [ 467, 471 ] ], "normalized": [] }, { "id": "PMID-8325322_T8", "type": "Protein", "text": [ "IL-2" ], "offsets": [ [ 570, 574 ] ], "normalized": [] }, { "id": "PMID-8325322_T9", "type": "Protein", "text": [ "CD4" ], "offsets": [ [ 717, 720 ] ], "normalized": [] }, { "id": "PMID-8325322_T10", "type": "Protein", "text": [ "CD4" ], "offsets": [ [ 744, 747 ] ], "normalized": [] }, { "id": "PMID-8325322_T11", "type": "Protein", "text": [ "CD45" ], "offsets": [ [ 748, 752 ] ], "normalized": [] }, { "id": "PMID-8325322_T12", "type": "Protein", "text": [ "IL-2" ], "offsets": [ [ 815, 819 ] ], "normalized": [] }, { "id": "PMID-8325322_T13", "type": "Protein", "text": [ "CD4" ], "offsets": [ [ 1493, 1496 ] ], "normalized": [] }, { "id": "PMID-8325322_T18", "type": "Entity", "text": [ "NF-AT binding sites" ], "offsets": [ [ 594, 613 ] ], "normalized": [] } ]

[ { "id": "PMID-8325322_E1", "type": "Positive_regulation", "trigger": { "text": [ "activation" ], "offsets": [ [ 356, 366 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "PMID-8325322_T3" } ] }, { "id": "PMID-8325322_E2", "type": "Regulation", "trigger": { "text": [ "regulate" ], "offsets": [ [ 458, 466 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "PMID-8325322_E4" } ] }, { "id": "PMID-8325322_E3", "type": "Regulation", "trigger": { "text": [ "regulate" ], "offsets": [ [ 458, 466 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "PMID-8325322_E4" }, { "role": "Cause", "ref_id": "PMID-8325322_E5" } ] }, { "id": "PMID-8325322_E4", "type": "Transcription", "trigger": { "text": [ "transcription" ], "offsets": [ [ 472, 485 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "PMID-8325322_T7" } ] }, { "id": "PMID-8325322_E5", "type": "Regulation", "trigger": { "text": [ "acting" ], "offsets": [ [ 544, 550 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "PMID-8325322_T8" }, { "role": "Site", "ref_id": "PMID-8325322_T18" } ] }, { "id": "PMID-8325322_E6", "type": "Transcription", "trigger": { "text": [ "transcription" ], "offsets": [ [ 820, 833 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "PMID-8325322_T12" } ] }, { "id": "PMID-8325322_E7", "type": "Regulation", "trigger": { "text": [ "controlled" ], "offsets": [ [ 846, 856 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "PMID-8325322_E6" } ] }, { "id": "PMID-8325322_E8", "type": "Binding", "trigger": { "text": [ "binding" ], "offsets": [ [ 958, 965 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "PMID-8325322_T8" }, { "role": "Site", "ref_id": "PMID-8325322_T18" } ] }, { "id": "PMID-8325322_E9", "type": "Positive_regulation", "trigger": { "text": [ "functional in promoting" ], "offsets": [ [ 1160, 1183 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "PMID-8325322_E6" } ] } ]

[ { "id": "PMID-8325322_1", "entity_ids": [ "PMID-8325322_T3", "PMID-8325322_T2" ] } ]

[]

[ { "id": "PMID-8383677__text", "type": "abstract", "text": [ "Stimulation of interleukin-1 alpha and interleukin-1 beta production in human monocytes by protein phosphatase 1 and 2A inhibitors. \nProtein phosphatases 1 and 2A are important in regulating cellular functions by controlling the phosphorylation state of their substrates. In human monocytes, the inhibitors of these phosphatases, okadaic acid and calyculin A, were found to increase the mRNA accumulation and cytokine production of interleukin-1 beta and interleukin-1 alpha. The increased mRNA accumulation was found to be primarily because of the increase in the transcription rate of the interleukin-1 genes. Stimulation of interleukin-1 gene transcription may be caused by the stimulation of transcription factor activities, including those of AP-1, by these protein phosphatase inhibitors. Okadaic acid increased the synthesis of the interleukin-1 beta precursor and mature forms and their secretion. This increased processing and secretion correlated with the stimulation of IL-1 beta convertase mRNA accumulation. The stimulation of interleukin-1 alpha production by okadaic acid was more modest than that of interleukin-1 beta. However, the phosphorylation of the precursor interleukin-1 alpha cytokine was increased. These results show that protein phosphatase 1 and 2A inhibitors exert multiple effects on cytokine production in human monocytes and suggest that these two phosphatases play important roles in regulating interleukin-1 production. " ], "offsets": [ [ 0, 1456 ] ] } ]

[ { "id": "PMID-8383677_T1", "type": "Protein", "text": [ "interleukin-1 alpha" ], "offsets": [ [ 15, 34 ] ], "normalized": [] }, { "id": "PMID-8383677_T2", "type": "Protein", "text": [ "interleukin-1 beta" ], "offsets": [ [ 39, 57 ] ], "normalized": [] }, { "id": "PMID-8383677_T3", "type": "Protein", "text": [ "protein phosphatase 1" ], "offsets": [ [ 91, 112 ] ], "normalized": [] }, { "id": "PMID-8383677_T4", "type": "Protein", "text": [ "2A" ], "offsets": [ [ 117, 119 ] ], "normalized": [] }, { "id": "PMID-8383677_T5", "type": "Protein", "text": [ "Protein phosphatases 1" ], "offsets": [ [ 133, 155 ] ], "normalized": [] }, { "id": "PMID-8383677_T6", "type": "Protein", "text": [ "2A" ], "offsets": [ [ 160, 162 ] ], "normalized": [] }, { "id": "PMID-8383677_T7", "type": "Protein", "text": [ "interleukin-1 beta" ], "offsets": [ [ 432, 450 ] ], "normalized": [] }, { "id": "PMID-8383677_T8", "type": "Protein", "text": [ "interleukin-1 alpha" ], "offsets": [ [ 455, 474 ] ], "normalized": [] }, { "id": "PMID-8383677_T9", "type": "Protein", "text": [ "AP-1" ], "offsets": [ [ 748, 752 ] ], "normalized": [] }, { "id": "PMID-8383677_T10", "type": "Protein", "text": [ "interleukin-1 beta" ], "offsets": [ [ 839, 857 ] ], "normalized": [] }, { "id": "PMID-8383677_T11", "type": "Protein", "text": [ "IL-1 beta convertase" ], "offsets": [ [ 981, 1001 ] ], "normalized": [] }, { "id": "PMID-8383677_T12", "type": "Protein", "text": [ "interleukin-1 alpha" ], "offsets": [ [ 1040, 1059 ] ], "normalized": [] }, { "id": "PMID-8383677_T13", "type": "Protein", "text": [ "interleukin-1 beta" ], "offsets": [ [ 1116, 1134 ] ], "normalized": [] }, { "id": "PMID-8383677_T14", "type": "Protein", "text": [ "interleukin-1 alpha" ], "offsets": [ [ 1182, 1201 ] ], "normalized": [] }, { "id": "PMID-8383677_T15", "type": "Protein", "text": [ "protein phosphatase 1" ], "offsets": [ [ 1250, 1271 ] ], "normalized": [] }, { "id": "PMID-8383677_T16", "type": "Protein", "text": [ "2A" ], "offsets": [ [ 1276, 1278 ] ], "normalized": [] } ]

[ { "id": "PMID-8383677_E1", "type": "Negative_regulation", "trigger": { "text": [ "Stimulation" ], "offsets": [ [ 0, 11 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "PMID-8383677_E5" }, { "role": "Cause", "ref_id": "PMID-8383677_T4" } ] }, { "id": "PMID-8383677_E2", "type": "Negative_regulation", "trigger": { "text": [ "Stimulation" ], "offsets": [ [ 0, 11 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "PMID-8383677_E6" }, { "role": "Cause", "ref_id": "PMID-8383677_T3" } ] }, { "id": "PMID-8383677_E3", "type": "Negative_regulation", "trigger": { "text": [ "Stimulation" ], "offsets": [ [ 0, 11 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "PMID-8383677_E5" }, { "role": "Cause", "ref_id": "PMID-8383677_T3" } ] }, { "id": "PMID-8383677_E4", "type": "Negative_regulation", "trigger": { "text": [ "Stimulation" ], "offsets": [ [ 0, 11 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "PMID-8383677_E6" }, { "role": "Cause", "ref_id": "PMID-8383677_T4" } ] }, { "id": "PMID-8383677_E5", "type": "Gene_expression", "trigger": { "text": [ "production" ], "offsets": [ [ 58, 68 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "PMID-8383677_T2" } ] }, { "id": "PMID-8383677_E6", "type": "Gene_expression", "trigger": { "text": [ "production" ], "offsets": [ [ 58, 68 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "PMID-8383677_T1" } ] }, { "id": "PMID-8383677_E7", "type": "Negative_regulation", "trigger": { "text": [ "inhibitors" ], "offsets": [ [ 120, 130 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "PMID-8383677_T4" } ] }, { "id": "PMID-8383677_E8", "type": "Negative_regulation", "trigger": { "text": [ "inhibitors" ], "offsets": [ [ 120, 130 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "PMID-8383677_T3" } ] }, { "id": "PMID-8383677_E9", "type": "Negative_regulation", "trigger": { "text": [ "inhibitors" ], "offsets": [ [ 296, 306 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "PMID-8383677_T6" } ] }, { "id": "PMID-8383677_E10", "type": "Negative_regulation", "trigger": { "text": [ "inhibitors" ], "offsets": [ [ 296, 306 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "PMID-8383677_T5" } ] }, { "id": "PMID-8383677_E11", "type": "Positive_regulation", "trigger": { "text": [ "increase" ], "offsets": [ [ 374, 382 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "PMID-8383677_E15" } ] }, { "id": "PMID-8383677_E12", "type": "Positive_regulation", "trigger": { "text": [ "increase" ], "offsets": [ [ 374, 382 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "PMID-8383677_E16" } ] }, { "id": "PMID-8383677_E13", "type": "Positive_regulation", "trigger": { "text": [ "increase" ], "offsets": [ [ 374, 382 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "PMID-8383677_E18" } ] }, { "id": "PMID-8383677_E14", "type": "Positive_regulation", "trigger": { "text": [ "increase" ], "offsets": [ [ 374, 382 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "PMID-8383677_E17" } ] }, { "id": "PMID-8383677_E15", "type": "Positive_regulation", "trigger": { "text": [ "mRNA accumulation" ], "offsets": [ [ 387, 404 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "PMID-8383677_T8" } ] }, { "id": "PMID-8383677_E16", "type": "Positive_regulation", "trigger": { "text": [ "mRNA accumulation" ], "offsets": [ [ 387, 404 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "PMID-8383677_T7" } ] }, { "id": "PMID-8383677_E17", "type": "Gene_expression", "trigger": { "text": [ "cytokine production" ], "offsets": [ [ 409, 428 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "PMID-8383677_T7" } ] }, { "id": "PMID-8383677_E18", "type": "Gene_expression", "trigger": { "text": [ "cytokine production" ], "offsets": [ [ 409, 428 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "PMID-8383677_T8" } ] }, { "id": "PMID-8383677_E19", "type": "Positive_regulation", "trigger": { "text": [ "because of" ], "offsets": [ [ 534, 544 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "PMID-8383677_E12" } ] }, { "id": "PMID-8383677_E20", "type": "Positive_regulation", "trigger": { "text": [ "because of" ], "offsets": [ [ 534, 544 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "PMID-8383677_E11" } ] }, { "id": "PMID-8383677_E21", "type": "Positive_regulation", "trigger": { "text": [ "stimulation" ], "offsets": [ [ 681, 692 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "PMID-8383677_T9" } ] }, { "id": "PMID-8383677_E22", "type": "Positive_regulation", "trigger": { "text": [ "increased" ], "offsets": [ [ 808, 817 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "PMID-8383677_E23" } ] }, { "id": "PMID-8383677_E23", "type": "Localization", "trigger": { "text": [ "secretion" ], "offsets": [ [ 895, 904 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "PMID-8383677_T10" } ] }, { "id": "PMID-8383677_E24", "type": "Positive_regulation", "trigger": { "text": [ "stimulation" ], "offsets": [ [ 966, 977 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "PMID-8383677_E25" } ] }, { "id": "PMID-8383677_E25", "type": "Positive_regulation", "trigger": { "text": [ "accumulation" ], "offsets": [ [ 1007, 1019 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "PMID-8383677_T11" } ] }, { "id": "PMID-8383677_E26", "type": "Positive_regulation", "trigger": { "text": [ "stimulation" ], "offsets": [ [ 1025, 1036 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "PMID-8383677_E27" } ] }, { "id": "PMID-8383677_E27", "type": "Gene_expression", "trigger": { "text": [ "production" ], "offsets": [ [ 1060, 1070 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "PMID-8383677_T12" } ] }, { "id": "PMID-8383677_E28", "type": "Gene_expression", "trigger": { "text": [ "production" ], "offsets": [ [ 1060, 1070 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "PMID-8383677_T13" } ] }, { "id": "PMID-8383677_E29", "type": "Phosphorylation", "trigger": { "text": [ "phosphorylation" ], "offsets": [ [ 1149, 1164 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "PMID-8383677_T14" } ] }, { "id": "PMID-8383677_E30", "type": "Positive_regulation", "trigger": { "text": [ "increased" ], "offsets": [ [ 1215, 1224 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "PMID-8383677_E29" } ] } ]

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[ { "id": "PMID-8386664__text", "type": "abstract", "text": [ "Human CD3-CD16+ natural killer cells express the hGATA-3 T cell transcription factor and an unrearranged 2.3-kb TcR delta transcript. \nIn this study we analyzed the T cell receptor(TcR) delta transcripts expressed by CD3-CD16+ cells and we investigated whether these cells expressed the hGATA-3 T cell transcription factor and the recombination-activating gene (RAG)-1. Multiple TcR delta transcripts deriving from an unrearranged TcR delta gene were detected in both polyclonal and clonal CD3-CD16+ natural killer(NK) cell lines. Two unrearranged TcR delta transcripts had a size similar to that of the functional TcR delta mRNA (2.3 and 1.3 kb) found in TcR gamma/delta+ T lymphocytes. Sequence analysis of nine different 2.3-kb cDNA clones obtained from NK-derived polyA+ RNA confirmed that they corresponded to an unrearranged TcR delta gene. These cDNA were 2343 bp long and their transcription initiation site was located 814 bp upstream from the J delta 1 segment. The sequence located upstream of the J delta 1 segment corresponded to the previously reported germ-line sequence. The J delta 1 segment was correctly spliced to C delta; in addition the four C delta exons were found to be already assembled. Two polyadenylation sites were present in the fourth C delta exon. However, only that located at the 3' end appeared to be utilized in the 2.3-kb cDNA. The expression of hGATA-3, a T cell-specific factor known to be involved in the regulation of the transcription of TcR delta locus, was analyzed by Northern blot, in cultured NK cell population and clones (but not in freshly derived cell populations). All NK clones and cell lines studied were found to express hGATA-3-specific mRNA, suggesting that hGATA-3 may be involved in the regulation of the unrearranged TcR delta gene expression in NK cells. Finally, no transcription of the RAG-1 gene could be detected in all NK cell lines or clones analyzed. " ], "offsets": [ [ 0, 1920 ] ] } ]

[ { "id": "PMID-8386664_T1", "type": "Protein", "text": [ "CD3" ], "offsets": [ [ 6, 9 ] ], "normalized": [] }, { "id": "PMID-8386664_T2", "type": "Protein", "text": [ "CD16" ], "offsets": [ [ 10, 14 ] ], "normalized": [] }, { "id": "PMID-8386664_T3", "type": "Protein", "text": [ "hGATA-3" ], "offsets": [ [ 49, 56 ] ], "normalized": [] }, { "id": "PMID-8386664_T4", "type": "Protein", "text": [ "TcR delta" ], "offsets": [ [ 112, 121 ] ], "normalized": [] }, { "id": "PMID-8386664_T5", "type": "Protein", "text": [ "T cell receptor(TcR) delta" ], "offsets": [ [ 165, 191 ] ], "normalized": [] }, { "id": "PMID-8386664_T6", "type": "Protein", "text": [ "CD3" ], "offsets": [ [ 217, 220 ] ], "normalized": [] }, { "id": "PMID-8386664_T7", "type": "Protein", "text": [ "CD16" ], "offsets": [ [ 221, 225 ] ], "normalized": [] }, { "id": "PMID-8386664_T8", "type": "Protein", "text": [ "hGATA-3" ], "offsets": [ [ 287, 294 ] ], "normalized": [] }, { "id": "PMID-8386664_T9", "type": "Protein", "text": [ "recombination-activating gene (RAG)-1" ], "offsets": [ [ 331, 368 ] ], "normalized": [] }, { "id": "PMID-8386664_T10", "type": "Protein", "text": [ "TcR delta" ], "offsets": [ [ 379, 388 ] ], "normalized": [] }, { "id": "PMID-8386664_T11", "type": "Protein", "text": [ "TcR delta" ], "offsets": [ [ 431, 440 ] ], "normalized": [] }, { "id": "PMID-8386664_T12", "type": "Protein", "text": [ "CD3" ], "offsets": [ [ 490, 493 ] ], "normalized": [] }, { "id": "PMID-8386664_T13", "type": "Protein", "text": [ "CD16" ], "offsets": [ [ 494, 498 ] ], "normalized": [] }, { "id": "PMID-8386664_T14", "type": "Protein", "text": [ "TcR delta" ], "offsets": [ [ 548, 557 ] ], "normalized": [] }, { "id": "PMID-8386664_T15", "type": "Protein", "text": [ "TcR delta" ], "offsets": [ [ 615, 624 ] ], "normalized": [] }, { "id": "PMID-8386664_T16", "type": "Protein", "text": [ "TcR gamma" ], "offsets": [ [ 656, 665 ] ], "normalized": [] }, { "id": "PMID-8386664_T17", "type": "Protein", "text": [ "delta" ], "offsets": [ [ 666, 671 ] ], "normalized": [] }, { "id": "PMID-8386664_T18", "type": "Protein", "text": [ "TcR delta" ], "offsets": [ [ 831, 840 ] ], "normalized": [] }, { "id": "PMID-8386664_T19", "type": "Protein", "text": [ "hGATA-3" ], "offsets": [ [ 1384, 1391 ] ], "normalized": [] }, { "id": "PMID-8386664_T20", "type": "Protein", "text": [ "TcR delta" ], "offsets": [ [ 1481, 1490 ] ], "normalized": [] }, { "id": "PMID-8386664_T21", "type": "Protein", "text": [ "hGATA-3" ], "offsets": [ [ 1677, 1684 ] ], "normalized": [] }, { "id": "PMID-8386664_T22", "type": "Protein", "text": [ "hGATA-3" ], "offsets": [ [ 1716, 1723 ] ], "normalized": [] }, { "id": "PMID-8386664_T23", "type": "Protein", "text": [ "TcR delta" ], "offsets": [ [ 1778, 1787 ] ], "normalized": [] }, { "id": "PMID-8386664_T24", "type": "Protein", "text": [ "RAG-1" ], "offsets": [ [ 1850, 1855 ] ], "normalized": [] } ]

[ { "id": "PMID-8386664_E1", "type": "Transcription", "trigger": { "text": [ "express" ], "offsets": [ [ 37, 44 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "PMID-8386664_T4" } ] }, { "id": "PMID-8386664_E2", "type": "Gene_expression", "trigger": { "text": [ "express" ], "offsets": [ [ 37, 44 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "PMID-8386664_T3" } ] }, { "id": "PMID-8386664_E3", "type": "Transcription", "trigger": { "text": [ "expressed" ], "offsets": [ [ 204, 213 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "PMID-8386664_T5" } ] }, { "id": "PMID-8386664_E4", "type": "Gene_expression", "trigger": { "text": [ "expressed" ], "offsets": [ [ 273, 282 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "PMID-8386664_T9" } ] }, { "id": "PMID-8386664_E5", "type": "Gene_expression", "trigger": { "text": [ "expressed" ], "offsets": [ [ 273, 282 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "PMID-8386664_T8" } ] }, { "id": "PMID-8386664_E6", "type": "Transcription", "trigger": { "text": [ "deriving" ], "offsets": [ [ 401, 409 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "PMID-8386664_T11" } ] }, { "id": "PMID-8386664_E7", "type": "Transcription", "trigger": { "text": [ "found" ], "offsets": [ [ 647, 652 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "PMID-8386664_T15" } ] }, { "id": "PMID-8386664_E8", "type": "Gene_expression", "trigger": { "text": [ "expression" ], "offsets": [ [ 1370, 1380 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "PMID-8386664_T19" } ] }, { "id": "PMID-8386664_E9", "type": "Regulation", "trigger": { "text": [ "involved in the regulation" ], "offsets": [ [ 1430, 1456 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "PMID-8386664_E10" }, { "role": "Cause", "ref_id": "PMID-8386664_T19" } ] }, { "id": "PMID-8386664_E10", "type": "Transcription", "trigger": { "text": [ "transcription" ], "offsets": [ [ 1464, 1477 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "PMID-8386664_T20" } ] }, { "id": "PMID-8386664_E11", "type": "Transcription", "trigger": { "text": [ "express" ], "offsets": [ [ 1669, 1676 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "PMID-8386664_T21" } ] }, { "id": "PMID-8386664_E12", "type": "Regulation", "trigger": { "text": [ "involved in the regulation" ], "offsets": [ [ 1731, 1757 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "PMID-8386664_E13" }, { "role": "Cause", "ref_id": "PMID-8386664_T22" } ] }, { "id": "PMID-8386664_E13", "type": "Gene_expression", "trigger": { "text": [ "expression" ], "offsets": [ [ 1793, 1803 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "PMID-8386664_T23" } ] }, { "id": "PMID-8386664_E14", "type": "Transcription", "trigger": { "text": [ "transcription" ], "offsets": [ [ 1829, 1842 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "PMID-8386664_T24" } ] } ]

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[ { "id": "PMID-8419337__text", "type": "abstract", "text": [ "Involvement of Alu sequences in the cell-specific regulation of transcription of the gamma chain of Fc and T cell receptors. \nThe Fc epsilon RI-gamma chains are expressed in a variety of hematopoietic cells where they play a critical role in signal transduction. They are part of the high affinity IgE receptor in mast cells, basophils, Langerhans cells, and possibly other cells; a component of the low affinity receptor for IgG (Fc gamma RIIIA or CD16) in natural killer cells and macrophages; and part of the T cell antigen receptor in subsets of T cells. Here we have investigated the transcriptional regulation of the gamma chain gene by analyzing the 2.5-kilobase sequence upstream of the transcription start site. This sequence contains a promoter specific to cells of hematopoietic lineage. However, the tissue specificity of this promoter is only partial because it is active in all of the hematopoietic cells tested here, regardless of whether they constitutively express Fc epsilon RI- gamma chain transcripts. We have identified two adjacent cis-acting regulatory elements, both of which are part of an Alu repeat. The first (-445/-366) is a positive element active in both basophils and T cells. The second (-365/-264) binds to nuclear factors, which appear to be different in basophils and T cells, and acts as a negative element in basophils and as a positive one in T cells. Thus, this Alu repeat (90% identical to Alu consensus sequences) has evolved to become both a positive and negative regulator. " ], "offsets": [ [ 0, 1518 ] ] } ]

[ { "id": "PMID-8419337_T1", "type": "Protein", "text": [ "Fc epsilon RI-gamma chains" ], "offsets": [ [ 130, 156 ] ], "normalized": [] }, { "id": "PMID-8419337_T2", "type": "Protein", "text": [ "Fc gamma RIIIA" ], "offsets": [ [ 431, 445 ] ], "normalized": [] }, { "id": "PMID-8419337_T3", "type": "Protein", "text": [ "CD16" ], "offsets": [ [ 449, 453 ] ], "normalized": [] }, { "id": "PMID-8419337_T4", "type": "Protein", "text": [ "Fc epsilon RI- gamma chain" ], "offsets": [ [ 982, 1008 ] ], "normalized": [] } ]

[ { "id": "PMID-8419337_E1", "type": "Gene_expression", "trigger": { "text": [ "expressed" ], "offsets": [ [ 161, 170 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "PMID-8419337_T1" } ] }, { "id": "PMID-8419337_E2", "type": "Transcription", "trigger": { "text": [ "express" ], "offsets": [ [ 974, 981 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "PMID-8419337_T4" } ] } ]

[]

[]

[ { "id": "PMID-8428000__text", "type": "abstract", "text": [ "Interleukin-3 expression by activated T cells involves an inducible, T-cell-specific factor and an octamer binding protein. \nInterleukin-3 (IL-3) is exclusively expressed by activated T and natural killer cells, a function that is tightly controlled both in a lineage-specific and in a stimulation-dependent manner. We have investigated the protein binding characteristics and functional importance of the ACT-1-activating region of the IL-3 promoter. This region binds an inducible, T-cell-specific factor over its 5' end, a site that is necessary for the expression of IL-3 in the absence of other upstream elements. Over its 3' end, it binds a factor that is ubiquitously and constitutively expressed. This factor is Oct-1 or an immunologically related octamer-binding protein, and it plays a role in coordinating the activity of several regulatory elements. These characteristics make the ACT-1 site analogous to the activating ARRE-1 site in the IL-2 promoter. Furthermore, and despite a lack of sequence homology, the promoters of IL-3 and IL-2 share an organizational pattern of regulatory elements that is likely to be important for the T-cell-specific expression of these genes. " ], "offsets": [ [ 0, 1188 ] ] } ]

[ { "id": "PMID-8428000_T1", "type": "Protein", "text": [ "Interleukin-3" ], "offsets": [ [ 0, 13 ] ], "normalized": [] }, { "id": "PMID-8428000_T2", "type": "Protein", "text": [ "Interleukin-3" ], "offsets": [ [ 125, 138 ] ], "normalized": [] }, { "id": "PMID-8428000_T3", "type": "Protein", "text": [ "IL-3" ], "offsets": [ [ 140, 144 ] ], "normalized": [] }, { "id": "PMID-8428000_T4", "type": "Protein", "text": [ "IL-3" ], "offsets": [ [ 437, 441 ] ], "normalized": [] }, { "id": "PMID-8428000_T5", "type": "Protein", "text": [ "IL-3" ], "offsets": [ [ 571, 575 ] ], "normalized": [] }, { "id": "PMID-8428000_T6", "type": "Protein", "text": [ "Oct-1" ], "offsets": [ [ 720, 725 ] ], "normalized": [] }, { "id": "PMID-8428000_T7", "type": "Protein", "text": [ "IL-2" ], "offsets": [ [ 951, 955 ] ], "normalized": [] }, { "id": "PMID-8428000_T8", "type": "Protein", "text": [ "IL-3" ], "offsets": [ [ 1037, 1041 ] ], "normalized": [] }, { "id": "PMID-8428000_T9", "type": "Protein", "text": [ "IL-2" ], "offsets": [ [ 1046, 1050 ] ], "normalized": [] }, { "id": "PMID-8428000_T13", "type": "Entity", "text": [ "ACT-1-activating region" ], "offsets": [ [ 406, 429 ] ], "normalized": [] }, { "id": "PMID-8428000_T19", "type": "Entity", "text": [ "ARRE-1 site" ], "offsets": [ [ 932, 943 ] ], "normalized": [] } ]

[ { "id": "PMID-8428000_E1", "type": "Gene_expression", "trigger": { "text": [ "expression" ], "offsets": [ [ 14, 24 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "PMID-8428000_T1" } ] }, { "id": "PMID-8428000_E2", "type": "Gene_expression", "trigger": { "text": [ "expressed" ], "offsets": [ [ 161, 170 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "PMID-8428000_T3" } ] }, { "id": "PMID-8428000_E3", "type": "Regulation", "trigger": { "text": [ "controlled" ], "offsets": [ [ 239, 249 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "PMID-8428000_T3" } ] }, { "id": "PMID-8428000_E4", "type": "Binding", "trigger": { "text": [ "binds" ], "offsets": [ [ 464, 469 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "PMID-8428000_T4" }, { "role": "Site", "ref_id": "PMID-8428000_T13" } ] }, { "id": "PMID-8428000_E5", "type": "Positive_regulation", "trigger": { "text": [ "necessary" ], "offsets": [ [ 539, 548 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "PMID-8428000_E6" } ] }, { "id": "PMID-8428000_E6", "type": "Gene_expression", "trigger": { "text": [ "expression" ], "offsets": [ [ 557, 567 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "PMID-8428000_T5" } ] }, { "id": "PMID-8428000_E7", "type": "Binding", "trigger": { "text": [ "binds" ], "offsets": [ [ 639, 644 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "PMID-8428000_T4" }, { "role": "Site", "ref_id": "PMID-8428000_T13" } ] }, { "id": "PMID-8428000_E8", "type": "Positive_regulation", "trigger": { "text": [ "activating" ], "offsets": [ [ 921, 931 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "PMID-8428000_T7" }, { "role": "Site", "ref_id": "PMID-8428000_T19" } ] }, { "id": "PMID-8428000_E9", "type": "Positive_regulation", "trigger": { "text": [ "important" ], "offsets": [ [ 1127, 1136 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "PMID-8428000_E12" } ] }, { "id": "PMID-8428000_E10", "type": "Positive_regulation", "trigger": { "text": [ "important" ], "offsets": [ [ 1127, 1136 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "PMID-8428000_E11" } ] }, { "id": "PMID-8428000_E11", "type": "Gene_expression", "trigger": { "text": [ "expression" ], "offsets": [ [ 1161, 1171 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "PMID-8428000_T8" } ] }, { "id": "PMID-8428000_E12", "type": "Gene_expression", "trigger": { "text": [ "expression" ], "offsets": [ [ 1161, 1171 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "PMID-8428000_T9" } ] } ]

[ { "id": "PMID-8428000_1", "entity_ids": [ "PMID-8428000_T3", "PMID-8428000_T2" ] } ]

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[ { "id": "PMID-8428943__text", "type": "abstract", "text": [ "ras protein activity is essential for T-cell antigen receptor signal transduction. \nIn a Jurkat cell model of T-cell activation an interleukin-2 promoter/reporter gene construct was activated by antigen receptor agonism in combination with the lymphokine interleukin-1. Antigen receptor signals could be mimicked by suboptimal activation of protein kinase C (PKC) with phorbol esters in combination with calcium mobilization by an ionophore. In cotransfection experiments, oncogenic rats obviated the need for PKC stimulation but did not replace either the calcium signal or interleukin-1. Activated ras expression also replaced the requirement for PKC stimulation in activation of the T-cell transcription factor NF-AT. A dominant inhibitory ras mutant specifically blocked antigen receptor agonism, indicating that ras activity is required for antigen receptor signaling. In addition, an inhibitor of PKC blocked both activated ras and phorbol ester stimulation, suggesting a role for ras upstream of PKC. " ], "offsets": [ [ 0, 1008 ] ] } ]

[ { "id": "PMID-8428943_T1", "type": "Protein", "text": [ "interleukin-2" ], "offsets": [ [ 131, 144 ] ], "normalized": [] } ]

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[ { "id": "PMID-8428966__text", "type": "abstract", "text": [ "Characterization of the nuclear and cytoplasmic components of the lymphoid-specific nuclear factor of activated T cells (NF-AT) complex. \nThe lymphoid-specific transcription complex, NF-AT, is involved in early gene activation in T cells and is assembled from a pre-existing, T cell restricted cytoplasmic factor and an inducible ubiquitous nuclear component within 30 min after activation through the antigen receptor. Recent studies have implicated the family of AP1 factors as components of the murine NF-AT complex. Evidence is provided here that the nuclear component of human NF-AT contains the phorbol ester-inducible transcription factor AP1 (Jun/Fos). We further characterize which AP1 family members can assume this role. Antisera to Fos inhibits NF-AT DNA binding as does an oligonucleotide containing a binding site for AP1. Constitutive expression in vivo of Fos, and to a lesser extent Fra-1, eliminates the requirement for phorbol 12-myristate 13-acetate (PMA) stimulation, leaving NF-AT-directed transcription responsive to calcium ionophore alone. Overexpression of cJun or JunD, but not JunB, also eliminates the requirement for PMA, indicating that many but not all Jun- and Fos-related proteins functionally activate NF-AT-dependent transcription in the presence of the cytoplasmic component. NF-AT DNA binding can be reconstituted in vitro using semi-purified AP1 proteins mixed with cytosol from T lymphocytes. Fos proteins are not needed for this reconstitution, and although JunB is not functional, it can participate in the NF-AT DNA binding complex. Finally, we have partially purified the cytoplasmic component of NF-AT and show by elution and renaturation from SDS-polyacrylamide gel electrophoresis gels that it has a molecular mass between 94 and 116 kDa and may have multiple differentially modified forms. " ], "offsets": [ [ 0, 1838 ] ] } ]

[ { "id": "PMID-8428966_T1", "type": "Protein", "text": [ "Fra-1" ], "offsets": [ [ 900, 905 ] ], "normalized": [] }, { "id": "PMID-8428966_T2", "type": "Protein", "text": [ "cJun" ], "offsets": [ [ 1083, 1087 ] ], "normalized": [] }, { "id": "PMID-8428966_T3", "type": "Protein", "text": [ "JunD" ], "offsets": [ [ 1091, 1095 ] ], "normalized": [] }, { "id": "PMID-8428966_T4", "type": "Protein", "text": [ "JunB" ], "offsets": [ [ 1105, 1109 ] ], "normalized": [] }, { "id": "PMID-8428966_T5", "type": "Protein", "text": [ "JunB" ], "offsets": [ [ 1499, 1503 ] ], "normalized": [] } ]

[ { "id": "PMID-8428966_E1", "type": "Gene_expression", "trigger": { "text": [ "expression" ], "offsets": [ [ 850, 860 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "PMID-8428966_T1" } ] }, { "id": "PMID-8428966_E2", "type": "Gene_expression", "trigger": { "text": [ "Overexpression" ], "offsets": [ [ 1065, 1079 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "PMID-8428966_T4" } ] }, { "id": "PMID-8428966_E3", "type": "Positive_regulation", "trigger": { "text": [ "Overexpression" ], "offsets": [ [ 1065, 1079 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "PMID-8428966_E6" } ] }, { "id": "PMID-8428966_E4", "type": "Positive_regulation", "trigger": { "text": [ "Overexpression" ], "offsets": [ [ 1065, 1079 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "PMID-8428966_E7" } ] }, { "id": "PMID-8428966_E5", "type": "Positive_regulation", "trigger": { "text": [ "Overexpression" ], "offsets": [ [ 1065, 1079 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "PMID-8428966_E2" } ] }, { "id": "PMID-8428966_E6", "type": "Gene_expression", "trigger": { "text": [ "expression" ], "offsets": [ [ 1069, 1079 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "PMID-8428966_T3" } ] }, { "id": "PMID-8428966_E7", "type": "Gene_expression", "trigger": { "text": [ "expression" ], "offsets": [ [ 1069, 1079 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "PMID-8428966_T2" } ] } ]

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[ { "id": "PMID-8436816__text", "type": "abstract", "text": [ "Protease treatment of nuclear extracts distinguishes between class II MHC X1 box DNA-binding proteins in wild-type and class II-deficient B cells. \nThe X box region is critical for directing the expression of class II major histocompatibility complex genes in B lymphocytes. Although several class II promoter-specific DNA binding factors have been described, only the X box region factor, RFX, shows a genetic correlation with class II expression, being deficient in some B cell lines derived from patients with class II-deficient congenital immunodeficiency. To further evaluate the role of X box DNA-binding proteins in class II gene expression, the role of the X box region was examined in both class II-positive and -negative lymphoid cells. In addition to the wild-type B cell line Raji, two class II transcriptional mutant cell lines, SJO and RJ2.2.5, and Jurkat, a class II negative T cell line, were examined. In contrast to wild-type B cells, neither of the class II mutant cell lines could use the X box region to direct the expression of a transiently transfected reporter gene, indicating that the X box-dependent transcriptional pathway is defective in these cells. The binding activity of the X1 box DNA-binding protein RFX was examined and found to be present in wild-type B cells and the mutant RJ2.2.5 but was absent in SJO and Jurkat. However, other X1 box-specific activities were detected in all these cell lines. To determine whether these different X1 box activities represented distinct DNA binding proteins or multimeric forms of the same factor(s), protease treatment of the crude nuclear extracts followed by DNA-binding assays were carried out and demonstrated that B cell extracts contain at least two X1-specific factors. One of these cleaved products (band 1 pk) correlates with RFX activity. A similar comparison with protease-treated extracts prepared from Jurkat cells demonstrated the presence of the band 1pk activity despite an absence of the native RFX activity. In contrast, protease treatment and analysis of SJO extracts showed no detectable levels of the band 1pk activity. These results demonstrate that multiple X1 box-specific DNA-binding activities exist in all lymphoid cells, but the presence of an actively binding RFX species correlates with class II transcription. " ], "offsets": [ [ 0, 2316 ] ] } ]

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[ { "id": "PMID-8441379__text", "type": "abstract", "text": [ "The human prointerleukin 1 beta gene requires DNA sequences both proximal and distal to the transcription start site for tissue-specific induction. \nIn these studies, we have identified DNA sequences and specific protein interactions necessary for transcriptional regulation of the human prointerleukin 1 beta (proIL-1 beta) gene. A cell-type-independent lipopolysaccharide (LPS)-responsive enhancer element located between -3757 and -2729 bp upstream from the transcription start site (cap site) consisted of at least six discrete subregions which were essential to the maximal induction by LPS in transfected monocytes. The enhancer also appeared to mediate phorbol myristate acetate induction in monocytes and IL-1 responsiveness in fibroblasts. Deletion and base substitution mutations along with DNA binding studies demonstrated that the enhancer contained a minimum of three functional protein binding sequences, two of which appeared to be important for gene induction. One of the essential proteins which bound to the enhancer was similar or identical to members of the C/EBP family of transcription factors required for both IL-1- and LPS-specific induction of the IL-6 gene (i.e., the NF-IL6 proteins). When ligated to the proIL-1 beta cap site-proximal region (located between -131 to +12), both the proIL-1 beta and the simian virus 40 enhancer elements functioned more efficiently in monocytes than in HeLa cells, which are not normally competent for IL-1 beta expression. When ligated to the murine c-fos promoter, however, the proIL-1 beta enhancer was inducible in phorbol myristate acetate-stimulated HeLa cells, suggesting the existence of a proIL-1 beta promoter-proximal requirement for tissue specificity. " ], "offsets": [ [ 0, 1727 ] ] } ]

[ { "id": "PMID-8441379_T1", "type": "Protein", "text": [ "human prointerleukin 1 beta" ], "offsets": [ [ 4, 31 ] ], "normalized": [] }, { "id": "PMID-8441379_T2", "type": "Protein", "text": [ "human prointerleukin 1 beta" ], "offsets": [ [ 282, 309 ] ], "normalized": [] }, { "id": "PMID-8441379_T3", "type": "Protein", "text": [ "proIL-1 beta" ], "offsets": [ [ 311, 323 ] ], "normalized": [] }, { "id": "PMID-8441379_T4", "type": "Protein", "text": [ "IL-6" ], "offsets": [ [ 1174, 1178 ] ], "normalized": [] }, { "id": "PMID-8441379_T5", "type": "Protein", "text": [ "NF-IL6" ], "offsets": [ [ 1195, 1201 ] ], "normalized": [] }, { "id": "PMID-8441379_T6", "type": "Protein", "text": [ "proIL-1 beta" ], "offsets": [ [ 1233, 1245 ] ], "normalized": [] }, { "id": "PMID-8441379_T7", "type": "Protein", "text": [ "IL-1 beta" ], "offsets": [ [ 1464, 1473 ] ], "normalized": [] }, { "id": "PMID-8441379_T8", "type": "Protein", "text": [ "c-fos" ], "offsets": [ [ 1513, 1518 ] ], "normalized": [] }, { "id": "PMID-8441379_T9", "type": "Protein", "text": [ "proIL-1 beta" ], "offsets": [ [ 1542, 1554 ] ], "normalized": [] }, { "id": "PMID-8441379_T10", "type": "Protein", "text": [ "proIL-1 beta" ], "offsets": [ [ 1660, 1672 ] ], "normalized": [] }, { "id": "PMID-8441379_T21", "type": "Entity", "text": [ "enhancer" ], "offsets": [ [ 1555, 1563 ] ], "normalized": [] }, { "id": "PMID-8441379_T23", "type": "Entity", "text": [ "promoter" ], "offsets": [ [ 1673, 1681 ] ], "normalized": [] } ]

[ { "id": "PMID-8441379_E1", "type": "Positive_regulation", "trigger": { "text": [ "requires" ], "offsets": [ [ 37, 45 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "PMID-8441379_E2" } ] }, { "id": "PMID-8441379_E2", "type": "Positive_regulation", "trigger": { "text": [ "induction" ], "offsets": [ [ 137, 146 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "PMID-8441379_T1" } ] }, { "id": "PMID-8441379_E3", "type": "Positive_regulation", "trigger": { "text": [ "necessary" ], "offsets": [ [ 234, 243 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "PMID-8441379_E4" } ] }, { "id": "PMID-8441379_E4", "type": "Regulation", "trigger": { "text": [ "transcriptional regulation" ], "offsets": [ [ 248, 274 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "PMID-8441379_T3" } ] }, { "id": "PMID-8441379_E5", "type": "Positive_regulation", "trigger": { "text": [ "important" ], "offsets": [ [ 947, 956 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "PMID-8441379_E6" } ] }, { "id": "PMID-8441379_E6", "type": "Gene_expression", "trigger": { "text": [ "induction" ], "offsets": [ [ 966, 975 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "PMID-8441379_T3" } ] }, { "id": "PMID-8441379_E7", "type": "Positive_regulation", "trigger": { "text": [ "required" ], "offsets": [ [ 1116, 1124 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "PMID-8441379_E9" }, { "role": "Cause", "ref_id": "PMID-8441379_T5" } ] }, { "id": "PMID-8441379_E8", "type": "Positive_regulation", "trigger": { "text": [ "required" ], "offsets": [ [ 1116, 1124 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "PMID-8441379_E9" } ] }, { "id": "PMID-8441379_E9", "type": "Positive_regulation", "trigger": { "text": [ "induction" ], "offsets": [ [ 1157, 1166 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "PMID-8441379_T4" } ] }, { "id": "PMID-8441379_E10", "type": "Gene_expression", "trigger": { "text": [ "expression" ], "offsets": [ [ 1474, 1484 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "PMID-8441379_T7" } ] }, { "id": "PMID-8441379_E11", "type": "Positive_regulation", "trigger": { "text": [ "When" ], "offsets": [ [ 1486, 1490 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "PMID-8441379_E12" } ] }, { "id": "PMID-8441379_E12", "type": "Positive_regulation", "trigger": { "text": [ "inducible" ], "offsets": [ [ 1568, 1577 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "PMID-8441379_T9" }, { "role": "Site", "ref_id": "PMID-8441379_T21" } ] }, { "id": "PMID-8441379_E13", "type": "Positive_regulation", "trigger": { "text": [ "requirement" ], "offsets": [ [ 1691, 1702 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "PMID-8441379_T10" }, { "role": "Cause", "ref_id": "PMID-8441379_T9" }, { "role": "Site", "ref_id": "PMID-8441379_T23" }, { "role": "CSite", "ref_id": "PMID-8441379_T21" } ] } ]

[ { "id": "PMID-8441379_1", "entity_ids": [ "PMID-8441379_T3", "PMID-8441379_T2" ] } ]

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[ { "id": "PMID-8443122__text", "type": "abstract", "text": [ "Expression of PILOT, a putative transcription factor, requires two signals and is cyclosporin A sensitive in T cells. \nFew known genes (IL-2, members of the IL-8 family, interferon-gamma) are induced in T cells only through the combined effect of phorbol myristic acetate (PMA) and a Ca(2+)-ionophore, and expression of only these genes can be fully suppressed by Cyclosporin A (CyA). We have identified a putative transcription factor, designated PILOT, with an identical dual signal requirement for expression. Induction of the PILOT gene is detectable in human T cells 20 min following activation in the presence of cycloheximide and is fully suppressed by CyA. The PILOT protein has a calculated M(r) of 42.6 kDa and contains three zinc fingers of the C2H2-type at the carboxyl-terminus which are highly homologous to the zinc finger regions of the transcription factors EGR1, EGR2, and pAT 133. In contrast to T cells, in fibroblasts PILOT gene expression requires only one signal (PMA) and is not affected by CyA. This observation directly demonstrates the existence of a Ca2+ signal-dependent regulatory element obligatory for expression of some genes in T cells but not in fibroblasts. This differential expression model will be valuable in the dissection of the dual signal pathway in T cells and the effects of CyA upon it. " ], "offsets": [ [ 0, 1334 ] ] } ]

[ { "id": "PMID-8443122_T1", "type": "Protein", "text": [ "PILOT" ], "offsets": [ [ 14, 19 ] ], "normalized": [] }, { "id": "PMID-8443122_T2", "type": "Protein", "text": [ "IL-2" ], "offsets": [ [ 136, 140 ] ], "normalized": [] }, { "id": "PMID-8443122_T3", "type": "Protein", "text": [ "interferon-gamma" ], "offsets": [ [ 170, 186 ] ], "normalized": [] }, { "id": "PMID-8443122_T4", "type": "Protein", "text": [ "PILOT" ], "offsets": [ [ 448, 453 ] ], "normalized": [] }, { "id": "PMID-8443122_T5", "type": "Protein", "text": [ "PILOT" ], "offsets": [ [ 530, 535 ] ], "normalized": [] }, { "id": "PMID-8443122_T6", "type": "Protein", "text": [ "PILOT" ], "offsets": [ [ 669, 674 ] ], "normalized": [] }, { "id": "PMID-8443122_T7", "type": "Protein", "text": [ "EGR1" ], "offsets": [ [ 875, 879 ] ], "normalized": [] }, { "id": "PMID-8443122_T8", "type": "Protein", "text": [ "EGR2" ], "offsets": [ [ 881, 885 ] ], "normalized": [] }, { "id": "PMID-8443122_T9", "type": "Protein", "text": [ "pAT 133" ], "offsets": [ [ 891, 898 ] ], "normalized": [] }, { "id": "PMID-8443122_T10", "type": "Protein", "text": [ "PILOT" ], "offsets": [ [ 939, 944 ] ], "normalized": [] } ]

[ { "id": "PMID-8443122_E1", "type": "Gene_expression", "trigger": { "text": [ "Expression" ], "offsets": [ [ 0, 10 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "PMID-8443122_T1" } ] }, { "id": "PMID-8443122_E2", "type": "Positive_regulation", "trigger": { "text": [ "requires" ], "offsets": [ [ 54, 62 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "PMID-8443122_E1" } ] }, { "id": "PMID-8443122_E3", "type": "Positive_regulation", "trigger": { "text": [ "induced" ], "offsets": [ [ 192, 199 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "PMID-8443122_T3" } ] }, { "id": "PMID-8443122_E4", "type": "Positive_regulation", "trigger": { "text": [ "induced" ], "offsets": [ [ 192, 199 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "PMID-8443122_T2" } ] }, { "id": "PMID-8443122_E5", "type": "Gene_expression", "trigger": { "text": [ "expression" ], "offsets": [ [ 306, 316 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "PMID-8443122_T3" } ] }, { "id": "PMID-8443122_E6", "type": "Gene_expression", "trigger": { "text": [ "expression" ], "offsets": [ [ 306, 316 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "PMID-8443122_T2" } ] }, { "id": "PMID-8443122_E7", "type": "Negative_regulation", "trigger": { "text": [ "suppressed" ], "offsets": [ [ 350, 360 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "PMID-8443122_E6" } ] }, { "id": "PMID-8443122_E8", "type": "Negative_regulation", "trigger": { "text": [ "suppressed" ], "offsets": [ [ 350, 360 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "PMID-8443122_E5" } ] }, { "id": "PMID-8443122_E9", "type": "Positive_regulation", "trigger": { "text": [ "requirement" ], "offsets": [ [ 485, 496 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "PMID-8443122_E10" } ] }, { "id": "PMID-8443122_E10", "type": "Gene_expression", "trigger": { "text": [ "expression" ], "offsets": [ [ 501, 511 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "PMID-8443122_T4" } ] }, { "id": "PMID-8443122_E11", "type": "Positive_regulation", "trigger": { "text": [ "Induction" ], "offsets": [ [ 513, 522 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "PMID-8443122_T5" } ] }, { "id": "PMID-8443122_E12", "type": "Negative_regulation", "trigger": { "text": [ "suppressed" ], "offsets": [ [ 646, 656 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "PMID-8443122_E11" } ] }, { "id": "PMID-8443122_E13", "type": "Gene_expression", "trigger": { "text": [ "expression" ], "offsets": [ [ 950, 960 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "PMID-8443122_T10" } ] }, { "id": "PMID-8443122_E14", "type": "Positive_regulation", "trigger": { "text": [ "requires" ], "offsets": [ [ 961, 969 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "PMID-8443122_E13" } ] }, { "id": "PMID-8443122_E15", "type": "Regulation", "trigger": { "text": [ "affected" ], "offsets": [ [ 1003, 1011 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "PMID-8443122_E13" } ] } ]

[]

[]

[ { "id": "PMID-8444885__text", "type": "abstract", "text": [ "Suppression of a cellular differentiation program by phorbol esters coincides with inhibition of binding of a cell-specific transcription factor (NF-E2) to an enhancer element required for expression of an erythroid-specific gene. \nInduction by hemin increases, while induction with 12-O-tetradecanoylphorbol-13-acetate (TPA) represses, erythroid-specific gene expression in the human cell line K562. We analyzed the effects of hemin or TPA induction on the binding and activity of transcription factors at a regulatory element found within the transcriptional regulatory sequences of many erythroid-specific genes. TPA induction increases the binding of ubiquitous AP-1 factors to this element. TPA induction inhibits the binding of the lineage limited transcription factor NF-E2 to this transcriptional control element. Hemin induction of K562 cells does not facilitate the binding of NF-E2 to its recognition site. Hemin induction appears to nonspecifically increase the expression of transiently transfected genes in K562 cells. Beyond this nonspecific increase in gene expression, hemin induction acts to increase the activity of the lineage limited transcription factor NF-E2. The divergent effects of hemin and TPA on gene expression in K562 cells are mediated, in part, by their contrasting effects on the transcription factor NF-E2. " ], "offsets": [ [ 0, 1342 ] ] } ]

[]

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[]

[]

[ { "id": "PMID-8449904__text", "type": "abstract", "text": [ "Transcriptional regulation of the pyruvate kinase erythroid-specific promoter. \nMammal pyruvate kinases are encoded by two genes. The L gene produces the erythroid (R-PK) or the hepatic (L-PK) isozymes by the alternative use of two promoters. We report the characterization of the cis- and trans-acting elements involved in the tissue-specific activity of the L gene erythroid promoter. A R-PK DNA fragment extending from -870 to +54 relative to the cap site confers erythroid specificity to a reporter gene. Within this region, we define a minimal promoter (-62 to +54) that displays erythroid-specific activity and contains two DNA binding sites. One, located at -50, binds members of the CCACC/Sp1 family and the other, located at -20, binds the erythroid factor GATA-1. Although the -20 GATA binding site (AGATAA) is also a potential TFIID binding site, it does not bind TFIID. Furthermore, the substitution of this GATA binding site by a canonical TFIID binding site suppresses the promoter activity. Mutations and deletions of both sites indicate that only the association of CCACC/Sp1 and GATA binding sites can drive efficient and tissue-specific expression of this R-PK minimal promoter. Finally, by co-transfection experiments, we study the elements involved in the hGATA-1 transactivation of the R-PK promoter in HeLa cells. " ], "offsets": [ [ 0, 1336 ] ] } ]

[ { "id": "PMID-8449904_T1", "type": "Protein", "text": [ "L" ], "offsets": [ [ 134, 135 ] ], "normalized": [] }, { "id": "PMID-8449904_T2", "type": "Protein", "text": [ "R-PK" ], "offsets": [ [ 165, 169 ] ], "normalized": [] }, { "id": "PMID-8449904_T3", "type": "Protein", "text": [ "L-PK" ], "offsets": [ [ 187, 191 ] ], "normalized": [] }, { "id": "PMID-8449904_T4", "type": "Protein", "text": [ "L" ], "offsets": [ [ 360, 361 ] ], "normalized": [] }, { "id": "PMID-8449904_T5", "type": "Protein", "text": [ "R-PK" ], "offsets": [ [ 389, 393 ] ], "normalized": [] }, { "id": "PMID-8449904_T6", "type": "Protein", "text": [ "GATA-1" ], "offsets": [ [ 766, 772 ] ], "normalized": [] }, { "id": "PMID-8449904_T7", "type": "Protein", "text": [ "R-PK" ], "offsets": [ [ 1174, 1178 ] ], "normalized": [] }, { "id": "PMID-8449904_T8", "type": "Protein", "text": [ "hGATA-1" ], "offsets": [ [ 1276, 1283 ] ], "normalized": [] }, { "id": "PMID-8449904_T9", "type": "Protein", "text": [ "R-PK" ], "offsets": [ [ 1307, 1311 ] ], "normalized": [] }, { "id": "PMID-8449904_T13", "type": "Entity", "text": [ "erythroid promoter" ], "offsets": [ [ 367, 385 ] ], "normalized": [] }, { "id": "PMID-8449904_T18", "type": "Entity", "text": [ "promoter" ], "offsets": [ [ 1312, 1320 ] ], "normalized": [] } ]

[ { "id": "PMID-8449904_E1", "type": "Gene_expression", "trigger": { "text": [ "produces" ], "offsets": [ [ 141, 149 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "PMID-8449904_T3" } ] }, { "id": "PMID-8449904_E2", "type": "Positive_regulation", "trigger": { "text": [ "by the alternative use of" ], "offsets": [ [ 202, 227 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "PMID-8449904_E1" } ] }, { "id": "PMID-8449904_E3", "type": "Positive_regulation", "trigger": { "text": [ "activity" ], "offsets": [ [ 344, 352 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "PMID-8449904_T4" }, { "role": "Site", "ref_id": "PMID-8449904_T13" } ] }, { "id": "PMID-8449904_E4", "type": "Binding", "trigger": { "text": [ "binds" ], "offsets": [ [ 739, 744 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "PMID-8449904_T6" } ] }, { "id": "PMID-8449904_E5", "type": "Positive_regulation", "trigger": { "text": [ "drive" ], "offsets": [ [ 1119, 1124 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "PMID-8449904_E6" } ] }, { "id": "PMID-8449904_E6", "type": "Gene_expression", "trigger": { "text": [ "expression" ], "offsets": [ [ 1155, 1165 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "PMID-8449904_T7" } ] }, { "id": "PMID-8449904_E7", "type": "Positive_regulation", "trigger": { "text": [ "transactivation" ], "offsets": [ [ 1284, 1299 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "PMID-8449904_T9" }, { "role": "Cause", "ref_id": "PMID-8449904_T8" }, { "role": "Site", "ref_id": "PMID-8449904_T18" } ] } ]

[]

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[ { "id": "PMID-8454603__text", "type": "abstract", "text": [ "Transcriptional regulation of interleukin 3 (IL3) in primary human T lymphocytes. Role of AP-1- and octamer-binding proteins in control of IL3 gene expression. \nWe have investigated the molecular and biochemical basis for activation of interleukin 3 (IL3) gene expression in primary human T lymphocytes following CD3 and CD2 receptor stimulation or activation by phytohemagglutinin plus phorbol 12-myristate 13-acetate. Using transfection and reporter gene assays specifically designed for primary T lymphocytes in conjunction with gel retardation assays, Western blot analyses and UV cross-linking studies, we found that c-Jun, c-Fos, and octamer-binding proteins play a major role in transcriptional activation of the IL3 gene via their interaction with two specific regions contained within the IL3 5'-flanking sequence. Additionally, the region between bases -107 and -59 of the IL3 promoter containing putative AP-2 and Sp1 binding motifs appears necessary for basal level expression of the IL3 gene. The data also indicate that CD2 receptor activation and phytohemagglutinin plus phorbol 12-myristate 13-acetate stimulation augment T cell IL3 gene expression through the same cis- and trans-activating signals. These results should contribute to a better understanding of the regulation of IL3 gene expression in human T lymphocytes. " ], "offsets": [ [ 0, 1340 ] ] } ]

[ { "id": "PMID-8454603_T1", "type": "Protein", "text": [ "interleukin 3" ], "offsets": [ [ 30, 43 ] ], "normalized": [] }, { "id": "PMID-8454603_T2", "type": "Protein", "text": [ "IL3" ], "offsets": [ [ 45, 48 ] ], "normalized": [] }, { "id": "PMID-8454603_T3", "type": "Protein", "text": [ "IL3" ], "offsets": [ [ 139, 142 ] ], "normalized": [] }, { "id": "PMID-8454603_T4", "type": "Protein", "text": [ "interleukin 3" ], "offsets": [ [ 236, 249 ] ], "normalized": [] }, { "id": "PMID-8454603_T5", "type": "Protein", "text": [ "IL3" ], "offsets": [ [ 251, 254 ] ], "normalized": [] }, { "id": "PMID-8454603_T6", "type": "Protein", "text": [ "CD2" ], "offsets": [ [ 321, 324 ] ], "normalized": [] }, { "id": "PMID-8454603_T7", "type": "Protein", "text": [ "phytohemagglutinin" ], "offsets": [ [ 363, 381 ] ], "normalized": [] }, { "id": "PMID-8454603_T8", "type": "Protein", "text": [ "c-Jun" ], "offsets": [ [ 622, 627 ] ], "normalized": [] }, { "id": "PMID-8454603_T9", "type": "Protein", "text": [ "c-Fos" ], "offsets": [ [ 629, 634 ] ], "normalized": [] }, { "id": "PMID-8454603_T10", "type": "Protein", "text": [ "IL3" ], "offsets": [ [ 720, 723 ] ], "normalized": [] }, { "id": "PMID-8454603_T11", "type": "Protein", "text": [ "IL3" ], "offsets": [ [ 798, 801 ] ], "normalized": [] }, { "id": "PMID-8454603_T12", "type": "Protein", "text": [ "IL3" ], "offsets": [ [ 883, 886 ] ], "normalized": [] }, { "id": "PMID-8454603_T13", "type": "Protein", "text": [ "Sp1" ], "offsets": [ [ 925, 928 ] ], "normalized": [] }, { "id": "PMID-8454603_T14", "type": "Protein", "text": [ "IL3" ], "offsets": [ [ 996, 999 ] ], "normalized": [] }, { "id": "PMID-8454603_T15", "type": "Protein", "text": [ "CD2" ], "offsets": [ [ 1034, 1037 ] ], "normalized": [] }, { "id": "PMID-8454603_T16", "type": "Protein", "text": [ "phytohemagglutinin" ], "offsets": [ [ 1062, 1080 ] ], "normalized": [] }, { "id": "PMID-8454603_T17", "type": "Protein", "text": [ "IL3" ], "offsets": [ [ 1145, 1148 ] ], "normalized": [] }, { "id": "PMID-8454603_T18", "type": "Protein", "text": [ "IL3" ], "offsets": [ [ 1296, 1299 ] ], "normalized": [] } ]

[ { "id": "PMID-8454603_E1", "type": "Transcription", "trigger": { "text": [ "Transcriptional" ], "offsets": [ [ 0, 15 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "PMID-8454603_T2" } ] }, { "id": "PMID-8454603_E2", "type": "Regulation", "trigger": { "text": [ "regulation" ], "offsets": [ [ 16, 26 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "PMID-8454603_E1" } ] }, { "id": "PMID-8454603_E3", "type": "Regulation", "trigger": { "text": [ "Role" ], "offsets": [ [ 82, 86 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "PMID-8454603_E4" } ] }, { "id": "PMID-8454603_E4", "type": "Regulation", "trigger": { "text": [ "control" ], "offsets": [ [ 128, 135 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "PMID-8454603_E5" } ] }, { "id": "PMID-8454603_E5", "type": "Gene_expression", "trigger": { "text": [ "expression" ], "offsets": [ [ 148, 158 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "PMID-8454603_T3" } ] }, { "id": "PMID-8454603_E6", "type": "Positive_regulation", "trigger": { "text": [ "activation" ], "offsets": [ [ 222, 232 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "PMID-8454603_E9" }, { "role": "Cause", "ref_id": "PMID-8454603_E11" } ] }, { "id": "PMID-8454603_E7", "type": "Positive_regulation", "trigger": { "text": [ "activation" ], "offsets": [ [ 222, 232 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "PMID-8454603_E9" } ] }, { "id": "PMID-8454603_E8", "type": "Positive_regulation", "trigger": { "text": [ "activation" ], "offsets": [ [ 222, 232 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "PMID-8454603_E9" }, { "role": "Cause", "ref_id": "PMID-8454603_E10" } ] }, { "id": "PMID-8454603_E9", "type": "Gene_expression", "trigger": { "text": [ "expression" ], "offsets": [ [ 261, 271 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "PMID-8454603_T5" } ] }, { "id": "PMID-8454603_E10", "type": "Positive_regulation", "trigger": { "text": [ "stimulation" ], "offsets": [ [ 334, 345 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "PMID-8454603_T6" } ] }, { "id": "PMID-8454603_E11", "type": "Positive_regulation", "trigger": { "text": [ "activation" ], "offsets": [ [ 349, 359 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "PMID-8454603_T7" } ] }, { "id": "PMID-8454603_E12", "type": "Positive_regulation", "trigger": { "text": [ "play a major role" ], "offsets": [ [ 665, 682 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "PMID-8454603_E16" } ] }, { "id": "PMID-8454603_E13", "type": "Positive_regulation", "trigger": { "text": [ "play a major role" ], "offsets": [ [ 665, 682 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "PMID-8454603_E16" }, { "role": "Cause", "ref_id": "PMID-8454603_E18" } ] }, { "id": "PMID-8454603_E14", "type": "Positive_regulation", "trigger": { "text": [ "play a major role" ], "offsets": [ [ 665, 682 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "PMID-8454603_E16" }, { "role": "Cause", "ref_id": "PMID-8454603_E17" } ] }, { "id": "PMID-8454603_E15", "type": "Transcription", "trigger": { "text": [ "transcriptional" ], "offsets": [ [ 686, 701 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "PMID-8454603_T10" } ] }, { "id": "PMID-8454603_E16", "type": "Positive_regulation", "trigger": { "text": [ "activation" ], "offsets": [ [ 702, 712 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "PMID-8454603_E15" } ] }, { "id": "PMID-8454603_E17", "type": "Binding", "trigger": { "text": [ "interaction" ], "offsets": [ [ 739, 750 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "PMID-8454603_T9" } ] }, { "id": "PMID-8454603_E18", "type": "Binding", "trigger": { "text": [ "interaction" ], "offsets": [ [ 739, 750 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "PMID-8454603_T8" } ] }, { "id": "PMID-8454603_E19", "type": "Positive_regulation", "trigger": { "text": [ "necessary" ], "offsets": [ [ 952, 961 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "PMID-8454603_E20" } ] }, { "id": "PMID-8454603_E20", "type": "Gene_expression", "trigger": { "text": [ "expression" ], "offsets": [ [ 978, 988 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "PMID-8454603_T14" } ] }, { "id": "PMID-8454603_E21", "type": "Positive_regulation", "trigger": { "text": [ "activation" ], "offsets": [ [ 1047, 1057 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "PMID-8454603_T15" } ] }, { "id": "PMID-8454603_E22", "type": "Positive_regulation", "trigger": { "text": [ "augment" ], "offsets": [ [ 1130, 1137 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "PMID-8454603_E23" } ] }, { "id": "PMID-8454603_E23", "type": "Gene_expression", "trigger": { "text": [ "expression" ], "offsets": [ [ 1154, 1164 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "PMID-8454603_T17" } ] }, { "id": "PMID-8454603_E24", "type": "Regulation", "trigger": { "text": [ "regulation" ], "offsets": [ [ 1282, 1292 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "PMID-8454603_E25" } ] }, { "id": "PMID-8454603_E25", "type": "Gene_expression", "trigger": { "text": [ "expression" ], "offsets": [ [ 1305, 1315 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "PMID-8454603_T18" } ] } ]

[ { "id": "PMID-8454603_1", "entity_ids": [ "PMID-8454603_T2", "PMID-8454603_T1" ] }, { "id": "PMID-8454603_2", "entity_ids": [ "PMID-8454603_T5", "PMID-8454603_T4" ] } ]

[]

[ { "id": "PMID-8455611__text", "type": "abstract", "text": [ "Transcriptional activation of human zeta 2 globin promoter by the alpha globin regulatory element (HS-40): functional role of specific nuclear factor-DNA complexes. \nWe studied the functional interaction between human embryonic zeta 2 globin promoter and the alpha globin regulatory element (HS-40) located 40 kb upstream of the zeta 2 globin gene. It was shown by transient expression assay that HS-40 behaved as an authentic enhancer for high-level zeta 2 globin promoter activity in K562 cells, an erythroid cell line of embryonic and/or fetal origin. Although sequences located between -559 and -88 of the zeta 2 globin gene were dispensable for its expression on enhancerless plasmids, they were required for the HS-40 enhancer-mediated activity of the zeta 2 globin promoter. Site-directed mutagenesis demonstrated that this HS-40 enhancer-zeta 2 globin promoter interaction is mediated by the two GATA-1 factor binding motifs located at -230 and -104, respectively. The functional domains of HS-40 were also mapped. Bal 31 deletion mapping data suggested that one GATA-1 motif, one GT motif, and two NF-E2/AP1 motifs together formed the functional core of HS-40 in the erythroid-specific activation of the zeta 2 globin promoter. Site-directed mutagenesis further demonstrated that the enhancer function of one of the two NF-E2/AP1 motifs of HS-40 is mediated through its binding to NF-E2 but not AP1 transcription factor. Finally, we did genomic footprinting of the HS-40 enhancer region in K562 cells, adult nucleated erythroblasts, and different nonerythroid cells. All sequence motifs within the functional core of HS-40, as mapped by transient expression analysis, appeared to bind a nuclear factor(s) in living K562 cells but not in nonerythroid cells. On the other hand, only one of the apparently nonfunctional sequence motifs was bound with factors in vivo. In comparison to K562, nucleated erythroblasts from adult human bone marrow exhibited a similar but nonidentical pattern of nuclear factor binding in vivo at the HS-40 region. These data suggest that transcriptional activation of human embryonic zeta 2 globin gene and the fetal/adult alpha globin genes is mediated by erythroid cell-specific and developmental stage-specific nuclear factor-DNA complexes which form at the enhancer (HS-40) and the globin promoters. " ], "offsets": [ [ 0, 2340 ] ] } ]

[ { "id": "PMID-8455611_T1", "type": "Protein", "text": [ "zeta 2 globin" ], "offsets": [ [ 36, 49 ] ], "normalized": [] }, { "id": "PMID-8455611_T2", "type": "Protein", "text": [ "alpha globin" ], "offsets": [ [ 66, 78 ] ], "normalized": [] }, { "id": "PMID-8455611_T3", "type": "Protein", "text": [ "zeta 2 globin" ], "offsets": [ [ 228, 241 ] ], "normalized": [] }, { "id": "PMID-8455611_T4", "type": "Protein", "text": [ "alpha globin" ], "offsets": [ [ 259, 271 ] ], "normalized": [] }, { "id": "PMID-8455611_T5", "type": "Protein", "text": [ "zeta 2 globin" ], "offsets": [ [ 329, 342 ] ], "normalized": [] }, { "id": "PMID-8455611_T6", "type": "Protein", "text": [ "zeta 2 globin" ], "offsets": [ [ 451, 464 ] ], "normalized": [] }, { "id": "PMID-8455611_T7", "type": "Protein", "text": [ "zeta 2 globin" ], "offsets": [ [ 610, 623 ] ], "normalized": [] }, { "id": "PMID-8455611_T8", "type": "Protein", "text": [ "zeta 2 globin" ], "offsets": [ [ 758, 771 ] ], "normalized": [] }, { "id": "PMID-8455611_T9", "type": "Protein", "text": [ "zeta 2 globin" ], "offsets": [ [ 846, 859 ] ], "normalized": [] }, { "id": "PMID-8455611_T10", "type": "Protein", "text": [ "GATA-1" ], "offsets": [ [ 904, 910 ] ], "normalized": [] }, { "id": "PMID-8455611_T11", "type": "Protein", "text": [ "GATA-1" ], "offsets": [ [ 1071, 1077 ] ], "normalized": [] }, { "id": "PMID-8455611_T12", "type": "Protein", "text": [ "zeta 2 globin" ], "offsets": [ [ 1213, 1226 ] ], "normalized": [] }, { "id": "PMID-8455611_T13", "type": "Protein", "text": [ "zeta 2 globin" ], "offsets": [ [ 2120, 2133 ] ], "normalized": [] }, { "id": "PMID-8455611_T14", "type": "Protein", "text": [ "alpha globin" ], "offsets": [ [ 2159, 2171 ] ], "normalized": [] }, { "id": "PMID-8455611_T16", "type": "Entity", "text": [ "promoter" ], "offsets": [ [ 50, 58 ] ], "normalized": [] }, { "id": "PMID-8455611_T18", "type": "Entity", "text": [ "promoter" ], "offsets": [ [ 465, 473 ] ], "normalized": [] }, { "id": "PMID-8455611_T24", "type": "Entity", "text": [ "promoter" ], "offsets": [ [ 772, 780 ] ], "normalized": [] }, { "id": "PMID-8455611_T27", "type": "Entity", "text": [ "promoter" ], "offsets": [ [ 1227, 1235 ] ], "normalized": [] } ]

[ { "id": "PMID-8455611_E1", "type": "Positive_regulation", "trigger": { "text": [ "Transcriptional activation" ], "offsets": [ [ 0, 26 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "PMID-8455611_T1" }, { "role": "Site", "ref_id": "PMID-8455611_T16" } ] }, { "id": "PMID-8455611_E2", "type": "Positive_regulation", "trigger": { "text": [ "behaved as an authentic enhancer" ], "offsets": [ [ 403, 435 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "PMID-8455611_T6" }, { "role": "Site", "ref_id": "PMID-8455611_T18" } ] }, { "id": "PMID-8455611_E3", "type": "Positive_regulation", "trigger": { "text": [ "dispensable" ], "offsets": [ [ 634, 645 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "PMID-8455611_E4" } ] }, { "id": "PMID-8455611_E4", "type": "Gene_expression", "trigger": { "text": [ "expression" ], "offsets": [ [ 654, 664 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "PMID-8455611_T7" } ] }, { "id": "PMID-8455611_E5", "type": "Positive_regulation", "trigger": { "text": [ "required" ], "offsets": [ [ 701, 709 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "PMID-8455611_E6" } ] }, { "id": "PMID-8455611_E6", "type": "Positive_regulation", "trigger": { "text": [ "mediated" ], "offsets": [ [ 733, 741 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "PMID-8455611_E7" } ] }, { "id": "PMID-8455611_E7", "type": "Regulation", "trigger": { "text": [ "activity" ], "offsets": [ [ 742, 750 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "PMID-8455611_T8" }, { "role": "Site", "ref_id": "PMID-8455611_T24" } ] }, { "id": "PMID-8455611_E8", "type": "Regulation", "trigger": { "text": [ "formed the functional core" ], "offsets": [ [ 1133, 1159 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "PMID-8455611_E9" } ] }, { "id": "PMID-8455611_E9", "type": "Positive_regulation", "trigger": { "text": [ "activation" ], "offsets": [ [ 1195, 1205 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "PMID-8455611_T12" }, { "role": "Site", "ref_id": "PMID-8455611_T27" } ] }, { "id": "PMID-8455611_E10", "type": "Transcription", "trigger": { "text": [ "transcriptional" ], "offsets": [ [ 2074, 2089 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "PMID-8455611_T13" } ] }, { "id": "PMID-8455611_E11", "type": "Transcription", "trigger": { "text": [ "transcriptional" ], "offsets": [ [ 2074, 2089 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "PMID-8455611_T14" } ] }, { "id": "PMID-8455611_E12", "type": "Positive_regulation", "trigger": { "text": [ "activation" ], "offsets": [ [ 2090, 2100 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "PMID-8455611_E10" } ] }, { "id": "PMID-8455611_E13", "type": "Positive_regulation", "trigger": { "text": [ "activation" ], "offsets": [ [ 2090, 2100 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "PMID-8455611_E11" } ] }, { "id": "PMID-8455611_E14", "type": "Positive_regulation", "trigger": { "text": [ "mediated" ], "offsets": [ [ 2181, 2189 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "PMID-8455611_E12" } ] }, { "id": "PMID-8455611_E15", "type": "Positive_regulation", "trigger": { "text": [ "mediated" ], "offsets": [ [ 2181, 2189 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "PMID-8455611_E13" } ] } ]

[]

[]

[ { "id": "PMID-8468462__text", "type": "abstract", "text": [ "Costimulation of peripheral blood T cell activation by human endothelial cells. Enhanced IL-2 transcription correlates with increased c-fos synthesis and increased Fos content of AP-1. \nEndothelial cells (EC) act as APC for resting PBL in vitro, and may have important roles in vivo in the pathogenesis of allograft rejection and delayed hypersensitivity. We previously reported that human umbilical vein EC provide costimulatory signals to PHA-stimulated PBL via CD2:lymphocyte function-associated Ag-3 and an unidentified ligand pair, resulting in a three- to eight-fold enhancement of IL-2 production. The physiologic relevance of this increase was demonstrated by the proliferative advantage provided by EC to PBL suboptimally stimulated with mAb OKT3. We now report that EC costimulation causes increased levels of IL-2 mRNA as a result of increased IL-2 transcription in PBL. We therefore examined the effects of EC on T cell nuclear factors known to regulate IL-2 transcription, including c-jun and c-fos-two components of the transcription factor AP-1, NFAT, and others. PBL constitutively express c-jun transcripts, and the level of c-jun mRNA is not altered by PHA activation in the absence or presence of EC. In contrast, c-fos mRNA is absent from resting T cells and is induced on PHA activation. EC alone do not induce c-fos mRNA but augment the level of c-fos mRNA in PHA-activated T cells by 3- to 10-fold. This effect is largely independent of the CD2:lymphocyte function-associated Ag-3 pathway. Gel-shift analysis reveals the constitutive presence of nuclear factors in resting PBL that bind to the proximal AP-1 site of the IL-2 promoter and that contain immunoreactive c-Jun but not c-Fos protein. In contrast, AP-1 from PHA-activated cells contains c-Jun and low levels of c-Fos. Strikingly, costimulation with EC results in a dramatic increase (up to 15-fold) in the c-Fos content of AP-1. Levels of other nuclear factors involved in IL-2 regulation were not altered by EC, although NFAT-DNA complexes migrated at a slightly different mobility. In summary, our data suggest that changes in the composition of transcription factor AP-1 is a key molecular mechanism for increasing IL-2 transcription and may underlie the phenomenon of costimulation by EC. " ], "offsets": [ [ 0, 2276 ] ] } ]

[ { "id": "PMID-8468462_T1", "type": "Protein", "text": [ "IL-2" ], "offsets": [ [ 89, 93 ] ], "normalized": [] }, { "id": "PMID-8468462_T2", "type": "Protein", "text": [ "c-fos" ], "offsets": [ [ 134, 139 ] ], "normalized": [] }, { "id": "PMID-8468462_T3", "type": "Protein", "text": [ "PHA" ], "offsets": [ [ 441, 444 ] ], "normalized": [] }, { "id": "PMID-8468462_T4", "type": "Protein", "text": [ "CD2" ], "offsets": [ [ 464, 467 ] ], "normalized": [] }, { "id": "PMID-8468462_T5", "type": "Protein", "text": [ "lymphocyte function-associated Ag-3" ], "offsets": [ [ 468, 503 ] ], "normalized": [] }, { "id": "PMID-8468462_T6", "type": "Protein", "text": [ "IL-2" ], "offsets": [ [ 588, 592 ] ], "normalized": [] }, { "id": "PMID-8468462_T7", "type": "Protein", "text": [ "IL-2" ], "offsets": [ [ 820, 824 ] ], "normalized": [] }, { "id": "PMID-8468462_T8", "type": "Protein", "text": [ "IL-2" ], "offsets": [ [ 855, 859 ] ], "normalized": [] }, { "id": "PMID-8468462_T9", "type": "Protein", "text": [ "IL-2" ], "offsets": [ [ 966, 970 ] ], "normalized": [] }, { "id": "PMID-8468462_T10", "type": "Protein", "text": [ "c-jun" ], "offsets": [ [ 996, 1001 ] ], "normalized": [] }, { "id": "PMID-8468462_T11", "type": "Protein", "text": [ "c-fos" ], "offsets": [ [ 1006, 1011 ] ], "normalized": [] }, { "id": "PMID-8468462_T12", "type": "Protein", "text": [ "c-jun" ], "offsets": [ [ 1106, 1111 ] ], "normalized": [] }, { "id": "PMID-8468462_T13", "type": "Protein", "text": [ "c-jun" ], "offsets": [ [ 1142, 1147 ] ], "normalized": [] }, { "id": "PMID-8468462_T14", "type": "Protein", "text": [ "PHA" ], "offsets": [ [ 1171, 1174 ] ], "normalized": [] }, { "id": "PMID-8468462_T15", "type": "Protein", "text": [ "c-fos" ], "offsets": [ [ 1233, 1238 ] ], "normalized": [] }, { "id": "PMID-8468462_T16", "type": "Protein", "text": [ "PHA" ], "offsets": [ [ 1293, 1296 ] ], "normalized": [] }, { "id": "PMID-8468462_T17", "type": "Protein", "text": [ "c-fos" ], "offsets": [ [ 1332, 1337 ] ], "normalized": [] }, { "id": "PMID-8468462_T18", "type": "Protein", "text": [ "c-fos" ], "offsets": [ [ 1368, 1373 ] ], "normalized": [] }, { "id": "PMID-8468462_T19", "type": "Protein", "text": [ "PHA" ], "offsets": [ [ 1382, 1385 ] ], "normalized": [] }, { "id": "PMID-8468462_T20", "type": "Protein", "text": [ "CD2" ], "offsets": [ [ 1464, 1467 ] ], "normalized": [] }, { "id": "PMID-8468462_T21", "type": "Protein", "text": [ "lymphocyte function-associated Ag-3" ], "offsets": [ [ 1468, 1503 ] ], "normalized": [] }, { "id": "PMID-8468462_T22", "type": "Protein", "text": [ "IL-2" ], "offsets": [ [ 1643, 1647 ] ], "normalized": [] }, { "id": "PMID-8468462_T23", "type": "Protein", "text": [ "c-Jun" ], "offsets": [ [ 1689, 1694 ] ], "normalized": [] }, { "id": "PMID-8468462_T24", "type": "Protein", "text": [ "c-Fos" ], "offsets": [ [ 1703, 1708 ] ], "normalized": [] }, { "id": "PMID-8468462_T25", "type": "Protein", "text": [ "PHA" ], "offsets": [ [ 1741, 1744 ] ], "normalized": [] }, { "id": "PMID-8468462_T26", "type": "Protein", "text": [ "c-Jun" ], "offsets": [ [ 1770, 1775 ] ], "normalized": [] }, { "id": "PMID-8468462_T27", "type": "Protein", "text": [ "c-Fos" ], "offsets": [ [ 1794, 1799 ] ], "normalized": [] }, { "id": "PMID-8468462_T28", "type": "Protein", "text": [ "c-Fos" ], "offsets": [ [ 1889, 1894 ] ], "normalized": [] }, { "id": "PMID-8468462_T29", "type": "Protein", "text": [ "IL-2" ], "offsets": [ [ 1956, 1960 ] ], "normalized": [] }, { "id": "PMID-8468462_T30", "type": "Protein", "text": [ "IL-2" ], "offsets": [ [ 2201, 2205 ] ], "normalized": [] }, { "id": "PMID-8468462_T53", "type": "Entity", "text": [ "proximal AP-1 site" ], "offsets": [ [ 1617, 1635 ] ], "normalized": [] } ]

[ { "id": "PMID-8468462_E1", "type": "Positive_regulation", "trigger": { "text": [ "Enhanced" ], "offsets": [ [ 80, 88 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "PMID-8468462_E2" } ] }, { "id": "PMID-8468462_E2", "type": "Transcription", "trigger": { "text": [ "transcription" ], "offsets": [ [ 94, 107 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "PMID-8468462_T1" } ] }, { "id": "PMID-8468462_E3", "type": "Binding", "trigger": { "text": [ "content of AP-1" ], "offsets": [ [ 168, 183 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "PMID-8468462_T5" } ] }, { "id": "PMID-8468462_E4", "type": "Positive_regulation", "trigger": { "text": [ "provide costimulatory signals" ], "offsets": [ [ 408, 437 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "PMID-8468462_E7" } ] }, { "id": "PMID-8468462_E5", "type": "Positive_regulation", "trigger": { "text": [ "provide costimulatory signals" ], "offsets": [ [ 408, 437 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "PMID-8468462_E6" } ] }, { "id": "PMID-8468462_E6", "type": "Binding", "trigger": { "text": [ ":" ], "offsets": [ [ 467, 468 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "PMID-8468462_T4" }, { "role": "Theme", "ref_id": "PMID-8468462_T5" } ] }, { "id": "PMID-8468462_E7", "type": "Binding", "trigger": { "text": [ "pair" ], "offsets": [ [ 531, 535 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "PMID-8468462_T4" } ] }, { "id": "PMID-8468462_E8", "type": "Positive_regulation", "trigger": { "text": [ "enhancement" ], "offsets": [ [ 573, 584 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "PMID-8468462_E9" } ] }, { "id": "PMID-8468462_E9", "type": "Gene_expression", "trigger": { "text": [ "production" ], "offsets": [ [ 593, 603 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "PMID-8468462_T6" } ] }, { "id": "PMID-8468462_E10", "type": "Positive_regulation", "trigger": { "text": [ "causes" ], "offsets": [ [ 793, 799 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "PMID-8468462_E11" }, { "role": "Cause", "ref_id": "PMID-8468462_E12" } ] }, { "id": "PMID-8468462_E11", "type": "Positive_regulation", "trigger": { "text": [ "increased" ], "offsets": [ [ 800, 809 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "PMID-8468462_T7" } ] }, { "id": "PMID-8468462_E12", "type": "Positive_regulation", "trigger": { "text": [ "increased" ], "offsets": [ [ 845, 854 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "PMID-8468462_E13" } ] }, { "id": "PMID-8468462_E13", "type": "Transcription", "trigger": { "text": [ "transcription" ], "offsets": [ [ 860, 873 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "PMID-8468462_T8" } ] }, { "id": "PMID-8468462_E14", "type": "Regulation", "trigger": { "text": [ "effects" ], "offsets": [ [ 908, 915 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "PMID-8468462_T10" } ] }, { "id": "PMID-8468462_E15", "type": "Regulation", "trigger": { "text": [ "effects" ], "offsets": [ [ 908, 915 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "PMID-8468462_T11" } ] }, { "id": "PMID-8468462_E16", "type": "Regulation", "trigger": { "text": [ "regulate" ], "offsets": [ [ 957, 965 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "PMID-8468462_E18" }, { "role": "Cause", "ref_id": "PMID-8468462_T11" } ] }, { "id": "PMID-8468462_E17", "type": "Regulation", "trigger": { "text": [ "regulate" ], "offsets": [ [ 957, 965 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "PMID-8468462_E18" }, { "role": "Cause", "ref_id": "PMID-8468462_T10" } ] }, { "id": "PMID-8468462_E18", "type": "Transcription", "trigger": { "text": [ "transcription" ], "offsets": [ [ 971, 984 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "PMID-8468462_T9" } ] }, { "id": "PMID-8468462_E19", "type": "Gene_expression", "trigger": { "text": [ "express" ], "offsets": [ [ 1098, 1105 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "PMID-8468462_T12" } ] }, { "id": "PMID-8468462_E20", "type": "Regulation", "trigger": { "text": [ "altered" ], "offsets": [ [ 1160, 1167 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "PMID-8468462_T13" } ] }, { "id": "PMID-8468462_E21", "type": "Transcription", "trigger": { "text": [ "absent" ], "offsets": [ [ 1247, 1253 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "PMID-8468462_T15" } ] }, { "id": "PMID-8468462_E22", "type": "Positive_regulation", "trigger": { "text": [ "induced" ], "offsets": [ [ 1282, 1289 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "PMID-8468462_T15" } ] }, { "id": "PMID-8468462_E23", "type": "Positive_regulation", "trigger": { "text": [ "induce" ], "offsets": [ [ 1325, 1331 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "PMID-8468462_T17" } ] }, { "id": "PMID-8468462_E24", "type": "Positive_regulation", "trigger": { "text": [ "augment" ], "offsets": [ [ 1347, 1354 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "PMID-8468462_T18" } ] }, { "id": "PMID-8468462_E25", "type": "Binding", "trigger": { "text": [ "bind" ], "offsets": [ [ 1605, 1609 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "PMID-8468462_T22" }, { "role": "Site", "ref_id": "PMID-8468462_T53" } ] }, { "id": "PMID-8468462_E26", "type": "Regulation", "trigger": { "text": [ "involved" ], "offsets": [ [ 1944, 1952 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "PMID-8468462_E27" } ] }, { "id": "PMID-8468462_E27", "type": "Regulation", "trigger": { "text": [ "regulation" ], "offsets": [ [ 1961, 1971 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "PMID-8468462_T29" } ] }, { "id": "PMID-8468462_E28", "type": "Regulation", "trigger": { "text": [ "is a key molecular mechanism" ], "offsets": [ [ 2157, 2185 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "PMID-8468462_E29" }, { "role": "Cause", "ref_id": "PMID-8468462_E30" } ] }, { "id": "PMID-8468462_E29", "type": "Positive_regulation", "trigger": { "text": [ "increasing" ], "offsets": [ [ 2190, 2200 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "PMID-8468462_E30" } ] }, { "id": "PMID-8468462_E30", "type": "Transcription", "trigger": { "text": [ "transcription" ], "offsets": [ [ 2206, 2219 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "PMID-8468462_T30" } ] } ]

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[]

[ { "id": "PMID-8473495__text", "type": "abstract", "text": [ "Negative transcriptional regulation of human interleukin 2 (IL-2) gene by glucocorticoids through interference with nuclear transcription factors AP-1 and NF-AT. \nIL-2 gene transcription is affected by several nuclear proteins. We asked whether dexamethasone (Dex) and cyclosporin A (CsA) inhibit IL-2 gene transcription by interfering with the activity of nuclear proteins that bind to the IL-2 promoter. Nuclear extracts from primary human T lymphocytes were analyzed by electrophoretic DNA mobility shift assays. Both Dex and CsA inhibited the binding of transcription factors AP-1 and NF-AT, but not of NF-kB and OCT-1/OAF, to their corresponding sites on the IL-2 gene promoter. To correlate changes in nuclear factor binding in vitro with transcriptional activity in vivo and define the structural requirements for IL-2 promoter repression, we used transient DNA transfections. Jurkat cells were transfected with plasmids containing either the intact IL-2 promoter or its AP-1, NF-AT, and NF-kB motifs. Dex inhibited the IL-2 promoter and the AP-1, but not the NF-AT and NF-kB plasmids. In contrast, CsA inhibited the IL-2 promoter and the NF-AT, but not the AP-1 and NF-kB plasmids. These results suggest that in human T lymphocytes both Dex and CsA inhibited IL-2 gene transcription through interference with transcription factors AP-1 and NF-AT. We propose that, while maximum inhibition may involve interaction with both transcription factors, AP-1 is the primary target of Dex. " ], "offsets": [ [ 0, 1489 ] ] } ]

[ { "id": "PMID-8473495_T1", "type": "Protein", "text": [ "interleukin 2" ], "offsets": [ [ 45, 58 ] ], "normalized": [] }, { "id": "PMID-8473495_T2", "type": "Protein", "text": [ "IL-2" ], "offsets": [ [ 60, 64 ] ], "normalized": [] }, { "id": "PMID-8473495_T3", "type": "Protein", "text": [ "IL-2" ], "offsets": [ [ 163, 167 ] ], "normalized": [] }, { "id": "PMID-8473495_T4", "type": "Protein", "text": [ "IL-2" ], "offsets": [ [ 297, 301 ] ], "normalized": [] }, { "id": "PMID-8473495_T5", "type": "Protein", "text": [ "IL-2" ], "offsets": [ [ 391, 395 ] ], "normalized": [] }, { "id": "PMID-8473495_T6", "type": "Protein", "text": [ "IL-2" ], "offsets": [ [ 664, 668 ] ], "normalized": [] }, { "id": "PMID-8473495_T7", "type": "Protein", "text": [ "IL-2" ], "offsets": [ [ 821, 825 ] ], "normalized": [] }, { "id": "PMID-8473495_T8", "type": "Protein", "text": [ "IL-2" ], "offsets": [ [ 957, 961 ] ], "normalized": [] }, { "id": "PMID-8473495_T9", "type": "Protein", "text": [ "IL-2" ], "offsets": [ [ 1027, 1031 ] ], "normalized": [] }, { "id": "PMID-8473495_T10", "type": "Protein", "text": [ "IL-2" ], "offsets": [ [ 1124, 1128 ] ], "normalized": [] }, { "id": "PMID-8473495_T11", "type": "Protein", "text": [ "IL-2" ], "offsets": [ [ 1267, 1271 ] ], "normalized": [] }, { "id": "PMID-8473495_T18", "type": "Entity", "text": [ "promoter" ], "offsets": [ [ 396, 404 ] ], "normalized": [] }, { "id": "PMID-8473495_T21", "type": "Entity", "text": [ "their corresponding sites" ], "offsets": [ [ 631, 656 ] ], "normalized": [] }, { "id": "PMID-8473495_T23", "type": "Entity", "text": [ "promoter" ], "offsets": [ [ 826, 834 ] ], "normalized": [] } ]

[ { "id": "PMID-8473495_E1", "type": "Negative_regulation", "trigger": { "text": [ "Negative transcriptional regulation" ], "offsets": [ [ 0, 35 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "PMID-8473495_T2" } ] }, { "id": "PMID-8473495_E2", "type": "Transcription", "trigger": { "text": [ "transcription" ], "offsets": [ [ 173, 186 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "PMID-8473495_T3" } ] }, { "id": "PMID-8473495_E3", "type": "Regulation", "trigger": { "text": [ "affected" ], "offsets": [ [ 190, 198 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "PMID-8473495_E2" } ] }, { "id": "PMID-8473495_E4", "type": "Negative_regulation", "trigger": { "text": [ "inhibit" ], "offsets": [ [ 289, 296 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "PMID-8473495_E5" } ] }, { "id": "PMID-8473495_E5", "type": "Transcription", "trigger": { "text": [ "transcription" ], "offsets": [ [ 307, 320 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "PMID-8473495_T4" } ] }, { "id": "PMID-8473495_E6", "type": "Binding", "trigger": { "text": [ "bind" ], "offsets": [ [ 379, 383 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "PMID-8473495_T5" }, { "role": "Site", "ref_id": "PMID-8473495_T18" } ] }, { "id": "PMID-8473495_E7", "type": "Negative_regulation", "trigger": { "text": [ "inhibited" ], "offsets": [ [ 533, 542 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "PMID-8473495_E8" } ] }, { "id": "PMID-8473495_E8", "type": "Binding", "trigger": { "text": [ "binding" ], "offsets": [ [ 547, 554 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "PMID-8473495_T6" }, { "role": "Site", "ref_id": "PMID-8473495_T21" } ] }, { "id": "PMID-8473495_E9", "type": "Positive_regulation", "trigger": { "text": [ "requirements" ], "offsets": [ [ 804, 816 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "PMID-8473495_E10" } ] }, { "id": "PMID-8473495_E10", "type": "Negative_regulation", "trigger": { "text": [ "repression" ], "offsets": [ [ 835, 845 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "PMID-8473495_T7" }, { "role": "Site", "ref_id": "PMID-8473495_T23" } ] }, { "id": "PMID-8473495_E11", "type": "Negative_regulation", "trigger": { "text": [ "inhibited" ], "offsets": [ [ 1013, 1022 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "PMID-8473495_T9" } ] }, { "id": "PMID-8473495_E12", "type": "Negative_regulation", "trigger": { "text": [ "inhibited" ], "offsets": [ [ 1110, 1119 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "PMID-8473495_T10" } ] }, { "id": "PMID-8473495_E13", "type": "Negative_regulation", "trigger": { "text": [ "inhibited" ], "offsets": [ [ 1257, 1266 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "PMID-8473495_E14" } ] }, { "id": "PMID-8473495_E14", "type": "Transcription", "trigger": { "text": [ "transcription" ], "offsets": [ [ 1277, 1290 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "PMID-8473495_T11" } ] }, { "id": "PMID-8473495_E15", "type": "Negative_regulation", "trigger": { "text": [ "inhibition" ], "offsets": [ [ 1386, 1396 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "PMID-8473495_E14" } ] }, { "id": "PMID-8473495_E16", "type": "Positive_regulation", "trigger": { "text": [ "involve" ], "offsets": [ [ 1401, 1408 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "PMID-8473495_E15" } ] } ]

[ { "id": "PMID-8473495_1", "entity_ids": [ "PMID-8473495_T2", "PMID-8473495_T1" ] } ]

[]

[ { "id": "PMID-8479911__text", "type": "abstract", "text": [ "Cell-specific expression of helix-loop-helix transcription factors encoded by the E2A gene. \nThe E2A gene encodes transcription factors of the helix-loop-helix family that are implicated in cell-specific gene expression as part of dimeric complexes that interact with E box enhancer elements. It has previously been shown that transcripts of the E2A gene can be detected in a wide range of cell types. We have now examined expression of the mouse E2A gene at the protein level using polyclonal antisera directed against distinct portions of the E2A protein to probe blots of cellular extracts. A 73 kDa protein was identified by this analysis: this protein is highly enriched in cell lines of B lymphoid origin as compared to pancreatic beta-cells and fibroblast cells. The detection of this protein selectively in extracts of lymphoid cells correlates with the presence of the E box-binding activity LEF1/BCF1 in these cells; this binding activity was previously shown to be efficiently recognized by antiserum directed against E2A gene products. Transfection of cells with full length E2A cDNA leads to appearance of protein co-migrating with the 73 kDa protein on SDS gel electrophoresis and co-migrating with LEF1/BCF1 on mobility shift analysis. Our results are consistent with the view that the DNA-binding activity LEF1/BCF1 is a homodimer of E2A proteins; the selective appearance of this putative cell-specific transcription factor in B lymphoid cells seems to be attributable, at least in part, to the elevated E2A protein concentrations in these cells. " ], "offsets": [ [ 0, 1564 ] ] } ]

[ { "id": "PMID-8479911_T1", "type": "Protein", "text": [ "E2A" ], "offsets": [ [ 82, 85 ] ], "normalized": [] }, { "id": "PMID-8479911_T2", "type": "Protein", "text": [ "E2A" ], "offsets": [ [ 97, 100 ] ], "normalized": [] }, { "id": "PMID-8479911_T3", "type": "Protein", "text": [ "E2A" ], "offsets": [ [ 346, 349 ] ], "normalized": [] }, { "id": "PMID-8479911_T4", "type": "Protein", "text": [ "E2A" ], "offsets": [ [ 447, 450 ] ], "normalized": [] }, { "id": "PMID-8479911_T5", "type": "Protein", "text": [ "E2A" ], "offsets": [ [ 545, 548 ] ], "normalized": [] }, { "id": "PMID-8479911_T6", "type": "Protein", "text": [ "E2A" ], "offsets": [ [ 1029, 1032 ] ], "normalized": [] }, { "id": "PMID-8479911_T7", "type": "Protein", "text": [ "E2A" ], "offsets": [ [ 1087, 1090 ] ], "normalized": [] }, { "id": "PMID-8479911_T8", "type": "Protein", "text": [ "E2A" ], "offsets": [ [ 1350, 1353 ] ], "normalized": [] }, { "id": "PMID-8479911_T9", "type": "Protein", "text": [ "E2A" ], "offsets": [ [ 1521, 1524 ] ], "normalized": [] } ]

[ { "id": "PMID-8479911_E1", "type": "Gene_expression", "trigger": { "text": [ "expression" ], "offsets": [ [ 14, 24 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "PMID-8479911_T1" } ] }, { "id": "PMID-8479911_E2", "type": "Gene_expression", "trigger": { "text": [ "detected" ], "offsets": [ [ 362, 370 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "PMID-8479911_T3" } ] }, { "id": "PMID-8479911_E3", "type": "Gene_expression", "trigger": { "text": [ "expression" ], "offsets": [ [ 423, 433 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "PMID-8479911_T4" } ] }, { "id": "PMID-8479911_E4", "type": "Gene_expression", "trigger": { "text": [ "Transfection" ], "offsets": [ [ 1048, 1060 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "PMID-8479911_T7" } ] }, { "id": "PMID-8479911_E5", "type": "Positive_regulation", "trigger": { "text": [ "Transfection" ], "offsets": [ [ 1048, 1060 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "PMID-8479911_E4" } ] }, { "id": "PMID-8479911_E6", "type": "Binding", "trigger": { "text": [ "binding activity" ], "offsets": [ [ 1305, 1321 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "PMID-8479911_T8" } ] }, { "id": "PMID-8479911_E7", "type": "Gene_expression", "trigger": { "text": [ "appearance" ], "offsets": [ [ 1378, 1388 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "PMID-8479911_T8" } ] }, { "id": "PMID-8479911_E8", "type": "Positive_regulation", "trigger": { "text": [ "attributable" ], "offsets": [ [ 1473, 1485 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "PMID-8479911_E9" }, { "role": "Cause", "ref_id": "PMID-8479911_E7" } ] }, { "id": "PMID-8479911_E9", "type": "Positive_regulation", "trigger": { "text": [ "elevated" ], "offsets": [ [ 1512, 1520 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "PMID-8479911_T9" } ] } ]

[]

[]

[ { "id": "PMID-8480425__text", "type": "abstract", "text": [ "HIV-1 Nef protein inhibits the recruitment of AP-1 DNA-binding activity in human T-cells. \nThe human immunodeficiency virus type 1 long terminal repeat, HIV-1-LTR, contains binding sites for several cellular transcription factors which contribute to HIV-1 gene expression. Our previous studies on the function of the HIV-1-encoded Nef protein suggested that Nef may be an inhibitor HIV-1 transcription. To determine whether Nef affects the binding of cellular factors implicated in HIV-1 regulation, 32P-labeled oligonucleotides corresponding to the binding sites were incubated with nuclear extracts prepared from Nef-expressing T-cell lines that were not stimulated or were stimulated with T-cell mitogens. We found that Nef inhibited the recruitment of AP-1 DNA-binding activity in mitogen-stimulated human T-cells. Additionally, Nef expressing cells were transiently transfected with a plasmid in which HIV-1 AP-1 DNA recognition sequences were cloned downstream of the chloramphenicol acetyltransferase (CAT) gene. Mitogen-mediated transcriptional activation of the CAT gene in this construct was inhibited in Nef-expressing cells but not in control cells. These studies suggest that, by inhibiting AP-1 activation, Nef may play a role in regulating HIV-1 gene expression in infected T-cells. " ], "offsets": [ [ 0, 1298 ] ] } ]

[ { "id": "PMID-8480425_T1", "type": "Protein", "text": [ "Nef" ], "offsets": [ [ 6, 9 ] ], "normalized": [] }, { "id": "PMID-8480425_T2", "type": "Protein", "text": [ "Nef" ], "offsets": [ [ 331, 334 ] ], "normalized": [] }, { "id": "PMID-8480425_T3", "type": "Protein", "text": [ "Nef" ], "offsets": [ [ 358, 361 ] ], "normalized": [] }, { "id": "PMID-8480425_T4", "type": "Protein", "text": [ "Nef" ], "offsets": [ [ 424, 427 ] ], "normalized": [] }, { "id": "PMID-8480425_T5", "type": "Protein", "text": [ "Nef" ], "offsets": [ [ 615, 618 ] ], "normalized": [] }, { "id": "PMID-8480425_T6", "type": "Protein", "text": [ "Nef" ], "offsets": [ [ 723, 726 ] ], "normalized": [] }, { "id": "PMID-8480425_T7", "type": "Protein", "text": [ "Nef" ], "offsets": [ [ 833, 836 ] ], "normalized": [] }, { "id": "PMID-8480425_T8", "type": "Protein", "text": [ "chloramphenicol acetyltransferase" ], "offsets": [ [ 974, 1007 ] ], "normalized": [] }, { "id": "PMID-8480425_T9", "type": "Protein", "text": [ "CAT" ], "offsets": [ [ 1009, 1012 ] ], "normalized": [] }, { "id": "PMID-8480425_T10", "type": "Protein", "text": [ "CAT" ], "offsets": [ [ 1071, 1074 ] ], "normalized": [] }, { "id": "PMID-8480425_T11", "type": "Protein", "text": [ "Nef" ], "offsets": [ [ 1115, 1118 ] ], "normalized": [] }, { "id": "PMID-8480425_T12", "type": "Protein", "text": [ "Nef" ], "offsets": [ [ 1221, 1224 ] ], "normalized": [] } ]

[ { "id": "PMID-8480425_E1", "type": "Gene_expression", "trigger": { "text": [ "expressing" ], "offsets": [ [ 619, 629 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "PMID-8480425_T5" } ] }, { "id": "PMID-8480425_E2", "type": "Gene_expression", "trigger": { "text": [ "expressing" ], "offsets": [ [ 837, 847 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "PMID-8480425_T7" } ] }, { "id": "PMID-8480425_E3", "type": "Transcription", "trigger": { "text": [ "transcriptional" ], "offsets": [ [ 1037, 1052 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "PMID-8480425_T10" } ] }, { "id": "PMID-8480425_E4", "type": "Positive_regulation", "trigger": { "text": [ "activation" ], "offsets": [ [ 1053, 1063 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "PMID-8480425_E3" } ] }, { "id": "PMID-8480425_E5", "type": "Negative_regulation", "trigger": { "text": [ "inhibited" ], "offsets": [ [ 1102, 1111 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "PMID-8480425_E4" } ] }, { "id": "PMID-8480425_E6", "type": "Gene_expression", "trigger": { "text": [ "expressing" ], "offsets": [ [ 1119, 1129 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "PMID-8480425_T11" } ] } ]

[ { "id": "PMID-8480425_1", "entity_ids": [ "PMID-8480425_T8", "PMID-8480425_T9" ] } ]

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[ { "id": "PMID-8491377__text", "type": "abstract", "text": [ "Cloning and functional characterization of early B-cell factor, a regulator of lymphocyte-specific gene expression. \nEarly B-cell factor (EBF) was identified previously as a tissue-specific and differentiation stage-specific DNA-binding protein that participates in the regulation of the pre-B and B lymphocyte-specific mb-1 gene. Partial amino acid sequences obtained from purified EBF were used to isolate cDNA clones, which by multiple criteria encode EBF. The recombinant polypeptide formed sequence-specific complexes with the EBF-binding site in the mb-1 promoter. The cDNA hybridized to multiple transcripts in pre-B and B-cell lines, but transcripts were not detected at significant levels in plasmacytoma, T-cell, and nonlymphoid cell lines. Expression of recombinant EBF in transfected nonlymphoid cells strongly activated transcription from reporter plasmids containing functional EBF-binding sites. Analysis of DNA binding by deletion mutants of EBF identified an amino-terminal cysteine-rich DNA-binding domain lacking obvious sequence similarity to known transcription factors. DNA-binding assays with cotranslated wild-type and truncated forms of EBF indicated that the protein interacts with its site as a homodimer. Deletions delineated a carboxy-terminal dimerization region containing two repeats of 15 amino acids that show similarity with the dimerization domains of basic-helix-loop-helix proteins. Together, these data suggest that EBF represents a novel regulator of B lymphocyte-specific gene expression. " ], "offsets": [ [ 0, 1530 ] ] } ]

[ { "id": "PMID-8491377_T1", "type": "Protein", "text": [ "early B-cell factor" ], "offsets": [ [ 43, 62 ] ], "normalized": [] }, { "id": "PMID-8491377_T2", "type": "Protein", "text": [ "Early B-cell factor" ], "offsets": [ [ 117, 136 ] ], "normalized": [] }, { "id": "PMID-8491377_T3", "type": "Protein", "text": [ "EBF" ], "offsets": [ [ 138, 141 ] ], "normalized": [] }, { "id": "PMID-8491377_T4", "type": "Protein", "text": [ "mb-1" ], "offsets": [ [ 320, 324 ] ], "normalized": [] }, { "id": "PMID-8491377_T5", "type": "Protein", "text": [ "EBF" ], "offsets": [ [ 383, 386 ] ], "normalized": [] }, { "id": "PMID-8491377_T6", "type": "Protein", "text": [ "EBF" ], "offsets": [ [ 455, 458 ] ], "normalized": [] }, { "id": "PMID-8491377_T7", "type": "Protein", "text": [ "EBF" ], "offsets": [ [ 532, 535 ] ], "normalized": [] }, { "id": "PMID-8491377_T8", "type": "Protein", "text": [ "mb-1" ], "offsets": [ [ 556, 560 ] ], "normalized": [] }, { "id": "PMID-8491377_T9", "type": "Protein", "text": [ "EBF" ], "offsets": [ [ 777, 780 ] ], "normalized": [] }, { "id": "PMID-8491377_T10", "type": "Protein", "text": [ "EBF" ], "offsets": [ [ 892, 895 ] ], "normalized": [] }, { "id": "PMID-8491377_T11", "type": "Protein", "text": [ "EBF" ], "offsets": [ [ 958, 961 ] ], "normalized": [] }, { "id": "PMID-8491377_T12", "type": "Protein", "text": [ "EBF" ], "offsets": [ [ 1162, 1165 ] ], "normalized": [] }, { "id": "PMID-8491377_T13", "type": "Protein", "text": [ "EBF" ], "offsets": [ [ 1455, 1458 ] ], "normalized": [] } ]

[ { "id": "PMID-8491377_E1", "type": "Binding", "trigger": { "text": [ "binding protein" ], "offsets": [ [ 229, 244 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "PMID-8491377_T3" } ] }, { "id": "PMID-8491377_E2", "type": "Regulation", "trigger": { "text": [ "participates in the regulation" ], "offsets": [ [ 250, 280 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "PMID-8491377_T4" }, { "role": "Cause", "ref_id": "PMID-8491377_T3" } ] }, { "id": "PMID-8491377_E3", "type": "Transcription", "trigger": { "text": [ "The cDNA hybridized" ], "offsets": [ [ 571, 590 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "PMID-8491377_T6" } ] }, { "id": "PMID-8491377_E4", "type": "Transcription", "trigger": { "text": [ "detected" ], "offsets": [ [ 667, 675 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "PMID-8491377_T6" } ] }, { "id": "PMID-8491377_E5", "type": "Binding", "trigger": { "text": [ "interacts" ], "offsets": [ [ 1193, 1202 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "PMID-8491377_T12" } ] }, { "id": "PMID-8491377_E6", "type": "Binding", "trigger": { "text": [ "homodimer" ], "offsets": [ [ 1222, 1231 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "PMID-8491377_T12" } ] } ]

[ { "id": "PMID-8491377_1", "entity_ids": [ "PMID-8491377_T3", "PMID-8491377_T2" ] } ]

[]

[ { "id": "PMID-8493578__text", "type": "abstract", "text": [ "Regulation of the Ets-related transcription factor Elf-1 by binding to the retinoblastoma protein. \nThe retinoblastoma gene product (Rb) is a nuclear phosphoprotein that regulates cell cycle progression. Elf-1 is a lymphoid-specific Ets transcription factor that regulates inducible gene expression during T cell activation. In this report, it is demonstrated that Elf-1 contains a sequence motif that is highly related to the Rb binding sites of several viral oncoproteins and binds to the pocket region of Rb both in vitro and in vivo. Elf-1 binds exclusively to the underphosphorylated form of Rb and fails to bind to Rb mutants derived from patients with retinoblastoma. Co-immunoprecipitation experiments demonstrated an association between Elf-1 and Rb in resting normal human T cells. After T cell activation, the phosphorylation of Rb results in the release of Elf-1, which is correlated temporally with the activation of Elf-1-mediated transcription. Overexpression of a phosphorylation-defective form of Rb inhibited Elf-1-dependent transcription during T cell activation. These results demonstrate that Rb interacts specifically with a lineage-restricted Ets transcription factor. This regulated interaction may be important for the coordination of lineage-specific effector functions such as lymphokine production with cell cycle progression in activated T cells. " ], "offsets": [ [ 0, 1376 ] ] } ]

[ { "id": "PMID-8493578_T1", "type": "Protein", "text": [ "Elf-1" ], "offsets": [ [ 51, 56 ] ], "normalized": [] }, { "id": "PMID-8493578_T2", "type": "Protein", "text": [ "retinoblastoma protein" ], "offsets": [ [ 75, 97 ] ], "normalized": [] }, { "id": "PMID-8493578_T3", "type": "Protein", "text": [ "retinoblastoma" ], "offsets": [ [ 104, 118 ] ], "normalized": [] }, { "id": "PMID-8493578_T4", "type": "Protein", "text": [ "Rb" ], "offsets": [ [ 133, 135 ] ], "normalized": [] }, { "id": "PMID-8493578_T5", "type": "Protein", "text": [ "Elf-1" ], "offsets": [ [ 204, 209 ] ], "normalized": [] }, { "id": "PMID-8493578_T6", "type": "Protein", "text": [ "Elf-1" ], "offsets": [ [ 365, 370 ] ], "normalized": [] }, { "id": "PMID-8493578_T7", "type": "Protein", "text": [ "Rb" ], "offsets": [ [ 427, 429 ] ], "normalized": [] }, { "id": "PMID-8493578_T8", "type": "Protein", "text": [ "Rb" ], "offsets": [ [ 508, 510 ] ], "normalized": [] }, { "id": "PMID-8493578_T9", "type": "Protein", "text": [ "Elf-1" ], "offsets": [ [ 538, 543 ] ], "normalized": [] }, { "id": "PMID-8493578_T10", "type": "Protein", "text": [ "Rb" ], "offsets": [ [ 597, 599 ] ], "normalized": [] }, { "id": "PMID-8493578_T11", "type": "Protein", "text": [ "Rb" ], "offsets": [ [ 621, 623 ] ], "normalized": [] }, { "id": "PMID-8493578_T12", "type": "Protein", "text": [ "Elf-1" ], "offsets": [ [ 746, 751 ] ], "normalized": [] }, { "id": "PMID-8493578_T13", "type": "Protein", "text": [ "Rb" ], "offsets": [ [ 756, 758 ] ], "normalized": [] }, { "id": "PMID-8493578_T14", "type": "Protein", "text": [ "Rb" ], "offsets": [ [ 840, 842 ] ], "normalized": [] }, { "id": "PMID-8493578_T15", "type": "Protein", "text": [ "Elf-1" ], "offsets": [ [ 869, 874 ] ], "normalized": [] }, { "id": "PMID-8493578_T16", "type": "Protein", "text": [ "Elf-1" ], "offsets": [ [ 930, 935 ] ], "normalized": [] }, { "id": "PMID-8493578_T17", "type": "Protein", "text": [ "Rb" ], "offsets": [ [ 1014, 1016 ] ], "normalized": [] }, { "id": "PMID-8493578_T18", "type": "Protein", "text": [ "Elf-1" ], "offsets": [ [ 1027, 1032 ] ], "normalized": [] }, { "id": "PMID-8493578_T19", "type": "Protein", "text": [ "Rb" ], "offsets": [ [ 1114, 1116 ] ], "normalized": [] } ]

[ { "id": "PMID-8493578_E1", "type": "Regulation", "trigger": { "text": [ "Regulation" ], "offsets": [ [ 0, 10 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "PMID-8493578_T1" }, { "role": "Cause", "ref_id": "PMID-8493578_E2" } ] }, { "id": "PMID-8493578_E2", "type": "Binding", "trigger": { "text": [ "binding" ], "offsets": [ [ 60, 67 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "PMID-8493578_T2" } ] }, { "id": "PMID-8493578_E3", "type": "Binding", "trigger": { "text": [ "binds" ], "offsets": [ [ 478, 483 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "PMID-8493578_T6" }, { "role": "Theme", "ref_id": "PMID-8493578_T8" } ] }, { "id": "PMID-8493578_E4", "type": "Binding", "trigger": { "text": [ "binds" ], "offsets": [ [ 544, 549 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "PMID-8493578_T9" }, { "role": "Theme", "ref_id": "PMID-8493578_T10" } ] }, { "id": "PMID-8493578_E5", "type": "Phosphorylation", "trigger": { "text": [ "underphosphorylated" ], "offsets": [ [ 569, 588 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "PMID-8493578_T10" } ] }, { "id": "PMID-8493578_E6", "type": "Negative_regulation", "trigger": { "text": [ "underphosphorylated" ], "offsets": [ [ 569, 588 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "PMID-8493578_E5" } ] }, { "id": "PMID-8493578_E7", "type": "Binding", "trigger": { "text": [ "bind" ], "offsets": [ [ 613, 617 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "PMID-8493578_T9" }, { "role": "Theme", "ref_id": "PMID-8493578_T11" } ] }, { "id": "PMID-8493578_E8", "type": "Binding", "trigger": { "text": [ "association" ], "offsets": [ [ 726, 737 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "PMID-8493578_T12" }, { "role": "Theme", "ref_id": "PMID-8493578_T13" } ] }, { "id": "PMID-8493578_E9", "type": "Phosphorylation", "trigger": { "text": [ "phosphorylation" ], "offsets": [ [ 821, 836 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "PMID-8493578_T14" } ] }, { "id": "PMID-8493578_E10", "type": "Positive_regulation", "trigger": { "text": [ "results" ], "offsets": [ [ 843, 850 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "PMID-8493578_E11" }, { "role": "Cause", "ref_id": "PMID-8493578_E9" } ] }, { "id": "PMID-8493578_E11", "type": "Localization", "trigger": { "text": [ "release" ], "offsets": [ [ 858, 865 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "PMID-8493578_T15" } ] }, { "id": "PMID-8493578_E12", "type": "Gene_expression", "trigger": { "text": [ "Overexpression" ], "offsets": [ [ 960, 974 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "PMID-8493578_T17" } ] }, { "id": "PMID-8493578_E13", "type": "Positive_regulation", "trigger": { "text": [ "Overexpression" ], "offsets": [ [ 960, 974 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "PMID-8493578_E12" } ] }, { "id": "PMID-8493578_E14", "type": "Phosphorylation", "trigger": { "text": [ "phosphorylation-defective form" ], "offsets": [ [ 980, 1010 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "PMID-8493578_T17" } ] }, { "id": "PMID-8493578_E15", "type": "Binding", "trigger": { "text": [ "interacts" ], "offsets": [ [ 1117, 1126 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "PMID-8493578_T19" } ] } ]

[]

[]

[ { "id": "PMID-8496329__text", "type": "abstract", "text": [ "Expression levels of the thyrotropin receptor gene in autoimmune thyroid disease: coregulation with parameters of thyroid function and inverse relation to major histocompatibility complex classes I and II. \nUsing a human TSH receptor (TSH-R) cDNA probe, we investigated TSH-R transcript levels in 13 human thyroid fragments by Northern blot analysis; 7 Graves' disease, 2 Hashimoto's disease, 3 endemic goiter, and 1 healthy thyroid gland were studied. TSH-R expression levels were variable, but displayed a close correlation to the expression of thyroid peroxidase (r = 0.703; P < 0.05), thyroglobulin (r = 0.817; P < 0.01), and the nuclear oncogene c-fos (r = 0.935; P < 0.001), but not c-myc. Overall, TSH-R transcript levels were low or absent in those thyroids in which expression of the major histocompatibility complex class I or II (MHC I or II) was high, thus establishing an inverse relation (MHC I, r = -0.791; P < 0.01; MHC II, r = -0.784; P < 0.01). In situ hybridization showed that apart from lymphocytes, thyroid cells themselves were the source of MHC II transcripts. gamma-Interferon expression was only detectable in 1 Hashimoto's goiter. Our findings suggest that next to lymphocyte infiltration, active regulatory events in the thyrocyte are responsible for the inverse relation between functional parameters (TSH-R, thyroid peroxidase, thyroglobulin, and c-fos) and immunological markers (MHC I and II). " ], "offsets": [ [ 0, 1426 ] ] } ]

[ { "id": "PMID-8496329_T1", "type": "Protein", "text": [ "thyrotropin receptor" ], "offsets": [ [ 25, 45 ] ], "normalized": [] }, { "id": "PMID-8496329_T2", "type": "Protein", "text": [ "TSH receptor" ], "offsets": [ [ 221, 233 ] ], "normalized": [] }, { "id": "PMID-8496329_T3", "type": "Protein", "text": [ "TSH-R" ], "offsets": [ [ 235, 240 ] ], "normalized": [] }, { "id": "PMID-8496329_T4", "type": "Protein", "text": [ "TSH-R" ], "offsets": [ [ 270, 275 ] ], "normalized": [] }, { "id": "PMID-8496329_T5", "type": "Protein", "text": [ "TSH-R" ], "offsets": [ [ 453, 458 ] ], "normalized": [] }, { "id": "PMID-8496329_T6", "type": "Protein", "text": [ "thyroid peroxidase" ], "offsets": [ [ 547, 565 ] ], "normalized": [] }, { "id": "PMID-8496329_T7", "type": "Protein", "text": [ "thyroglobulin" ], "offsets": [ [ 589, 602 ] ], "normalized": [] }, { "id": "PMID-8496329_T8", "type": "Protein", "text": [ "c-fos" ], "offsets": [ [ 651, 656 ] ], "normalized": [] }, { "id": "PMID-8496329_T9", "type": "Protein", "text": [ "c-myc" ], "offsets": [ [ 689, 694 ] ], "normalized": [] }, { "id": "PMID-8496329_T10", "type": "Protein", "text": [ "TSH-R" ], "offsets": [ [ 705, 710 ] ], "normalized": [] }, { "id": "PMID-8496329_T11", "type": "Protein", "text": [ "gamma-Interferon" ], "offsets": [ [ 1085, 1101 ] ], "normalized": [] }, { "id": "PMID-8496329_T12", "type": "Protein", "text": [ "TSH-R" ], "offsets": [ [ 1331, 1336 ] ], "normalized": [] }, { "id": "PMID-8496329_T13", "type": "Protein", "text": [ "thyroid peroxidase" ], "offsets": [ [ 1338, 1356 ] ], "normalized": [] }, { "id": "PMID-8496329_T14", "type": "Protein", "text": [ "thyroglobulin" ], "offsets": [ [ 1358, 1371 ] ], "normalized": [] }, { "id": "PMID-8496329_T15", "type": "Protein", "text": [ "c-fos" ], "offsets": [ [ 1377, 1382 ] ], "normalized": [] } ]

[ { "id": "PMID-8496329_E1", "type": "Gene_expression", "trigger": { "text": [ "Expression" ], "offsets": [ [ 0, 10 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "PMID-8496329_T1" } ] }, { "id": "PMID-8496329_E2", "type": "Regulation", "trigger": { "text": [ "coregulation" ], "offsets": [ [ 82, 94 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "PMID-8496329_E1" } ] }, { "id": "PMID-8496329_E3", "type": "Transcription", "trigger": { "text": [ "transcript levels" ], "offsets": [ [ 276, 293 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "PMID-8496329_T4" } ] }, { "id": "PMID-8496329_E4", "type": "Gene_expression", "trigger": { "text": [ "expression" ], "offsets": [ [ 459, 469 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "PMID-8496329_T5" } ] }, { "id": "PMID-8496329_E5", "type": "Gene_expression", "trigger": { "text": [ "expression" ], "offsets": [ [ 533, 543 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "PMID-8496329_T7" } ] }, { "id": "PMID-8496329_E6", "type": "Gene_expression", "trigger": { "text": [ "expression" ], "offsets": [ [ 533, 543 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "PMID-8496329_T8" } ] }, { "id": "PMID-8496329_E7", "type": "Gene_expression", "trigger": { "text": [ "expression" ], "offsets": [ [ 533, 543 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "PMID-8496329_T6" } ] }, { "id": "PMID-8496329_E8", "type": "Gene_expression", "trigger": { "text": [ "expression" ], "offsets": [ [ 533, 543 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "PMID-8496329_T9" } ] }, { "id": "PMID-8496329_E9", "type": "Transcription", "trigger": { "text": [ "transcript levels" ], "offsets": [ [ 711, 728 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "PMID-8496329_T10" } ] }, { "id": "PMID-8496329_E10", "type": "Gene_expression", "trigger": { "text": [ "expression" ], "offsets": [ [ 1102, 1112 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "PMID-8496329_T11" } ] } ]

[ { "id": "PMID-8496329_1", "entity_ids": [ "PMID-8496329_T2", "PMID-8496329_T3" ] } ]

[]

[ { "id": "PMID-8504248__text", "type": "abstract", "text": [ "Regulation of the beta-globin locus. \nTranscription of the human beta-globin gene cluster depends upon upstream regulatory sequences, which are collectively termed the locus control region. Recent studies have provided new insights into how the individual genes of the cluster are regulated through development. The crux of transcriptional activation is how the locus control region communicates with the gene-proximal regulatory elements. " ], "offsets": [ [ 0, 440 ] ] } ]

[ { "id": "PMID-8504248_T1", "type": "Protein", "text": [ "beta-globin" ], "offsets": [ [ 18, 29 ] ], "normalized": [] }, { "id": "PMID-8504248_T2", "type": "Protein", "text": [ "beta-globin" ], "offsets": [ [ 65, 76 ] ], "normalized": [] } ]

[ { "id": "PMID-8504248_E1", "type": "Regulation", "trigger": { "text": [ "Regulation" ], "offsets": [ [ 0, 10 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "PMID-8504248_T1" } ] }, { "id": "PMID-8504248_E2", "type": "Transcription", "trigger": { "text": [ "Transcription" ], "offsets": [ [ 38, 51 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "PMID-8504248_T2" } ] }, { "id": "PMID-8504248_E3", "type": "Regulation", "trigger": { "text": [ "depends" ], "offsets": [ [ 90, 97 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "PMID-8504248_E2" } ] }, { "id": "PMID-8504248_E4", "type": "Regulation", "trigger": { "text": [ "regulated" ], "offsets": [ [ 281, 290 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "PMID-8504248_T2" } ] } ]

[]

[]

[ { "id": "PMID-8504932__text", "type": "abstract", "text": [ "Ectopic expression of a conditional GATA-2/estrogen receptor chimera arrests erythroid differentiation in a hormone-dependent manner. \nThe GATA factors are a family of transcriptional regulatory proteins in eukaryotes that share extensive homology in their DNA-binding domains. One enigmatic aspect of GATA factor expression is that several GATA proteins, which ostensibly share the same DNA-binding site specificity, are coexpressed in erythroid cells. To elucidate the roles of individual GATA factors in erythropoiesis, conditional alleles of GATA-1, GATA-2, and GATA-3 were prepared by fusing each of the factors to the hormone-binding domain of the human estrogen receptor (ER). These GATA/ER chimeric factors were shown to be hormone-inducible trans-activating proteins in transient transfection assays. When stably introduced into primary erythroblasts or conditionally transformed erythroid progenitors cells, exogenous GATA-2/ER promoted proliferation and inhibited terminal differentiation in an estrogen-dependent manner. These phenotypic effects are specifically attributable to the action of ectopically expressed GATA-2/ER because erythroblasts expressing exogenous GATA-2 are constitutively arrested in differentiation and because erythroid progenitors expressing either Gal/ER or GATA-3/ER do not display a hormone-responsive block in differentiation. Thus, the GATA-2 transcription factor appears to play a role in regulating the self-renewal capacity of early erythroid progenitor cells. " ], "offsets": [ [ 0, 1506 ] ] } ]

[ { "id": "PMID-8504932_T1", "type": "Protein", "text": [ "GATA-2" ], "offsets": [ [ 36, 42 ] ], "normalized": [] }, { "id": "PMID-8504932_T2", "type": "Protein", "text": [ "estrogen receptor" ], "offsets": [ [ 43, 60 ] ], "normalized": [] }, { "id": "PMID-8504932_T3", "type": "Protein", "text": [ "GATA-1" ], "offsets": [ [ 546, 552 ] ], "normalized": [] }, { "id": "PMID-8504932_T4", "type": "Protein", "text": [ "GATA-2" ], "offsets": [ [ 554, 560 ] ], "normalized": [] }, { "id": "PMID-8504932_T5", "type": "Protein", "text": [ "GATA-3" ], "offsets": [ [ 566, 572 ] ], "normalized": [] }, { "id": "PMID-8504932_T6", "type": "Protein", "text": [ "estrogen receptor" ], "offsets": [ [ 660, 677 ] ], "normalized": [] }, { "id": "PMID-8504932_T7", "type": "Protein", "text": [ "ER" ], "offsets": [ [ 679, 681 ] ], "normalized": [] }, { "id": "PMID-8504932_T8", "type": "Protein", "text": [ "ER" ], "offsets": [ [ 695, 697 ] ], "normalized": [] }, { "id": "PMID-8504932_T9", "type": "Protein", "text": [ "GATA-2" ], "offsets": [ [ 928, 934 ] ], "normalized": [] }, { "id": "PMID-8504932_T10", "type": "Protein", "text": [ "ER" ], "offsets": [ [ 935, 937 ] ], "normalized": [] }, { "id": "PMID-8504932_T11", "type": "Protein", "text": [ "GATA-2" ], "offsets": [ [ 1127, 1133 ] ], "normalized": [] }, { "id": "PMID-8504932_T12", "type": "Protein", "text": [ "ER" ], "offsets": [ [ 1134, 1136 ] ], "normalized": [] }, { "id": "PMID-8504932_T13", "type": "Protein", "text": [ "GATA-2" ], "offsets": [ [ 1180, 1186 ] ], "normalized": [] }, { "id": "PMID-8504932_T14", "type": "Protein", "text": [ "ER" ], "offsets": [ [ 1290, 1292 ] ], "normalized": [] }, { "id": "PMID-8504932_T15", "type": "Protein", "text": [ "GATA-3" ], "offsets": [ [ 1296, 1302 ] ], "normalized": [] }, { "id": "PMID-8504932_T16", "type": "Protein", "text": [ "ER" ], "offsets": [ [ 1303, 1305 ] ], "normalized": [] }, { "id": "PMID-8504932_T17", "type": "Protein", "text": [ "GATA-2" ], "offsets": [ [ 1378, 1384 ] ], "normalized": [] } ]

[ { "id": "PMID-8504932_E1", "type": "Gene_expression", "trigger": { "text": [ "expressing" ], "offsets": [ [ 1159, 1169 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "PMID-8504932_T13" } ] } ]

[ { "id": "PMID-8504932_1", "entity_ids": [ "PMID-8504932_T6", "PMID-8504932_T7" ] } ]

[]

[ { "id": "PMID-8506326__text", "type": "abstract", "text": [ "Molecular basis of a multiple lymphokine deficiency in a patient with severe combined immunodeficiency. \nWe have previously reported that the T lymphocytes of a child with severe combined immunodeficiency are defective in the transcription of several lymphokine genes that include IL2, IL3, IL4, and IL5, which encode interleukins 2, 3, 4, and 5 (IL-2, -3, -4, and -5). To determine whether the defect in the patient's T lymphocytes involved a trans-acting factor common to the affected lymphokine genes, we examined the ability of nuclear factors from the patient's T lymphocytes to bind response elements present in the regulatory region of IL2. Nuclear factor NF-kB, activation protein 1 (AP-1), OCT-1, and NF-IL-2B binding activity were normal. In contrast, the binding of the nuclear factor of activated T cells (NF-AT) to its response element in the IL2 enhancer and to an NF-AT-like response element present in the IL4 enhancer was abnormal. To ascertain whether the abnormal NF-AT binding activity was related to an impaired function, we transfected patient and control T lymphocytes with constructs containing the reporter gene encoding chloramphenicol acetyl transferase (CAT) under the control of the entire IL2 regulatory region or of multimers of individual enhancer sequences. CAT expression directed by the IL2 regulatory region or by a multimer of the NF-AT-binding site was markedly lower in the patient relative to controls. In contrast, CAT gene expression directed by a multimer of the OCT-1 proximal (OCT-1p)-binding site was equivalent in patient and controls. These results indicate that an abnormality of/or influencing NF-AT may underlie the multiple lymphokine deficiency in this patient. " ], "offsets": [ [ 0, 1715 ] ] } ]

[ { "id": "PMID-8506326_T1", "type": "Protein", "text": [ "IL2" ], "offsets": [ [ 281, 284 ] ], "normalized": [] }, { "id": "PMID-8506326_T2", "type": "Protein", "text": [ "IL3" ], "offsets": [ [ 286, 289 ] ], "normalized": [] }, { "id": "PMID-8506326_T3", "type": "Protein", "text": [ "IL4" ], "offsets": [ [ 291, 294 ] ], "normalized": [] }, { "id": "PMID-8506326_T4", "type": "Protein", "text": [ "IL5" ], "offsets": [ [ 300, 303 ] ], "normalized": [] }, { "id": "PMID-8506326_T5", "type": "Protein", "text": [ "interleukins 2" ], "offsets": [ [ 318, 332 ] ], "normalized": [] }, { "id": "PMID-8506326_T6", "type": "Protein", "text": [ "3" ], "offsets": [ [ 334, 335 ] ], "normalized": [] }, { "id": "PMID-8506326_T7", "type": "Protein", "text": [ "4" ], "offsets": [ [ 337, 338 ] ], "normalized": [] }, { "id": "PMID-8506326_T8", "type": "Protein", "text": [ "5" ], "offsets": [ [ 344, 345 ] ], "normalized": [] }, { "id": "PMID-8506326_T9", "type": "Protein", "text": [ "IL-2" ], "offsets": [ [ 347, 351 ] ], "normalized": [] }, { "id": "PMID-8506326_T10", "type": "Protein", "text": [ "-3" ], "offsets": [ [ 353, 355 ] ], "normalized": [] }, { "id": "PMID-8506326_T11", "type": "Protein", "text": [ "-4" ], "offsets": [ [ 357, 359 ] ], "normalized": [] }, { "id": "PMID-8506326_T12", "type": "Protein", "text": [ "-5" ], "offsets": [ [ 365, 367 ] ], "normalized": [] }, { "id": "PMID-8506326_T13", "type": "Protein", "text": [ "IL2" ], "offsets": [ [ 643, 646 ] ], "normalized": [] }, { "id": "PMID-8506326_T14", "type": "Protein", "text": [ "OCT-1" ], "offsets": [ [ 699, 704 ] ], "normalized": [] }, { "id": "PMID-8506326_T15", "type": "Protein", "text": [ "IL2" ], "offsets": [ [ 856, 859 ] ], "normalized": [] }, { "id": "PMID-8506326_T16", "type": "Protein", "text": [ "IL4" ], "offsets": [ [ 922, 925 ] ], "normalized": [] }, { "id": "PMID-8506326_T17", "type": "Protein", "text": [ "chloramphenicol acetyl transferase" ], "offsets": [ [ 1146, 1180 ] ], "normalized": [] }, { "id": "PMID-8506326_T18", "type": "Protein", "text": [ "CAT" ], "offsets": [ [ 1182, 1185 ] ], "normalized": [] }, { "id": "PMID-8506326_T19", "type": "Protein", "text": [ "IL2" ], "offsets": [ [ 1219, 1222 ] ], "normalized": [] }, { "id": "PMID-8506326_T20", "type": "Protein", "text": [ "CAT" ], "offsets": [ [ 1291, 1294 ] ], "normalized": [] }, { "id": "PMID-8506326_T21", "type": "Protein", "text": [ "IL2" ], "offsets": [ [ 1322, 1325 ] ], "normalized": [] }, { "id": "PMID-8506326_T22", "type": "Protein", "text": [ "CAT" ], "offsets": [ [ 1456, 1459 ] ], "normalized": [] }, { "id": "PMID-8506326_T23", "type": "Protein", "text": [ "OCT-1" ], "offsets": [ [ 1506, 1511 ] ], "normalized": [] }, { "id": "PMID-8506326_T27", "type": "Entity", "text": [ "response elements" ], "offsets": [ [ 589, 606 ] ], "normalized": [] }, { "id": "PMID-8506326_T30", "type": "Entity", "text": [ "enhancer" ], "offsets": [ [ 860, 868 ] ], "normalized": [] }, { "id": "PMID-8506326_T31", "type": "Entity", "text": [ "enhancer" ], "offsets": [ [ 926, 934 ] ], "normalized": [] } ]

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[ { "id": "PMID-8506326_1", "entity_ids": [ "PMID-8506326_T18", "PMID-8506326_T17" ] } ]

[]

[ { "id": "PMID-8507862__text", "type": "abstract", "text": [ "Expression of mRNA for the GATA-binding proteins in human eosinophils and basophils: potential role in gene transcription. \nThe expression of the hematopoietic transcription factors GATA-1, GATA-2, and GATA-3 was studied in eosinophils and basophils. Eosinophils express mRNA for GATA-1, GATA-2, and GATA-3. Basophils express GATA-2 and GATA-3. Treatment of HL-60 eosinophilic sublines with either interleukin-5 or butyric acid increased the expression of GATA-1 mRNA concomitant with the expression of eosinophil-specific genes, whereas levels of GATA-2 mRNA remained relatively constant. The presence of mRNA for these proteins in eosinophils and basophils suggests that gene transcription in these lineages may be regulated by GATA-binding proteins. " ], "offsets": [ [ 0, 753 ] ] } ]

[ { "id": "PMID-8507862_T1", "type": "Protein", "text": [ "GATA-1" ], "offsets": [ [ 182, 188 ] ], "normalized": [] }, { "id": "PMID-8507862_T2", "type": "Protein", "text": [ "GATA-2" ], "offsets": [ [ 190, 196 ] ], "normalized": [] }, { "id": "PMID-8507862_T3", "type": "Protein", "text": [ "GATA-3" ], "offsets": [ [ 202, 208 ] ], "normalized": [] }, { "id": "PMID-8507862_T4", "type": "Protein", "text": [ "GATA-1" ], "offsets": [ [ 280, 286 ] ], "normalized": [] }, { "id": "PMID-8507862_T5", "type": "Protein", "text": [ "GATA-2" ], "offsets": [ [ 288, 294 ] ], "normalized": [] }, { "id": "PMID-8507862_T6", "type": "Protein", "text": [ "GATA-3" ], "offsets": [ [ 300, 306 ] ], "normalized": [] }, { "id": "PMID-8507862_T7", "type": "Protein", "text": [ "GATA-2" ], "offsets": [ [ 326, 332 ] ], "normalized": [] }, { "id": "PMID-8507862_T8", "type": "Protein", "text": [ "GATA-3" ], "offsets": [ [ 337, 343 ] ], "normalized": [] }, { "id": "PMID-8507862_T9", "type": "Protein", "text": [ "interleukin-5" ], "offsets": [ [ 398, 411 ] ], "normalized": [] }, { "id": "PMID-8507862_T10", "type": "Protein", "text": [ "GATA-1" ], "offsets": [ [ 456, 462 ] ], "normalized": [] }, { "id": "PMID-8507862_T11", "type": "Protein", "text": [ "GATA-2" ], "offsets": [ [ 548, 554 ] ], "normalized": [] } ]

[ { "id": "PMID-8507862_E1", "type": "Gene_expression", "trigger": { "text": [ "expression" ], "offsets": [ [ 128, 138 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "PMID-8507862_T2" } ] }, { "id": "PMID-8507862_E2", "type": "Gene_expression", "trigger": { "text": [ "expression" ], "offsets": [ [ 128, 138 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "PMID-8507862_T3" } ] }, { "id": "PMID-8507862_E3", "type": "Gene_expression", "trigger": { "text": [ "expression" ], "offsets": [ [ 128, 138 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "PMID-8507862_T1" } ] }, { "id": "PMID-8507862_E4", "type": "Transcription", "trigger": { "text": [ "express mRNA" ], "offsets": [ [ 263, 275 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "PMID-8507862_T6" } ] }, { "id": "PMID-8507862_E5", "type": "Transcription", "trigger": { "text": [ "express mRNA" ], "offsets": [ [ 263, 275 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "PMID-8507862_T5" } ] }, { "id": "PMID-8507862_E6", "type": "Transcription", "trigger": { "text": [ "express mRNA" ], "offsets": [ [ 263, 275 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "PMID-8507862_T4" } ] }, { "id": "PMID-8507862_E7", "type": "Gene_expression", "trigger": { "text": [ "express" ], "offsets": [ [ 318, 325 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "PMID-8507862_T7" } ] }, { "id": "PMID-8507862_E8", "type": "Gene_expression", "trigger": { "text": [ "express" ], "offsets": [ [ 318, 325 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "PMID-8507862_T8" } ] }, { "id": "PMID-8507862_E9", "type": "Positive_regulation", "trigger": { "text": [ "increased" ], "offsets": [ [ 428, 437 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "PMID-8507862_E10" } ] }, { "id": "PMID-8507862_E10", "type": "Transcription", "trigger": { "text": [ "expression" ], "offsets": [ [ 442, 452 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "PMID-8507862_T10" } ] }, { "id": "PMID-8507862_E11", "type": "Positive_regulation", "trigger": { "text": [ "constant" ], "offsets": [ [ 580, 588 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "PMID-8507862_T11" } ] }, { "id": "PMID-8507862_E12", "type": "Localization", "trigger": { "text": [ "presence" ], "offsets": [ [ 594, 602 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "PMID-8507862_T6" } ] }, { "id": "PMID-8507862_E13", "type": "Localization", "trigger": { "text": [ "presence" ], "offsets": [ [ 594, 602 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "PMID-8507862_T4" } ] }, { "id": "PMID-8507862_E14", "type": "Localization", "trigger": { "text": [ "presence" ], "offsets": [ [ 594, 602 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "PMID-8507862_T5" } ] } ]

[]

[]

[ { "id": "PMID-8513868__text", "type": "abstract", "text": [ "Dependence for the proliferative response to erythropoietin on an established erythroid differentiation program in a human hematopoietic cell line, UT-7. \nErythroid differentiation involves the activation of a number of erythroid-specific genes, most of which, including the globin genes and the erythropoietin receptor (Epo-R) gene, are, at least in part, regulated by the transcription factor GATA-1. In order to understand the relationship, if any, between expression of GATA-1, response to Epo and erythroid differentiation, we analyzed the expression of GATA-1, Epo-R and globin genes in an Epo-dependent human cell line, UT-7 Epo. The results were compared to those obtained with the parental granulocyte-macrophage colony-stimulating factor (GM-CSF)-dependent cell line, UT-7, which has a predominantly megakaryoblastic phenotype and is unable to proliferate continuously in the presence of Epo. UT-7 Epo and UT-7 expressed similar levels of GATA-1 mRNA and binding activity. The two lines also expressed comparable levels of Epo-R mRNA while the number of Epo-binding sites on UT-7 Epo cells was one-sixth the number of UT-7 cells (2400 +/- 3 vs. 13,800 +/- 300). This difference in the number of binding sites could be due to differences in cell surface (UT-7 cells are 20% smaller than the parental UT-7 cells) or in receptor turnover. By Northern analysis, UT-7 cells expressed detectable levels of beta- and gamma-globin but not alpha-globin. In comparison, UT-7 Epo cells expressed alpha-globin and higher levels of gamma-globin (5-fold) and beta-globin (from barely to clearly detectable). Globin chains (alpha, beta and gamma) were clearly detectable by affinity chromatography in UT-7 Epo but not in UT-7 cells. The frequency of the cells which expressed beta- and gamma- globin genes in the two cell populations was measured by immunofluorescence with beta- and gamma-specific antibodies. The number of gamma-positive cells and their fluorescence intensity were higher in UT-7 Epo than in UT-7 cells (0 to 17% barely positive cells and 23 to 40% clearly positive cells, respectively), indicating that the increase in globin mRNA observed in UT-7 Epo is due to both an increase of gene expression per cell and an increase in numbers of cells containing gamma-globin. The levels of GATA-1, Epo-R and globin mRNA expressed were not affected by a 24-hour incubation of either cell line with Epo, GM-CSF or interleukin-3 (IL-3). (ABSTRACT TRUNCATED AT 400 WORDS) " ], "offsets": [ [ 0, 2475 ] ] } ]

[ { "id": "PMID-8513868_T1", "type": "Protein", "text": [ "erythropoietin" ], "offsets": [ [ 45, 59 ] ], "normalized": [] }, { "id": "PMID-8513868_T2", "type": "Protein", "text": [ "erythropoietin receptor" ], "offsets": [ [ 296, 319 ] ], "normalized": [] }, { "id": "PMID-8513868_T3", "type": "Protein", "text": [ "Epo-R" ], "offsets": [ [ 321, 326 ] ], "normalized": [] }, { "id": "PMID-8513868_T4", "type": "Protein", "text": [ "GATA-1" ], "offsets": [ [ 395, 401 ] ], "normalized": [] }, { "id": "PMID-8513868_T5", "type": "Protein", "text": [ "GATA-1" ], "offsets": [ [ 474, 480 ] ], "normalized": [] }, { "id": "PMID-8513868_T6", "type": "Protein", "text": [ "Epo" ], "offsets": [ [ 494, 497 ] ], "normalized": [] }, { "id": "PMID-8513868_T7", "type": "Protein", "text": [ "GATA-1" ], "offsets": [ [ 559, 565 ] ], "normalized": [] }, { "id": "PMID-8513868_T8", "type": "Protein", "text": [ "Epo-R" ], "offsets": [ [ 567, 572 ] ], "normalized": [] }, { "id": "PMID-8513868_T9", "type": "Protein", "text": [ "Epo" ], "offsets": [ [ 596, 599 ] ], "normalized": [] }, { "id": "PMID-8513868_T10", "type": "Protein", "text": [ "granulocyte-macrophage colony-stimulating factor" ], "offsets": [ [ 699, 747 ] ], "normalized": [] }, { "id": "PMID-8513868_T11", "type": "Protein", "text": [ "GM-CSF" ], "offsets": [ [ 749, 755 ] ], "normalized": [] }, { "id": "PMID-8513868_T12", "type": "Protein", "text": [ "Epo" ], "offsets": [ [ 898, 901 ] ], "normalized": [] }, { "id": "PMID-8513868_T13", "type": "Protein", "text": [ "GATA-1" ], "offsets": [ [ 949, 955 ] ], "normalized": [] }, { "id": "PMID-8513868_T14", "type": "Protein", "text": [ "Epo-R" ], "offsets": [ [ 1033, 1038 ] ], "normalized": [] }, { "id": "PMID-8513868_T15", "type": "Protein", "text": [ "Epo" ], "offsets": [ [ 1064, 1067 ] ], "normalized": [] }, { "id": "PMID-8513868_T16", "type": "Protein", "text": [ "alpha-globin" ], "offsets": [ [ 1441, 1453 ] ], "normalized": [] }, { "id": "PMID-8513868_T17", "type": "Protein", "text": [ "alpha-globin" ], "offsets": [ [ 1495, 1507 ] ], "normalized": [] }, { "id": "PMID-8513868_T18", "type": "Protein", "text": [ "beta-globin" ], "offsets": [ [ 1555, 1566 ] ], "normalized": [] }, { "id": "PMID-8513868_T19", "type": "Protein", "text": [ "Globin chains (alpha" ], "offsets": [ [ 1604, 1624 ] ], "normalized": [] }, { "id": "PMID-8513868_T20", "type": "Protein", "text": [ "beta" ], "offsets": [ [ 1626, 1630 ] ], "normalized": [] }, { "id": "PMID-8513868_T21", "type": "Protein", "text": [ "gamma" ], "offsets": [ [ 1635, 1640 ] ], "normalized": [] }, { "id": "PMID-8513868_T22", "type": "Protein", "text": [ "GATA-1" ], "offsets": [ [ 2297, 2303 ] ], "normalized": [] }, { "id": "PMID-8513868_T23", "type": "Protein", "text": [ "Epo-R" ], "offsets": [ [ 2305, 2310 ] ], "normalized": [] }, { "id": "PMID-8513868_T24", "type": "Protein", "text": [ "Epo" ], "offsets": [ [ 2404, 2407 ] ], "normalized": [] }, { "id": "PMID-8513868_T25", "type": "Protein", "text": [ "GM-CSF" ], "offsets": [ [ 2409, 2415 ] ], "normalized": [] }, { "id": "PMID-8513868_T26", "type": "Protein", "text": [ "interleukin-3" ], "offsets": [ [ 2419, 2432 ] ], "normalized": [] }, { "id": "PMID-8513868_T27", "type": "Protein", "text": [ "IL-3" ], "offsets": [ [ 2434, 2438 ] ], "normalized": [] } ]

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[]

[ { "id": "PMID-8523529__text", "type": "abstract", "text": [ "Protein kinase C-zeta mediates NF-kappa B activation in human immunodeficiency virus-infected monocytes. \nThe molecular mechanisms regulating human immunodeficiency virus (HIV) persistence in a major cell reservoir such as the macrophage remain unknown. NF-kappa B is a transcription factor involved in the regulation of the HIV long terminal repeat and is selectively activated following HIV infection of human macrophages. Although little information as to what signal transduction pathways mediate NF-kappa B activation in monocytes-macrophages is available, our previous work indicated that classical protein kinase C (PKC) isoenzymes were not involved in the HIV-mediated NF-kappa B activation. In this study, we have focused on atypical PKC isoenzymes. PKC-zeta belongs to this family and is known to be an important step in NF-kappa B activation in other cell systems. Immunoblotting experiments with U937 cells demonstrate that PKC-zeta is present in these cells, and its expression can be downmodulated by antisense oligonucleotides (AO). The HIV-mediated NF-kappa B activation is selectively reduced by AO to PKC-zeta. In addition, cotransfection of a negative dominant molecule of PKC-zeta (PKC-zeta mut) with NF-kappa B-dependent reporter genes selectively inhibits the HIV- but not phorbol myristate acetate- or lipopolysaccharide-mediated activation of NF-kappa B. That PKC-zeta is specific in regulating NF-kappa B is concluded from the inability of PKC-zeta(mut) to interfere with the basal or phorbol myristate acetate-inducible CREB- or AP1-dependent transcriptional activity. Lastly, we demonstrate a selective inhibition of p24 production by HIV-infected human macrophages when treated with AO to PKC-zeta. Altogether, these results suggest that atypical PKC isoenzymes, including PKC-zeta, participate in the signal transduction pathways by which HIV infection results in the activation of NF-kappa B in human monocytic cells and macrophages. " ], "offsets": [ [ 0, 1964 ] ] } ]

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[]

[]

[ { "id": "PMID-8524816__text", "type": "abstract", "text": [ "Inhibition of NF-AT-dependent transcription by NF-kappa B: implications for differential gene expression in T helper cell subsets. \nActivation of individual CD4+ T cells results in differential lymphokine expression: interleukin 2 (IL-2) is preferentially produced by T helper type 1 (TH1) cells, which are involved in cell-mediated immune responses, whereas IL-4 is synthesized by TH2 cells, which are essential for humoral immunity. The Ca(2+)-dependent factor NF-ATp plays a key role in the inducible transcription of both these lymphokine genes. However, while IL2 expression requires the contribution of Ca(2+)- and protein kinase C-dependent signals, we report that activation of human IL4 transcription through the Ca(2+)-dependent pathway is diminished by protein kinase C stimulation in Jurkat T cells. This phenomenon is due to mutually exclusive binding of NF-ATp and NF-kappa B to the P sequence, an element located 69 bp upstream of the IL4 transcription initiation site. Human IL4 promoter-mediated transcription is downregulated in Jurkat cells stimulated with the NF-kappa B-activating cytokine tumor necrosis factor alpha and suppressed in RelA-overexpressing cells. In contrast, protein kinase C stimulation or RelA overexpression does not affect the activity of a human IL4 promoter containing a mouse P sequence, which is a higher-affinity site for NF-ATp and a lower-affinity site for RelA. Thus, competition between two general transcriptional activators, RelA and NF-ATp, mediates the inhibitory effect of protein kinase C stimulation on IL4 expression and may contribute to differential gene expression in TH cells. " ], "offsets": [ [ 0, 1640 ] ] } ]

[ { "id": "PMID-8524816_T1", "type": "Protein", "text": [ "CD4" ], "offsets": [ [ 157, 160 ] ], "normalized": [] }, { "id": "PMID-8524816_T2", "type": "Protein", "text": [ "interleukin 2" ], "offsets": [ [ 217, 230 ] ], "normalized": [] }, { "id": "PMID-8524816_T3", "type": "Protein", "text": [ "IL-2" ], "offsets": [ [ 232, 236 ] ], "normalized": [] }, { "id": "PMID-8524816_T4", "type": "Protein", "text": [ "IL-4" ], "offsets": [ [ 359, 363 ] ], "normalized": [] }, { "id": "PMID-8524816_T5", "type": "Protein", "text": [ "NF-ATp" ], "offsets": [ [ 463, 469 ] ], "normalized": [] }, { "id": "PMID-8524816_T6", "type": "Protein", "text": [ "IL2" ], "offsets": [ [ 565, 568 ] ], "normalized": [] }, { "id": "PMID-8524816_T7", "type": "Protein", "text": [ "IL4" ], "offsets": [ [ 692, 695 ] ], "normalized": [] }, { "id": "PMID-8524816_T8", "type": "Protein", "text": [ "NF-ATp" ], "offsets": [ [ 868, 874 ] ], "normalized": [] }, { "id": "PMID-8524816_T9", "type": "Protein", "text": [ "IL4" ], "offsets": [ [ 950, 953 ] ], "normalized": [] }, { "id": "PMID-8524816_T10", "type": "Protein", "text": [ "IL4" ], "offsets": [ [ 991, 994 ] ], "normalized": [] }, { "id": "PMID-8524816_T11", "type": "Protein", "text": [ "tumor necrosis factor alpha" ], "offsets": [ [ 1111, 1138 ] ], "normalized": [] }, { "id": "PMID-8524816_T12", "type": "Protein", "text": [ "RelA" ], "offsets": [ [ 1157, 1161 ] ], "normalized": [] }, { "id": "PMID-8524816_T13", "type": "Protein", "text": [ "RelA" ], "offsets": [ [ 1229, 1233 ] ], "normalized": [] }, { "id": "PMID-8524816_T14", "type": "Protein", "text": [ "IL4" ], "offsets": [ [ 1289, 1292 ] ], "normalized": [] }, { "id": "PMID-8524816_T15", "type": "Protein", "text": [ "NF-ATp" ], "offsets": [ [ 1369, 1375 ] ], "normalized": [] }, { "id": "PMID-8524816_T16", "type": "Protein", "text": [ "RelA" ], "offsets": [ [ 1406, 1410 ] ], "normalized": [] }, { "id": "PMID-8524816_T17", "type": "Protein", "text": [ "RelA" ], "offsets": [ [ 1478, 1482 ] ], "normalized": [] }, { "id": "PMID-8524816_T18", "type": "Protein", "text": [ "NF-ATp" ], "offsets": [ [ 1487, 1493 ] ], "normalized": [] }, { "id": "PMID-8524816_T19", "type": "Protein", "text": [ "IL4" ], "offsets": [ [ 1561, 1564 ] ], "normalized": [] }, { "id": "PMID-8524816_T38", "type": "Entity", "text": [ "promoter" ], "offsets": [ [ 1293, 1301 ] ], "normalized": [] } ]

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"ref_id": "PMID-8524816_E14" } ] }, { "id": "PMID-8524816_E16", "type": "Positive_regulation", "trigger": { "text": [ "due to" ], "offsets": [ [ 831, 837 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "PMID-8524816_E14" }, { "role": "Cause", "ref_id": "PMID-8524816_E17" } ] }, { "id": "PMID-8524816_E17", "type": "Binding", "trigger": { "text": [ "binding" ], "offsets": [ [ 857, 864 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "PMID-8524816_T8" } ] }, { "id": "PMID-8524816_E18", "type": "Gene_expression", "trigger": { "text": [ "overexpressing" ], "offsets": [ [ 1162, 1176 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "PMID-8524816_T12" } ] }, { "id": "PMID-8524816_E19", "type": "Positive_regulation", "trigger": { "text": [ "overexpressing" ], "offsets": [ [ 1162, 1176 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "PMID-8524816_E18" } ] }, { "id": "PMID-8524816_E20", "type": "Positive_regulation", "trigger": { "text": [ "overexpression" ], "offsets": [ [ 1234, 1248 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "PMID-8524816_E21" } ] }, { "id": "PMID-8524816_E21", "type": "Gene_expression", "trigger": { "text": [ "overexpression" ], "offsets": [ [ 1234, 1248 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "PMID-8524816_T13" } ] }, { "id": "PMID-8524816_E22", "type": "Regulation", "trigger": { "text": [ "affect" ], "offsets": [ [ 1258, 1264 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "PMID-8524816_T14" }, { "role": "Site", "ref_id": "PMID-8524816_T38" } ] }, { "id": "PMID-8524816_E23", "type": "Regulation", "trigger": { "text": [ "affect" ], "offsets": [ [ 1258, 1264 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "PMID-8524816_T14" }, { "role": "Cause", "ref_id": "PMID-8524816_E20" }, { "role": "Site", "ref_id": "PMID-8524816_T38" } ] }, { "id": "PMID-8524816_E24", "type": "Binding", "trigger": { "text": [ "higher-affinity site" ], "offsets": [ [ 1344, 1364 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "PMID-8524816_T15" } ] }, { "id": "PMID-8524816_E25", "type": "Binding", "trigger": { "text": [ "lower-affinity site" ], "offsets": [ [ 1382, 1401 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "PMID-8524816_T16" } ] }, { "id": "PMID-8524816_E26", "type": "Binding", "trigger": { "text": [ "competition" ], "offsets": [ [ 1418, 1429 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "PMID-8524816_T18" } ] }, { "id": "PMID-8524816_E27", "type": "Negative_regulation", "trigger": { "text": [ "competition" ], "offsets": [ [ 1418, 1429 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "PMID-8524816_E26" }, { "role": "Cause", "ref_id": "PMID-8524816_T17" } ] }, { "id": "PMID-8524816_E28", "type": "Binding", "trigger": { "text": [ "competition" ], "offsets": [ [ 1418, 1429 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "PMID-8524816_T17" } ] }, { "id": "PMID-8524816_E29", "type": "Negative_regulation", "trigger": { "text": [ "competition" ], "offsets": [ [ 1418, 1429 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "PMID-8524816_E28" }, { "role": "Cause", "ref_id": "PMID-8524816_T18" } ] }, { "id": "PMID-8524816_E30", "type": "Positive_regulation", "trigger": { "text": [ "mediates" ], "offsets": [ [ 1495, 1503 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "PMID-8524816_E32" }, { "role": "Cause", "ref_id": "PMID-8524816_E29" } ] }, { "id": "PMID-8524816_E31", "type": "Positive_regulation", "trigger": { "text": [ "mediates" ], "offsets": [ [ 1495, 1503 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "PMID-8524816_E32" }, { "role": "Cause", "ref_id": "PMID-8524816_E27" } ] }, { "id": "PMID-8524816_E32", "type": "Negative_regulation", "trigger": { "text": [ "inhibitory" ], "offsets": [ [ 1508, 1518 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "PMID-8524816_E33" } ] }, { "id": "PMID-8524816_E33", "type": "Gene_expression", "trigger": { "text": [ "expression" ], "offsets": [ [ 1565, 1575 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "PMID-8524816_T19" } ] } ]

[ { "id": "PMID-8524816_1", "entity_ids": [ "PMID-8524816_T3", "PMID-8524816_T2" ] } ]

[]

[ { "id": "PMID-8530384__text", "type": "abstract", "text": [ "Functional characterization of the murine homolog of the B cell-specific coactivator BOB.1/OBF.1. \nB cell-specific transcriptional promoter activity mediated by the octamer motif requires the Oct1 or Oct2 protein and additional B cell-restricted cofactors. One such cofactor, BOB.1/OBF.1, was recently isolated from human B cells. Here, we describe the isolation and detailed characterization of the murine homolog. Full-length cDNAs and genomic clones were isolated, and the gene structure was determined. Comparison of the deduced amino acids shows 88% sequence identity between mouse and human BOB.1/OBF.1. The NH2-terminal 126 amino acids of BOB.1/OBF.1 are both essential and sufficient for interaction with the POU domains of either Oct1 or Oct2. This protein-protein interaction does not require the simultaneous binding of Oct proteins to DNA, and high resolution footprinting of the Oct-DNA interaction reveals that binding of BOB.1/OBF.1 to Oct1 or Oct2 does not alter the interaction with DNA. BOB.1/OBF.1 can efficiently activate octamer-dependent promoters in fibroblasts; however, it fails to stimulate octamer-dependent enhancer activity. Fusion of subdomains of BOB.1/OBF.1 with the GAL4 DNA binding domain reveals that both NH2- and COOH-terminal domains of BOB.1/OBF.1 contribute to full transactivation function, the COOH-terminal domain is more efficient in this transactivation assay. Consistent with the failure of full-length BOB.1/OBF.1 to stimulate octamer-dependent enhancer elements in non B cells, the GAL4 fusions likewise only stimulate from a promoter-proximal position. " ], "offsets": [ [ 0, 1602 ] ] } ]

[ { "id": "PMID-8530384_T1", "type": "Protein", "text": [ "BOB.1" ], "offsets": [ [ 85, 90 ] ], "normalized": [] }, { "id": "PMID-8530384_T2", "type": "Protein", "text": [ "OBF.1" ], "offsets": [ [ 91, 96 ] ], "normalized": [] }, { "id": "PMID-8530384_T3", "type": "Protein", "text": [ "Oct1" ], "offsets": [ [ 192, 196 ] ], "normalized": [] }, { "id": "PMID-8530384_T4", "type": "Protein", "text": [ "Oct2" ], "offsets": [ [ 200, 204 ] ], "normalized": [] }, { "id": "PMID-8530384_T5", "type": "Protein", "text": [ "BOB.1" ], "offsets": [ [ 276, 281 ] ], "normalized": [] }, { "id": "PMID-8530384_T6", "type": "Protein", "text": [ "OBF.1" ], "offsets": [ [ 282, 287 ] ], "normalized": [] }, { "id": "PMID-8530384_T7", "type": "Protein", "text": [ "BOB.1" ], "offsets": [ [ 597, 602 ] ], "normalized": [] }, { "id": "PMID-8530384_T8", "type": "Protein", "text": [ "OBF.1" ], "offsets": [ [ 603, 608 ] ], "normalized": [] }, { "id": "PMID-8530384_T9", "type": "Protein", "text": [ "BOB.1" ], "offsets": [ [ 646, 651 ] ], "normalized": [] }, { "id": "PMID-8530384_T10", "type": "Protein", "text": [ "OBF.1" ], "offsets": [ [ 652, 657 ] ], "normalized": [] }, { "id": "PMID-8530384_T11", "type": "Protein", "text": [ "Oct1" ], "offsets": [ [ 739, 743 ] ], "normalized": [] }, { "id": "PMID-8530384_T12", "type": "Protein", "text": [ "Oct2" ], "offsets": [ [ 747, 751 ] ], "normalized": [] }, { "id": "PMID-8530384_T13", "type": "Protein", "text": [ "BOB.1" ], "offsets": [ [ 936, 941 ] ], "normalized": [] }, { "id": "PMID-8530384_T14", "type": "Protein", "text": [ "OBF.1" ], "offsets": [ [ 942, 947 ] ], "normalized": [] }, { "id": "PMID-8530384_T15", "type": "Protein", "text": [ "Oct1" ], "offsets": [ [ 951, 955 ] ], "normalized": [] }, { "id": "PMID-8530384_T16", "type": "Protein", "text": [ "Oct2" ], "offsets": [ [ 959, 963 ] ], "normalized": [] }, { "id": "PMID-8530384_T17", "type": "Protein", "text": [ "BOB.1" ], "offsets": [ [ 1005, 1010 ] ], "normalized": [] }, { "id": "PMID-8530384_T18", "type": "Protein", "text": [ "OBF.1" ], "offsets": [ [ 1011, 1016 ] ], "normalized": [] }, { "id": "PMID-8530384_T19", "type": "Protein", "text": [ "BOB.1" ], "offsets": [ [ 1178, 1183 ] ], "normalized": [] }, { "id": "PMID-8530384_T20", "type": "Protein", "text": [ "OBF.1" ], "offsets": [ [ 1184, 1189 ] ], "normalized": [] }, { "id": "PMID-8530384_T21", "type": "Protein", "text": [ "GAL4" ], "offsets": [ [ 1199, 1203 ] ], "normalized": [] }, { "id": "PMID-8530384_T22", "type": "Protein", "text": [ "BOB.1" ], "offsets": [ [ 1275, 1280 ] ], "normalized": [] }, { "id": "PMID-8530384_T23", "type": "Protein", "text": [ "OBF.1" ], "offsets": [ [ 1281, 1286 ] ], "normalized": [] }, { "id": "PMID-8530384_T24", "type": "Protein", "text": [ "BOB.1" ], "offsets": [ [ 1449, 1454 ] ], "normalized": [] }, { "id": "PMID-8530384_T25", "type": "Protein", "text": [ "OBF.1" ], "offsets": [ [ 1455, 1460 ] ], "normalized": [] }, { "id": "PMID-8530384_T26", "type": "Protein", "text": [ "GAL4" ], "offsets": [ [ 1530, 1534 ] ], "normalized": [] }, { "id": "PMID-8530384_T27", "type": "Entity", "text": [ "NH2-terminal 126 amino acids" ], "offsets": [ [ 614, 642 ] ], "normalized": [] }, { "id": "PMID-8530384_T30", "type": "Entity", "text": [ "POU domains" ], "offsets": [ [ 717, 728 ] ], "normalized": [] } ]

[ { "id": "PMID-8530384_E1", "type": "Positive_regulation", "trigger": { "text": [ "essential and sufficient" ], "offsets": [ [ 667, 691 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "PMID-8530384_E4" }, { "role": "Cause", "ref_id": "PMID-8530384_T9" }, { "role": "CSite", "ref_id": "PMID-8530384_T27" } ] }, { "id": "PMID-8530384_E2", "type": "Positive_regulation", "trigger": { "text": [ "essential and sufficient" ], "offsets": [ [ 667, 691 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "PMID-8530384_E3" }, { "role": "Cause", "ref_id": "PMID-8530384_T9" }, { "role": "CSite", "ref_id": "PMID-8530384_T27" } ] }, { "id": "PMID-8530384_E3", "type": "Binding", "trigger": { "text": [ "interaction" ], "offsets": [ [ 696, 707 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "PMID-8530384_T9" }, { "role": "Theme", "ref_id": "PMID-8530384_T11" }, { "role": "Site", "ref_id": "PMID-8530384_T30" } ] }, { "id": "PMID-8530384_E4", "type": "Binding", "trigger": { "text": [ "interaction" ], "offsets": [ [ 696, 707 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "PMID-8530384_T9" }, { "role": "Theme", "ref_id": "PMID-8530384_T12" }, { "role": "Site", "ref_id": "PMID-8530384_T30" } ] }, { "id": "PMID-8530384_E5", "type": "Positive_regulation", "trigger": { "text": [ "require" ], "offsets": [ [ 795, 802 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "PMID-8530384_E4" } ] }, { "id": "PMID-8530384_E6", "type": "Positive_regulation", "trigger": { "text": [ "require" ], "offsets": [ [ 795, 802 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "PMID-8530384_E3" } ] }, { "id": "PMID-8530384_E7", "type": "Binding", "trigger": { "text": [ "binding" ], "offsets": [ [ 925, 932 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "PMID-8530384_T13" }, { "role": "Theme", "ref_id": "PMID-8530384_T15" } ] }, { "id": "PMID-8530384_E8", "type": "Binding", "trigger": { "text": [ "binding" ], "offsets": [ [ 925, 932 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "PMID-8530384_T13" }, { "role": "Theme", "ref_id": "PMID-8530384_T16" } ] } ]

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[]

[ { "id": "PMID-8543789__text", "type": "abstract", "text": [ "Polymorphic nucleotides within the human IL-4 promoter that mediate overexpression of the gene. \nAtopy, which predisposes individuals to develop asthma, severe systemic anaphylaxis, and atopic dermatitis, is usually associated with dramatically elevated total serum IgE levels and is thought to be controlled by a major susceptibility gene and multiple minor susceptibility genes. A recent sib-pair analysis revealed a tight linkage between markers on 5q31.1 and a major susceptibility gene controlling total serum IgE levels. Due to its location within this cluster and its biologic role in Ig class switching and Th2 cell differentiation, the IL-4 gene has emerged as one major candidate for the atopy gene. In one model, polymorphisms within IL-4 regulatory elements might result in overexpression of the gene, amplifying Th2 cell differentiation and class switching to IgE. In support of this model, we report that the human IL-4 promoter exists in multiple allelic forms that exhibit distinct transcriptional activities in IL-4-positive T cells. A particular allele has an unusually high transcriptional activity. A nucleotide substitution within a recently described OAP40 element located just upstream of an NF-AT site (P sequence) appears to be largely responsible for the increased promotor strength of this particular allelic form of the IL-4 promoter. In EMSAs, this substitution results in a markedly enhanced affinity for sequence-specific complexes exhibiting an AP-1 specificity. The identification of allelic nucleotides, which results in overexpression of the IL-4 gene, provides specific targets for a comprehensive screening of atopic and nonatopic individuals and may provide a clue for genetic predisposition for atopy. " ], "offsets": [ [ 0, 1741 ] ] } ]

[ { "id": "PMID-8543789_T1", "type": "Protein", "text": [ "IL-4" ], "offsets": [ [ 41, 45 ] ], "normalized": [] }, { "id": "PMID-8543789_T2", "type": "Protein", "text": [ "IL-4" ], "offsets": [ [ 645, 649 ] ], "normalized": [] }, { "id": "PMID-8543789_T3", "type": "Protein", "text": [ "IL-4" ], "offsets": [ [ 745, 749 ] ], "normalized": [] }, { "id": "PMID-8543789_T4", "type": "Protein", "text": [ "IL-4" ], "offsets": [ [ 929, 933 ] ], "normalized": [] }, { "id": "PMID-8543789_T5", "type": "Protein", "text": [ "IL-4" ], "offsets": [ [ 1028, 1032 ] ], "normalized": [] }, { "id": "PMID-8543789_T6", "type": "Protein", "text": [ "IL-4" ], "offsets": [ [ 1348, 1352 ] ], "normalized": [] }, { "id": "PMID-8543789_T7", "type": "Protein", "text": [ "IL-4" ], "offsets": [ [ 1577, 1581 ] ], "normalized": [] }, { "id": "PMID-8543789_T8", "type": "Entity", "text": [ "promoter" ], "offsets": [ [ 46, 54 ] ], "normalized": [] } ]

[ { "id": "PMID-8543789_E1", "type": "Positive_regulation", "trigger": { "text": [ "mediate" ], "offsets": [ [ 60, 67 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "PMID-8543789_E2" }, { "role": "Cause", "ref_id": "PMID-8543789_T1" }, { "role": "CSite", "ref_id": "PMID-8543789_T8" } ] }, { "id": "PMID-8543789_E2", "type": "Positive_regulation", "trigger": { "text": [ "overexpression" ], "offsets": [ [ 68, 82 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "PMID-8543789_E3" } ] }, { "id": "PMID-8543789_E3", "type": "Gene_expression", "trigger": { "text": [ "overexpression" ], "offsets": [ [ 68, 82 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "PMID-8543789_T1" } ] }, { "id": "PMID-8543789_E4", "type": "Positive_regulation", "trigger": { "text": [ "result" ], "offsets": [ [ 776, 782 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "PMID-8543789_E6" } ] }, { "id": "PMID-8543789_E5", "type": "Gene_expression", "trigger": { "text": [ "overexpression" ], "offsets": [ [ 786, 800 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "PMID-8543789_T3" } ] }, { "id": "PMID-8543789_E6", "type": "Positive_regulation", "trigger": { "text": [ "overexpression" ], "offsets": [ [ 786, 800 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "PMID-8543789_E5" } ] }, { "id": "PMID-8543789_E7", "type": "Transcription", "trigger": { "text": [ "transcriptional" ], "offsets": [ [ 998, 1013 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "PMID-8543789_T4" } ] }, { "id": "PMID-8543789_E8", "type": "Gene_expression", "trigger": { "text": [ "positive" ], "offsets": [ [ 1033, 1041 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "PMID-8543789_T5" } ] }, { "id": "PMID-8543789_E9", "type": "Positive_regulation", "trigger": { "text": [ "high" ], "offsets": [ [ 1088, 1092 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "PMID-8543789_E10" } ] }, { "id": "PMID-8543789_E10", "type": "Transcription", "trigger": { "text": [ "transcriptional activity" ], "offsets": [ [ 1093, 1117 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "PMID-8543789_T4" } ] }, { "id": "PMID-8543789_E11", "type": "Positive_regulation", "trigger": { "text": [ "results" ], "offsets": [ [ 1544, 1551 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "PMID-8543789_E12" } ] }, { "id": "PMID-8543789_E12", "type": "Positive_regulation", "trigger": { "text": [ "overexpression" ], "offsets": [ [ 1555, 1569 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "PMID-8543789_E13" } ] }, { "id": "PMID-8543789_E13", "type": "Gene_expression", "trigger": { "text": [ "overexpression" ], "offsets": [ [ 1555, 1569 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "PMID-8543789_T7" } ] } ]

[]

[]

[ { "id": "PMID-8543841__text", "type": "abstract", "text": [ "IL-10 cooperates with TNF-alpha to activate HIV-1 from latently and acutely infected cells of monocyte/macrophage lineage. \nIL-10 is elevated in HIV-1-infected individuals and has been implicated in disease progression. In this study, we investigated the effects of IL-10 on the activation of HIV-1 from infected monocytes and macrophages. Although IL-10 alone did not induce HIV-1 replication, in the presence of TNF-alpha, IL-10 markedly enhanced virion production from a chronically infected promonocytic cell line (U1) and in acutely infected monocyte-derived macrophages. Neutralizing mAbs to IL-10 and TNF-alpha indicated that both cytokines were essential for the induction and were required to generate a synergistic increase in virus expression. The effects of the two cytokines were distinguishable functionally since pretreatment with TNF-alpha attenuated the cytokine cooperativity, while pretreatment with IL-10 potentiated their cooperativity, suggesting that IL-10 and TNF-alpha play different roles in the activation of virus. Northern blot analysis as well as Ab blocking and cytokine secretion studies indicated that the induction of either endogenous TNF-alpha or IL-10 was not involved in the cooperativity, nor was an up-regulation of TNF-alpha receptors. In combination with TNF-alpha, IL-10 stimulated activating protein-1 (AP-1) and nuclear factor (NF)-kappa B binding activities and cooperated to increase HIV-1 steady-state mRNA levels and enhance long terminal repeat-directed transcription through activation of the NF-kappa B binding sites, suggesting the IL-10 effect occurs at least in part at the transcriptional level. These results indicate that IL-10, in addition to down-regulating the cellular immune response to HIV-1, may also play a role in TNF-alpha-mediated activation of HIV-1 replication in the monocyte/macrophage lineage. " ], "offsets": [ [ 0, 1868 ] ] } ]

[ { "id": "PMID-8543841_T1", "type": "Protein", "text": [ "IL-10" ], "offsets": [ [ 0, 5 ] ], "normalized": [] }, { "id": "PMID-8543841_T2", "type": "Protein", "text": [ "TNF-alpha" ], "offsets": [ [ 22, 31 ] ], "normalized": [] }, { "id": "PMID-8543841_T3", "type": "Protein", "text": [ "IL-10" ], "offsets": [ [ 124, 129 ] ], "normalized": [] }, { "id": "PMID-8543841_T4", "type": "Protein", "text": [ "IL-10" ], "offsets": [ [ 266, 271 ] ], "normalized": [] }, { "id": "PMID-8543841_T5", "type": "Protein", "text": [ "IL-10" ], "offsets": [ [ 349, 354 ] ], "normalized": [] }, { "id": "PMID-8543841_T6", "type": "Protein", "text": [ "TNF-alpha" ], "offsets": [ [ 414, 423 ] ], "normalized": [] }, { "id": "PMID-8543841_T7", "type": "Protein", "text": [ "IL-10" ], "offsets": [ [ 425, 430 ] ], "normalized": [] }, { "id": "PMID-8543841_T8", "type": "Protein", "text": [ "IL-10" ], "offsets": [ [ 598, 603 ] ], "normalized": [] }, { "id": "PMID-8543841_T9", "type": "Protein", "text": [ "TNF-alpha" ], "offsets": [ [ 608, 617 ] ], "normalized": [] }, { "id": "PMID-8543841_T10", "type": "Protein", "text": [ "TNF-alpha" ], "offsets": [ [ 846, 855 ] ], "normalized": [] }, { "id": "PMID-8543841_T11", "type": "Protein", "text": [ "IL-10" ], "offsets": [ [ 919, 924 ] ], "normalized": [] }, { "id": "PMID-8543841_T12", "type": "Protein", "text": [ "IL-10" ], "offsets": [ [ 974, 979 ] ], "normalized": [] }, { "id": "PMID-8543841_T13", "type": "Protein", "text": [ "TNF-alpha" ], "offsets": [ [ 984, 993 ] ], "normalized": [] }, { "id": "PMID-8543841_T14", "type": "Protein", "text": [ "TNF-alpha" ], "offsets": [ [ 1170, 1179 ] ], "normalized": [] }, { "id": "PMID-8543841_T15", "type": "Protein", "text": [ "IL-10" ], "offsets": [ [ 1183, 1188 ] ], "normalized": [] }, { "id": "PMID-8543841_T16", "type": "Protein", "text": [ "TNF-alpha" ], "offsets": [ [ 1297, 1306 ] ], "normalized": [] }, { "id": "PMID-8543841_T17", "type": "Protein", "text": [ "IL-10" ], "offsets": [ [ 1308, 1313 ] ], "normalized": [] }, { "id": "PMID-8543841_T18", "type": "Protein", "text": [ "IL-10" ], "offsets": [ [ 1585, 1590 ] ], "normalized": [] }, { "id": "PMID-8543841_T19", "type": "Protein", "text": [ "IL-10" ], "offsets": [ [ 1680, 1685 ] ], "normalized": [] }, { "id": "PMID-8543841_T20", "type": "Protein", "text": [ "TNF-alpha" ], "offsets": [ [ 1781, 1790 ] ], "normalized": [] } ]

[ { "id": "PMID-8543841_E1", "type": "Positive_regulation", "trigger": { "text": [ "elevated" ], "offsets": [ [ 133, 141 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "PMID-8543841_T3" } ] }, { "id": "PMID-8543841_E2", "type": "Positive_regulation", "trigger": { "text": [ "induction" ], "offsets": [ [ 1139, 1148 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "PMID-8543841_T15" } ] }, { "id": "PMID-8543841_E3", "type": "Positive_regulation", "trigger": { "text": [ "induction" ], "offsets": [ [ 1139, 1148 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "PMID-8543841_T14" } ] } ]

[]

[]

[ { "id": "PMID-8555489__text", "type": "abstract", "text": [ "The promoter and 5' flanking sequences controlling human B29 gene expression. \nThe product of the B-cell-specific B29 gene (B29, Ig beta, CD79b) is essential for Ig-mediated B-cell activation via the B-cell antigen receptor complex (BCR) on human and murine B lymphocytes. To better understand the regulation of this pivotal gene, we have analyzed the human genomic DNA sequence upstream of the B29 ATG start codon for transcriptional control activity. The human B29 gene lacks either a TATA or a CAAT box and transcription is initiated at multiple sites. The minimal promoter of the human B29 gene is contained within a 193-bp region 5' of these multiple start sites. This minimal promoter exhibits B-cell-specific activity and contains SP1, ETS, OCT, and IKAROS/LYF-1 transcription factor motifs. All these motifs are strikingly conserved in sequence and placement relative to the previously characterized murine B29 promoter. Additional upstream gene segments dramatically affected B29 minimal promoter activity. A newly identified motif called the B29 conserved sequence (BCS), found upstream of both human and murine B29 promoters, appears to stimulate B29 transcription through a novel mechanism. A single BCS had little effect either on the minimal B29 promoter or on a heterologous promoter. Instead, the BCS stimulated transcription by counteracting 5' negative regulatory DNA sequences that block the activity of the B29 minimal promoter in its absence. These findings indicate that B29 gene expression is controlled by the complex interplay of positive and negative regulatory elements. " ], "offsets": [ [ 0, 1598 ] ] } ]

[ { "id": "PMID-8555489_T1", "type": "Protein", "text": [ "B29" ], "offsets": [ [ 57, 60 ] ], "normalized": [] }, { "id": "PMID-8555489_T2", "type": "Protein", "text": [ "B29" ], "offsets": [ [ 114, 117 ] ], "normalized": [] }, { "id": "PMID-8555489_T3", "type": "Protein", "text": [ "B29" ], "offsets": [ [ 124, 127 ] ], "normalized": [] }, { "id": "PMID-8555489_T4", "type": "Protein", "text": [ "Ig beta" ], "offsets": [ [ 129, 136 ] ], "normalized": [] }, { "id": "PMID-8555489_T5", "type": "Protein", "text": [ "CD79b" ], "offsets": [ [ 138, 143 ] ], "normalized": [] }, { "id": "PMID-8555489_T6", "type": "Protein", "text": [ "B29" ], "offsets": [ [ 395, 398 ] ], "normalized": [] }, { "id": "PMID-8555489_T7", "type": "Protein", "text": [ "B29" ], "offsets": [ [ 463, 466 ] ], "normalized": [] }, { "id": "PMID-8555489_T8", "type": "Protein", "text": [ "B29" ], "offsets": [ [ 590, 593 ] ], "normalized": [] }, { "id": "PMID-8555489_T9", "type": "Protein", "text": [ "B29" ], "offsets": [ [ 915, 918 ] ], "normalized": [] }, { "id": "PMID-8555489_T10", "type": "Protein", "text": [ "B29" ], "offsets": [ [ 985, 988 ] ], "normalized": [] }, { "id": "PMID-8555489_T11", "type": "Protein", "text": [ "B29" ], "offsets": [ [ 1052, 1055 ] ], "normalized": [] }, { "id": "PMID-8555489_T12", "type": "Protein", "text": [ "B29" ], "offsets": [ [ 1122, 1125 ] ], "normalized": [] }, { "id": "PMID-8555489_T13", "type": "Protein", "text": [ "B29" ], "offsets": [ [ 1158, 1161 ] ], "normalized": [] }, { "id": "PMID-8555489_T14", "type": "Protein", "text": [ "B29" ], "offsets": [ [ 1256, 1259 ] ], "normalized": [] }, { "id": "PMID-8555489_T15", "type": "Protein", "text": [ "B29" ], "offsets": [ [ 1427, 1430 ] ], "normalized": [] }, { "id": "PMID-8555489_T16", "type": "Protein", "text": [ "B29" ], "offsets": [ [ 1493, 1496 ] ], "normalized": [] }, { "id": "PMID-8555489_T22", "type": "Entity", "text": [ "minimal promoter" ], "offsets": [ [ 989, 1005 ] ], "normalized": [] }, { "id": "PMID-8555489_T26", "type": "Entity", "text": [ "promoter" ], "offsets": [ [ 1260, 1268 ] ], "normalized": [] }, { "id": "PMID-8555489_T29", "type": "Entity", "text": [ "minimal promoter" ], "offsets": [ [ 1431, 1447 ] ], "normalized": [] } ]

[ { "id": "PMID-8555489_E1", "type": "Regulation", "trigger": { "text": [ "controlling" ], "offsets": [ [ 39, 50 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "PMID-8555489_E2" } ] }, { "id": "PMID-8555489_E2", "type": "Gene_expression", "trigger": { "text": [ "expression" ], "offsets": [ [ 66, 76 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "PMID-8555489_T1" } ] }, { "id": "PMID-8555489_E3", "type": "Regulation", "trigger": { "text": [ "regulation" ], "offsets": [ [ 298, 308 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "PMID-8555489_T6" } ] }, { "id": "PMID-8555489_E4", "type": "Transcription", "trigger": { "text": [ "initiated" ], "offsets": [ [ 527, 536 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "PMID-8555489_T7" } ] }, { "id": "PMID-8555489_E5", "type": "Regulation", "trigger": { "text": [ "affected" ], "offsets": [ [ 976, 984 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "PMID-8555489_T10" }, { "role": "Site", "ref_id": "PMID-8555489_T22" } ] }, { "id": "PMID-8555489_E6", "type": "Regulation", "trigger": { "text": [ "stimulate" ], "offsets": [ [ 1148, 1157 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "PMID-8555489_E7" }, { "role": "Cause", "ref_id": "PMID-8555489_T11" } ] }, { "id": "PMID-8555489_E7", "type": "Transcription", "trigger": { "text": [ "transcription" ], "offsets": [ [ 1162, 1175 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "PMID-8555489_T13" } ] }, { "id": "PMID-8555489_E8", "type": "Regulation", "trigger": { "text": [ "effect" ], "offsets": [ [ 1227, 1233 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "PMID-8555489_T14" }, { "role": "Site", "ref_id": "PMID-8555489_T26" } ] }, { "id": "PMID-8555489_E9", "type": "Positive_regulation", "trigger": { "text": [ "stimulated" ], "offsets": [ [ 1317, 1327 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "PMID-8555489_E7" } ] }, { "id": "PMID-8555489_E10", "type": "Negative_regulation", "trigger": { "text": [ "block" ], "offsets": [ [ 1401, 1406 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "PMID-8555489_T15" }, { "role": "Site", "ref_id": "PMID-8555489_T29" } ] }, { "id": "PMID-8555489_E11", "type": "Gene_expression", "trigger": { "text": [ "expression" ], "offsets": [ [ 1502, 1512 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "PMID-8555489_T16" } ] }, { "id": "PMID-8555489_E12", "type": "Regulation", "trigger": { "text": [ "controlled" ], "offsets": [ [ 1516, 1526 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "PMID-8555489_E11" } ] } ]

[ { "id": "PMID-8555489_1", "entity_ids": [ "PMID-8555489_T3", "PMID-8555489_T4", "PMID-8555489_T5" ] } ]

[]

[ { "id": "PMID-8557975__text", "type": "abstract", "text": [ "MEK1 and the extracellular signal-regulated kinases are required for the stimulation of IL-2 gene transcription in T cells. \nTCR engagement stimulates the activation of the protein kinase Raf-1. Active Raf-1 phosphorylates and activates the mitogen-activated protein (MAP) kinase/extracellular signal-regulated kinase kinase 1 (MEK1), which in turn phosphorylates and activates the MAP kinases/extracellular signal regulated kinases, ERK1 and ERK2. Raf-1 activity promotes IL-2 production in activated T lymphocytes. Therefore, we sought to determine whether MEK1 and ERK activities also stimulate IL-2 gene transcription. Expression of constitutively active Raf-1 or MEK1 in Jurkat T cells enhanced the stimulation of IL-2 promoter-driven transcription stimulated by a calcium ionophore and PMA, and together with a calcium ionophore the expression of each protein was sufficient to stimulate NF-AT activity. Expression of MEK1-interfering mutants inhibited the stimulation of IL-2 promoter-driven transcription and blocked the ability of constitutively active Ras and Raf-1 to costimulate NF-AT activity with a calcium ionophore. Expression of the MAP kinase-specific phosphatase, MKP-1, which blocks ERK activation, inhibited IL-2 promoter and NF-AT-driven transcription stimulated by a calcium ionophore and PMA, and in addition, MKP-1 neutralized the transcriptional enhancement caused by active Raf-1 and MEK1 expression. We conclude that the MAP kinase signal transduction pathway consisting of Raf-1, MEK1, and ERK1 and ERK2 functions in the stimulation IL-2 gene transcription in activated T lymphocytes. " ], "offsets": [ [ 0, 1614 ] ] } ]

[ { "id": "PMID-8557975_T1", "type": "Protein", "text": [ "MEK1" ], "offsets": [ [ 0, 4 ] ], "normalized": [] }, { "id": "PMID-8557975_T2", "type": "Protein", "text": [ "IL-2" ], "offsets": [ [ 88, 92 ] ], "normalized": [] }, { "id": "PMID-8557975_T3", "type": "Protein", "text": [ "Raf-1" ], "offsets": [ [ 188, 193 ] ], "normalized": [] }, { "id": "PMID-8557975_T4", "type": "Protein", "text": [ "Raf-1" ], "offsets": [ [ 202, 207 ] ], "normalized": [] }, { "id": "PMID-8557975_T5", "type": "Protein", "text": [ "mitogen-activated protein (MAP) kinase/extracellular signal-regulated kinase kinase 1" ], "offsets": [ [ 241, 326 ] ], "normalized": [] }, { "id": "PMID-8557975_T6", "type": "Protein", "text": [ "MEK1" ], "offsets": [ [ 328, 332 ] ], "normalized": [] }, { "id": "PMID-8557975_T7", "type": "Protein", "text": [ "ERK1" ], "offsets": [ [ 434, 438 ] ], "normalized": [] }, { "id": "PMID-8557975_T8", "type": "Protein", "text": [ "ERK2" ], "offsets": [ [ 443, 447 ] ], "normalized": [] }, { "id": "PMID-8557975_T9", "type": "Protein", "text": [ "Raf-1" ], "offsets": [ [ 449, 454 ] ], "normalized": [] }, { "id": "PMID-8557975_T10", "type": "Protein", "text": [ "IL-2" ], "offsets": [ [ 473, 477 ] ], "normalized": [] }, { "id": "PMID-8557975_T11", "type": "Protein", "text": [ "MEK1" ], "offsets": [ [ 559, 563 ] ], "normalized": [] }, { "id": "PMID-8557975_T12", "type": "Protein", "text": [ "IL-2" ], "offsets": [ [ 598, 602 ] ], "normalized": [] }, { "id": "PMID-8557975_T13", "type": "Protein", "text": [ "Raf-1" ], "offsets": [ [ 659, 664 ] ], "normalized": [] }, { "id": "PMID-8557975_T14", "type": "Protein", "text": [ "MEK1" ], "offsets": [ [ 668, 672 ] ], "normalized": [] }, { "id": "PMID-8557975_T15", "type": "Protein", "text": [ "IL-2" ], "offsets": [ [ 719, 723 ] ], "normalized": [] }, { "id": "PMID-8557975_T16", "type": "Protein", "text": [ "MEK1" ], "offsets": [ [ 924, 928 ] ], "normalized": [] }, { "id": "PMID-8557975_T17", "type": "Protein", "text": [ "IL-2" ], "offsets": [ [ 978, 982 ] ], "normalized": [] }, { "id": "PMID-8557975_T18", "type": "Protein", "text": [ "Raf-1" ], "offsets": [ [ 1070, 1075 ] ], "normalized": [] }, { "id": "PMID-8557975_T19", "type": "Protein", "text": [ "MKP-1" ], "offsets": [ [ 1183, 1188 ] ], "normalized": [] }, { "id": "PMID-8557975_T20", "type": "Protein", "text": [ "IL-2" ], "offsets": [ [ 1229, 1233 ] ], "normalized": [] }, { "id": "PMID-8557975_T21", "type": "Protein", "text": [ "MKP-1" ], "offsets": [ [ 1334, 1339 ] ], "normalized": [] }, { "id": "PMID-8557975_T22", "type": "Protein", "text": [ "Raf-1" ], "offsets": [ [ 1401, 1406 ] ], "normalized": [] }, { "id": "PMID-8557975_T23", "type": "Protein", "text": [ "MEK1" ], "offsets": [ [ 1411, 1415 ] ], "normalized": [] }, { "id": "PMID-8557975_T24", "type": "Protein", "text": [ "Raf-1" ], "offsets": [ [ 1502, 1507 ] ], "normalized": [] }, { "id": "PMID-8557975_T25", "type": "Protein", "text": [ "MEK1" ], "offsets": [ [ 1509, 1513 ] ], "normalized": [] }, { "id": "PMID-8557975_T26", "type": "Protein", "text": [ "ERK1" ], "offsets": [ [ 1519, 1523 ] ], "normalized": [] }, { "id": "PMID-8557975_T27", "type": "Protein", "text": [ "ERK2" ], "offsets": [ [ 1528, 1532 ] ], "normalized": [] }, { "id": "PMID-8557975_T28", "type": "Protein", "text": [ "IL-2" ], "offsets": [ [ 1562, 1566 ] ], "normalized": [] } ]

[ { "id": "PMID-8557975_E1", "type": "Positive_regulation", "trigger": { "text": [ "required" ], "offsets": [ [ 56, 64 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "PMID-8557975_E3" }, { "role": "Cause", "ref_id": "PMID-8557975_T1" } ] }, { "id": "PMID-8557975_E2", "type": "Positive_regulation", "trigger": { "text": [ "required" ], "offsets": [ [ 56, 64 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "PMID-8557975_E3" } ] }, { "id": "PMID-8557975_E3", "type": "Positive_regulation", "trigger": { "text": [ "stimulation" ], "offsets": [ [ 73, 84 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "PMID-8557975_E4" } ] }, { "id": "PMID-8557975_E4", "type": "Transcription", "trigger": { "text": [ "transcription" ], "offsets": [ [ 98, 111 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "PMID-8557975_T2" } ] }, { "id": "PMID-8557975_E5", "type": "Positive_regulation", "trigger": { "text": [ "stimulates the activation" ], "offsets": [ [ 140, 165 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "PMID-8557975_T3" } ] }, { "id": "PMID-8557975_E6", "type": "Phosphorylation", "trigger": { "text": [ "phosphorylates" ], "offsets": [ [ 208, 222 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "PMID-8557975_T6" } ] }, { "id": "PMID-8557975_E7", "type": "Positive_regulation", "trigger": { "text": [ "phosphorylates" ], "offsets": [ [ 208, 222 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "PMID-8557975_E6" }, { "role": "Cause", "ref_id": "PMID-8557975_T4" } ] }, { "id": "PMID-8557975_E8", "type": "Positive_regulation", "trigger": { "text": [ "activates" ], "offsets": [ [ 227, 236 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "PMID-8557975_T6" }, { "role": "Cause", "ref_id": "PMID-8557975_T4" } ] }, { "id": "PMID-8557975_E9", "type": "Phosphorylation", "trigger": { "text": [ "phosphorylates" ], "offsets": [ [ 349, 363 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "PMID-8557975_T7" } ] }, { "id": "PMID-8557975_E10", "type": "Positive_regulation", "trigger": { "text": [ "phosphorylates" ], "offsets": [ [ 349, 363 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "PMID-8557975_E9" }, { "role": "Cause", "ref_id": "PMID-8557975_T6" } ] }, { "id": "PMID-8557975_E11", "type": "Positive_regulation", "trigger": { "text": [ "phosphorylates" ], "offsets": [ [ 349, 363 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "PMID-8557975_E12" }, { "role": "Cause", "ref_id": "PMID-8557975_T6" } ] }, { "id": "PMID-8557975_E12", "type": "Phosphorylation", "trigger": { "text": [ "phosphorylates" ], "offsets": [ [ 349, 363 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "PMID-8557975_T8" } ] }, { "id": "PMID-8557975_E13", "type": "Positive_regulation", "trigger": { "text": [ "activates" ], "offsets": [ [ 368, 377 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "PMID-8557975_T7" }, { "role": "Cause", "ref_id": "PMID-8557975_T6" } ] }, { "id": "PMID-8557975_E14", "type": "Positive_regulation", "trigger": { "text": [ "activates" ], "offsets": [ [ 368, 377 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "PMID-8557975_T8" }, { "role": "Cause", "ref_id": "PMID-8557975_T6" } ] }, { "id": "PMID-8557975_E15", "type": "Positive_regulation", "trigger": { "text": [ "promotes" ], "offsets": [ [ 464, 472 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "PMID-8557975_E16" }, { "role": "Cause", "ref_id": "PMID-8557975_T9" } ] }, { "id": "PMID-8557975_E16", "type": "Gene_expression", "trigger": { "text": [ "production" ], "offsets": [ [ 478, 488 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "PMID-8557975_T10" } ] }, { "id": "PMID-8557975_E17", "type": "Positive_regulation", "trigger": { "text": [ "stimulate" ], "offsets": [ [ 588, 597 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "PMID-8557975_E19" } ] }, { "id": "PMID-8557975_E18", "type": "Positive_regulation", "trigger": { "text": [ "stimulate" ], "offsets": [ [ 588, 597 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "PMID-8557975_E19" }, { "role": "Cause", "ref_id": "PMID-8557975_T11" } ] }, { "id": "PMID-8557975_E19", "type": "Transcription", "trigger": { "text": [ "transcription" ], "offsets": [ [ 608, 621 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "PMID-8557975_T12" } ] }, { "id": "PMID-8557975_E20", "type": "Positive_regulation", "trigger": { "text": [ "Expression" ], "offsets": [ [ 623, 633 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "PMID-8557975_T13" } ] }, { "id": "PMID-8557975_E21", "type": "Positive_regulation", "trigger": { "text": [ "Expression" ], "offsets": [ [ 623, 633 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "PMID-8557975_T14" } ] }, { "id": "PMID-8557975_E22", "type": "Gene_expression", "trigger": { "text": [ "expression" ], "offsets": [ [ 839, 849 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "PMID-8557975_T14" } ] }, { "id": "PMID-8557975_E23", "type": "Gene_expression", "trigger": { "text": [ "expression" ], "offsets": [ [ 839, 849 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "PMID-8557975_T13" } ] }, { "id": "PMID-8557975_E24", "type": "Gene_expression", "trigger": { "text": [ "Expression" ], "offsets": [ [ 1132, 1142 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "PMID-8557975_T19" } ] }, { "id": "PMID-8557975_E25", "type": "Positive_regulation", "trigger": { "text": [ "expression" ], "offsets": [ [ 1416, 1426 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "PMID-8557975_T23" } ] }, { "id": "PMID-8557975_E26", "type": "Positive_regulation", "trigger": { "text": [ "expression" ], "offsets": [ [ 1416, 1426 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "PMID-8557975_T22" } ] }, { "id": "PMID-8557975_E27", "type": "Regulation", "trigger": { "text": [ "functions" ], "offsets": [ [ 1533, 1542 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "PMID-8557975_E32" }, { "role": "Cause", "ref_id": "PMID-8557975_T26" } ] }, { "id": "PMID-8557975_E28", "type": "Regulation", "trigger": { "text": [ "functions" ], "offsets": [ [ 1533, 1542 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "PMID-8557975_E32" }, { "role": "Cause", "ref_id": "PMID-8557975_T27" } ] }, { "id": "PMID-8557975_E29", "type": "Regulation", "trigger": { "text": [ "functions" ], "offsets": [ [ 1533, 1542 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "PMID-8557975_E32" } ] }, { "id": "PMID-8557975_E30", "type": "Regulation", "trigger": { "text": [ "functions" ], "offsets": [ [ 1533, 1542 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "PMID-8557975_E32" }, { "role": "Cause", "ref_id": "PMID-8557975_T24" } ] }, { "id": "PMID-8557975_E31", "type": "Regulation", "trigger": { "text": [ "functions" ], "offsets": [ [ 1533, 1542 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "PMID-8557975_E32" }, { "role": "Cause", "ref_id": "PMID-8557975_T25" } ] }, { "id": "PMID-8557975_E32", "type": "Positive_regulation", "trigger": { "text": [ "stimulation" ], "offsets": [ [ 1550, 1561 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "PMID-8557975_E33" } ] }, { "id": "PMID-8557975_E33", "type": "Transcription", "trigger": { "text": [ "transcription" ], "offsets": [ [ 1572, 1585 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "PMID-8557975_T28" } ] } ]

[ { "id": "PMID-8557975_1", "entity_ids": [ "PMID-8557975_T6", "PMID-8557975_T5" ] } ]

[]

[ { "id": "PMID-8562512__text", "type": "abstract", "text": [ "Cross-linking of Fc gamma receptors activates HIV-1 long terminal repeat-driven transcription in human monocytes. \nElevation of the levels of circulating immune complexes frequently accompanies HIV-1 infection and is a prognostic indicator of clinical progression from asymptomatic infection to AIDS. Here we report that cross-linking of Fc gamma RI or Fc gamma RII by adherent human IgG or by specific anti-Fc gamma R mAb activates HIV-1 gene expression in the human monocytic cell line BF24 and increased HIV RNA expression in monocytes from HIV infected patients as assayed by reverse transcription-PCR. In THP-1 cells, Fc gamma R cross-linking induced NF-kappa B, which is known to bind to the regulatory region of the long terminal repeat (LTR) of HIV-1 and to activate HIV-1 transcription. Anti-TNF-alpha antibody but not anti-IL-1 beta antibody strongly inhibited both the induction of HIV-1-LTR-driven transcription and the induction of NF-kappa B by Fc gamma R cross-linking. These results indicate that Fc gamma R can mediate a TNF-alpha-dependent induction of HIV-1 gene transcription and suggest that immune complexes may contribute to the pathophysiology of HIV-1 infection by augmenting viral replication in monocytes. " ], "offsets": [ [ 0, 1233 ] ] } ]

[ { "id": "PMID-8562512_T1", "type": "Protein", "text": [ "Fc gamma RI" ], "offsets": [ [ 338, 349 ] ], "normalized": [] }, { "id": "PMID-8562512_T2", "type": "Protein", "text": [ "Fc gamma RII" ], "offsets": [ [ 353, 365 ] ], "normalized": [] }, { "id": "PMID-8562512_T3", "type": "Protein", "text": [ "TNF-alpha" ], "offsets": [ [ 801, 810 ] ], "normalized": [] }, { "id": "PMID-8562512_T4", "type": "Protein", "text": [ "IL-1 beta" ], "offsets": [ [ 833, 842 ] ], "normalized": [] }, { "id": "PMID-8562512_T5", "type": "Protein", "text": [ "TNF-alpha" ], "offsets": [ [ 1038, 1047 ] ], "normalized": [] } ]

[ { "id": "PMID-8562512_E1", "type": "Binding", "trigger": { "text": [ "cross-linking" ], "offsets": [ [ 321, 334 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "PMID-8562512_T1" } ] }, { "id": "PMID-8562512_E2", "type": "Binding", "trigger": { "text": [ "cross-linking" ], "offsets": [ [ 321, 334 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "PMID-8562512_T2" } ] } ]

[]

[]

[ { "id": "PMID-8562886__text", "type": "abstract", "text": [ "The effect of Toremifene on the expression of some genes in human mononuclear cells. \nToremifene exerts multiple and varied effects on the gene expression of human peripheral mononuclear cells. After short-term, in vitro exposure to therapeutical levels, distinct changes in P-glycoprotein, steroid receptors, p53 and Bcl-2 expression take place. In view of the increasing use of antiestrogens in cancer therapy and prevention, there is obvious merit in long-term in vivo studies to be conducted. " ], "offsets": [ [ 0, 497 ] ] } ]

[ { "id": "PMID-8562886_T1", "type": "Protein", "text": [ "p53" ], "offsets": [ [ 310, 313 ] ], "normalized": [] }, { "id": "PMID-8562886_T2", "type": "Protein", "text": [ "Bcl-2" ], "offsets": [ [ 318, 323 ] ], "normalized": [] } ]

[ { "id": "PMID-8562886_E1", "type": "Regulation", "trigger": { "text": [ "changes" ], "offsets": [ [ 264, 271 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "PMID-8562886_E4" } ] }, { "id": "PMID-8562886_E2", "type": "Regulation", "trigger": { "text": [ "changes" ], "offsets": [ [ 264, 271 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "PMID-8562886_E3" } ] }, { "id": "PMID-8562886_E3", "type": "Gene_expression", "trigger": { "text": [ "expression" ], "offsets": [ [ 324, 334 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "PMID-8562886_T2" } ] }, { "id": "PMID-8562886_E4", "type": "Gene_expression", "trigger": { "text": [ "expression" ], "offsets": [ [ 324, 334 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "PMID-8562886_T1" } ] } ]

[]

[]

[ { "id": "PMID-8566023__text", "type": "abstract", "text": [ "Identification of an ionomycin/cyclosporin A-responsive element within the human T cell receptor gamma enhancer. \nActivation through the Ca2+/calcineurin pathway is essential to the transcription of many cytokine genes. The conserved cis-acting sequence, GGAAAA, and transcription factors binding to this sequence are involved in the response to increased intracellular Ca2+ concentrations. Here we report the identification and importance of the same sequence in a non-cytokine gene, the human T cell receptor gamma (TCRG) enhancer. Results from site-directed mutations and electrophoretic mobility shift assays strongly suggest that this sequence mediates the ionomycin-induced activation of the TCRG enhancer. Our studies provide an explanation for a previous observation that TCRG mRNA levels, but not mRNA levels for T cell receptor alpha and -beta, are increased by ionomycin treatment. " ], "offsets": [ [ 0, 893 ] ] } ]

[ { "id": "PMID-8566023_T1", "type": "Protein", "text": [ "T cell receptor gamma" ], "offsets": [ [ 81, 102 ] ], "normalized": [] }, { "id": "PMID-8566023_T2", "type": "Protein", "text": [ "T cell receptor gamma" ], "offsets": [ [ 495, 516 ] ], "normalized": [] }, { "id": "PMID-8566023_T3", "type": "Protein", "text": [ "TCRG" ], "offsets": [ [ 518, 522 ] ], "normalized": [] }, { "id": "PMID-8566023_T4", "type": "Protein", "text": [ "TCRG" ], "offsets": [ [ 698, 702 ] ], "normalized": [] }, { "id": "PMID-8566023_T5", "type": "Protein", "text": [ "TCRG" ], "offsets": [ [ 780, 784 ] ], "normalized": [] }, { "id": "PMID-8566023_T8", "type": "Entity", "text": [ "enhancer" ], "offsets": [ [ 703, 711 ] ], "normalized": [] } ]

[ { "id": "PMID-8566023_E1", "type": "Positive_regulation", "trigger": { "text": [ "mediates" ], "offsets": [ [ 649, 657 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "PMID-8566023_E2" } ] }, { "id": "PMID-8566023_E2", "type": "Positive_regulation", "trigger": { "text": [ "activation" ], "offsets": [ [ 680, 690 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "PMID-8566023_T4" }, { "role": "Site", "ref_id": "PMID-8566023_T8" } ] }, { "id": "PMID-8566023_E3", "type": "Positive_regulation", "trigger": { "text": [ "increased" ], "offsets": [ [ 859, 868 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "PMID-8566023_T5" } ] } ]

[ { "id": "PMID-8566023_1", "entity_ids": [ "PMID-8566023_T2", "PMID-8566023_T3" ] } ]

[]

[ { "id": "PMID-8573121__text", "type": "abstract", "text": [ "Inhibition of NF-kappa B activation in human T-cell lines by anetholdithiolthione. \nNuclear factor (NF)-kappa B is a redox sensitive cytosolic transcription factor. Redox regulation of NF-kappa B has been implicated in the activation of the human immuno-deficiency virus (HIV). Therefore, inhibition of NF-kappa B activation may be an effective strategy for acquired immunodeficiency syndrome therapy. Anetholdithiolthione (ADT, 5-[p-methoxyphenyl]-3H-1,2-dithiol-3-thione) is an antioxidant which has been used to protect against acetaminophen- and CCl4-induced hepatotoxicity, lipid peroxidation, radiation injury, and also has been used clinically as an anti-choleretic agent. The present study examined the effect of ADT pretreatment on NF-kappa B activation in response to a variety of stimuli such as H2O2, phorbol myristate acetate (PMA) or tumor necrosis factor alpha (TNF alpha). PMA and TNF alpha induced activation of (NF)-kappa B in human Jurkat T-cells was partially inhibited by ADT (0.1 mM) pretreatment. ADT (0.1 mM) also inhibited H2O2 induced activation of the transcription factor in the peroxide sensitive human Wurzburg T-cells. Furthermore, ADT treated Wurzburg cells had significantly higher glutathione levels as compared with untreated cells. H2O2 induced lipid peroxidation in Wurzburg cells was remarkably inhibited by ADT pretreatment. ADT, a pro-glutathione antioxidant, was observed to be capable of modulating NF-kappa B activation. " ], "offsets": [ [ 0, 1464 ] ] } ]

[ { "id": "PMID-8573121_T1", "type": "Protein", "text": [ "tumor necrosis factor alpha" ], "offsets": [ [ 848, 875 ] ], "normalized": [] }, { "id": "PMID-8573121_T2", "type": "Protein", "text": [ "TNF alpha" ], "offsets": [ [ 877, 886 ] ], "normalized": [] }, { "id": "PMID-8573121_T3", "type": "Protein", "text": [ "TNF alpha" ], "offsets": [ [ 897, 906 ] ], "normalized": [] } ]

[]

[ { "id": "PMID-8573121_1", "entity_ids": [ "PMID-8573121_T1", "PMID-8573121_T2" ] } ]

[]

[ { "id": "PMID-8577772__text", "type": "abstract", "text": [ "In vivo anergized CD4+ T cells express perturbed AP-1 and NF-kappa B transcription factors. \nAnergy is a major mechanism to ensure antigen-specific tolerance in T lymphocytes in the adult. In vivo, anergy has mainly been studied at the cellular level. In this study, we used the T-cell-activating superantigen staphylococcal enterotoxin A (SEA) to investigate molecular mechanisms of T-lymphocyte anergy in vivo. Injection of SEA to adult mice activates CD4+ T cells expressing certain T-cell receptor (TCR) variable region beta-chain families and induces strong and rapid production of interleukin 2 (IL-2). In contrast, repeated injections of SEA cause CD4+ T-cell deletion and anergy in the remaining CD4+ T cells, characterized by reduced expression of IL-2 at mRNA and protein levels. We analyzed expression of AP-1, NF-kappa B, NF-AT, and octamer binding transcription factors, which are known to be involved in the regulation of IL-2 gene promoter activity. Large amounts of AP-1 and NF-kappa B and significant quantities of NF-AT were induced in SEA-activated CD4+ spleen T cells, whereas Oct-1 and Oct-2 DNA binding activity was similar in both resting and activated T cells. In contrast, anergic CD4+ T cells contained severely reduced levels of AP-1 and Fos/Jun-containing NF-AT complexes but expressed significant amounts of NF-kappa B and Oct binding proteins after SEA stimulation. Resolution of the NF-kappa B complex demonstrated predominant expression of p50-p65 heterodimers in activated CD4+ T cells, while anergic cells mainly expressed the transcriptionally inactive p50 homodimer. These alterations of transcription factors are likely to be responsible for repression of IL-2 in anergic T cells. " ], "offsets": [ [ 0, 1718 ] ] } ]

[ { "id": "PMID-8577772_T1", "type": "Protein", "text": [ "CD4" ], "offsets": [ [ 18, 21 ] ], "normalized": [] }, { "id": "PMID-8577772_T2", "type": "Protein", "text": [ "staphylococcal enterotoxin A" ], "offsets": [ [ 310, 338 ] ], "normalized": [] }, { "id": "PMID-8577772_T3", "type": "Protein", "text": [ "SEA" ], "offsets": [ [ 340, 343 ] ], "normalized": [] }, { "id": "PMID-8577772_T4", "type": "Protein", "text": [ "SEA" ], "offsets": [ [ 426, 429 ] ], "normalized": [] }, { "id": "PMID-8577772_T5", "type": "Protein", "text": [ "CD4" ], "offsets": [ [ 454, 457 ] ], "normalized": [] }, { "id": "PMID-8577772_T6", "type": "Protein", "text": [ "interleukin 2" ], "offsets": [ [ 587, 600 ] ], "normalized": [] }, { "id": "PMID-8577772_T7", "type": "Protein", "text": [ "IL-2" ], "offsets": [ [ 602, 606 ] ], "normalized": [] }, { "id": "PMID-8577772_T8", "type": "Protein", "text": [ "SEA" ], "offsets": [ [ 645, 648 ] ], "normalized": [] }, { "id": "PMID-8577772_T9", "type": "Protein", "text": [ "CD4" ], "offsets": [ [ 655, 658 ] ], "normalized": [] }, { "id": "PMID-8577772_T10", "type": "Protein", "text": [ "CD4" ], "offsets": [ [ 704, 707 ] ], "normalized": [] }, { "id": "PMID-8577772_T11", "type": "Protein", "text": [ "IL-2" ], "offsets": [ [ 757, 761 ] ], "normalized": [] }, { "id": "PMID-8577772_T12", "type": "Protein", "text": [ "IL-2" ], "offsets": [ [ 936, 940 ] ], "normalized": [] }, { "id": "PMID-8577772_T13", "type": "Protein", "text": [ "SEA" ], "offsets": [ [ 1054, 1057 ] ], "normalized": [] }, { "id": "PMID-8577772_T14", "type": "Protein", "text": [ "CD4" ], "offsets": [ [ 1068, 1071 ] ], "normalized": [] }, { "id": "PMID-8577772_T15", "type": "Protein", "text": [ "Oct-1" ], "offsets": [ [ 1097, 1102 ] ], "normalized": [] }, { "id": "PMID-8577772_T16", "type": "Protein", "text": [ "Oct-2" ], "offsets": [ [ 1107, 1112 ] ], "normalized": [] }, { "id": "PMID-8577772_T17", "type": "Protein", "text": [ "CD4" ], "offsets": [ [ 1206, 1209 ] ], "normalized": [] }, { "id": "PMID-8577772_T18", "type": "Protein", "text": [ "Fos" ], "offsets": [ [ 1265, 1268 ] ], "normalized": [] }, { "id": "PMID-8577772_T19", "type": "Protein", "text": [ "Jun" ], "offsets": [ [ 1269, 1272 ] ], "normalized": [] }, { "id": "PMID-8577772_T20", "type": "Protein", "text": [ "SEA" ], "offsets": [ [ 1379, 1382 ] ], "normalized": [] }, { "id": "PMID-8577772_T21", "type": "Protein", "text": [ "p50" ], "offsets": [ [ 1472, 1475 ] ], "normalized": [] }, { "id": "PMID-8577772_T22", "type": "Protein", "text": [ "p65" ], "offsets": [ [ 1476, 1479 ] ], "normalized": [] }, { "id": "PMID-8577772_T23", "type": "Protein", "text": [ "CD4" ], "offsets": [ [ 1506, 1509 ] ], "normalized": [] }, { "id": "PMID-8577772_T24", "type": "Protein", "text": [ "p50" ], "offsets": [ [ 1588, 1591 ] ], "normalized": [] }, { "id": "PMID-8577772_T25", "type": "Protein", "text": [ "IL-2" ], "offsets": [ [ 1693, 1697 ] ], "normalized": [] } ]

[ { "id": "PMID-8577772_E1", "type": "Positive_regulation", "trigger": { "text": [ "induces" ], "offsets": [ [ 548, 555 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "PMID-8577772_E2" } ] }, { "id": "PMID-8577772_E2", "type": "Gene_expression", "trigger": { "text": [ "production" ], "offsets": [ [ 573, 583 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "PMID-8577772_T7" } ] }, { "id": "PMID-8577772_E3", "type": "Negative_regulation", "trigger": { "text": [ "reduced" ], "offsets": [ [ 735, 742 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "PMID-8577772_E5" } ] }, { "id": "PMID-8577772_E4", "type": "Negative_regulation", "trigger": { "text": [ "reduced" ], "offsets": [ [ 735, 742 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "PMID-8577772_E6" } ] }, { "id": "PMID-8577772_E5", "type": "Transcription", "trigger": { "text": [ "mRNA" ], "offsets": [ [ 765, 769 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "PMID-8577772_T11" } ] }, { "id": "PMID-8577772_E6", "type": "Gene_expression", "trigger": { "text": [ "protein" ], "offsets": [ [ 774, 781 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "PMID-8577772_T11" } ] }, { "id": "PMID-8577772_E7", "type": "Binding", "trigger": { "text": [ "binding activity" ], "offsets": [ [ 1117, 1133 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "PMID-8577772_T15" } ] }, { "id": "PMID-8577772_E8", "type": "Binding", "trigger": { "text": [ "binding activity" ], "offsets": [ [ 1117, 1133 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "PMID-8577772_T16" } ] }, { "id": "PMID-8577772_E9", "type": "Negative_regulation", "trigger": { "text": [ "reduced" ], "offsets": [ [ 1238, 1245 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "PMID-8577772_T19" } ] }, { "id": "PMID-8577772_E10", "type": "Negative_regulation", "trigger": { "text": [ "reduced" ], "offsets": [ [ 1238, 1245 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "PMID-8577772_T18" } ] }, { "id": "PMID-8577772_E11", "type": "Gene_expression", "trigger": { "text": [ "expression" ], "offsets": [ [ 1458, 1468 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "PMID-8577772_T22" } ] }, { "id": "PMID-8577772_E12", "type": "Gene_expression", "trigger": { "text": [ "expression" ], "offsets": [ [ 1458, 1468 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "PMID-8577772_T21" } ] }, { "id": "PMID-8577772_E13", "type": "Gene_expression", "trigger": { "text": [ "expressed" ], "offsets": [ [ 1547, 1556 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "PMID-8577772_T24" } ] }, { "id": "PMID-8577772_E14", "type": "Negative_regulation", "trigger": { "text": [ "repression" ], "offsets": [ [ 1679, 1689 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "PMID-8577772_T25" }, { "role": "Cause", "ref_id": "PMID-8577772_E13" } ] } ]

[ { "id": "PMID-8577772_1", "entity_ids": [ "PMID-8577772_T2", "PMID-8577772_T3" ] }, { "id": "PMID-8577772_2", "entity_ids": [ "PMID-8577772_T7", "PMID-8577772_T6" ] } ]

[]

[ { "id": "PMID-8600942__text", "type": "abstract", "text": [ "Surfactant suppresses NF-kappa B activation in human monocytic cells. \nIn addition to biophysical properties, pulmonary surfactant has immunomodulatory activity. We previously demonstrated that both synthetic (Exosurf) and modified natural surfactant (Survanta) downregulated endotoxin-stimulated inflammatory cytokine mRNA levels and protein products (tumor necrosis factor-alpha [TNF], interleukin-1-beta [IL-1], interleukin-6 [IL-6]) in human alveolar macrophages. In this study, we report that both Exosurf and Survanta suppress TNF mRNA and secretion (85 +/- 4% mean percent inhibition +/- SEM by Exosurf; 71 +/- 6% by Survanta) by endotoxin-stimulated THP-1, a human monocytic cell line. Because surfactant downregulated inflammatory cytokine production similarly in both normal human alveolar macrophages and the THP-1 cell line, we used this cell line to investigate whether surfactant affected transcriptional mechanisms. Specifically, we examined nuclear factor-kappa B (NF-kappa B) activation because it is crucial in transcriptional regulation of many inflammatory cytokine genes including TNF, IL-1, and IL-6. Electrophoretic mobility shift assays showed that both surfactants decreased activation of NF-kappa B. The presence of both p65 and p50 NF-kappa B components in LPS-activated THP-1 cells was confirmed by specific antibody induction of supershifts in mobility assays. These results are the first to suggest that surfactant's suppressive effects on inflammatory cytokine production may involve transcriptional regulation through inhibition of NF-kappa B activation. " ], "offsets": [ [ 0, 1587 ] ] } ]

[ { "id": "PMID-8600942_T1", "type": "Protein", "text": [ "tumor necrosis factor-alpha" ], "offsets": [ [ 353, 380 ] ], "normalized": [] }, { "id": "PMID-8600942_T2", "type": "Protein", "text": [ "TNF" ], "offsets": [ [ 382, 385 ] ], "normalized": [] }, { "id": "PMID-8600942_T3", "type": "Protein", "text": [ "interleukin-1-beta" ], "offsets": [ [ 388, 406 ] ], "normalized": [] }, { "id": "PMID-8600942_T4", "type": "Protein", "text": [ "IL-1" ], "offsets": [ [ 408, 412 ] ], "normalized": [] }, { "id": "PMID-8600942_T5", "type": "Protein", "text": [ "interleukin-6" ], "offsets": [ [ 415, 428 ] ], "normalized": [] }, { "id": "PMID-8600942_T6", "type": "Protein", "text": [ "IL-6" ], "offsets": [ [ 430, 434 ] ], "normalized": [] }, { "id": "PMID-8600942_T7", "type": "Protein", "text": [ "TNF" ], "offsets": [ [ 533, 536 ] ], "normalized": [] }, { "id": "PMID-8600942_T8", "type": "Protein", "text": [ "TNF" ], "offsets": [ [ 1102, 1105 ] ], "normalized": [] }, { "id": "PMID-8600942_T9", "type": "Protein", "text": [ "IL-1" ], "offsets": [ [ 1107, 1111 ] ], "normalized": [] }, { "id": "PMID-8600942_T10", "type": "Protein", "text": [ "IL-6" ], "offsets": [ [ 1117, 1121 ] ], "normalized": [] }, { "id": "PMID-8600942_T11", "type": "Protein", "text": [ "p65" ], "offsets": [ [ 1247, 1250 ] ], "normalized": [] }, { "id": "PMID-8600942_T12", "type": "Protein", "text": [ "p50" ], "offsets": [ [ 1255, 1258 ] ], "normalized": [] } ]

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[]

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[ { "id": "PMID-8602529__text", "type": "abstract", "text": [ "A mammalian histone deacetylase related to the yeast transcriptional regulator Rpd3p [see comments] \nTrapoxin is a microbially derived cyclotetrapeptide that inhibits histone deacetylation in vivo and causes mammalian cells to arrest in the cell cycle. A trapoxin affinity matrix was used to isolate two nuclear proteins that copurified with histone deacetylase activity. Both proteins were identified by peptide microsequencing, and a complementary DNA encoding the histone deacetylase catalytic subunit (HD1) was cloned from a human Jurkat T cell library. As the predicted protein is very similar to the yeast transcriptional regulator Rpd3p, these results support a role for histone deacetylase as a key regulator of eukaryotic transcription. " ], "offsets": [ [ 0, 746 ] ] } ]

[ { "id": "PMID-8602529_T1", "type": "Protein", "text": [ "Rpd3p" ], "offsets": [ [ 79, 84 ] ], "normalized": [] }, { "id": "PMID-8602529_T2", "type": "Protein", "text": [ "HD1" ], "offsets": [ [ 506, 509 ] ], "normalized": [] }, { "id": "PMID-8602529_T3", "type": "Protein", "text": [ "Rpd3p" ], "offsets": [ [ 638, 643 ] ], "normalized": [] } ]

[]

[]

[]

[ { "id": "PMID-8605348__text", "type": "abstract", "text": [ "Coexpression of the interleukin-13 and interleukin-4 genes correlates with their physical linkage in the cytokine gene cluster on human chromosome 5q23-31. \nInterleukin-13 (IL-13) and IL-4 are cytokines produced by T cells that are encoded by the q23-31 region of human chromosome 5. To investigate the regulation of IL-13 gene expression by T cells, we isolated and sequenced the human IL-13 gene, analyzed its 5'-flanking region for potential transcriptional activation elements, and examined its expression in nontransformed T-lineage cell populations. The human IL-13 gene was located 12.5-kb upstream of the IL-4 gene and 2-kb downstream of a CpG island. The IL-13 gene 5' flank region included a segment with sequence homology to P elements of the IL-4 promoter involved in transcriptional activation in T cells. Mutation of the IL-13 P element site significantly reduced IL-13 promoter activity in response to T-cell activation. Oligonucleotides containing the IL-13 or IL-4 P element sites specifically bound the transcriptional activator protein, nuclear factor-activated T cells, preformed (NF-ATp), when incubated with nuclear protein extracts from activated T cells. Similar to IL-4, IL-13 mRNA expression was highest in T-cell populations enriched for cells that had previously been primed in vivo or in vitro, indicating that priming increases the expression of the IL-13 and IL-4 genes in a coordinate manner. Because the primed T cells contain higher levels of nuclear NF-ATp, capable of binding to P elements of the IL-4 and IL-13 promoters, than do freshly-isolated T cells, the NF-AT-binding P elements are attractive candidates to mediate the coordinate expression of these two cytokine genes. " ], "offsets": [ [ 0, 1714 ] ] } ]

[ { "id": "PMID-8605348_T1", "type": "Protein", "text": [ "interleukin-13" ], "offsets": [ [ 20, 34 ] ], "normalized": [] }, { "id": "PMID-8605348_T2", "type": "Protein", "text": [ "interleukin-4" ], "offsets": [ [ 39, 52 ] ], "normalized": [] }, { "id": "PMID-8605348_T3", "type": "Protein", "text": [ "Interleukin-13" ], "offsets": [ [ 157, 171 ] ], "normalized": [] }, { "id": "PMID-8605348_T4", "type": "Protein", "text": [ "IL-13" ], "offsets": [ [ 173, 178 ] ], "normalized": [] }, { "id": "PMID-8605348_T5", "type": "Protein", "text": [ "IL-4" ], "offsets": [ [ 184, 188 ] ], "normalized": [] }, { "id": "PMID-8605348_T6", "type": "Protein", "text": [ "IL-13" ], "offsets": [ [ 317, 322 ] ], "normalized": [] }, { "id": "PMID-8605348_T7", "type": "Protein", "text": [ "IL-13" ], "offsets": [ [ 387, 392 ] ], "normalized": [] }, { "id": "PMID-8605348_T8", "type": "Protein", "text": [ "IL-13" ], "offsets": [ [ 566, 571 ] ], "normalized": [] }, { "id": "PMID-8605348_T9", "type": "Protein", "text": [ "IL-4" ], "offsets": [ [ 613, 617 ] ], "normalized": [] }, { "id": "PMID-8605348_T10", "type": "Protein", "text": [ "IL-13" ], "offsets": [ [ 664, 669 ] ], "normalized": [] }, { "id": "PMID-8605348_T11", "type": "Protein", "text": [ "IL-4" ], "offsets": [ [ 754, 758 ] ], "normalized": [] }, { "id": "PMID-8605348_T12", "type": "Protein", "text": [ "IL-13" ], "offsets": [ [ 835, 840 ] ], "normalized": [] }, { "id": "PMID-8605348_T13", "type": "Protein", "text": [ "IL-13" ], "offsets": [ [ 878, 883 ] ], "normalized": [] }, { "id": "PMID-8605348_T14", "type": "Protein", "text": [ "IL-13" ], "offsets": [ [ 968, 973 ] ], "normalized": [] }, { "id": "PMID-8605348_T15", "type": "Protein", "text": [ "IL-4" ], "offsets": [ [ 977, 981 ] ], "normalized": [] }, { "id": "PMID-8605348_T16", "type": "Protein", "text": [ "NF-ATp" ], "offsets": [ [ 1101, 1107 ] ], "normalized": [] }, { "id": "PMID-8605348_T17", "type": "Protein", "text": [ "IL-4" ], "offsets": [ [ 1190, 1194 ] ], "normalized": [] }, { "id": "PMID-8605348_T18", "type": "Protein", "text": [ "IL-13" ], "offsets": [ [ 1196, 1201 ] ], "normalized": [] }, { "id": "PMID-8605348_T19", "type": "Protein", "text": [ "IL-13" ], "offsets": [ [ 1380, 1385 ] ], "normalized": [] }, { "id": "PMID-8605348_T20", "type": "Protein", "text": [ "IL-4" ], "offsets": [ [ 1390, 1394 ] ], "normalized": [] }, { "id": "PMID-8605348_T21", "type": "Protein", "text": [ "NF-ATp" ], "offsets": [ [ 1485, 1491 ] ], "normalized": [] }, { "id": "PMID-8605348_T22", "type": "Protein", "text": [ "IL-4" ], "offsets": [ [ 1533, 1537 ] ], "normalized": [] }, { "id": "PMID-8605348_T23", "type": "Protein", "text": [ "IL-13" ], "offsets": [ [ 1542, 1547 ] ], "normalized": [] }, { "id": "PMID-8605348_T30", "type": "Entity", "text": [ "P elements" ], "offsets": [ [ 736, 746 ] ], "normalized": [] }, { "id": "PMID-8605348_T34", "type": "Entity", "text": [ "promoter" ], "offsets": [ [ 884, 892 ] ], "normalized": [] }, { "id": "PMID-8605348_T36", "type": "Entity", "text": [ "P element sites" ], "offsets": [ [ 982, 997 ] ], "normalized": [] }, { "id": "PMID-8605348_T43", "type": "Entity", "text": [ "P elements" ], "offsets": [ [ 1515, 1525 ] ], "normalized": [] } ]

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"id": "PMID-8605348_E6", "type": "Regulation", "trigger": { "text": [ "regulation" ], "offsets": [ [ 303, 313 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "PMID-8605348_E7" } ] }, { "id": "PMID-8605348_E7", "type": "Gene_expression", "trigger": { "text": [ "expression" ], "offsets": [ [ 328, 338 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "PMID-8605348_T6" } ] }, { "id": "PMID-8605348_E8", "type": "Gene_expression", "trigger": { "text": [ "expression" ], "offsets": [ [ 499, 509 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "PMID-8605348_T7" } ] }, { "id": "PMID-8605348_E9", "type": "Regulation", "trigger": { "text": [ "involved" ], "offsets": [ [ 768, 776 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "PMID-8605348_E10" }, { "role": "Cause", "ref_id": "PMID-8605348_T11" }, { "role": "CSite", "ref_id": "PMID-8605348_T30" } ] }, { "id": "PMID-8605348_E10", "type": "Positive_regulation", "trigger": { "text": [ "transcriptional activation" ], "offsets": [ [ 780, 806 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "PMID-8605348_T11" } ] }, { "id": "PMID-8605348_E11", "type": "Negative_regulation", "trigger": { "text": [ "reduced" ], "offsets": [ [ 870, 877 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "PMID-8605348_E12" } ] }, { "id": "PMID-8605348_E12", "type": "Regulation", "trigger": { "text": [ "in response to" ], "offsets": [ [ 902, 916 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "PMID-8605348_T13" }, { "role": "Site", "ref_id": "PMID-8605348_T34" } ] }, { "id": "PMID-8605348_E13", "type": "Binding", "trigger": { "text": [ "bound" ], "offsets": [ [ 1011, 1016 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "PMID-8605348_T14" }, { "role": "Theme", "ref_id": "PMID-8605348_T16" }, { "role": "Site", "ref_id": "PMID-8605348_T36" } ] }, { "id": "PMID-8605348_E14", "type": "Binding", "trigger": { "text": [ "bound" ], "offsets": [ [ 1011, 1016 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "PMID-8605348_T15" }, { "role": "Theme", "ref_id": "PMID-8605348_T16" }, { "role": "Site", "ref_id": "PMID-8605348_T36" } ] }, { "id": "PMID-8605348_E15", "type": "Transcription", "trigger": { "text": [ "expression" ], "offsets": [ [ 1207, 1217 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "PMID-8605348_T17" } ] }, { "id": "PMID-8605348_E16", "type": "Transcription", "trigger": { "text": [ "expression" ], "offsets": [ [ 1207, 1217 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "PMID-8605348_T18" } ] }, { "id": "PMID-8605348_E17", "type": "Positive_regulation", "trigger": { "text": [ "increases" ], "offsets": [ [ 1348, 1357 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "PMID-8605348_E19" } ] }, { "id": "PMID-8605348_E18", "type": "Positive_regulation", "trigger": { "text": [ "increases" ], "offsets": [ [ 1348, 1357 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "PMID-8605348_E20" } ] }, { "id": "PMID-8605348_E19", "type": "Gene_expression", "trigger": { "text": [ "expression" ], "offsets": [ [ 1362, 1372 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "PMID-8605348_T19" } ] }, { "id": "PMID-8605348_E20", "type": "Gene_expression", "trigger": { "text": [ "expression" ], "offsets": [ [ 1362, 1372 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "PMID-8605348_T20" } ] }, { "id": "PMID-8605348_E21", "type": "Positive_regulation", "trigger": { "text": [ "higher levels" ], "offsets": [ [ 1460, 1473 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "PMID-8605348_T21" } ] }, { "id": "PMID-8605348_E22", "type": "Binding", "trigger": { "text": [ "binding" ], "offsets": [ [ 1504, 1511 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "PMID-8605348_T21" }, { "role": "Theme", "ref_id": "PMID-8605348_T22" }, { "role": "Site", "ref_id": "PMID-8605348_T43" } ] }, { "id": "PMID-8605348_E23", "type": "Binding", "trigger": { "text": [ "binding" ], "offsets": [ [ 1504, 1511 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "PMID-8605348_T21" }, { "role": "Theme", "ref_id": "PMID-8605348_T23" }, { "role": "Site", "ref_id": "PMID-8605348_T43" } ] }, { "id": "PMID-8605348_E24", "type": "Positive_regulation", "trigger": { "text": [ "mediate" ], "offsets": [ [ 1651, 1658 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "PMID-8605348_E26" } ] }, { "id": "PMID-8605348_E25", "type": "Positive_regulation", "trigger": { "text": [ "mediate" ], "offsets": [ [ 1651, 1658 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "PMID-8605348_E27" } ] }, { "id": "PMID-8605348_E26", "type": "Gene_expression", "trigger": { "text": [ "expression" ], "offsets": [ [ 1674, 1684 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "PMID-8605348_T23" } ] }, { "id": "PMID-8605348_E27", "type": "Gene_expression", "trigger": { "text": [ "expression" ], "offsets": [ [ 1674, 1684 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "PMID-8605348_T22" } ] } ]

[ { "id": "PMID-8605348_1", "entity_ids": [ "PMID-8605348_T4", "PMID-8605348_T3" ] } ]

[]

[ { "id": "PMID-8605359__text", "type": "abstract", "text": [ "Transactivation of the interleukin-1alpha promoter by human T-cell leukemia virus type I and type II Tax proteins. \nHuman T-cell leukemia virus type I (HTLV-I)-infected T-cell lines constitutively produce high levels of interleukin-1alpha (IL-1alpha). To analyze the mechanisms that lead to the expression of IL-1alpha in HTLV-I-infected cell lines, we studied regulatory regions of the human IL-1alpha promoter involved in activation of the IL-1alpha gene. IL-1alpha promoter constructs drive transcription of the chloramphenicol acetyltransferase (CAT) reporter gene in HTLV-I-positive MT-2 cells, which constitutively produce IL-1alpha. In a cotransfection assay, the Tax protein of both HTLV-I and HTLV-II specifically activated transcription from the IL-1alpha promoter in an uninfected Jurkat cell line. A mutant Tax protein deficient in transactivation of genes by the nuclear factor (NF)-kappaB pathway was unable to induce transcriptional activity of IL-1alpha promoter-CAT constructs, but was rescued by exogenous provision of p65/p50 NF-kappaB. We found that two IL-1alpha kappaB-like sites (positions -1,065 to -1,056 and +646 to +655) specifically formed a complex with NF-kappaB-containing nuclear extract from MT-2 cells and that NF-kappaB bound with higher affinity to the 3' NF-kappaB binding site than to the 5' NF-kappaB site. Moreover, deletion of either 5' or 3' NF-kappaB sites reduced IL-1alpha promoter activity in MT-2 cells and transactivation of the IL-1alpha promoter by exogenous NF-kappaB and Tax in Jurkat cells. These data suggest a general role for Tax induction of IL-1alpha gene transcription by the NF-kappaB pathway. Expression of IL-1alpha by HTLV-I productively infected cells may be important in the hypercalcemia, osteolytic bone lesions, neutrophilia, elevation of C-reactive protein, and fever frequently seen in patients with HTLV-I-induced adult T-cell leukemia/lymphoma. " ], "offsets": [ [ 0, 1917 ] ] } ]

[ { "id": "PMID-8605359_T1", "type": "Protein", "text": [ "interleukin-1alpha" ], "offsets": [ [ 23, 41 ] ], "normalized": [] }, { "id": "PMID-8605359_T2", "type": "Protein", "text": [ "Tax" ], "offsets": [ [ 101, 104 ] ], "normalized": [] }, { "id": "PMID-8605359_T3", "type": "Protein", "text": [ "interleukin-1alpha" ], "offsets": [ [ 220, 238 ] ], "normalized": [] }, { "id": "PMID-8605359_T4", "type": "Protein", "text": [ "IL-1alpha" ], "offsets": [ [ 240, 249 ] ], "normalized": [] }, { "id": "PMID-8605359_T5", "type": "Protein", "text": [ "IL-1alpha" ], "offsets": [ [ 309, 318 ] ], "normalized": [] }, { "id": "PMID-8605359_T6", "type": "Protein", "text": [ "IL-1alpha" ], "offsets": [ [ 393, 402 ] ], "normalized": [] }, { "id": "PMID-8605359_T7", "type": "Protein", "text": [ "IL-1alpha" ], "offsets": [ [ 442, 451 ] ], "normalized": [] }, { "id": "PMID-8605359_T8", "type": "Protein", "text": [ "IL-1alpha" ], "offsets": [ [ 458, 467 ] ], "normalized": [] }, { "id": "PMID-8605359_T9", "type": "Protein", "text": [ "chloramphenicol acetyltransferase" ], "offsets": [ [ 515, 548 ] ], "normalized": [] }, { "id": "PMID-8605359_T10", "type": "Protein", "text": [ "CAT" ], "offsets": [ [ 550, 553 ] ], "normalized": [] }, { "id": "PMID-8605359_T11", "type": "Protein", "text": [ "IL-1alpha" ], "offsets": [ [ 629, 638 ] ], "normalized": [] }, { "id": "PMID-8605359_T12", "type": "Protein", "text": [ "Tax" ], "offsets": [ [ 671, 674 ] ], "normalized": [] }, { "id": "PMID-8605359_T13", "type": "Protein", "text": [ "IL-1alpha" ], "offsets": [ [ 756, 765 ] ], "normalized": [] }, { "id": "PMID-8605359_T14", "type": "Protein", "text": [ "Tax" ], "offsets": [ [ 819, 822 ] ], "normalized": [] }, { "id": "PMID-8605359_T15", "type": "Protein", "text": [ "IL-1alpha" ], "offsets": [ [ 960, 969 ] ], "normalized": [] }, { "id": "PMID-8605359_T16", "type": "Protein", "text": [ "CAT" ], "offsets": [ [ 979, 982 ] ], "normalized": [] }, { "id": "PMID-8605359_T17", "type": "Protein", "text": [ "p65" ], "offsets": [ [ 1037, 1040 ] ], "normalized": [] }, { "id": "PMID-8605359_T18", "type": "Protein", "text": [ "p50" ], "offsets": [ [ 1041, 1044 ] ], "normalized": [] }, { "id": "PMID-8605359_T19", "type": "Protein", "text": [ "IL-1alpha" ], "offsets": [ [ 1074, 1083 ] ], "normalized": [] }, { "id": "PMID-8605359_T20", "type": "Protein", "text": [ "IL-1alpha" ], "offsets": [ [ 1408, 1417 ] ], "normalized": [] }, { "id": "PMID-8605359_T21", "type": "Protein", "text": [ "IL-1alpha" ], "offsets": [ [ 1477, 1486 ] ], "normalized": [] }, { "id": "PMID-8605359_T22", "type": "Protein", "text": [ "Tax" ], "offsets": [ [ 1523, 1526 ] ], "normalized": [] }, { "id": "PMID-8605359_T23", "type": "Protein", "text": [ "Tax" ], "offsets": [ [ 1582, 1585 ] ], "normalized": [] }, { "id": "PMID-8605359_T24", "type": "Protein", "text": [ "IL-1alpha" ], "offsets": [ [ 1599, 1608 ] ], "normalized": [] }, { "id": "PMID-8605359_T25", "type": "Protein", "text": [ "IL-1alpha" ], "offsets": [ [ 1668, 1677 ] ], "normalized": [] }, { "id": "PMID-8605359_T27", "type": "Entity", "text": [ "promoter" ], "offsets": [ [ 42, 50 ] ], "normalized": [] }, { "id": "PMID-8605359_T35", "type": "Entity", "text": [ "promoter" ], "offsets": [ [ 1487, 1495 ] ], "normalized": [] } ]

[ { "id": "PMID-8605359_E1", "type": "Positive_regulation", "trigger": { "text": [ "Transactivation" ], "offsets": [ [ 0, 15 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "PMID-8605359_T1" }, { "role": "Cause", "ref_id": "PMID-8605359_T2" }, { "role": "Site", "ref_id": "PMID-8605359_T27" } ] }, { "id": "PMID-8605359_E2", "type": "Gene_expression", "trigger": { "text": [ "produce" ], "offsets": [ [ 197, 204 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "PMID-8605359_T4" } ] }, { "id": "PMID-8605359_E3", "type": "Positive_regulation", "trigger": { "text": [ "high levels" ], "offsets": [ [ 205, 216 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "PMID-8605359_E2" } ] }, { "id": "PMID-8605359_E4", "type": "Gene_expression", "trigger": { "text": [ "expression" ], "offsets": [ [ 295, 305 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "PMID-8605359_T5" } ] }, { "id": "PMID-8605359_E5", "type": "Positive_regulation", "trigger": { "text": [ "activation" ], "offsets": [ [ 424, 434 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "PMID-8605359_T7" } ] }, { "id": "PMID-8605359_E6", "type": "Gene_expression", "trigger": { "text": [ "produce" ], "offsets": [ [ 621, 628 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "PMID-8605359_T11" } ] }, { "id": "PMID-8605359_E7", "type": "Negative_regulation", "trigger": { "text": [ "reduced" ], "offsets": [ [ 1400, 1407 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "PMID-8605359_E9" } ] }, { "id": "PMID-8605359_E8", "type": "Negative_regulation", "trigger": { "text": [ "reduced" ], "offsets": [ [ 1400, 1407 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "PMID-8605359_E10" } ] }, { "id": "PMID-8605359_E9", "type": "Positive_regulation", "trigger": { "text": [ "transactivation" ], "offsets": [ [ 1454, 1469 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "PMID-8605359_T21" }, { "role": "Site", "ref_id": "PMID-8605359_T35" } ] }, { "id": "PMID-8605359_E10", "type": "Positive_regulation", "trigger": { "text": [ "transactivation" ], "offsets": [ [ 1454, 1469 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "PMID-8605359_T21" }, { "role": "Cause", "ref_id": "PMID-8605359_T22" }, { "role": "Site", "ref_id": "PMID-8605359_T35" } ] }, { "id": "PMID-8605359_E11", "type": "Regulation", "trigger": { "text": [ "general role" ], "offsets": [ [ 1565, 1577 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "PMID-8605359_E14" }, { "role": "Cause", "ref_id": "PMID-8605359_E12" } ] }, { "id": "PMID-8605359_E12", "type": "Positive_regulation", "trigger": { "text": [ "induction" ], "offsets": [ [ 1586, 1595 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "PMID-8605359_T23" } ] }, { "id": "PMID-8605359_E13", "type": "Transcription", "trigger": { "text": [ "transcription" ], "offsets": [ [ 1614, 1627 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "PMID-8605359_T24" } ] }, { "id": "PMID-8605359_E14", "type": "Positive_regulation", "trigger": { "text": [ "by" ], "offsets": [ [ 1628, 1630 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "PMID-8605359_E13" } ] }, { "id": "PMID-8605359_E15", "type": "Gene_expression", "trigger": { "text": [ "Expression" ], "offsets": [ [ 1654, 1664 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "PMID-8605359_T25" } ] } ]

[ { "id": "PMID-8605359_1", "entity_ids": [ "PMID-8605359_T9", "PMID-8605359_T10" ] }, { "id": "PMID-8605359_2", "entity_ids": [ "PMID-8605359_T4", "PMID-8605359_T3" ] } ]

[]

[ { "id": "PMID-8605587__text", "type": "abstract", "text": [ "Soluble tumor necrosis factor receptors inhibit phorbol myristate acetate and cytokine-induced HIV-1 expression chronically infected U1 cells. \nRecombinant human tumor necrosis factor (TNF) binding protein-1 (r-h TBP-1) and recombinant human soluble dimeric TNF receptor (rhu TNFR:Fc) were used to determine the relative contributions of TNF to phorbol myristate acetate (PMA) and cytokine-induced human immunodeficiency virus type 1 (HIV-1) replication in chronically infected cell lines. Treatment of HIV-1-infected promonocytic U1 cells with r-h-TBP-1 or rhu TNFR:Fc reduced PMA-induced HIV-1 p24 antigen production in a concentration-dependent manner, with a maximal inhibition of approximately 90%. Maximal inhibition of p24 antigen production in T-lymphocytic ACH-2 cells was 47% with r-hTBP-1 and 42% with rhu TNFR:Fc. r-hTBP-1 and rhu TNFR:Fc also decreased p24 antigen synthesized by U1 cells in response to other stimuli, including phytohemagglutinin (PHA)-induced supernatant, granulocyte-macrophage colony-stimulating factor, interleukin-6, and TNF. Addition of r-hTBP-1 to U1 cells during the last 4 h of a 24 h incubation with PMA still inhibited p24 antigen production by 15%. U1 cells stimulated with 10(-7) M PMA released approximately 1 ng/ml endogenous TBP-1 with an initial peak observed at 1 h and a second peak at 24 h after PMA stimulation. r-hTBP-1 also partially reversed inhibition of U1 cellular proliferation caused by PMA. Both r-hTBP-1 and rhu TNFR:Fc blocked PMA induction of nuclear factor (NK)- kappa B DNA-binding activity in U1 cells in association with decreases in HIV-1 replication. We conclude that soluble TNF receptors can inhibit stimuli-induced HIV-1 expression and NK- kappa B DNA-binding activity in chronically infected U1 cells. " ], "offsets": [ [ 0, 1776 ] ] } ]

[ { "id": "PMID-8605587_T1", "type": "Protein", "text": [ "p24" ], "offsets": [ [ 596, 599 ] ], "normalized": [] }, { "id": "PMID-8605587_T2", "type": "Protein", "text": [ "p24" ], "offsets": [ [ 726, 729 ] ], "normalized": [] }, { "id": "PMID-8605587_T3", "type": "Protein", "text": [ "p24" ], "offsets": [ [ 866, 869 ] ], "normalized": [] }, { "id": "PMID-8605587_T4", "type": "Protein", "text": [ "granulocyte-macrophage colony-stimulating factor" ], "offsets": [ [ 988, 1036 ] ], "normalized": [] }, { "id": "PMID-8605587_T5", "type": "Protein", "text": [ "interleukin-6" ], "offsets": [ [ 1038, 1051 ] ], "normalized": [] }, { "id": "PMID-8605587_T6", "type": "Protein", "text": [ "p24" ], "offsets": [ [ 1161, 1164 ] ], "normalized": [] }, { "id": "PMID-8605587_T7", "type": "Protein", "text": [ "TBP-1" ], "offsets": [ [ 1272, 1277 ] ], "normalized": [] } ]

[ { "id": "PMID-8605587_E1", "type": "Negative_regulation", "trigger": { "text": [ "reduced" ], "offsets": [ [ 570, 577 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "PMID-8605587_E2" } ] }, { "id": "PMID-8605587_E2", "type": "Positive_regulation", "trigger": { "text": [ "induced" ], "offsets": [ [ 582, 589 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "PMID-8605587_E3" } ] }, { "id": "PMID-8605587_E3", "type": "Gene_expression", "trigger": { "text": [ "production" ], "offsets": [ [ 608, 618 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "PMID-8605587_T1" } ] }, { "id": "PMID-8605587_E4", "type": "Negative_regulation", "trigger": { "text": [ "inhibition" ], "offsets": [ [ 712, 722 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "PMID-8605587_E5" } ] }, { "id": "PMID-8605587_E5", "type": "Gene_expression", "trigger": { "text": [ "production" ], "offsets": [ [ 738, 748 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "PMID-8605587_T2" } ] }, { "id": "PMID-8605587_E6", "type": "Negative_regulation", "trigger": { "text": [ "decreased" ], "offsets": [ [ 856, 865 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "PMID-8605587_E12" } ] }, { "id": "PMID-8605587_E7", "type": "Negative_regulation", "trigger": { "text": [ "decreased" ], "offsets": [ [ 856, 865 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "PMID-8605587_E11" } ] }, { "id": "PMID-8605587_E8", "type": "Negative_regulation", "trigger": { "text": [ "decreased" ], "offsets": [ [ 856, 865 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "PMID-8605587_E10" } ] }, { "id": "PMID-8605587_E9", "type": "Gene_expression", "trigger": { "text": [ "synthesized" ], "offsets": [ [ 878, 889 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "PMID-8605587_T3" } ] }, { "id": "PMID-8605587_E10", "type": "Positive_regulation", "trigger": { "text": [ "in response to" ], "offsets": [ [ 902, 916 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "PMID-8605587_E9" }, { "role": "Cause", "ref_id": "PMID-8605587_T5" } ] }, { "id": "PMID-8605587_E11", "type": "Positive_regulation", "trigger": { "text": [ "in response to" ], "offsets": [ [ 902, 916 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "PMID-8605587_E9" }, { "role": "Cause", "ref_id": "PMID-8605587_T4" } ] }, { "id": "PMID-8605587_E12", "type": "Positive_regulation", "trigger": { "text": [ "in response to" ], "offsets": [ [ 902, 916 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "PMID-8605587_E9" } ] }, { "id": "PMID-8605587_E13", "type": "Negative_regulation", "trigger": { "text": [ "inhibited" ], "offsets": [ [ 1151, 1160 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "PMID-8605587_E14" } ] }, { "id": "PMID-8605587_E14", "type": "Gene_expression", "trigger": { "text": [ "production" ], "offsets": [ [ 1173, 1183 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "PMID-8605587_T6" } ] }, { "id": "PMID-8605587_E15", "type": "Localization", "trigger": { "text": [ "released" ], "offsets": [ [ 1230, 1238 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "PMID-8605587_T7" } ] }, { "id": "PMID-8605587_E16", "type": "Positive_regulation", "trigger": { "text": [ "after" ], "offsets": [ [ 1341, 1346 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "PMID-8605587_E15" } ] } ]

[]

[]

[ { "id": "PMID-8608243__text", "type": "abstract", "text": [ "AM580, a stable benzoic derivative of retinoic acid, has powerful and selective cyto-differentiating effects on acute promyelocytic leukemia cells. \nAll-trans retinoic acid (ATRA) is successfully used in the cyto-differentiating treatment of acute promyelocytic leukemia (APL). Paradoxically, APL cells express PML-RAR, an aberrant form of the retinoic acid receptor type alpha (RAR alpha) derived from the leukemia-specific t(15;17) chromosomal translocation. We show here that AM580, a stable retinobenzoic derivative originally synthesized as a RAR alpha agonist, is a powerful inducer of granulocytic maturation in NB4, an APL-derived cell line, and in freshly isolated APL blasts. After treatment of APL cells with AM580 either alone or in combination with granulocyte colony-stimulating factor (G-CSF), the compound induces granulocytic maturation, as assessed by determination of the levels of leukocyte alkaline phosphatase, CD11b, CD33, and G-CSF receptor mRNA, at concentrations that are 10- to 100-fold lower than those of ATRA necessary to produce similar effects. By contrast, AM580 is not effective as ATRA in modulating the expression of these differentiation markers in the HL-60 cell line and in freshly isolated granulocytes obtained from the peripheral blood of chronic myelogenous leukemia patients during the stable phase of the disease. In NB4 cells, two other synthetic nonselective RAR ligands are capable of inducing LAP as much as AM580, whereas RAR beta- or RAR gamma-specific ligands are totally ineffective. These results show that AM580 is more powerful than ATRA in modulating the expression of differentiation antigens only in cells in which PML-RAR is present. Binding experiments, using COS-7 cells transiently transfected with PML-RAR and the normal RAR alpha, show that AM580 has a lower affinity than ATRA for both receptors. However, in the presence of PML-RAR, the synthetic retinoid is a much better transactivator of retinoic acid-responsive element-containing promoters than the natural retinoid, whereas, in the presence of RAR alpha, AM580 and ATRA have similar activity. This may explain the strong cyto-differentiating potential of AM580 in PML-RAR-containing leukemic cells. " ], "offsets": [ [ 0, 2222 ] ] } ]

[ { "id": "PMID-8608243_T1", "type": "Protein", "text": [ "PML-RAR" ], "offsets": [ [ 311, 318 ] ], "normalized": [] }, { "id": "PMID-8608243_T2", "type": "Protein", "text": [ "retinoic acid receptor type alpha" ], "offsets": [ [ 344, 377 ] ], "normalized": [] }, { "id": "PMID-8608243_T3", "type": "Protein", "text": [ "RAR alpha" ], "offsets": [ [ 379, 388 ] ], "normalized": [] }, { "id": "PMID-8608243_T4", "type": "Protein", "text": [ "RAR alpha" ], "offsets": [ [ 548, 557 ] ], "normalized": [] }, { "id": "PMID-8608243_T5", "type": "Protein", "text": [ "granulocyte colony-stimulating factor" ], "offsets": [ [ 762, 799 ] ], "normalized": [] }, { "id": "PMID-8608243_T6", "type": "Protein", "text": [ "G-CSF" ], "offsets": [ [ 801, 806 ] ], "normalized": [] }, { "id": "PMID-8608243_T7", "type": "Protein", "text": [ "leukocyte alkaline phosphatase" ], "offsets": [ [ 901, 931 ] ], "normalized": [] }, { "id": "PMID-8608243_T8", "type": "Protein", "text": [ "CD11b" ], "offsets": [ [ 933, 938 ] ], "normalized": [] }, { "id": "PMID-8608243_T9", "type": "Protein", "text": [ "CD33" ], "offsets": [ [ 940, 944 ] ], "normalized": [] }, { "id": "PMID-8608243_T10", "type": "Protein", "text": [ "G-CSF receptor" ], "offsets": [ [ 950, 964 ] ], "normalized": [] }, { "id": "PMID-8608243_T11", "type": "Protein", "text": [ "LAP" ], "offsets": [ [ 1442, 1445 ] ], "normalized": [] }, { "id": "PMID-8608243_T12", "type": "Protein", "text": [ "RAR beta" ], "offsets": [ [ 1472, 1480 ] ], "normalized": [] }, { "id": "PMID-8608243_T13", "type": "Protein", "text": [ "RAR gamma" ], "offsets": [ [ 1485, 1494 ] ], "normalized": [] }, { "id": "PMID-8608243_T14", "type": "Protein", "text": [ "PML-RAR" ], "offsets": [ [ 1674, 1681 ] ], "normalized": [] }, { "id": "PMID-8608243_T15", "type": "Protein", "text": [ "PML-RAR" ], "offsets": [ [ 1762, 1769 ] ], "normalized": [] }, { "id": "PMID-8608243_T16", "type": "Protein", "text": [ "RAR alpha" ], "offsets": [ [ 1785, 1794 ] ], "normalized": [] }, { "id": "PMID-8608243_T17", "type": "Protein", "text": [ "PML-RAR" ], "offsets": [ [ 1891, 1898 ] ], "normalized": [] }, { "id": "PMID-8608243_T18", "type": "Protein", "text": [ "RAR alpha" ], "offsets": [ [ 2067, 2076 ] ], "normalized": [] }, { "id": "PMID-8608243_T19", "type": "Protein", "text": [ "PML-RAR" ], "offsets": [ [ 2187, 2194 ] ], "normalized": [] } ]

[ { "id": "PMID-8608243_E1", "type": "Gene_expression", "trigger": { "text": [ "express" ], "offsets": [ [ 303, 310 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "PMID-8608243_T1" } ] }, { "id": "PMID-8608243_E2", "type": "Positive_regulation", "trigger": { "text": [ "derived" ], "offsets": [ [ 390, 397 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "PMID-8608243_T1" } ] }, { "id": "PMID-8608243_E3", "type": "Regulation", "trigger": { "text": [ "modulating" ], "offsets": [ [ 1124, 1134 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "PMID-8608243_E8" } ] }, { "id": "PMID-8608243_E4", "type": "Regulation", "trigger": { "text": [ "modulating" ], "offsets": [ [ 1124, 1134 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "PMID-8608243_E9" } ] }, { "id": "PMID-8608243_E5", "type": "Regulation", "trigger": { "text": [ "modulating" ], "offsets": [ [ 1124, 1134 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "PMID-8608243_E7" } ] }, { "id": "PMID-8608243_E6", "type": "Regulation", "trigger": { "text": [ "modulating" ], "offsets": [ [ 1124, 1134 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "PMID-8608243_E10" } ] }, { "id": "PMID-8608243_E7", "type": "Gene_expression", "trigger": { "text": [ "expression" ], "offsets": [ [ 1139, 1149 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "PMID-8608243_T7" } ] }, { "id": "PMID-8608243_E8", "type": "Gene_expression", "trigger": { "text": [ "expression" ], "offsets": [ [ 1139, 1149 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "PMID-8608243_T10" } ] }, { "id": "PMID-8608243_E9", "type": "Gene_expression", "trigger": { "text": [ "expression" ], "offsets": [ [ 1139, 1149 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "PMID-8608243_T9" } ] }, { "id": "PMID-8608243_E10", "type": "Gene_expression", "trigger": { "text": [ "expression" ], "offsets": [ [ 1139, 1149 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "PMID-8608243_T8" } ] }, { "id": "PMID-8608243_E11", "type": "Positive_regulation", "trigger": { "text": [ "inducing" ], "offsets": [ [ 1433, 1441 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "PMID-8608243_T11" } ] }, { "id": "PMID-8608243_E12", "type": "Gene_expression", "trigger": { "text": [ "present" ], "offsets": [ [ 1685, 1692 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "PMID-8608243_T14" } ] }, { "id": "PMID-8608243_E13", "type": "Binding", "trigger": { "text": [ "affinity" ], "offsets": [ [ 1824, 1832 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "PMID-8608243_T15" } ] }, { "id": "PMID-8608243_E14", "type": "Binding", "trigger": { "text": [ "affinity" ], "offsets": [ [ 1824, 1832 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "PMID-8608243_T16" } ] }, { "id": "PMID-8608243_E15", "type": "Gene_expression", "trigger": { "text": [ "containing" ], "offsets": [ [ 2195, 2205 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "PMID-8608243_T19" } ] } ]

[ { "id": "PMID-8608243_1", "entity_ids": [ "PMID-8608243_T2", "PMID-8608243_T3" ] }, { "id": "PMID-8608243_2", "entity_ids": [ "PMID-8608243_T5", "PMID-8608243_T6" ] } ]

[]

[ { "id": "PMID-8613707__text", "type": "abstract", "text": [ "Transcriptional basis for hyporesponsiveness of the human inducible nitric oxide synthase gene to lipopolysaccharide/interferon-gamma. \nThe work reported here resolves, at the level of gene regulation, the controversy as to whether or not human monocytes/macrophages can produce nitric oxide (NO) when stimulated with lipopolysaccharide (LPS), with or without co-stimulation by interferon-gamma (IFN-gamma). Studies included structural comparison of the promoters for human and mouse inducible NO synthase (iNOS) genes, transfection and assay of human and mouse iNOS promoter regions in response to LPS +/- IFN-gamma, and electrophoretic mobility shift assays of kappa B response elements. Two explanations for hyporesponsiveness of the human iNOS promoter to LPS +/- IFN-gamma were found: (1) multiple inactivating nucleotide substitutions in the human counterpart of the enhancer element that has been shown to regulate LPS/IFN-gamma induced expression of the mouse iNOS gene; and (2) and absence of one or more nuclear factors in human macrophages (e.g., an LPS-inducible nuclear factor-kappa B/Rel complex), that is (are) required for maximal expression of the gene. The importance of resolution of this controversy is that future research in this area should be directed toward the understanding of alternative mechanisms that can result in the successful production of NO. " ], "offsets": [ [ 0, 1379 ] ] } ]

[ { "id": "PMID-8613707_T1", "type": "Protein", "text": [ "inducible nitric oxide synthase" ], "offsets": [ [ 58, 89 ] ], "normalized": [] }, { "id": "PMID-8613707_T2", "type": "Protein", "text": [ "interferon-gamma" ], "offsets": [ [ 117, 133 ] ], "normalized": [] }, { "id": "PMID-8613707_T3", "type": "Protein", "text": [ "interferon-gamma" ], "offsets": [ [ 378, 394 ] ], "normalized": [] }, { "id": "PMID-8613707_T4", "type": "Protein", "text": [ "IFN-gamma" ], "offsets": [ [ 396, 405 ] ], "normalized": [] }, { "id": "PMID-8613707_T5", "type": "Protein", "text": [ "inducible NO synthase" ], "offsets": [ [ 484, 505 ] ], "normalized": [] }, { "id": "PMID-8613707_T6", "type": "Protein", "text": [ "iNOS" ], "offsets": [ [ 507, 511 ] ], "normalized": [] }, { "id": "PMID-8613707_T7", "type": "Protein", "text": [ "iNOS" ], "offsets": [ [ 562, 566 ] ], "normalized": [] }, { "id": "PMID-8613707_T8", "type": "Protein", "text": [ "IFN-gamma" ], "offsets": [ [ 607, 616 ] ], "normalized": [] }, { "id": "PMID-8613707_T9", "type": "Protein", "text": [ "iNOS" ], "offsets": [ [ 743, 747 ] ], "normalized": [] }, { "id": "PMID-8613707_T10", "type": "Protein", "text": [ "IFN-gamma" ], "offsets": [ [ 768, 777 ] ], "normalized": [] }, { "id": "PMID-8613707_T11", "type": "Protein", "text": [ "IFN-gamma" ], "offsets": [ [ 926, 935 ] ], "normalized": [] }, { "id": "PMID-8613707_T12", "type": "Protein", "text": [ "iNOS" ], "offsets": [ [ 968, 972 ] ], "normalized": [] }, { "id": "PMID-8613707_T15", "type": "Entity", "text": [ "promoter regions" ], "offsets": [ [ 567, 583 ] ], "normalized": [] }, { "id": "PMID-8613707_T20", "type": "Entity", "text": [ "promoter" ], "offsets": [ [ 748, 756 ] ], "normalized": [] } ]

[ { "id": "PMID-8613707_E1", "type": "Regulation", "trigger": { "text": [ "hyporesponsiveness" ], "offsets": [ [ 26, 44 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "PMID-8613707_T1" }, { "role": "Cause", "ref_id": "PMID-8613707_T2" } ] }, { "id": "PMID-8613707_E2", "type": "Negative_regulation", "trigger": { "text": [ "hyporesponsiveness" ], "offsets": [ [ 26, 44 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "PMID-8613707_E4" } ] }, { "id": "PMID-8613707_E3", "type": "Negative_regulation", "trigger": { "text": [ "hyporesponsiveness" ], "offsets": [ [ 26, 44 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "PMID-8613707_E1" } ] }, { "id": "PMID-8613707_E4", "type": "Regulation", "trigger": { "text": [ "hyporesponsiveness" ], "offsets": [ [ 26, 44 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "PMID-8613707_T1" } ] }, { "id": "PMID-8613707_E5", "type": "Regulation", "trigger": { "text": [ "response" ], "offsets": [ [ 587, 595 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "PMID-8613707_T7" }, { "role": "Cause", "ref_id": "PMID-8613707_T8" }, { "role": "Site", "ref_id": "PMID-8613707_T15" } ] }, { "id": "PMID-8613707_E6", "type": "Regulation", "trigger": { "text": [ "response" ], "offsets": [ [ 587, 595 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "PMID-8613707_T7" }, { "role": "Site", "ref_id": "PMID-8613707_T15" } ] }, { "id": "PMID-8613707_E7", "type": "Positive_regulation", "trigger": { "text": [ "explanations" ], "offsets": [ [ 694, 706 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "PMID-8613707_E16" } ] }, { "id": "PMID-8613707_E8", "type": "Positive_regulation", "trigger": { "text": [ "explanations" ], "offsets": [ [ 694, 706 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "PMID-8613707_E16" }, { "role": "Cause", "ref_id": "PMID-8613707_E18" } ] }, { "id": "PMID-8613707_E9", "type": "Positive_regulation", "trigger": { "text": [ "explanations" ], "offsets": [ [ 694, 706 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "PMID-8613707_E14" }, { "role": "Cause", "ref_id": "PMID-8613707_E18" } ] }, { "id": "PMID-8613707_E10", "type": "Positive_regulation", "trigger": { "text": [ "explanations" ], "offsets": [ [ 694, 706 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "PMID-8613707_E16" }, { "role": "Cause", "ref_id": "PMID-8613707_E17" } ] }, { "id": "PMID-8613707_E11", "type": "Positive_regulation", "trigger": { "text": [ "explanations" ], "offsets": [ [ 694, 706 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "PMID-8613707_E14" }, { "role": "Cause", "ref_id": "PMID-8613707_E17" } ] }, { "id": "PMID-8613707_E12", "type": "Positive_regulation", "trigger": { "text": [ "explanations" ], "offsets": [ [ 694, 706 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "PMID-8613707_E14" } ] }, { "id": "PMID-8613707_E13", "type": "Regulation", "trigger": { "text": [ "hyporesponsiveness" ], "offsets": [ [ 711, 729 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "PMID-8613707_T9" }, { "role": "Cause", "ref_id": "PMID-8613707_T10" }, { "role": "Site", "ref_id": "PMID-8613707_T20" } ] }, { "id": "PMID-8613707_E14", "type": "Negative_regulation", "trigger": { "text": [ "hyporesponsiveness" ], "offsets": [ [ 711, 729 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "PMID-8613707_E15" } ] }, { "id": "PMID-8613707_E15", "type": "Regulation", "trigger": { "text": [ "hyporesponsiveness" ], "offsets": [ [ 711, 729 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "PMID-8613707_T9" }, { "role": "Site", "ref_id": "PMID-8613707_T20" } ] }, { "id": "PMID-8613707_E16", "type": "Negative_regulation", "trigger": { "text": [ "hyporesponsiveness" ], "offsets": [ [ 711, 729 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "PMID-8613707_E13" } ] }, { "id": "PMID-8613707_E17", "type": "Negative_regulation", "trigger": { "text": [ "regulate" ], "offsets": [ [ 913, 921 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "PMID-8613707_E19" } ] }, { "id": "PMID-8613707_E18", "type": "Negative_regulation", "trigger": { "text": [ "regulate" ], "offsets": [ [ 913, 921 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "PMID-8613707_E20" } ] }, { "id": "PMID-8613707_E19", "type": "Positive_regulation", "trigger": { "text": [ "induced" ], "offsets": [ [ 936, 943 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "PMID-8613707_E21" } ] }, { "id": "PMID-8613707_E20", "type": "Positive_regulation", "trigger": { "text": [ "induced" ], "offsets": [ [ 936, 943 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "PMID-8613707_E21" }, { "role": "Cause", "ref_id": "PMID-8613707_T11" } ] }, { "id": "PMID-8613707_E21", "type": "Gene_expression", "trigger": { "text": [ "expression" ], "offsets": [ [ 944, 954 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "PMID-8613707_T12" } ] }, { "id": "PMID-8613707_E22", "type": "Positive_regulation", "trigger": { "text": [ "required" ], "offsets": [ [ 1126, 1134 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "PMID-8613707_E23" } ] }, { "id": "PMID-8613707_E23", "type": "Gene_expression", "trigger": { "text": [ "expression" ], "offsets": [ [ 1147, 1157 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "PMID-8613707_T12" } ] } ]

[ { "id": "PMID-8613707_1", "entity_ids": [ "PMID-8613707_T3", "PMID-8613707_T4" ] }, { "id": "PMID-8613707_2", "entity_ids": [ "PMID-8613707_T5", "PMID-8613707_T6" ] } ]

[]

[ { "id": "PMID-8617207__text", "type": "abstract", "text": [ "GATA transcription factors associate with a novel class of nuclear bodies in erythroblasts and megakaryocytes. \nThe nuclear distribution of GATA transcription factors in murine haemopoietic cells was examined by indirect immunofluorescence. Specific bright foci of GATA-1 fluorescence were observed in erythroleukaemia cells and primary murine erythroblasts and megakaryocytes, in addition to diffuse nucleoplasmic localization. These foci, which were preferentially found adjacent to nucleoli or at the nuclear periphery, did not represent sites of active transcription or binding of GATA-1 to consensus sites in the beta-globin loci. Immunoelectron microscopy demonstrated the presence of intensely labelled structures likely to represent the GATA-1 foci seen by immunofluorescence. The GATA-1 nuclear bodies differed from previously described nuclear structures and there was no co-localization with nuclear antigens involved in RNA processing or other ubiquitous (Spl, c-Jun and TBP) or haemopoietic (NF-E2) transcription factors. Interestingly, GATA-2 and GATA-3 proteins also localized to the same nuclear bodies in cell lines co-expressing GATA-1 and -2 or GATA-1 and -3 gene products. This pattern of distribution is, thus far, unique to the GATA transcription factors and suggests a protein-protein interaction with other components of the nuclear bodies via the GATA zinc finger domain. " ], "offsets": [ [ 0, 1397 ] ] } ]

[ { "id": "PMID-8617207_T1", "type": "Protein", "text": [ "GATA-1" ], "offsets": [ [ 265, 271 ] ], "normalized": [] }, { "id": "PMID-8617207_T2", "type": "Protein", "text": [ "GATA-1" ], "offsets": [ [ 585, 591 ] ], "normalized": [] }, { "id": "PMID-8617207_T3", "type": "Protein", "text": [ "beta-globin" ], "offsets": [ [ 618, 629 ] ], "normalized": [] }, { "id": "PMID-8617207_T4", "type": "Protein", "text": [ "GATA-1" ], "offsets": [ [ 745, 751 ] ], "normalized": [] }, { "id": "PMID-8617207_T5", "type": "Protein", "text": [ "GATA-1" ], "offsets": [ [ 789, 795 ] ], "normalized": [] }, { "id": "PMID-8617207_T6", "type": "Protein", "text": [ "c-Jun" ], "offsets": [ [ 973, 978 ] ], "normalized": [] }, { "id": "PMID-8617207_T7", "type": "Protein", "text": [ "TBP" ], "offsets": [ [ 983, 986 ] ], "normalized": [] }, { "id": "PMID-8617207_T8", "type": "Protein", "text": [ "GATA-2" ], "offsets": [ [ 1050, 1056 ] ], "normalized": [] }, { "id": "PMID-8617207_T9", "type": "Protein", "text": [ "GATA-3" ], "offsets": [ [ 1061, 1067 ] ], "normalized": [] }, { "id": "PMID-8617207_T10", "type": "Protein", "text": [ "GATA-1" ], "offsets": [ [ 1147, 1153 ] ], "normalized": [] }, { "id": "PMID-8617207_T11", "type": "Protein", "text": [ "-2" ], "offsets": [ [ 1158, 1160 ] ], "normalized": [] }, { "id": "PMID-8617207_T12", "type": "Protein", "text": [ "GATA-1" ], "offsets": [ [ 1164, 1170 ] ], "normalized": [] }, { "id": "PMID-8617207_T13", "type": "Protein", "text": [ "-3" ], "offsets": [ [ 1175, 1177 ] ], "normalized": [] }, { "id": "PMID-8617207_T15", "type": "Entity", "text": [ "nucleoplasmic" ], "offsets": [ [ 401, 414 ] ], "normalized": [] }, { "id": "PMID-8617207_T18", "type": "Entity", "text": [ "nucleoli" ], "offsets": [ [ 485, 493 ] ], "normalized": [] }, { "id": "PMID-8617207_T19", "type": "Entity", "text": [ "nuclear periphery" ], "offsets": [ [ 504, 521 ] ], "normalized": [] }, { "id": "PMID-8617207_T21", "type": "Entity", "text": [ "consensus sites" ], "offsets": [ [ 595, 610 ] ], "normalized": [] }, { "id": "PMID-8617207_T24", "type": "Entity", "text": [ "nuclear bodies" ], "offsets": [ [ 1104, 1118 ] ], "normalized": [] } ]

[ { "id": "PMID-8617207_E1", "type": "Gene_expression", "trigger": { "text": [ "bright foci" ], "offsets": [ [ 250, 261 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "PMID-8617207_T1" } ] }, { "id": "PMID-8617207_E2", "type": "Localization", "trigger": { "text": [ "localization" ], "offsets": [ [ 415, 427 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "PMID-8617207_T1" }, { "role": "ToLoc", "ref_id": "PMID-8617207_T15" } ] }, { "id": "PMID-8617207_E3", "type": "Localization", "trigger": { "text": [ "found" ], "offsets": [ [ 467, 472 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "PMID-8617207_T1" }, { "role": "AtLoc", "ref_id": "PMID-8617207_T19" } ] }, { "id": "PMID-8617207_E4", "type": "Localization", "trigger": { "text": [ "found" ], "offsets": [ [ 467, 472 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "PMID-8617207_T1" }, { "role": "AtLoc", "ref_id": "PMID-8617207_T18" } ] }, { "id": "PMID-8617207_E5", "type": "Binding", "trigger": { "text": [ "binding" ], "offsets": [ [ 574, 581 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "PMID-8617207_T2" }, { "role": "Theme", "ref_id": "PMID-8617207_T3" }, { "role": "Site", "ref_id": "PMID-8617207_T21" } ] }, { "id": "PMID-8617207_E6", "type": "Localization", "trigger": { "text": [ "co-localization" ], "offsets": [ [ 882, 897 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "PMID-8617207_T6" } ] }, { "id": "PMID-8617207_E7", "type": "Localization", "trigger": { "text": [ "co-localization" ], "offsets": [ [ 882, 897 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "PMID-8617207_T7" } ] }, { "id": "PMID-8617207_E8", "type": "Localization", "trigger": { "text": [ "localized" ], "offsets": [ [ 1082, 1091 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "PMID-8617207_T8" }, { "role": "AtLoc", "ref_id": "PMID-8617207_T24" } ] }, { "id": "PMID-8617207_E9", "type": "Localization", "trigger": { "text": [ "localized" ], "offsets": [ [ 1082, 1091 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "PMID-8617207_T9" }, { "role": "AtLoc", "ref_id": "PMID-8617207_T24" } ] }, { "id": "PMID-8617207_E10", "type": "Gene_expression", "trigger": { "text": [ "co-expressing" ], "offsets": [ [ 1133, 1146 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "PMID-8617207_T10" } ] }, { "id": "PMID-8617207_E11", "type": "Gene_expression", "trigger": { "text": [ "co-expressing" ], "offsets": [ [ 1133, 1146 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "PMID-8617207_T13" } ] }, { "id": "PMID-8617207_E12", "type": "Gene_expression", "trigger": { "text": [ "co-expressing" ], "offsets": [ [ 1133, 1146 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "PMID-8617207_T12" } ] }, { "id": "PMID-8617207_E13", "type": "Gene_expression", "trigger": { "text": [ "co-expressing" ], "offsets": [ [ 1133, 1146 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "PMID-8617207_T11" } ] } ]

[]

[]

[ { "id": "PMID-8627768__text", "type": "abstract", "text": [ "Permanent occupancy of the human immunodeficiency virus type 1 enhancer by NF-kappa B is needed for persistent viral replication in monocytes. \nThis work aimed to ascertain the role of kappaB-responsive elements of the human immunodeficiency virus type 1 (HIV-1) enhancer not only in early initiation but also in long-term maintenance of proviral transcription in cells of the monocytic lineage. For this purpose, we used three main approaches. The first was to abruptly terminate tumor necrosis factor-induced NF-kappaB binding to the enhancer sequences in U1 monocytic cells, using a short pulse of exogenous tumor necrosis factor. This resulted in concomitant decrease in nuclear NF-kappaB DNA-binding activity and endogenous long terminal repeat transcriptional activity. The second was to suppress the permanent NF-kappaB translocation induced by HIV-1 replication itself in chronically infected U937 cells, using a specific proteasome inhibitor (Z-LLL-H). As early as 2 h after addition of the inhibitor to the culture medium, there was an inhibition of both constitutive activation of NF-kappaB and HIV-1 genome expression. The third approach was to monitor the replication competence in U937 cells of an infectious HIV-1 provirus carrying point mutations in the kappaB-responsive elements of both long terminal repeats. Compared with its wild-type counterpart, this mutated provirus showed a profoundly decreased, Z-LLL-H-insensitive transcriptional and replicative activity in U937 monocytes. Together, our results indicate that occupancy of the viral enhancer by NF-kappaB (p50/p65) heterodimers is required for ongoing transcription of integrated HIV provirus in monocytes, even in cells chronically infected and permanently producing functional HIV Tat protein. Thus, the ability of HIV-1 replication to activate NF-kappaB is crucial to the intense self-perpetuated viral transcription observed in cells of the monocytic lineage. " ], "offsets": [ [ 0, 1942 ] ] } ]

[ { "id": "PMID-8627768_T1", "type": "Protein", "text": [ "p50" ], "offsets": [ [ 1584, 1587 ] ], "normalized": [] }, { "id": "PMID-8627768_T2", "type": "Protein", "text": [ "p65" ], "offsets": [ [ 1588, 1591 ] ], "normalized": [] }, { "id": "PMID-8627768_T3", "type": "Protein", "text": [ "Tat" ], "offsets": [ [ 1761, 1764 ] ], "normalized": [] } ]

[ { "id": "PMID-8627768_E1", "type": "Binding", "trigger": { "text": [ "occupancy" ], "offsets": [ [ 1538, 1547 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "PMID-8627768_T2" } ] }, { "id": "PMID-8627768_E2", "type": "Binding", "trigger": { "text": [ "occupancy" ], "offsets": [ [ 1538, 1547 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "PMID-8627768_T1" } ] }, { "id": "PMID-8627768_E3", "type": "Gene_expression", "trigger": { "text": [ "producing" ], "offsets": [ [ 1736, 1745 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "PMID-8627768_T3" } ] } ]

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[ { "id": "PMID-8627791__text", "type": "abstract", "text": [ "Efficient transcription and replication of simian immunodeficiency virus in the absence of NF-kappaB and Sp1 binding elements. \nTen mutants of the simian immunodeficiency virus (SIV) SIVmac239 bearing deletions (delta) or substitutions (subst) in the NF-kappaB and/or Sp1 binding elements were created, and the replicative capacities of the mutants were analyzed. All mutants, including one extensively mutagenized strain entirely missing the NF-kappaB and four Spl binding elements, replicated with wild-type kinetics and to a wild-type level in peripheral blood mononuclear cell cultures in 50 to 100% of the experiments. One group of mutants replicated very similarly to SIVmac239 in kinetics and yield in CEMxl74 cells (2xNFKappaB > or = SlVmac239 approximately deltaNFkappaB approximately deltaSpl234 approximately substNFkappaB approximately substSpl2 approximately substSp23), while a second group replicated with delayed or slightly delayed kinetics in CEMxl74 cells (SIVmac239 > substSp34 > deltaNFkappaBdeltaSpl234 approximately deltaNFkappaBdeltaSp1 > substSpl234). Reversions or additional mutations were not detected in the U3 and R regions of proviral DNA from CEMxl74 cells infected with the SIVmac239 mutants. Similar results were obtained when mutants of SIVmacMER (a macrophage-competent derivative of SIVmac239) were tested in peripheral blood mononuclear cell and CEMx174 cultures. However, the growth of most mutated viruses was suppressed in primary rhesus monkey alveolar macrophages (SIVmacMER approximately 2xNFkappaB approximately substNFkappaB > deltaNFkappaB > deltaNFkappaBdeltaSpl234 approximately deltaNFkappaBdeltaSpl > deltaSpl234 approximately substSpl2 > substSp23 approximately substSp34 approximately substSpl234 > or = SIVmac239). Thus, changes in the Sp1 binding sites had the most dramatic effects on SIVmac replication in primary macrophage cultures. Analysis of long terminal repeat-driven secreted alkaline phosphatase activity in transient assays showed that, unlike human immunodeficiency virus type 1, the SIV long terminal repeat possesses an enhancer region just upstream of the NF-kappaB element which maintains significant levels of basal transcription in the absence of NF-kappaB and Sp1 sites. This region is responsive to transactivation by Tat. In addition, the SIV TATA box was shown to be stronger than that of human immunodeficiency virus type 1. Therefore, the surprisingly high replicative capacity of NF-kappaB and Sp1 binding site mutants of SIVmac is due to unique features or the enhancer/promoter region. " ], "offsets": [ [ 0, 2569 ] ] } ]

[ { "id": "PMID-8627791_T1", "type": "Protein", "text": [ "Sp1" ], "offsets": [ [ 105, 108 ] ], "normalized": [] }, { "id": "PMID-8627791_T2", "type": "Protein", "text": [ "Sp1" ], "offsets": [ [ 268, 271 ] ], "normalized": [] }, { "id": "PMID-8627791_T3", "type": "Protein", "text": [ "Spl" ], "offsets": [ [ 462, 465 ] ], "normalized": [] }, { "id": "PMID-8627791_T4", "type": "Protein", "text": [ "Sp1" ], "offsets": [ [ 1790, 1793 ] ], "normalized": [] }, { "id": "PMID-8627791_T5", "type": "Protein", "text": [ "Sp1" ], "offsets": [ [ 2235, 2238 ] ], "normalized": [] }, { "id": "PMID-8627791_T6", "type": "Protein", "text": [ "Tat" ], "offsets": [ [ 2294, 2297 ] ], "normalized": [] }, { "id": "PMID-8627791_T7", "type": "Protein", "text": [ "Sp1" ], "offsets": [ [ 2475, 2478 ] ], "normalized": [] } ]

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[ { "id": "PMID-8628274__text", "type": "abstract", "text": [ "Inactivation of IkappaBbeta by the tax protein of human T-cell leukemia virus type 1: a potential mechanism for constitutive induction of NF-kappaB. \nIn resting T lymphocytes, the transcription factor NF-kappaB is sequestered in the cytoplasm via interactions with members of the I kappa B family of inhibitors, including IkappaBalpha and IkappaBbeta. During normal T-cell activation, IkappaBalpha is rapidly phosphorylated, ubiquitinated, and degraded by the 26S proteasome, thus permitting the release of functional NF-kappaB. In contrast to its transient pattern of nuclear induction during an immune response, NF-kappaB is constitutively activated in cells expressing the Tax transforming protein of human T-cell leukemia virus type I (HTLV-1). Recent studies indicate that HTLV-1 Tax targets IkappaBalpha to the ubiquitin-proteasome pathway. However, it remains unclear how this viral protein induces a persistent rather than transient NF-kappaB response. In this report, we provide evidence that in addition to acting on IkappaBalpha, Tax stimulates the turnover Of IkappaBbeta via a related targeting mechanism. Like IkappaBalpha, Tax-mediated breakdown of IkappaBbeta in transfected T lymphocytes is blocked either by cell-permeable proteasome inhibitors or by mutation Of IkappaBbeta at two serine residues present within its N-terminal region. Despite the dual specificity of HTLV-1 Tax for IkappaBalpha and IkappaBbeta at the protein level, Tax selectively stimulates NF-kappaB-directed transcription of the IkappaBalpha gene. Consequently, IkappaBbeta protein expression is chronically downregulated in HTLV-1-infected T lymphocytes. These findings with IkappaBbeta provide a potential mechanism for the constitutive activation of NF-kappaB in Tax-expressing cells. " ], "offsets": [ [ 0, 1778 ] ] } ]

[ { "id": "PMID-8628274_T1", "type": "Protein", "text": [ "IkappaBbeta" ], "offsets": [ [ 16, 27 ] ], "normalized": [] }, { "id": "PMID-8628274_T2", "type": "Protein", "text": [ "tax" ], "offsets": [ [ 35, 38 ] ], "normalized": [] }, { "id": "PMID-8628274_T3", "type": "Protein", "text": [ "IkappaBalpha" ], "offsets": [ [ 322, 334 ] ], "normalized": [] }, { "id": "PMID-8628274_T4", "type": "Protein", "text": [ "IkappaBbeta" ], "offsets": [ [ 339, 350 ] ], "normalized": [] }, { "id": "PMID-8628274_T5", "type": "Protein", "text": [ "IkappaBalpha" ], "offsets": [ [ 385, 397 ] ], "normalized": [] }, { "id": "PMID-8628274_T6", "type": "Protein", "text": [ "Tax" ], "offsets": [ [ 676, 679 ] ], "normalized": [] }, { "id": "PMID-8628274_T7", "type": "Protein", "text": [ "Tax" ], "offsets": [ [ 785, 788 ] ], "normalized": [] }, { "id": "PMID-8628274_T8", "type": "Protein", "text": [ "IkappaBalpha" ], "offsets": [ [ 797, 809 ] ], "normalized": [] }, { "id": "PMID-8628274_T9", "type": "Protein", "text": [ "IkappaBalpha" ], "offsets": [ [ 1027, 1039 ] ], "normalized": [] }, { "id": "PMID-8628274_T10", "type": "Protein", "text": [ "Tax" ], "offsets": [ [ 1041, 1044 ] ], "normalized": [] }, { "id": "PMID-8628274_T11", "type": "Protein", "text": [ "IkappaBbeta" ], "offsets": [ [ 1072, 1083 ] ], "normalized": [] }, { "id": "PMID-8628274_T12", "type": "Protein", "text": [ "IkappaBalpha" ], "offsets": [ [ 1124, 1136 ] ], "normalized": [] }, { "id": "PMID-8628274_T13", "type": "Protein", "text": [ "Tax" ], "offsets": [ [ 1138, 1141 ] ], "normalized": [] }, { "id": "PMID-8628274_T14", "type": "Protein", "text": [ "IkappaBbeta" ], "offsets": [ [ 1164, 1175 ] ], "normalized": [] }, { "id": "PMID-8628274_T15", "type": "Protein", "text": [ "IkappaBbeta" ], "offsets": [ [ 1281, 1292 ] ], "normalized": [] }, { "id": "PMID-8628274_T16", "type": "Protein", "text": [ "Tax" ], "offsets": [ [ 1393, 1396 ] ], "normalized": [] }, { "id": "PMID-8628274_T17", "type": "Protein", "text": [ "IkappaBalpha" ], "offsets": [ [ 1401, 1413 ] ], "normalized": [] }, { "id": "PMID-8628274_T18", "type": "Protein", "text": [ "IkappaBbeta" ], "offsets": [ [ 1418, 1429 ] ], "normalized": [] }, { "id": "PMID-8628274_T19", "type": "Protein", "text": [ "Tax" ], "offsets": [ [ 1452, 1455 ] ], "normalized": [] }, { "id": "PMID-8628274_T20", "type": "Protein", "text": [ "IkappaBalpha" ], "offsets": [ [ 1519, 1531 ] ], "normalized": [] }, { "id": "PMID-8628274_T21", "type": "Protein", "text": [ "IkappaBbeta" ], "offsets": [ [ 1552, 1563 ] ], "normalized": [] }, { "id": "PMID-8628274_T22", "type": "Protein", "text": [ "IkappaBbeta" ], "offsets": [ [ 1666, 1677 ] ], "normalized": [] }, { "id": "PMID-8628274_T23", "type": "Protein", "text": [ "Tax" ], "offsets": [ [ 1756, 1759 ] ], "normalized": [] } ]

[ { "id": "PMID-8628274_E1", "type": "Negative_regulation", "trigger": { "text": [ "Inactivation" ], "offsets": [ [ 0, 12 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "PMID-8628274_T1" }, { "role": "Cause", "ref_id": "PMID-8628274_T2" } ] }, { "id": "PMID-8628274_E2", "type": "Binding", "trigger": { "text": [ "interactions" ], "offsets": [ [ 247, 259 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "PMID-8628274_T3" } ] }, { "id": "PMID-8628274_E3", "type": "Binding", "trigger": { "text": [ "interactions" ], "offsets": [ [ 247, 259 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "PMID-8628274_T4" } ] }, { "id": "PMID-8628274_E4", "type": "Phosphorylation", "trigger": { "text": [ "phosphorylated" ], "offsets": [ [ 409, 423 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "PMID-8628274_T5" } ] }, { "id": "PMID-8628274_E5", "type": "Protein_catabolism", "trigger": { "text": [ "degraded" ], "offsets": [ [ 444, 452 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "PMID-8628274_T5" } ] }, { "id": "PMID-8628274_E6", "type": "Positive_regulation", "trigger": { "text": [ "by" ], "offsets": [ [ 453, 455 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "PMID-8628274_E5" } ] }, { "id": "PMID-8628274_E7", "type": "Gene_expression", "trigger": { "text": [ "expressing" ], "offsets": [ [ 661, 671 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "PMID-8628274_T6" } ] }, { "id": "PMID-8628274_E8", "type": "Positive_regulation", "trigger": { "text": [ "targets" ], "offsets": [ [ 789, 796 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "PMID-8628274_E9" }, { "role": "Cause", "ref_id": "PMID-8628274_T7" } ] }, { "id": "PMID-8628274_E9", "type": "Protein_catabolism", "trigger": { "text": [ "ubiquitin-proteasome pathway" ], "offsets": [ [ 817, 845 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "PMID-8628274_T8" } ] }, { "id": "PMID-8628274_E10", "type": "Regulation", "trigger": { "text": [ "acting" ], "offsets": [ [ 1017, 1023 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "PMID-8628274_T9" }, { "role": "Cause", "ref_id": "PMID-8628274_T10" } ] }, { "id": "PMID-8628274_E11", "type": "Positive_regulation", "trigger": { "text": [ "mediated" ], "offsets": [ [ 1142, 1150 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "PMID-8628274_E12" }, { "role": "Cause", "ref_id": "PMID-8628274_T13" } ] }, { "id": "PMID-8628274_E12", "type": "Protein_catabolism", "trigger": { "text": [ "breakdown" ], "offsets": [ [ 1151, 1160 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "PMID-8628274_T14" } ] }, { "id": "PMID-8628274_E13", "type": "Gene_expression", "trigger": { "text": [ "transfected" ], "offsets": [ [ 1179, 1190 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "PMID-8628274_T13" } ] }, { "id": "PMID-8628274_E14", "type": "Positive_regulation", "trigger": { "text": [ "transfected" ], "offsets": [ [ 1179, 1190 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "PMID-8628274_E13" } ] }, { "id": "PMID-8628274_E15", "type": "Negative_regulation", "trigger": { "text": [ "blocked" ], "offsets": [ [ 1208, 1215 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "PMID-8628274_E13" } ] }, { "id": "PMID-8628274_E16", "type": "Positive_regulation", "trigger": { "text": [ "stimulates" ], "offsets": [ [ 1468, 1478 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "PMID-8628274_E17" }, { "role": "Cause", "ref_id": "PMID-8628274_T19" } ] }, { "id": "PMID-8628274_E17", "type": "Positive_regulation", "trigger": { "text": [ "directed" ], "offsets": [ [ 1489, 1497 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "PMID-8628274_E18" } ] }, { "id": "PMID-8628274_E18", "type": "Transcription", "trigger": { "text": [ "transcription" ], "offsets": [ [ 1498, 1511 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "PMID-8628274_T20" } ] }, { "id": "PMID-8628274_E19", "type": "Gene_expression", "trigger": { "text": [ "expression" ], "offsets": [ [ 1572, 1582 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "PMID-8628274_T21" } ] }, { "id": "PMID-8628274_E20", "type": "Negative_regulation", "trigger": { "text": [ "downregulated" ], "offsets": [ [ 1598, 1611 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "PMID-8628274_E19" } ] }, { "id": "PMID-8628274_E21", "type": "Gene_expression", "trigger": { "text": [ "expressing" ], "offsets": [ [ 1760, 1770 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "PMID-8628274_T23" } ] } ]

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[ { "id": "PMID-8628295__text", "type": "abstract", "text": [ "Role of EGR1 in regulation of stimulus-dependent CD44 transcription in B lymphocytes. \nThe immediate-early gene egr-1 encodes a transcription factor (EGR1) that links B-cell antigen receptor (BCR) signals to downstream activation events through the regulation of previously unidentified target genes. Here we identify the gene encoding the lymphocyte homing and migration protein CD44 as a target of EGR1 regulation in B cells. BCR-induced increases in CD44 mRNA expression and transcription levels are shown to occur in EGR1-expressing but not in nonexpressing subclones of the B-cell line WEHI-231. Kinetics of egr-1 transcription and the appearance of nuclear EGR1 protein precede CD44 induction and occur within 30 min after stimulation in the EGR1-expressing subclone. A single EGR1 binding motif is demonstrated at bp -301 of the human CD44 promoter. Cotransfection of a CD44 promoter-chloramphenicol acetyltransferase reporter construct with an egr-1 expression vector resulted in a 6.5- to 8.5-fold induction of transcriptional activity relative to an empty expression vector. The EGR1 binding motif was shown to be necessary for stimulus-induced expression of a CD44 promoter-chloramphenicol acetyltransferase reporter construct in nontransformed B lymphocytes and was required for transactivation by an EGR1 expression vector in a B-cell line. These studies identify EGR1 as an intermediary linking BCR-derived signals to the induction of CD44. The relevance of these molecular events to BCR signal transduction and antigen-stimulated B-cell-mediated immune responses is discussed. " ], "offsets": [ [ 0, 1592 ] ] } ]

[ { "id": "PMID-8628295_T1", "type": "Protein", "text": [ "EGR1" ], "offsets": [ [ 8, 12 ] ], "normalized": [] }, { "id": "PMID-8628295_T2", "type": "Protein", "text": [ "CD44" ], "offsets": [ [ 49, 53 ] ], "normalized": [] }, { "id": "PMID-8628295_T3", "type": "Protein", "text": [ "egr-1" ], "offsets": [ [ 112, 117 ] ], "normalized": [] }, { "id": "PMID-8628295_T4", "type": "Protein", "text": [ "EGR1" ], "offsets": [ [ 150, 154 ] ], "normalized": [] }, { "id": "PMID-8628295_T5", "type": "Protein", "text": [ "CD44" ], "offsets": [ [ 380, 384 ] ], "normalized": [] }, { "id": "PMID-8628295_T6", "type": "Protein", "text": [ "EGR1" ], "offsets": [ [ 400, 404 ] ], "normalized": [] }, { "id": "PMID-8628295_T7", "type": "Protein", "text": [ "CD44" ], "offsets": [ [ 453, 457 ] ], "normalized": [] }, { "id": "PMID-8628295_T8", "type": "Protein", "text": [ "EGR1" ], "offsets": [ [ 521, 525 ] ], "normalized": [] }, { "id": "PMID-8628295_T9", "type": "Protein", "text": [ "egr-1" ], "offsets": [ [ 613, 618 ] ], "normalized": [] }, { "id": "PMID-8628295_T10", "type": "Protein", "text": [ "EGR1" ], "offsets": [ [ 663, 667 ] ], "normalized": [] }, { "id": "PMID-8628295_T11", "type": "Protein", "text": [ "CD44" ], "offsets": [ [ 684, 688 ] ], "normalized": [] }, { "id": "PMID-8628295_T12", "type": "Protein", "text": [ "EGR1" ], "offsets": [ [ 748, 752 ] ], "normalized": [] }, { "id": "PMID-8628295_T13", "type": "Protein", "text": [ "EGR1" ], "offsets": [ [ 783, 787 ] ], "normalized": [] }, { "id": "PMID-8628295_T14", "type": "Protein", "text": [ "CD44" ], "offsets": [ [ 842, 846 ] ], "normalized": [] }, { "id": "PMID-8628295_T15", "type": "Protein", "text": [ "CD44" ], "offsets": [ [ 877, 881 ] ], "normalized": [] }, { "id": "PMID-8628295_T16", "type": "Protein", "text": [ "chloramphenicol acetyltransferase" ], "offsets": [ [ 891, 924 ] ], "normalized": [] }, { "id": "PMID-8628295_T17", "type": "Protein", "text": [ "egr-1" ], "offsets": [ [ 952, 957 ] ], "normalized": [] }, { "id": "PMID-8628295_T18", "type": "Protein", "text": [ "EGR1" ], "offsets": [ [ 1089, 1093 ] ], "normalized": [] }, { "id": "PMID-8628295_T19", "type": "Protein", "text": [ "CD44" ], "offsets": [ [ 1171, 1175 ] ], "normalized": [] }, { "id": "PMID-8628295_T20", "type": "Protein", "text": [ "chloramphenicol acetyltransferase" ], "offsets": [ [ 1185, 1218 ] ], "normalized": [] }, { "id": "PMID-8628295_T21", "type": "Protein", "text": [ "EGR1" ], "offsets": [ [ 1313, 1317 ] ], "normalized": [] }, { "id": "PMID-8628295_T22", "type": "Protein", "text": [ "EGR1" ], "offsets": [ [ 1377, 1381 ] ], "normalized": [] }, { "id": "PMID-8628295_T23", "type": "Protein", "text": [ "CD44" ], "offsets": [ [ 1449, 1453 ] ], "normalized": [] }, { "id": "PMID-8628295_T35", "type": "Entity", "text": [ "nuclear" ], "offsets": [ [ 655, 662 ] ], "normalized": [] } ]

[ { "id": "PMID-8628295_E1", "type": "Regulation", "trigger": { "text": [ "Role" ], "offsets": [ [ 0, 4 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "PMID-8628295_E2" }, { "role": "Cause", "ref_id": "PMID-8628295_T1" } ] }, { "id": "PMID-8628295_E2", "type": "Regulation", "trigger": { "text": [ "regulation" ], "offsets": [ [ 16, 26 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "PMID-8628295_E3" } ] }, { "id": "PMID-8628295_E3", "type": "Positive_regulation", "trigger": { "text": [ "dependent" ], "offsets": [ [ 39, 48 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "PMID-8628295_E4" } ] }, { "id": "PMID-8628295_E4", "type": "Transcription", "trigger": { "text": [ "transcription" ], "offsets": [ [ 54, 67 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "PMID-8628295_T2" } ] }, { "id": "PMID-8628295_E5", "type": "Regulation", "trigger": { "text": [ "regulation" ], "offsets": [ [ 405, 415 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "PMID-8628295_T5" }, { "role": "Cause", "ref_id": "PMID-8628295_T6" } ] }, { "id": "PMID-8628295_E6", "type": "Positive_regulation", "trigger": { "text": [ "increases" ], "offsets": [ [ 440, 449 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "PMID-8628295_E7" } ] }, { "id": "PMID-8628295_E7", "type": "Transcription", "trigger": { "text": [ "expression and transcription" ], "offsets": [ [ 463, 491 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "PMID-8628295_T6" } ] }, { "id": "PMID-8628295_E8", "type": "Gene_expression", "trigger": { "text": [ "expressing" ], "offsets": [ [ 526, 536 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "PMID-8628295_T8" } ] }, { "id": "PMID-8628295_E9", "type": "Gene_expression", "trigger": { "text": [ "nonexpressing" ], "offsets": [ [ 548, 561 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "PMID-8628295_T8" } ] }, { "id": "PMID-8628295_E10", "type": "Transcription", "trigger": { "text": [ "transcription" ], "offsets": [ [ 619, 632 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "PMID-8628295_T9" } ] }, { "id": "PMID-8628295_E11", "type": "Localization", "trigger": { "text": [ "appearance" ], "offsets": [ [ 641, 651 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "PMID-8628295_T10" }, { "role": "AtLoc", "ref_id": "PMID-8628295_T35" } ] }, { "id": "PMID-8628295_E12", "type": "Positive_regulation", "trigger": { "text": [ "induction" ], "offsets": [ [ 689, 698 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "PMID-8628295_T11" } ] }, { "id": "PMID-8628295_E13", "type": "Positive_regulation", "trigger": { "text": [ "occur" ], "offsets": [ [ 703, 708 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "PMID-8628295_E11" } ] }, { "id": "PMID-8628295_E14", "type": "Positive_regulation", "trigger": { "text": [ "occur" ], "offsets": [ [ 703, 708 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "PMID-8628295_E10" } ] }, { "id": "PMID-8628295_E15", "type": "Gene_expression", "trigger": { "text": [ "expressing" ], "offsets": [ [ 753, 763 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "PMID-8628295_T12" } ] }, { "id": "PMID-8628295_E16", "type": "Positive_regulation", "trigger": { "text": [ "Cotransfection" ], "offsets": [ [ 857, 871 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "PMID-8628295_E17" } ] }, { "id": "PMID-8628295_E17", "type": "Gene_expression", "trigger": { "text": [ "expression" ], "offsets": [ [ 958, 968 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "PMID-8628295_T17" } ] }, { "id": "PMID-8628295_E18", "type": "Positive_regulation", "trigger": { "text": [ "induction" ], "offsets": [ [ 1007, 1016 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "PMID-8628295_E19" } ] }, { "id": "PMID-8628295_E19", "type": "Transcription", "trigger": { "text": [ "transcriptional activity" ], "offsets": [ [ 1020, 1044 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "PMID-8628295_T15" } ] }, { "id": "PMID-8628295_E20", "type": "Positive_regulation", "trigger": { "text": [ "intermediary linking" ], "offsets": [ [ 1388, 1408 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "PMID-8628295_T22" } ] }, { "id": "PMID-8628295_E21", "type": "Positive_regulation", "trigger": { "text": [ "intermediary linking" ], "offsets": [ [ 1388, 1408 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "PMID-8628295_E22" }, { "role": "Cause", "ref_id": "PMID-8628295_E20" } ] }, { "id": "PMID-8628295_E22", "type": "Positive_regulation", "trigger": { "text": [ "induction" ], "offsets": [ [ 1436, 1445 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "PMID-8628295_T23" } ] } ]

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[ { "id": "PMID-8628306__text", "type": "abstract", "text": [ "Identification of an inducible regulator of c-myb expression during T-cell activation. \nResting T cells express very low levels of c-Myb protein. During T-cell activation, c-myb expression is induced and much of the increase in expression occurs at the transcriptional level. We identified a region of the c-myb 5' flanking sequence that increased c-myb expression during T-cell activation. In vivo footprinting by ligation-mediated PCR was performed to correlate in vivo protein binding with functional activity. A protein footprint was visible over this region of the c-myb 5' flanking sequence in activated T cells but not in unactivated T cells. An electrophoretic mobility shift assay (EMSA) with nuclear extract from activated T cells and an oligonucleotide of this binding site demonstrated a new protein-DNA complex, referred to as CMAT for c-myb in activated T cells; this complex was not present in unactivated T cells. Because the binding site showed some sequence similarity with the nuclear factor of activated T cells (NFAT) binding site, we compared the kinetics of induction of the two binding complexes and the molecular masses of the two proteins. Studies of the kinetics of induction showed that the NFAT EMSA binding complex appeared earlier than the CMAT complex. The NFAT protein migrated more slowly in a sodium dodecyl sulfate-polyacrylamide gel than the CMAT protein did. In addition, an antibody against NFAT did not cross-react with the CMAT protein. The appearance of the CMAT binding complex was inhibited by both cyclosporin A and rapamycin. The CMAT protein appears to be a novel inducible protein involved in the regulation of c-myb expression during T-cell activation. " ], "offsets": [ [ 0, 1702 ] ] } ]

[ { "id": "PMID-8628306_T1", "type": "Protein", "text": [ "c-myb" ], "offsets": [ [ 44, 49 ] ], "normalized": [] }, { "id": "PMID-8628306_T2", "type": "Protein", "text": [ "c-Myb" ], "offsets": [ [ 131, 136 ] ], "normalized": [] }, { "id": "PMID-8628306_T3", "type": "Protein", "text": [ "c-myb" ], "offsets": [ [ 172, 177 ] ], "normalized": [] }, { "id": "PMID-8628306_T4", "type": "Protein", "text": [ "c-myb" ], "offsets": [ [ 306, 311 ] ], "normalized": [] }, { "id": "PMID-8628306_T5", "type": "Protein", "text": [ "c-myb" ], "offsets": [ [ 348, 353 ] ], "normalized": [] }, { "id": "PMID-8628306_T6", "type": "Protein", "text": [ "c-myb" ], "offsets": [ [ 570, 575 ] ], "normalized": [] }, { "id": "PMID-8628306_T7", "type": "Protein", "text": [ "c-myb" ], "offsets": [ [ 849, 854 ] ], "normalized": [] }, { "id": "PMID-8628306_T8", "type": "Protein", "text": [ "c-myb" ], "offsets": [ [ 1659, 1664 ] ], "normalized": [] } ]

[ { "id": "PMID-8628306_E1", "type": "Regulation", "trigger": { "text": [ "regulator" ], "offsets": [ [ 31, 40 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "PMID-8628306_E2" } ] }, { "id": "PMID-8628306_E2", "type": "Gene_expression", "trigger": { "text": [ "expression" ], "offsets": [ [ 50, 60 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "PMID-8628306_T1" } ] }, { "id": "PMID-8628306_E3", "type": "Gene_expression", "trigger": { "text": [ "express" ], "offsets": [ [ 104, 111 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "PMID-8628306_T2" } ] }, { "id": "PMID-8628306_E4", "type": "Gene_expression", "trigger": { "text": [ "expression" ], "offsets": [ [ 178, 188 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "PMID-8628306_T3" } ] }, { "id": "PMID-8628306_E5", "type": "Positive_regulation", "trigger": { "text": [ "induced" ], "offsets": [ [ 192, 199 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "PMID-8628306_E4" } ] }, { "id": "PMID-8628306_E6", "type": "Positive_regulation", "trigger": { "text": [ "increased" ], "offsets": [ [ 338, 347 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "PMID-8628306_E7" } ] }, { "id": "PMID-8628306_E7", "type": "Gene_expression", "trigger": { "text": [ "expression" ], "offsets": [ [ 354, 364 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "PMID-8628306_T5" } ] }, { "id": "PMID-8628306_E8", "type": "Regulation", "trigger": { "text": [ "regulation" ], "offsets": [ [ 1645, 1655 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "PMID-8628306_E9" } ] }, { "id": "PMID-8628306_E9", "type": "Gene_expression", "trigger": { "text": [ "expression" ], "offsets": [ [ 1665, 1675 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "PMID-8628306_T8" } ] } ]

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[ { "id": "PMID-8631821__text", "type": "abstract", "text": [ "Structural and functional characterization of the human CD36 gene promoter: identification of a proximal PEBP2/CBF site. \nCD36 is a cell surface glycoprotein composed of a single polypeptide chain, which interacts with thrombospondin, collagens type I and IV, oxidized low density lipoprotein, fatty acids, anionic phospholipids, and erythrocytes parasitized with Plasmodium falciparum. Its expression is restricted to a few cell types, including monocyte/macrophages. In these cells, CD36 is involved in phagocytosis of apoptotic cells, and foam cell formation by uptake of oxidized low density lipoprotein. To study the molecular mechanisms that control the transcription of the CD36 gene in monocytic cells we have isolated and analyzed the CD36 promoter. Transient expression experiments of 5'-deletion fragments of the CD36 promoter coupled to luciferase demonstrated that as few as 158 base pairs upstream from the transcription initiation site were sufficient to direct the monocyte-specific transcription of the reporter gene. Within the above region, the fragment spanning nucleotides -158 to -90 was required for optimal transcription in monocytic cells. Biochemical analysis of the region -158/-90 revealed a binding site for transcription factors of the polyomavirus enhancer-binding protein 2/core-binding factor (PEBP2/CBF) family at position -103. Disruption of the PEBP2/CBF site markedly diminished the role of the PEBP2/CBF factors in the constitutive transcription of the CD36 gene. The involvement of members of the PEBP2/CBF family in chromosome translocations associated with acute myeloid leukemia, and in the transcriptional regulation of the myeloid-specific genes encoding for myeloperoxidase, elastase, and the colony-stimulating factor receptor, highlights the relevance of the regulation of the CD36 gene promoter in monocytic cells by members of the PEBP2/CBF family. " ], "offsets": [ [ 0, 1898 ] ] } ]

[ { "id": "PMID-8631821_T1", "type": "Protein", "text": [ "CD36" ], "offsets": [ [ 56, 60 ] ], "normalized": [] }, { "id": "PMID-8631821_T2", "type": "Protein", "text": [ "CD36" ], "offsets": [ [ 122, 126 ] ], "normalized": [] }, { "id": "PMID-8631821_T3", "type": "Protein", "text": [ "CD36" ], "offsets": [ [ 485, 489 ] ], "normalized": [] }, { "id": "PMID-8631821_T4", "type": "Protein", "text": [ "CD36" ], "offsets": [ [ 681, 685 ] ], "normalized": [] }, { "id": "PMID-8631821_T5", "type": "Protein", "text": [ "CD36" ], "offsets": [ [ 744, 748 ] ], "normalized": [] }, { "id": "PMID-8631821_T6", "type": "Protein", "text": [ "CD36" ], "offsets": [ [ 824, 828 ] ], "normalized": [] }, { "id": "PMID-8631821_T7", "type": "Protein", "text": [ "CD36" ], "offsets": [ [ 1491, 1495 ] ], "normalized": [] }, { "id": "PMID-8631821_T8", "type": "Protein", "text": [ "myeloperoxidase" ], "offsets": [ [ 1703, 1718 ] ], "normalized": [] }, { "id": "PMID-8631821_T9", "type": "Protein", "text": [ "CD36" ], "offsets": [ [ 1824, 1828 ] ], "normalized": [] }, { "id": "PMID-8631821_T19", "type": "Entity", "text": [ "promoter" ], "offsets": [ [ 1834, 1842 ] ], "normalized": [] } ]

[ { "id": "PMID-8631821_E1", "type": "Binding", "trigger": { "text": [ "interacts" ], "offsets": [ [ 204, 213 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "PMID-8631821_T2" } ] }, { "id": "PMID-8631821_E2", "type": "Gene_expression", "trigger": { "text": [ "expression" ], "offsets": [ [ 391, 401 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "PMID-8631821_T2" } ] }, { "id": "PMID-8631821_E3", "type": "Regulation", "trigger": { "text": [ "control" ], "offsets": [ [ 648, 655 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "PMID-8631821_E4" } ] }, { "id": "PMID-8631821_E4", "type": "Transcription", "trigger": { "text": [ "transcription" ], "offsets": [ [ 660, 673 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "PMID-8631821_T4" } ] }, { "id": "PMID-8631821_E5", "type": "Negative_regulation", "trigger": { "text": [ "diminished" ], "offsets": [ [ 1405, 1415 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "PMID-8631821_E6" } ] }, { "id": "PMID-8631821_E6", "type": "Regulation", "trigger": { "text": [ "role" ], "offsets": [ [ 1420, 1424 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "PMID-8631821_E7" } ] }, { "id": "PMID-8631821_E7", "type": "Transcription", "trigger": { "text": [ "transcription" ], "offsets": [ [ 1470, 1483 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "PMID-8631821_T7" } ] }, { "id": "PMID-8631821_E8", "type": "Regulation", "trigger": { "text": [ "transcriptional regulation" ], "offsets": [ [ 1633, 1659 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "PMID-8631821_T8" } ] }, { "id": "PMID-8631821_E9", "type": "Regulation", "trigger": { "text": [ "regulation" ], "offsets": [ [ 1806, 1816 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "PMID-8631821_T9" }, { "role": "Site", "ref_id": "PMID-8631821_T19" } ] } ]

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[ { "id": "PMID-8632999__text", "type": "abstract", "text": [ "CNI-1493 inhibits monocyte/macrophage tumor necrosis factor by suppression of translation efficiency. \nTumor necrosis factor (TNF) mediates a wide variety of disease states including septic shock, acute and chronic inflammation, and cachexia. Recently, a multivalent guanylhydrazone (CNI-1493) developed as an inhibitor of macrophage activation was shown to suppress TNF production and protect against tissue inflammation and endotoxin lethality [Bianchi, M., Ulrich, P., Bloom, O., Meistrell, M., Zimmerman, G.A., Schmidtmayerova, H., Bukrinsky, M., Donnelley, T., Bucala, R., Sherry, B., Manogue, K.R., Tortolani, A.J., Cerami, A.& Tracey, K.J.(1995) Mol.Med.1, 254-266, and Bianchi, M., Bloom, O., Raabe, T., Cohen, P. S., Chesney, J., Sherry, B., Schmidtmayerova, H., Zhang, X., Bukrinsky, M., Ulrich, P., Cerami, A.& Tracey, J.(1996) J.Exp.Med., in press]. We have now elucidated the mechanism by which CNI-1493 inhibits macrophage TNF synthesis and show here that it acts through suppression of TNF translation efficiency. CNI-1493 blocked neither the lipopolysaccharide (LPS)-induced increases in the expression of TNF mRNA nor the translocation of nuclear factor NF-kappa B to the nucleus in macrophages activated by 15 min of LPS stimulation, indicating that CNI-1493 does not interfere with early NF-kappa B-mediated transcriptional regulation of TNF. However, synthesis of the 26-kDa membrane form of TNF was effectively blocked by CNI-1493. Further evidence for the translational suppression of TNF is given by experiments using chloram-phenicol acetyltransferase (CAT) constructs containing elements of the TNF gene that are involved in TNF translational regulation. Both the 5' and 3' untranslated regions of the TNF gene were required to elicit maximal translational suppression by CNI-1493. Identification of the molecular target through which CNI- 1493 inhibits TNF translation should provide insight into the regulation of macrophage activation and mechanisms of inflammation. " ], "offsets": [ [ 0, 1995 ] ] } ]

[ { "id": "PMID-8632999_T1", "type": "Protein", "text": [ "chloram-phenicol acetyltransferase" ], "offsets": [ [ 1541, 1575 ] ], "normalized": [] }, { "id": "PMID-8632999_T2", "type": "Protein", "text": [ "CAT" ], "offsets": [ [ 1577, 1580 ] ], "normalized": [] } ]

[]

[ { "id": "PMID-8632999_1", "entity_ids": [ "PMID-8632999_T1", "PMID-8632999_T2" ] } ]

[]

[ { "id": "PMID-8634413__text", "type": "abstract", "text": [ "STAT-related transcription factors are constitutively activated in peripheral blood cells from acute leukemia patients. \nA signal transduction pathway activated by many cytokines has recently been elaborated. The JAK kinases and the signal transducers and activators of transcription (STAT) factors have been found to be essential components. In this report, we describe the presence of constitutively activated STAT factors in peripheral blood cells from patients with acute leukemia. We used oligonucleotide probes from the beta-casein and IRF-1 gene promoters and the ISRE probe to detect STAT proteins in nuclear extracts from acute leukemia cells in bandshift assays. Specific DNA protein complex formation was observed with the probes from the beta-casein and IRF-1 gene promoters, but not with the ISRE oligonucleotide probe, when cell extracts from acute lymphoblastic leukemia (ALL) and acute myeloid leukemia (AML) were investigated. We used nonradioactive oligonucleotides as competitors to show the specificity of the complex formation. Specific antibodies directed against the individual STAT proteins were used in supershift experiments. STAT5- and STAT1-related factors were detected in ALL and STAT1-, STAT3-, and STAT5-related proteins were present in nuclear cell extracts from AML. Since the cells were not treated with cytokines before the nuclear proteins were extracted, we conclude that these factors are constitutively activated in vivo. It is likely that the constitutive activation of STAT proteins is a part of the events of leukemogenesis. " ], "offsets": [ [ 0, 1568 ] ] } ]

[ { "id": "PMID-8634413_T1", "type": "Protein", "text": [ "beta-casein" ], "offsets": [ [ 526, 537 ] ], "normalized": [] }, { "id": "PMID-8634413_T2", "type": "Protein", "text": [ "IRF-1" ], "offsets": [ [ 542, 547 ] ], "normalized": [] }, { "id": "PMID-8634413_T3", "type": "Protein", "text": [ "beta-casein" ], "offsets": [ [ 750, 761 ] ], "normalized": [] }, { "id": "PMID-8634413_T4", "type": "Protein", "text": [ "IRF-1" ], "offsets": [ [ 766, 771 ] ], "normalized": [] }, { "id": "PMID-8634413_T5", "type": "Protein", "text": [ "STAT5" ], "offsets": [ [ 1152, 1157 ] ], "normalized": [] }, { "id": "PMID-8634413_T6", "type": "Protein", "text": [ "STAT1" ], "offsets": [ [ 1163, 1168 ] ], "normalized": [] }, { "id": "PMID-8634413_T7", "type": "Protein", "text": [ "STAT1" ], "offsets": [ [ 1210, 1215 ] ], "normalized": [] }, { "id": "PMID-8634413_T8", "type": "Protein", "text": [ "STAT3" ], "offsets": [ [ 1218, 1223 ] ], "normalized": [] }, { "id": "PMID-8634413_T9", "type": "Protein", "text": [ "STAT5" ], "offsets": [ [ 1230, 1235 ] ], "normalized": [] }, { "id": "PMID-8634413_T11", "type": "Entity", "text": [ "promoters" ], "offsets": [ [ 777, 786 ] ], "normalized": [] } ]

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[ { "id": "PMID-8635523__text", "type": "abstract", "text": [ "Reversible differentiation of human monoblastic leukemia U937 cells by ML-9, an inhibitor of myosin light chain kinase. \nHuman monoblastic leukemia U937 cells are induced to differentiate into monocytes and macrophages by various agents. We have shown that 1-(5-chloronaphthalene-1-sulfonyl)-1H-hexahydro-1,4-diazepine hydrochloride (ML-9), an inhibitor of myosin light chain kinase, induces differentiation of monocytoid leukemia cell lines U937 and THP-1 but not of myeloblastic leukemic ML-1 cell or erythroleukemia K562 cells. In the present study, we further analyzed the effect of ML-9 in comparison with that of 1 alpha, 25-dihydroxyvitamin D3 (VD3) a typical inducer of monocytic differentiation. ML-9 induced nitroblue tetrazolium (NBT)-reducing activity of U937 cell more rapidly than VD3: This differentiation marker was induced significantly after incubation with ML-9 and VD3 for 4 hours and 1 day, respectively. ML-9 also induced alpha-naphthyl acetate esterase (ANAE) activity, another monocytic differentiation marker, more rapidly than VD3. The maximum levels of these markers induced by ML-9 were comparable to those induced by VD3, but after removal of ML-9 from the medium by washing the cells, the expressions of theses markers decreased within 4 hours and reached basal levels in 1 day, indicating that ML-9's induction of expression of differentiation-associated phenotypes was reversible. The growth inhibition of U937 cells by ML-9 was also reversible. Similar effects were observed in another line of human monoblastic cells, THP-1. ML-9 had little or no effect on the morphology of U937 cells but increased the expression of monocyte-macrophage lineage-associated surface antigen, CD14, to some extent. Irreversible terminal differentiation induced by VD3 is associated with down regulation of the expression of c-myc and upregulation of the expression of c-fos and c-jun, but ML-9 did not affect the expression of these oncogenes appreciably. ML-9-induced differentiation was also reversible when the cells were cultured with cultured with ML-9 plus an anti-cancer drug such as 1-beta-D-arabino-furanosylcytosine or daunomycin. it became irreversible, however, upon simultaneous treatment with dexamethasone and transforming growth factor-beta 1 (TGF-beta 1), which did not induce differentiation of U937 cells but caused growth arrest of the cells in the G0/G1 phase of the cell cycle. These results suggest that ML-9 should be useful for studying the mechanisms of monocytic differentiation. " ], "offsets": [ [ 0, 2522 ] ] } ]

[ { "id": "PMID-8635523_T1", "type": "Protein", "text": [ "CD14" ], "offsets": [ [ 1708, 1712 ] ], "normalized": [] }, { "id": "PMID-8635523_T2", "type": "Protein", "text": [ "c-myc" ], "offsets": [ [ 1839, 1844 ] ], "normalized": [] }, { "id": "PMID-8635523_T3", "type": "Protein", "text": [ "c-fos" ], "offsets": [ [ 1883, 1888 ] ], "normalized": [] }, { "id": "PMID-8635523_T4", "type": "Protein", "text": [ "c-jun" ], "offsets": [ [ 1893, 1898 ] ], "normalized": [] }, { "id": "PMID-8635523_T5", "type": "Protein", "text": [ "transforming growth factor-beta 1" ], "offsets": [ [ 2240, 2273 ] ], "normalized": [] }, { "id": "PMID-8635523_T6", "type": "Protein", "text": [ "TGF-beta 1" ], "offsets": [ [ 2275, 2285 ] ], "normalized": [] } ]

[ { "id": "PMID-8635523_E1", "type": "Positive_regulation", "trigger": { "text": [ "increased" ], "offsets": [ [ 1624, 1633 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "PMID-8635523_E2" } ] }, { "id": "PMID-8635523_E2", "type": "Gene_expression", "trigger": { "text": [ "expression" ], "offsets": [ [ 1638, 1648 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "PMID-8635523_T1" } ] }, { "id": "PMID-8635523_E3", "type": "Negative_regulation", "trigger": { "text": [ "down regulation" ], "offsets": [ [ 1802, 1817 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "PMID-8635523_E4" } ] }, { "id": "PMID-8635523_E4", "type": "Gene_expression", "trigger": { "text": [ "expression" ], "offsets": [ [ 1825, 1835 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "PMID-8635523_T2" } ] }, { "id": "PMID-8635523_E5", "type": "Positive_regulation", "trigger": { "text": [ "upregulation" ], "offsets": [ [ 1849, 1861 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "PMID-8635523_E7" } ] }, { "id": "PMID-8635523_E6", "type": "Positive_regulation", "trigger": { "text": [ "upregulation" ], "offsets": [ [ 1849, 1861 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "PMID-8635523_E8" } ] }, { "id": "PMID-8635523_E7", "type": "Gene_expression", "trigger": { "text": [ "expression" ], "offsets": [ [ 1869, 1879 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "PMID-8635523_T3" } ] }, { "id": "PMID-8635523_E8", "type": "Gene_expression", "trigger": { "text": [ "expression" ], "offsets": [ [ 1869, 1879 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "PMID-8635523_T4" } ] }, { "id": "PMID-8635523_E9", "type": "Regulation", "trigger": { "text": [ "affect" ], "offsets": [ [ 1917, 1923 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "PMID-8635523_E12" } ] }, { "id": "PMID-8635523_E10", "type": "Regulation", "trigger": { "text": [ "affect" ], "offsets": [ [ 1917, 1923 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "PMID-8635523_E14" } ] }, { "id": "PMID-8635523_E11", "type": "Regulation", "trigger": { "text": [ "affect" ], "offsets": [ [ 1917, 1923 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "PMID-8635523_E13" } ] }, { "id": "PMID-8635523_E12", "type": "Gene_expression", "trigger": { "text": [ "expression" ], "offsets": [ [ 1928, 1938 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "PMID-8635523_T4" } ] }, { "id": "PMID-8635523_E13", "type": "Gene_expression", "trigger": { "text": [ "expression" ], "offsets": [ [ 1928, 1938 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "PMID-8635523_T2" } ] }, { "id": "PMID-8635523_E14", "type": "Gene_expression", "trigger": { "text": [ "expression" ], "offsets": [ [ 1928, 1938 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "PMID-8635523_T3" } ] } ]

[ { "id": "PMID-8635523_1", "entity_ids": [ "PMID-8635523_T5", "PMID-8635523_T6" ] } ]

[]

[ { "id": "PMID-8641346__text", "type": "abstract", "text": [ "Interferon-gamma modulates the lipopolysaccharide-induced expression of AP-1 and NF-kappa B at the mRNA and protein level in human monocytes. \nInterferon-gamma (IFN-gamma) modulates the expression of several cytokines by human monocytes at the transcriptional level. In view of these findings, we analyzed the effects of IFN-gamma on the expression of different transcription factors in activated human monocytes. Priming of human monocytes with IFN-gamma resulted in the down regulation of c-fos and c-jun mRNA in response to stimulation with lipopolysaccharide (LPS) compared to the effects of LPS alone. Not only was this effect observed at the mRNA level, but activator protein-1 (AP-1) DNA binding capacity was affected as well, A strong reduction was observed in the LPS-induced DNA-binding activity of AP-1 in the presence of IFN-gamma. LPS-stimulated monocytes showed an increased expression of p105 mRNA, the precursor of the p50 subunit of the transcription factor nuclear factor-kappa B (NF-kappa B), while no effect was noticed on the expression of p65 mRNA. In contrast, IFN-gamma priming did not affect the expression of p105 transcripts but enhanced the expression of p65 mRNA (two-fold). Priming with IFN-gamma followed by LPS stimulation resulted in a further increase in the expression of p65 mRNA. This was due to an increase in the half-life of p65 mRNA (75 vs 150 minutes). Electrophoretic mobility shift assays (EMSAs) demonstrated that unstimulated monocytes predominantly expressed p50 NF-kappa B. Stimulation with LPS or IFN-gamma resulted in the expression of p50 and p65 subunits, while the combination of IFN-gamma plus LPS caused a further increase in the expression of NF-kappa B. With Western blotting, it was shown that nuclear extracts from monocytes contained p50 and p65 protein in response to LPS and IFN-gamma stimulation. However, the combined stimulation did not result in enhanced p50 and p65 protein expression. The effects of IFN-gamma on the transcription factors were specific, since no change was observed in the expression of NF-IL-6 or I kappa B alpha, the inhibitor of NF-kappa B. We conclude that the effects of IFN-gamma on the expression of the transcription factors AP-1 and NF-kappa B may be important for the modulatory effects of IFN-gamma on the cytokine expression in activated human monocytes. " ], "offsets": [ [ 0, 2352 ] ] } ]

[ { "id": "PMID-8641346_T1", "type": "Protein", "text": [ "Interferon-gamma" ], "offsets": [ [ 0, 16 ] ], "normalized": [] }, { "id": "PMID-8641346_T2", "type": "Protein", "text": [ "Interferon-gamma" ], "offsets": [ [ 143, 159 ] ], "normalized": [] }, { "id": "PMID-8641346_T3", "type": "Protein", "text": [ "IFN-gamma" ], "offsets": [ [ 161, 170 ] ], "normalized": [] }, { "id": "PMID-8641346_T4", "type": "Protein", "text": [ "IFN-gamma" ], "offsets": [ [ 321, 330 ] ], "normalized": [] }, { "id": "PMID-8641346_T5", "type": "Protein", "text": [ "IFN-gamma" ], "offsets": [ [ 446, 455 ] ], "normalized": [] }, { "id": "PMID-8641346_T6", "type": "Protein", "text": [ "c-fos" ], "offsets": [ [ 491, 496 ] ], "normalized": [] }, { "id": "PMID-8641346_T7", "type": "Protein", "text": [ "c-jun" ], "offsets": [ [ 501, 506 ] ], "normalized": [] }, { "id": "PMID-8641346_T8", "type": "Protein", "text": [ "IFN-gamma" ], "offsets": [ [ 833, 842 ] ], "normalized": [] }, { "id": "PMID-8641346_T9", "type": "Protein", "text": [ "p105" ], "offsets": [ [ 903, 907 ] ], "normalized": [] }, { "id": "PMID-8641346_T10", "type": "Protein", "text": [ "p50" ], "offsets": [ [ 935, 938 ] ], "normalized": [] }, { "id": "PMID-8641346_T11", "type": "Protein", "text": [ "p65" ], "offsets": [ [ 1061, 1064 ] ], "normalized": [] }, { "id": "PMID-8641346_T12", "type": "Protein", "text": [ "IFN-gamma" ], "offsets": [ [ 1084, 1093 ] ], "normalized": [] }, { "id": "PMID-8641346_T13", "type": "Protein", "text": [ "p105" ], "offsets": [ [ 1135, 1139 ] ], "normalized": [] }, { "id": "PMID-8641346_T14", "type": "Protein", "text": [ "p65" ], "offsets": [ [ 1183, 1186 ] ], "normalized": [] }, { "id": "PMID-8641346_T15", "type": "Protein", "text": [ "IFN-gamma" ], "offsets": [ [ 1217, 1226 ] ], "normalized": [] }, { "id": "PMID-8641346_T16", "type": "Protein", "text": [ "p65" ], "offsets": [ [ 1307, 1310 ] ], "normalized": [] }, { "id": "PMID-8641346_T17", "type": "Protein", "text": [ "p65" ], "offsets": [ [ 1365, 1368 ] ], "normalized": [] }, { "id": "PMID-8641346_T18", "type": "Protein", "text": [ "p50" ], "offsets": [ [ 1506, 1509 ] ], "normalized": [] }, { "id": "PMID-8641346_T19", "type": "Protein", "text": [ "IFN-gamma" ], "offsets": [ [ 1546, 1555 ] ], "normalized": [] }, { "id": "PMID-8641346_T20", "type": "Protein", "text": [ "p50" ], "offsets": [ [ 1586, 1589 ] ], "normalized": [] }, { "id": "PMID-8641346_T21", "type": "Protein", "text": [ "p65" ], "offsets": [ [ 1594, 1597 ] ], "normalized": [] }, { "id": "PMID-8641346_T22", "type": "Protein", "text": [ "IFN-gamma" ], "offsets": [ [ 1633, 1642 ] ], "normalized": [] }, { "id": "PMID-8641346_T23", "type": "Protein", "text": [ "p50" ], "offsets": [ [ 1794, 1797 ] ], "normalized": [] }, { "id": "PMID-8641346_T24", "type": "Protein", "text": [ "p65" ], "offsets": [ [ 1802, 1805 ] ], "normalized": [] }, { "id": "PMID-8641346_T25", "type": "Protein", "text": [ "IFN-gamma" ], "offsets": [ [ 1837, 1846 ] ], "normalized": [] }, { "id": "PMID-8641346_T26", "type": "Protein", "text": [ "p50" ], "offsets": [ [ 1921, 1924 ] ], "normalized": [] }, { "id": "PMID-8641346_T27", "type": "Protein", "text": [ "p65" ], "offsets": [ [ 1929, 1932 ] ], "normalized": [] }, { "id": "PMID-8641346_T28", "type": "Protein", "text": [ "IFN-gamma" ], "offsets": [ [ 1968, 1977 ] ], "normalized": [] }, { "id": "PMID-8641346_T29", "type": "Protein", "text": [ "NF-IL-6" ], "offsets": [ [ 2072, 2079 ] ], "normalized": [] }, { "id": "PMID-8641346_T30", "type": "Protein", "text": [ "I kappa B alpha" ], "offsets": [ [ 2083, 2098 ] ], "normalized": [] }, { "id": "PMID-8641346_T31", "type": "Protein", "text": [ "IFN-gamma" ], "offsets": [ [ 2161, 2170 ] ], "normalized": [] }, { "id": "PMID-8641346_T32", "type": "Protein", "text": [ "IFN-gamma" ], "offsets": [ [ 2285, 2294 ] ], "normalized": [] } ]

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"PMID-8641346_E6", "type": "Transcription", "trigger": { "text": [ "expression" ], "offsets": [ [ 1047, 1057 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "PMID-8641346_T11" } ] }, { "id": "PMID-8641346_E7", "type": "Regulation", "trigger": { "text": [ "affect" ], "offsets": [ [ 1110, 1116 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "PMID-8641346_E8" } ] }, { "id": "PMID-8641346_E8", "type": "Transcription", "trigger": { "text": [ "expression" ], "offsets": [ [ 1121, 1131 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "PMID-8641346_T13" } ] }, { "id": "PMID-8641346_E9", "type": "Positive_regulation", "trigger": { "text": [ "enhanced" ], "offsets": [ [ 1156, 1164 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "PMID-8641346_E10" } ] }, { "id": "PMID-8641346_E10", "type": "Transcription", "trigger": { "text": [ "expression" ], "offsets": [ [ 1169, 1179 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "PMID-8641346_T14" } ] }, { "id": "PMID-8641346_E11", "type": "Positive_regulation", "trigger": { "text": [ "increase" ], "offsets": [ [ 1277, 1285 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "PMID-8641346_E12" } ] }, { "id": "PMID-8641346_E12", "type": "Transcription", "trigger": { "text": [ "expression" ], "offsets": [ [ 1293, 1303 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "PMID-8641346_T16" } ] }, { "id": "PMID-8641346_E13", "type": "Positive_regulation", "trigger": { "text": [ "due to" ], "offsets": [ [ 1326, 1332 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "PMID-8641346_E11" }, { "role": "Cause", "ref_id": "PMID-8641346_E14" } ] }, { "id": "PMID-8641346_E14", "type": "Positive_regulation", "trigger": { "text": [ "increase" ], "offsets": [ [ 1336, 1344 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "PMID-8641346_T17" } ] }, { "id": "PMID-8641346_E15", "type": "Gene_expression", "trigger": { "text": [ "expressed" ], "offsets": [ [ 1496, 1505 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "PMID-8641346_T18" } ] }, { "id": "PMID-8641346_E16", "type": "Positive_regulation", "trigger": { "text": [ "resulted" ], "offsets": [ [ 1556, 1564 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "PMID-8641346_E20" } ] }, { "id": "PMID-8641346_E17", "type": "Positive_regulation", "trigger": { "text": [ "resulted" ], "offsets": [ [ 1556, 1564 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "PMID-8641346_E20" }, { "role": "Cause", "ref_id": "PMID-8641346_T19" } ] }, { "id": "PMID-8641346_E18", "type": "Positive_regulation", "trigger": { "text": [ "resulted" ], "offsets": [ [ 1556, 1564 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "PMID-8641346_E21" }, { "role": "Cause", "ref_id": "PMID-8641346_T19" } ] }, { "id": "PMID-8641346_E19", "type": "Positive_regulation", "trigger": { "text": [ "resulted" ], "offsets": [ [ 1556, 1564 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "PMID-8641346_T19" } ] }, { "id": "PMID-8641346_E20", "type": "Gene_expression", "trigger": { "text": [ "expression" ], "offsets": [ [ 1572, 1582 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "PMID-8641346_T20" } ] }, { "id": "PMID-8641346_E21", "type": "Gene_expression", "trigger": { "text": [ "expression" ], "offsets": [ [ 1572, 1582 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "PMID-8641346_T21" } ] }, { "id": "PMID-8641346_E22", "type": "Gene_expression", "trigger": { "text": [ "contained" ], "offsets": [ [ 1784, 1793 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "PMID-8641346_T24" } ] }, { "id": "PMID-8641346_E23", "type": "Gene_expression", "trigger": { "text": [ "contained" ], "offsets": [ [ 1784, 1793 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "PMID-8641346_T23" } ] }, { "id": "PMID-8641346_E24", "type": "Positive_regulation", "trigger": { "text": [ "in response to" ], "offsets": [ [ 1814, 1828 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "PMID-8641346_E23" }, { "role": "Cause", "ref_id": "PMID-8641346_T25" } ] }, { "id": "PMID-8641346_E25", "type": "Positive_regulation", "trigger": { "text": [ "in response to" ], "offsets": [ [ 1814, 1828 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "PMID-8641346_E22" }, { "role": "Cause", "ref_id": "PMID-8641346_T25" } ] }, { "id": "PMID-8641346_E26", "type": "Positive_regulation", "trigger": { "text": [ "in response to" ], "offsets": [ [ 1814, 1828 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "PMID-8641346_E23" } ] }, { "id": "PMID-8641346_E27", "type": "Positive_regulation", "trigger": { "text": [ "in response to" ], "offsets": [ [ 1814, 1828 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "PMID-8641346_E22" } ] }, { "id": "PMID-8641346_E28", "type": "Positive_regulation", "trigger": { "text": [ "enhanced" ], "offsets": [ [ 1912, 1920 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "PMID-8641346_E31" }, { "role": "Cause", "ref_id": "PMID-8641346_T25" } ] }, { "id": "PMID-8641346_E29", "type": "Positive_regulation", "trigger": { "text": [ "enhanced" ], "offsets": [ [ 1912, 1920 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "PMID-8641346_E30" }, { "role": "Cause", "ref_id": "PMID-8641346_T25" } ] }, { "id": "PMID-8641346_E30", "type": "Gene_expression", "trigger": { "text": [ "expression" ], "offsets": [ [ 1941, 1951 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "PMID-8641346_T27" } ] }, { "id": "PMID-8641346_E31", "type": "Gene_expression", "trigger": { "text": [ "expression" ], "offsets": [ [ 1941, 1951 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "PMID-8641346_T26" } ] }, { "id": "PMID-8641346_E32", "type": "Regulation", "trigger": { "text": [ "change" ], "offsets": [ [ 2031, 2037 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "PMID-8641346_E34" }, { "role": "Cause", "ref_id": "PMID-8641346_T28" } ] }, { "id": "PMID-8641346_E33", "type": "Regulation", "trigger": { "text": [ "change" ], "offsets": [ [ 2031, 2037 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "PMID-8641346_E35" }, { "role": "Cause", "ref_id": "PMID-8641346_T28" } ] }, { "id": "PMID-8641346_E34", "type": "Gene_expression", "trigger": { "text": [ "expression" ], "offsets": [ [ 2058, 2068 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "PMID-8641346_T30" } ] }, { "id": "PMID-8641346_E35", "type": "Gene_expression", "trigger": { "text": [ "expression" ], "offsets": [ [ 2058, 2068 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "PMID-8641346_T29" } ] } ]

[ { "id": "PMID-8641346_1", "entity_ids": [ "PMID-8641346_T2", "PMID-8641346_T3" ] } ]

[]

[ { "id": "PMID-8641353__text", "type": "abstract", "text": [ "Expression of c-fos and c-jun proteins and AP-1 binding activity during cell cycle progression of HL60 cells and phytohemagglutinin-stimulated lymphocytes. \nThe protein products of the c-fos (p62c-fos) and c-jun (p39c-jun) genes are members of the AP-1 transcription factor family and are thought to play important roles in the regulation of gene expression during the cell cycle. Most studies on the expression of these proteins in relation to the cell cycle have been performed at the mRNA level, and therefore do not give direct information about the presence of the proteins during the cell cycle. We have used Western blotting to investigate the presence of these proteins during the cell cycles of two different cellular systems: a continuously growing myeloid leukemic cell line, HL60, and normal cells stimulated into cycle, phyto- hemagglutinin (PHA)-stimulated normal human peripheral blood lymphocytes (PBL). The binding activity of transcription factor AP-1, which consists of dimers of Fos and Jun family proteins, was also studied using a gel shift assay. We found nuclear p62c-fos, p39c-jun, and AP-1 binding activity throughout the cell cycle both in HL60 cells and in PHA-stimulated PBL, and we postulate that these proteins are required throughout the cell cycle and not transiently in the G0 to G1 transition as previous mRNA studies have indicated. We demonstrated an uncoupling of AP-1 binding activity from p62c-fos, and p39c-jun AP-1 activity was expressed more strongly in the G1- and G2/M-phase enriched samples than in the S-phase enriched samples of HL60 cells, while levels of nuclear p62c-fos and p39c-jun were constant. Nuclei of unstimulated PBL from different donors expressed p62c-fos and p39c-jun, but AP-1 was not detected in the majority of samples. Following PHA stimulation of PBL, the increase in AP-1 activity was delayed with respect to the augmentation of p39c-jun expression. We also observed that cytoplasmic p62c-fos and p39c-jun were present in HL60 cells and PHA-stimulated PBL. However, no cytoplasmic p62c-fos was detected in unstimulated PBL, although in some cases cytoplasmic p39c-jun was detected, suggesting that subcellular compartmentalization of these proteinsmay occur under certain circumstances. " ], "offsets": [ [ 0, 2256 ] ] } ]

[ { "id": "PMID-8641353_T1", "type": "Protein", "text": [ "c-fos" ], "offsets": [ [ 14, 19 ] ], "normalized": [] }, { "id": "PMID-8641353_T2", "type": "Protein", "text": [ "c-jun" ], "offsets": [ [ 24, 29 ] ], "normalized": [] }, { "id": "PMID-8641353_T3", "type": "Protein", "text": [ "phytohemagglutinin" ], "offsets": [ [ 113, 131 ] ], "normalized": [] }, { "id": "PMID-8641353_T4", "type": "Protein", "text": [ "c-fos" ], "offsets": [ [ 185, 190 ] ], "normalized": [] }, { "id": "PMID-8641353_T5", "type": "Protein", "text": [ "p62c-fos" ], "offsets": [ [ 192, 200 ] ], "normalized": [] }, { "id": "PMID-8641353_T6", "type": "Protein", "text": [ "c-jun" ], "offsets": [ [ 206, 211 ] ], "normalized": [] }, { "id": "PMID-8641353_T7", "type": "Protein", "text": [ "p39c-jun" ], "offsets": [ [ 213, 221 ] ], "normalized": [] }, { "id": "PMID-8641353_T8", "type": "Protein", "text": [ "phyto- hemagglutinin" ], "offsets": [ [ 833, 853 ] ], "normalized": [] }, { "id": "PMID-8641353_T9", "type": "Protein", "text": [ "PHA" ], "offsets": [ [ 855, 858 ] ], "normalized": [] }, { "id": "PMID-8641353_T10", "type": "Protein", "text": [ "p62c-fos" ], "offsets": [ [ 1087, 1095 ] ], "normalized": [] }, { "id": "PMID-8641353_T11", "type": "Protein", "text": [ "p39c-jun" ], "offsets": [ [ 1097, 1105 ] ], "normalized": [] }, { "id": "PMID-8641353_T12", "type": "Protein", "text": [ "PHA" ], "offsets": [ [ 1185, 1188 ] ], "normalized": [] }, { "id": "PMID-8641353_T13", "type": "Protein", "text": [ "p62c-fos" ], "offsets": [ [ 1429, 1437 ] ], "normalized": [] }, { "id": "PMID-8641353_T14", "type": "Protein", "text": [ "p39c-jun" ], "offsets": [ [ 1443, 1451 ] ], "normalized": [] }, { "id": "PMID-8641353_T15", "type": "Protein", "text": [ "p62c-fos" ], "offsets": [ [ 1613, 1621 ] ], "normalized": [] }, { "id": "PMID-8641353_T16", "type": "Protein", "text": [ "p39c-jun" ], "offsets": [ [ 1626, 1634 ] ], "normalized": [] }, { "id": "PMID-8641353_T17", "type": "Protein", "text": [ "p62c-fos" ], "offsets": [ [ 1709, 1717 ] ], "normalized": [] }, { "id": "PMID-8641353_T18", "type": "Protein", "text": [ "p39c-jun" ], "offsets": [ [ 1722, 1730 ] ], "normalized": [] }, { "id": "PMID-8641353_T19", "type": "Protein", "text": [ "PHA" ], "offsets": [ [ 1796, 1799 ] ], "normalized": [] }, { "id": "PMID-8641353_T20", "type": "Protein", "text": [ "p39c-jun" ], "offsets": [ [ 1898, 1906 ] ], "normalized": [] }, { "id": "PMID-8641353_T21", "type": "Protein", "text": [ "p62c-fos" ], "offsets": [ [ 1953, 1961 ] ], "normalized": [] }, { "id": "PMID-8641353_T22", "type": "Protein", "text": [ "p39c-jun" ], "offsets": [ [ 1966, 1974 ] ], "normalized": [] }, { "id": "PMID-8641353_T23", "type": "Protein", "text": [ "PHA" ], "offsets": [ [ 2006, 2009 ] ], "normalized": [] }, { "id": "PMID-8641353_T24", "type": "Protein", "text": [ "p62c-fos" ], "offsets": [ [ 2050, 2058 ] ], "normalized": [] }, { "id": "PMID-8641353_T25", "type": "Protein", "text": [ "p39c-jun" ], "offsets": [ [ 2128, 2136 ] ], "normalized": [] }, { "id": "PMID-8641353_T31", "type": "Entity", "text": [ "nuclear" ], "offsets": [ [ 1079, 1086 ] ], "normalized": [] }, { "id": "PMID-8641353_T33", "type": "Entity", "text": [ "Nuclei" ], "offsets": [ [ 1650, 1656 ] ], "normalized": [] } ]

[ { "id": "PMID-8641353_E1", "type": "Gene_expression", "trigger": { "text": [ "Expression" ], "offsets": [ [ 0, 10 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "PMID-8641353_T2" } ] }, { "id": "PMID-8641353_E2", "type": "Gene_expression", "trigger": { "text": [ "Expression" ], "offsets": [ [ 0, 10 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "PMID-8641353_T1" } ] }, { "id": "PMID-8641353_E3", "type": "Transcription", "trigger": { "text": [ "at the mRNA level" ], "offsets": [ [ 480, 497 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "PMID-8641353_T5" } ] }, { "id": "PMID-8641353_E4", "type": "Transcription", "trigger": { "text": [ "at the mRNA level" ], "offsets": [ [ 480, 497 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "PMID-8641353_T7" } ] }, { "id": "PMID-8641353_E5", "type": "Gene_expression", "trigger": { "text": [ "presence" ], "offsets": [ [ 554, 562 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "PMID-8641353_T7" } ] }, { "id": "PMID-8641353_E6", "type": "Gene_expression", "trigger": { "text": [ "presence" ], "offsets": [ [ 554, 562 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "PMID-8641353_T5" } ] }, { "id": "PMID-8641353_E7", "type": "Gene_expression", "trigger": { "text": [ "presence" ], "offsets": [ [ 651, 659 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "PMID-8641353_T5" } ] }, { "id": "PMID-8641353_E8", "type": "Gene_expression", "trigger": { "text": [ "presence" ], "offsets": [ [ 651, 659 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "PMID-8641353_T7" } ] }, { "id": "PMID-8641353_E9", "type": "Localization", "trigger": { "text": [ "found" ], "offsets": [ [ 1073, 1078 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "PMID-8641353_T10" }, { "role": "AtLoc", "ref_id": "PMID-8641353_T31" } ] }, { "id": "PMID-8641353_E10", "type": "Localization", "trigger": { "text": [ "found" ], "offsets": [ [ 1073, 1078 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "PMID-8641353_T11" }, { "role": "AtLoc", "ref_id": "PMID-8641353_T31" } ] }, { "id": "PMID-8641353_E11", "type": "Positive_regulation", "trigger": { "text": [ "constant" ], "offsets": [ [ 1640, 1648 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "PMID-8641353_T16" } ] }, { "id": "PMID-8641353_E12", "type": "Positive_regulation", "trigger": { "text": [ "constant" ], "offsets": [ [ 1640, 1648 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "PMID-8641353_T15" } ] }, { "id": "PMID-8641353_E13", "type": "Localization", "trigger": { "text": [ "expressed" ], "offsets": [ [ 1699, 1708 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "PMID-8641353_T17" }, { "role": "AtLoc", "ref_id": "PMID-8641353_T33" } ] }, { "id": "PMID-8641353_E14", "type": "Localization", "trigger": { "text": [ "expressed" ], "offsets": [ [ 1699, 1708 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "PMID-8641353_T18" }, { "role": "AtLoc", "ref_id": "PMID-8641353_T33" } ] }, { "id": "PMID-8641353_E15", "type": "Positive_regulation", "trigger": { "text": [ "augmentation" ], "offsets": [ [ 1882, 1894 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "PMID-8641353_E16" } ] }, { "id": "PMID-8641353_E16", "type": "Gene_expression", "trigger": { "text": [ "expression" ], "offsets": [ [ 1907, 1917 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "PMID-8641353_T20" } ] }, { "id": "PMID-8641353_E17", "type": "Gene_expression", "trigger": { "text": [ "present" ], "offsets": [ [ 1980, 1987 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "PMID-8641353_T22" } ] }, { "id": "PMID-8641353_E18", "type": "Gene_expression", "trigger": { "text": [ "present" ], "offsets": [ [ 1980, 1987 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "PMID-8641353_T21" } ] }, { "id": "PMID-8641353_E19", "type": "Gene_expression", "trigger": { "text": [ "detected" ], "offsets": [ [ 2063, 2071 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "PMID-8641353_T24" } ] }, { "id": "PMID-8641353_E20", "type": "Gene_expression", "trigger": { "text": [ "detected" ], "offsets": [ [ 2141, 2149 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "PMID-8641353_T25" } ] } ]

[ { "id": "PMID-8641353_1", "entity_ids": [ "PMID-8641353_T8", "PMID-8641353_T9" ] }, { "id": "PMID-8641353_2", "entity_ids": [ "PMID-8641353_T5", "PMID-8641353_T4" ] }, { "id": "PMID-8641353_3", "entity_ids": [ "PMID-8641353_T7", "PMID-8641353_T6" ] } ]

[]

[ { "id": "PMID-8641467__text", "type": "abstract", "text": [ "Involvement of intracellular Ca2+ in oxidant-induced NF-kappa B activation. \nIn human Jurkat T cells and its subclone Wurzburg cells oxidant challenge elevated [Ca2+]i by mobilizing Ca2+ from intracellular stores. In Jurkat cells this effect was rapid and transient, but in Wurzburg cells the response was slow and sustained. H2O2-induced NF-kappaB activation in Wurzburg cells was not influenced by the presence of extracellular EGTA but was totally inhibited in cells that were loaded with esterified EGTA. In Jurkat cells that are not sensitive to H2O2-induced NF-kappaB activation, H2O2 potentiated NF-kappaB activation in the presence of sustained high [Ca2+]i following thapsigargin treatment. NF-kappaB regulatory effect of alpha-lipoate and N-acetylcysteine appeared to be, at least in part, due to their ability to stabilize elevation of [Ca2+]i following oxidant challenge. Results of this study indicate that a sustained elevated [Ca2+]i is a significant factor in oxidant-induced NF-kappaB activation. " ], "offsets": [ [ 0, 1014 ] ] } ]

[]

[]

[]

[]

[ { "id": "PMID-8642282__text", "type": "abstract", "text": [ "A cell type-specific enhancer in the human B7.1 gene regulated by NF-kappaB. \nThe costimulatory molecule B7.1 provides a second signal critical for T cell activation. The distribution of this integral membrane protein is restricted to certain tissues where its level of expression is modulated by multiple exogenous stimuli. To identify the molecular basis for specificity and inducibility, the chromatin configuration of the human B7.1 gene was examined in intact nuclei from various cell types. The identification of a tissue-specific deoxyribonuclease I hypersensitive site approximately 3kb upstream of the transcription start site led to the characterization of a cell type-specific enhancer region. This 183-bp region was both cell type specific and responsive to two distinct stimuli, lipopolysaccharide and dibutyryl cAMP, known to regulate B7.1 expression. Deletional and site-directed mutagenesis revealed the presence of multiple functionally critical cis elements within this region, one of which was a nuclear factor (NF)-kappaB consensus sequence. In B7.1-positive B cells, this element bound several members of the NF-kappaB family, transcription factors already implicated in signal transduction pathways relevant to B7.1 expression. This is the first description, to our knowledge, of regulatory elements that control expression of a gene encoding a B7 costimulatory molecule. " ], "offsets": [ [ 0, 1394 ] ] } ]

[ { "id": "PMID-8642282_T1", "type": "Protein", "text": [ "B7.1" ], "offsets": [ [ 43, 47 ] ], "normalized": [] }, { "id": "PMID-8642282_T2", "type": "Protein", "text": [ "B7.1" ], "offsets": [ [ 105, 109 ] ], "normalized": [] }, { "id": "PMID-8642282_T3", "type": "Protein", "text": [ "deoxyribonuclease I" ], "offsets": [ [ 537, 556 ] ], "normalized": [] }, { "id": "PMID-8642282_T4", "type": "Protein", "text": [ "B7.1" ], "offsets": [ [ 849, 853 ] ], "normalized": [] }, { "id": "PMID-8642282_T5", "type": "Protein", "text": [ "B7.1" ], "offsets": [ [ 1065, 1069 ] ], "normalized": [] }, { "id": "PMID-8642282_T6", "type": "Protein", "text": [ "B7.1" ], "offsets": [ [ 1233, 1237 ] ], "normalized": [] } ]

[ { "id": "PMID-8642282_E1", "type": "Regulation", "trigger": { "text": [ "regulated" ], "offsets": [ [ 53, 62 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "PMID-8642282_T1" } ] }, { "id": "PMID-8642282_E2", "type": "Gene_expression", "trigger": { "text": [ "distribution" ], "offsets": [ [ 171, 183 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "PMID-8642282_T2" } ] }, { "id": "PMID-8642282_E3", "type": "Gene_expression", "trigger": { "text": [ "expression" ], "offsets": [ [ 270, 280 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "PMID-8642282_T2" } ] }, { "id": "PMID-8642282_E4", "type": "Regulation", "trigger": { "text": [ "modulated" ], "offsets": [ [ 284, 293 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "PMID-8642282_E3" } ] }, { "id": "PMID-8642282_E5", "type": "Regulation", "trigger": { "text": [ "regulate" ], "offsets": [ [ 840, 848 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "PMID-8642282_E6" } ] }, { "id": "PMID-8642282_E6", "type": "Gene_expression", "trigger": { "text": [ "expression" ], "offsets": [ [ 854, 864 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "PMID-8642282_T4" } ] }, { "id": "PMID-8642282_E7", "type": "Gene_expression", "trigger": { "text": [ "positive" ], "offsets": [ [ 1070, 1078 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "PMID-8642282_T5" } ] }, { "id": "PMID-8642282_E8", "type": "Gene_expression", "trigger": { "text": [ "expression" ], "offsets": [ [ 1238, 1248 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "PMID-8642282_T6" } ] } ]

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[ { "id": "PMID-8645086__text", "type": "abstract", "text": [ "Heat shock induces HIV-1 replication in chronically infected promyelocyte cell line OM10.1. \nA long period of clinical latency before development of symptoms is characteristic of human immunodeficiency virus type 1 (HIV-1) infection. OM10.1, a promyelocyte cell line latently infected with HIV-1, has been developed as a model for studying the mechanism of viral latency and the activation of virus expression. We found that this latently infected cell line with heat shock at 42 degrees C for 2 h resulted in a high level of HIV-1 production without addition of any cytokines. The mechanism of activation was analyzed by using anti-TNF-alpha antibody and various inhibitors. Although the TNF-alpha level in culture supernatants was below the sensitivity of an ELISA assay system, addition of anti-TNF-alpha antibody in culture medium could partially suppress the heat shock induced HIV-1 production. Staurosporine (PKC inhibitor), pentoxifylline (NF-kappa B inhibitor), and Ro5-3335 (HIV-1 Tat inhibitor) also inhibited significantly the heat shock induced virus activation. In particular, staurosporine achieved approximately 90% inhibition of the HIV-1 antigen expression in heat shock-treated OM10.1 at a non-toxic concentration. Although the mechanism of HIV-1 activation with heat shock has not been fully elucidated yet, it is presumed PKC plays an important role in HIV-1 activation. Thus, the present observations will provide a further insight into the pathogenesis of HIV-1 infections. " ], "offsets": [ [ 0, 1497 ] ] } ]

[ { "id": "PMID-8645086_T1", "type": "Protein", "text": [ "TNF-alpha" ], "offsets": [ [ 633, 642 ] ], "normalized": [] }, { "id": "PMID-8645086_T2", "type": "Protein", "text": [ "TNF-alpha" ], "offsets": [ [ 689, 698 ] ], "normalized": [] }, { "id": "PMID-8645086_T3", "type": "Protein", "text": [ "TNF-alpha" ], "offsets": [ [ 798, 807 ] ], "normalized": [] }, { "id": "PMID-8645086_T4", "type": "Protein", "text": [ "Tat" ], "offsets": [ [ 991, 994 ] ], "normalized": [] } ]

[ { "id": "PMID-8645086_E1", "type": "Negative_regulation", "trigger": { "text": [ "inhibitor" ], "offsets": [ [ 995, 1004 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "PMID-8645086_T4" } ] } ]

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[ { "id": "PMID-8645254__text", "type": "abstract", "text": [ "Abundant expression of erythroid transcription factor P45 NF-E2 mRNA in human peripheral granurocytes. \nTranscription factor NF-E2 is crucial for regulation of erythroid-specific gene expression. p45 subunit of NF-E2 contains a basic-leucine zipper domain and dimerizes with the small Maf family protein to form functional NF-E2 complex. While p45 expression was shown to be restricted to erythroid cells, megakaryocytes and mast cells in hematopoietic lineage, we found in this study that p45 mRNA is abundantly transcribed in the granulocyte fraction of human peripheral blood cells. As neutrophils occupy approximately 92% of the cells in granulocyte fraction of human peripheral blood cells. As neutrophils occupy approximately 92% of the cells in this fraction, the cells expressing p45 is most likely to be neutrophils. p45 mRNA is also expressed in HL-60 promyelocytes, albeit the expression level is much lower than that of the granulocyte fraction. HL-60 cells were found to express mafK mRNA, indicating the presence of genuine NF-E2 complex in the cells. Although p45 mRNA is transcribed from two different promoters, aNF-E2 promoter and fNF-E2 promoter, in erythroid and megakaryocytic lineage cells, p45 mRNA is transcribed only from aNF-E2 promoter. The expression of p45 megakaryocytic lineage cells, p45 mRNA is transcribed only from aNF-E2 promoter. The expression of p45 mRNA in the neutrophils declined rapidly after transfer of the cells to in vitro culture and G-CSF could not sustain the expression from the down-regulation, suggesting the E2 may also participate in the regulation of neutrophil-specific gene expression. " ], "offsets": [ [ 0, 1644 ] ] } ]

[ { "id": "PMID-8645254_T1", "type": "Protein", "text": [ "erythroid transcription factor P45 NF-E2" ], "offsets": [ [ 23, 63 ] ], "normalized": [] }, { "id": "PMID-8645254_T2", "type": "Protein", "text": [ "p45" ], "offsets": [ [ 196, 199 ] ], "normalized": [] }, { "id": "PMID-8645254_T3", "type": "Protein", "text": [ "p45" ], "offsets": [ [ 344, 347 ] ], "normalized": [] }, { "id": "PMID-8645254_T4", "type": "Protein", "text": [ "p45" ], "offsets": [ [ 490, 493 ] ], "normalized": [] }, { "id": "PMID-8645254_T5", "type": "Protein", "text": [ "p45" ], "offsets": [ [ 788, 791 ] ], "normalized": [] }, { "id": "PMID-8645254_T6", "type": "Protein", "text": [ "p45" ], "offsets": [ [ 826, 829 ] ], "normalized": [] }, { "id": "PMID-8645254_T7", "type": "Protein", "text": [ "mafK" ], "offsets": [ [ 992, 996 ] ], "normalized": [] }, { "id": "PMID-8645254_T8", "type": "Protein", "text": [ "p45" ], "offsets": [ [ 1075, 1078 ] ], "normalized": [] }, { "id": "PMID-8645254_T9", "type": "Protein", "text": [ "p45" ], "offsets": [ [ 1213, 1216 ] ], "normalized": [] }, { "id": "PMID-8645254_T10", "type": "Protein", "text": [ "p45" ], "offsets": [ [ 1282, 1285 ] ], "normalized": [] }, { "id": "PMID-8645254_T11", "type": "Protein", "text": [ "p45" ], "offsets": [ [ 1316, 1319 ] ], "normalized": [] }, { "id": "PMID-8645254_T12", "type": "Protein", "text": [ "p45" ], "offsets": [ [ 1385, 1388 ] ], "normalized": [] }, { "id": "PMID-8645254_T13", "type": "Protein", "text": [ "G-CSF" ], "offsets": [ [ 1482, 1487 ] ], "normalized": [] } ]

[ { "id": "PMID-8645254_E1", "type": "Transcription", "trigger": { "text": [ "expression" ], "offsets": [ [ 9, 19 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "PMID-8645254_T1" } ] }, { "id": "PMID-8645254_E2", "type": "Binding", "trigger": { "text": [ "dimerizes" ], "offsets": [ [ 260, 269 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "PMID-8645254_T2" } ] }, { "id": "PMID-8645254_E3", "type": "Gene_expression", "trigger": { "text": [ "expression" ], "offsets": [ [ 348, 358 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "PMID-8645254_T3" } ] }, { "id": "PMID-8645254_E4", "type": "Transcription", "trigger": { "text": [ "transcribed" ], "offsets": [ [ 513, 524 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "PMID-8645254_T4" } ] }, { "id": "PMID-8645254_E5", "type": "Gene_expression", "trigger": { "text": [ "expressing" ], "offsets": [ [ 777, 787 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "PMID-8645254_T5" } ] }, { "id": "PMID-8645254_E6", "type": "Transcription", "trigger": { "text": [ "expressed" ], "offsets": [ [ 843, 852 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "PMID-8645254_T6" } ] }, { "id": "PMID-8645254_E7", "type": "Transcription", "trigger": { "text": [ "expression" ], "offsets": [ [ 888, 898 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "PMID-8645254_T6" } ] }, { "id": "PMID-8645254_E8", "type": "Transcription", "trigger": { "text": [ "express" ], "offsets": [ [ 984, 991 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "PMID-8645254_T7" } ] }, { "id": "PMID-8645254_E9", "type": "Transcription", "trigger": { "text": [ "transcribed" ], "offsets": [ [ 1087, 1098 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "PMID-8645254_T8" } ] }, { "id": "PMID-8645254_E10", "type": "Positive_regulation", "trigger": { "text": [ "from" ], "offsets": [ [ 1099, 1103 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "PMID-8645254_E9" } ] }, { "id": "PMID-8645254_E11", "type": "Transcription", "trigger": { "text": [ "transcribed" ], "offsets": [ [ 1225, 1236 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "PMID-8645254_T9" } ] }, { "id": "PMID-8645254_E12", "type": "Positive_regulation", "trigger": { "text": [ "from" ], "offsets": [ [ 1242, 1246 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "PMID-8645254_E11" } ] }, { "id": "PMID-8645254_E13", "type": "Gene_expression", "trigger": { "text": [ "expression" ], "offsets": [ [ 1268, 1278 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "PMID-8645254_T10" } ] }, { "id": "PMID-8645254_E14", "type": "Transcription", "trigger": { "text": [ "transcribed" ], "offsets": [ [ 1328, 1339 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "PMID-8645254_T11" } ] }, { "id": "PMID-8645254_E15", "type": "Positive_regulation", "trigger": { "text": [ "from" ], "offsets": [ [ 1345, 1349 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "PMID-8645254_E14" } ] }, { "id": "PMID-8645254_E16", "type": "Transcription", "trigger": { "text": [ "expression" ], "offsets": [ [ 1371, 1381 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "PMID-8645254_T12" } ] }, { "id": "PMID-8645254_E17", "type": "Negative_regulation", "trigger": { "text": [ "declined" ], "offsets": [ [ 1413, 1421 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "PMID-8645254_E16" } ] }, { "id": "PMID-8645254_E18", "type": "Negative_regulation", "trigger": { "text": [ "sustain" ], "offsets": [ [ 1498, 1505 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "PMID-8645254_E17" }, { "role": "Cause", "ref_id": "PMID-8645254_T13" } ] } ]

[]

[]

[ { "id": "PMID-8649822__text", "type": "abstract", "text": [ "Identification of a human LIM-Hox gene, hLH-2, aberrantly expressed in chronic myelogenous leukaemia and located on 9q33-34.1. \nWe describe the isolation of human LH-2, a putative transcription factor containing two cysteine-rich regions (LIM domains) and a homeobox (Hox) DNA-binding domain. High levels of hLH-2 expression were observed in all cases of chronic myelogenous leukaemia (CML) tested, regardless of disease status. hLH-2 was mapped to chromosome 9Q33-34.1, in the same region as the reciprocal translocation that creates the BCR-ABL chimera of the Philadelphia chromosome (Ph'), the hallmark of CML; hLH-2 was retained on the derivative 9 chromosome and is therefore centromeric of c-ABL. The proximity of hLH-2 to the breakpoint on chromosome 9 raises the possibility of cis-activation by the t(9;22)(q34;q11) translocation. In addition to finding hLH-2 expression in all cases of CML, expression was observed in lymphoid malignancies and myeloid cell lines, but not in primary cases of acute myelogenous leukaemia. The role of hLH-2 in the development or progression of leukaemia is not known. However, hLH-2 may prove useful as a marker of CML for monitoring residual disease. " ], "offsets": [ [ 0, 1194 ] ] } ]

[ { "id": "PMID-8649822_T1", "type": "Protein", "text": [ "hLH-2" ], "offsets": [ [ 40, 45 ] ], "normalized": [] }, { "id": "PMID-8649822_T2", "type": "Protein", "text": [ "LH-2" ], "offsets": [ [ 163, 167 ] ], "normalized": [] }, { "id": "PMID-8649822_T3", "type": "Protein", "text": [ "hLH-2" ], "offsets": [ [ 308, 313 ] ], "normalized": [] }, { "id": "PMID-8649822_T4", "type": "Protein", "text": [ "hLH-2" ], "offsets": [ [ 429, 434 ] ], "normalized": [] }, { "id": "PMID-8649822_T5", "type": "Protein", "text": [ "BCR" ], "offsets": [ [ 539, 542 ] ], "normalized": [] }, { "id": "PMID-8649822_T6", "type": "Protein", "text": [ "ABL" ], "offsets": [ [ 543, 546 ] ], "normalized": [] }, { "id": "PMID-8649822_T7", "type": "Protein", "text": [ "hLH-2" ], "offsets": [ [ 614, 619 ] ], "normalized": [] }, { "id": "PMID-8649822_T8", "type": "Protein", "text": [ "c-ABL" ], "offsets": [ [ 696, 701 ] ], "normalized": [] }, { "id": "PMID-8649822_T9", "type": "Protein", "text": [ "hLH-2" ], "offsets": [ [ 720, 725 ] ], "normalized": [] }, { "id": "PMID-8649822_T10", "type": "Protein", "text": [ "hLH-2" ], "offsets": [ [ 863, 868 ] ], "normalized": [] }, { "id": "PMID-8649822_T11", "type": "Protein", "text": [ "hLH-2" ], "offsets": [ [ 1043, 1048 ] ], "normalized": [] }, { "id": "PMID-8649822_T12", "type": "Protein", "text": [ "hLH-2" ], "offsets": [ [ 1119, 1124 ] ], "normalized": [] } ]

[ { "id": "PMID-8649822_E1", "type": "Gene_expression", "trigger": { "text": [ "expressed" ], "offsets": [ [ 58, 67 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "PMID-8649822_T1" } ] }, { "id": "PMID-8649822_E2", "type": "Positive_regulation", "trigger": { "text": [ "High levels" ], "offsets": [ [ 293, 304 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "PMID-8649822_E3" } ] }, { "id": "PMID-8649822_E3", "type": "Gene_expression", "trigger": { "text": [ "expression" ], "offsets": [ [ 314, 324 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "PMID-8649822_T3" } ] }, { "id": "PMID-8649822_E4", "type": "Positive_regulation", "trigger": { "text": [ "cis-activation" ], "offsets": [ [ 786, 800 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "PMID-8649822_T9" } ] }, { "id": "PMID-8649822_E5", "type": "Gene_expression", "trigger": { "text": [ "expression" ], "offsets": [ [ 869, 879 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "PMID-8649822_T10" } ] }, { "id": "PMID-8649822_E6", "type": "Gene_expression", "trigger": { "text": [ "expression" ], "offsets": [ [ 901, 911 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "PMID-8649822_T10" } ] } ]

[]

[]

[ { "id": "PMID-8652841__text", "type": "abstract", "text": [ "BCL-6 expression during B-cell activation. \nTranslocations involving the BCL-6 gene are common in the diffuse large cell subtype of non-Hodgkin's lymphoma. Invariably, the BCL-6 coding region is intact, but its 5' untranslated region is replaced with sequences from the translocation partner. The present study shows that BCL-6 expression is regulated in lymphocytes during mitogenic stimulation. Resting B and T lymphocytes contain high levels of BCL-6 mRNA. Stimulation of mouse B cells with anti-IgM or IgD antibodies, bacterial lipopolysaccharide, phorbol 12-myristate 13-acetate plus ionomycin, or CD40 ligand led to a five-fold to 35-fold decrease in BCL-6 mRNA levels. Similar downregulation of BCL-6 mRNA was seen in human B cells stimulated with Staphylococcus aureus plus interleukin-2 or anti-IgM antibodies and in human T lymphocytes stimulated with phytohemagglutinin. BCL-6 mRNA levels began to decrease 8 to 16 hours after stimulation, before cells entered S phase. Although polyclonal activation of B cells in vitro invariably decreased BCL-6 MRNA expression, activated B cells from human germinal centers expressed BCL-6 mRNA at levels comparable to the levels in resting B cells. Despite these similar mRNA levels, BCL-6 protein expression was threefold to 34-fold higher in germinal center B cells than in resting B cells, suggesting that BCL-6 protein levels are controlled by translational or posttranslational mechanisms. These observations suggest that the germinal center reaction provides unique activation signals to B cells that allow for continued, high-level BCL-6 expression. " ], "offsets": [ [ 0, 1606 ] ] } ]

[ { "id": "PMID-8652841_T1", "type": "Protein", "text": [ "BCL-6" ], "offsets": [ [ 0, 5 ] ], "normalized": [] }, { "id": "PMID-8652841_T2", "type": "Protein", "text": [ "BCL-6" ], "offsets": [ [ 73, 78 ] ], "normalized": [] }, { "id": "PMID-8652841_T3", "type": "Protein", "text": [ "BCL-6" ], "offsets": [ [ 172, 177 ] ], "normalized": [] }, { "id": "PMID-8652841_T4", "type": "Protein", "text": [ "BCL-6" ], "offsets": [ [ 322, 327 ] ], "normalized": [] }, { "id": "PMID-8652841_T5", "type": "Protein", "text": [ "BCL-6" ], "offsets": [ [ 448, 453 ] ], "normalized": [] }, { "id": "PMID-8652841_T6", "type": "Protein", "text": [ "CD40 ligand" ], "offsets": [ [ 603, 614 ] ], "normalized": [] }, { "id": "PMID-8652841_T7", "type": "Protein", "text": [ "BCL-6" ], "offsets": [ [ 657, 662 ] ], "normalized": [] }, { "id": "PMID-8652841_T8", "type": "Protein", "text": [ "BCL-6" ], "offsets": [ [ 702, 707 ] ], "normalized": [] }, { "id": "PMID-8652841_T9", "type": "Protein", "text": [ "interleukin-2" ], "offsets": [ [ 782, 795 ] ], "normalized": [] }, { "id": "PMID-8652841_T10", "type": "Protein", "text": [ "phytohemagglutinin" ], "offsets": [ [ 862, 880 ] ], "normalized": [] }, { "id": "PMID-8652841_T11", "type": "Protein", "text": [ "BCL-6" ], "offsets": [ [ 882, 887 ] ], "normalized": [] }, { "id": "PMID-8652841_T12", "type": "Protein", "text": [ "BCL-6" ], "offsets": [ [ 1053, 1058 ] ], "normalized": [] }, { "id": "PMID-8652841_T13", "type": "Protein", "text": [ "BCL-6" ], "offsets": [ [ 1132, 1137 ] ], "normalized": [] }, { "id": "PMID-8652841_T14", "type": "Protein", "text": [ "BCL-6" ], "offsets": [ [ 1233, 1238 ] ], "normalized": [] }, { "id": "PMID-8652841_T15", "type": "Protein", "text": [ "BCL-6" ], "offsets": [ [ 1358, 1363 ] ], "normalized": [] }, { "id": "PMID-8652841_T16", "type": "Protein", "text": [ "BCL-6" ], "offsets": [ [ 1588, 1593 ] ], "normalized": [] } ]

[ { "id": "PMID-8652841_E1", "type": "Gene_expression", "trigger": { "text": [ "expression" ], "offsets": [ [ 6, 16 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "PMID-8652841_T1" } ] }, { "id": "PMID-8652841_E2", "type": "Gene_expression", "trigger": { "text": [ "expression" ], "offsets": [ [ 328, 338 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "PMID-8652841_T4" } ] }, { "id": "PMID-8652841_E3", "type": "Regulation", "trigger": { "text": [ "regulated" ], "offsets": [ [ 342, 351 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "PMID-8652841_E2" } ] }, { "id": "PMID-8652841_E4", "type": "Negative_regulation", "trigger": { "text": [ "decrease" ], "offsets": [ [ 645, 653 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "PMID-8652841_T7" } ] }, { "id": "PMID-8652841_E5", "type": "Negative_regulation", "trigger": { "text": [ "downregulation" ], "offsets": [ [ 684, 698 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "PMID-8652841_T8" } ] }, { "id": "PMID-8652841_E6", "type": "Negative_regulation", "trigger": { "text": [ "decrease" ], "offsets": [ [ 909, 917 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "PMID-8652841_T11" } ] }, { "id": "PMID-8652841_E7", "type": "Negative_regulation", "trigger": { "text": [ "decreased" ], "offsets": [ [ 1043, 1052 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "PMID-8652841_E8" } ] }, { "id": "PMID-8652841_E8", "type": "Transcription", "trigger": { "text": [ "expression" ], "offsets": [ [ 1064, 1074 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "PMID-8652841_T12" } ] }, { "id": "PMID-8652841_E9", "type": "Transcription", "trigger": { "text": [ "expressed" ], "offsets": [ [ 1122, 1131 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "PMID-8652841_T13" } ] }, { "id": "PMID-8652841_E10", "type": "Gene_expression", "trigger": { "text": [ "expression" ], "offsets": [ [ 1247, 1257 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "PMID-8652841_T14" } ] }, { "id": "PMID-8652841_E11", "type": "Regulation", "trigger": { "text": [ "controlled" ], "offsets": [ [ 1383, 1393 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "PMID-8652841_T15" } ] }, { "id": "PMID-8652841_E12", "type": "Positive_regulation", "trigger": { "text": [ "allow" ], "offsets": [ [ 1556, 1561 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "PMID-8652841_E14" } ] }, { "id": "PMID-8652841_E13", "type": "Positive_regulation", "trigger": { "text": [ "allow" ], "offsets": [ [ 1556, 1561 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "PMID-8652841_E15" } ] }, { "id": "PMID-8652841_E14", "type": "Positive_regulation", "trigger": { "text": [ "high-level" ], "offsets": [ [ 1577, 1587 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "PMID-8652841_E15" } ] }, { "id": "PMID-8652841_E15", "type": "Gene_expression", "trigger": { "text": [ "expression" ], "offsets": [ [ 1594, 1604 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "PMID-8652841_T16" } ] } ]

[]

[]

[ { "id": "PMID-8657101__text", "type": "abstract", "text": [ "A novel interferon regulatory factor family transcription factor, ICSAT/Pip/LSIRF, that negatively regulates the activity of interferon-regulated genes. \nWe have isolated a novel cDNA clone encoding interferon (IFN) consensus sequence-binding protein in adult T-cell leukemia cell line or activated T cells (ICSAT); this protein is the human homolog of the recently cloned Pip/LSIRF. ICSAT is structurally most closely related to the previously cloned ICSBP, a member of the IFN regulatory factor (IRF) family of proteins that binds to interferon consensus sequences (ICSs) found in many promoters of the IFN-regulated genes. Among T-cell lines investigated, ICSAT was abundantly expressed in human T-cell leukemia virus type 1 (HTLV-1)-infected T cells. When the HTLV-1 tax gene was expressed or phorbol myristake acetate-A23187 stimulation was used, ICSAT expression was induced in Jurkat cells which otherwise do not express ICSAT. When the binding of ICSAT to four different ICSs was tested, the relative differences in binding affinities for those ICSs were determined. To study the functional role of ICSAT, we performed cotransfection experiments with the human embryonal carcinoma cell line N-Tera2. ICSAT was demonstrated to possess repressive function over the gene activation induced by IFN stimulation or by IRF-1 cotransfection. Such repressive function is similar to that seen in IRF-2 or ICSBP. However, we have found that ICSAT has a different repressive effect from that of IRF-2 or ICSBP in some IFN-responsive reporter constructs. These results suggest that a novel mechanism of gene regulation by \"differential repression\" is used by multiple members of repressor proteins with different repressive effects on the IFN-responsive genes. " ], "offsets": [ [ 0, 1756 ] ] } ]

[ { "id": "PMID-8657101_T1", "type": "Protein", "text": [ "ICSAT" ], "offsets": [ [ 66, 71 ] ], "normalized": [] }, { "id": "PMID-8657101_T2", "type": "Protein", "text": [ "Pip" ], "offsets": [ [ 72, 75 ] ], "normalized": [] }, { "id": "PMID-8657101_T3", "type": "Protein", "text": [ "LSIRF" ], "offsets": [ [ 76, 81 ] ], "normalized": [] }, { "id": "PMID-8657101_T4", "type": "Protein", "text": [ "interferon (IFN) consensus sequence-binding protein in adult T-cell leukemia cell line or activated T cells" ], "offsets": [ [ 199, 306 ] ], "normalized": [] }, { "id": "PMID-8657101_T5", "type": "Protein", "text": [ "ICSAT" ], "offsets": [ [ 308, 313 ] ], "normalized": [] }, { "id": "PMID-8657101_T6", "type": "Protein", "text": [ "Pip" ], "offsets": [ [ 373, 376 ] ], "normalized": [] }, { "id": "PMID-8657101_T7", "type": "Protein", "text": [ "LSIRF" ], "offsets": [ [ 377, 382 ] ], "normalized": [] }, { "id": "PMID-8657101_T8", "type": "Protein", "text": [ "ICSAT" ], "offsets": [ [ 384, 389 ] ], "normalized": [] }, { "id": "PMID-8657101_T9", "type": "Protein", "text": [ "ICSBP" ], "offsets": [ [ 452, 457 ] ], "normalized": [] }, { "id": "PMID-8657101_T10", "type": "Protein", "text": [ "ICSAT" ], "offsets": [ [ 659, 664 ] ], "normalized": [] }, { "id": "PMID-8657101_T11", "type": "Protein", "text": [ "tax" ], "offsets": [ [ 771, 774 ] ], "normalized": [] }, { "id": "PMID-8657101_T12", "type": "Protein", "text": [ "ICSAT" ], "offsets": [ [ 852, 857 ] ], "normalized": [] }, { "id": "PMID-8657101_T13", "type": "Protein", "text": [ "ICSAT" ], "offsets": [ [ 928, 933 ] ], "normalized": [] }, { "id": "PMID-8657101_T14", "type": "Protein", "text": [ "ICSAT" ], "offsets": [ [ 955, 960 ] ], "normalized": [] }, { "id": "PMID-8657101_T15", "type": "Protein", "text": [ "ICSAT" ], "offsets": [ [ 1107, 1112 ] ], "normalized": [] }, { "id": "PMID-8657101_T16", "type": "Protein", "text": [ "ICSAT" ], "offsets": [ [ 1208, 1213 ] ], "normalized": [] }, { "id": "PMID-8657101_T17", "type": "Protein", "text": [ "IRF-1" ], "offsets": [ [ 1320, 1325 ] ], "normalized": [] }, { "id": "PMID-8657101_T18", "type": "Protein", "text": [ "IRF-2" ], "offsets": [ [ 1394, 1399 ] ], "normalized": [] }, { "id": "PMID-8657101_T19", "type": "Protein", "text": [ "ICSBP" ], "offsets": [ [ 1403, 1408 ] ], "normalized": [] }, { "id": "PMID-8657101_T20", "type": "Protein", "text": [ "ICSAT" ], "offsets": [ [ 1438, 1443 ] ], "normalized": [] }, { "id": "PMID-8657101_T21", "type": "Protein", "text": [ "IRF-2" ], "offsets": [ [ 1491, 1496 ] ], "normalized": [] }, { "id": "PMID-8657101_T22", "type": "Protein", "text": [ "ICSBP" ], "offsets": [ [ 1500, 1505 ] ], "normalized": [] } ]

[ { "id": "PMID-8657101_E1", "type": "Binding", "trigger": { "text": [ "binds" ], "offsets": [ [ 527, 532 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "PMID-8657101_T9" } ] }, { "id": "PMID-8657101_E2", "type": "Gene_expression", "trigger": { "text": [ "expressed" ], "offsets": [ [ 680, 689 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "PMID-8657101_T10" } ] }, { "id": "PMID-8657101_E3", "type": "Gene_expression", "trigger": { "text": [ "expressed" ], "offsets": [ [ 784, 793 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "PMID-8657101_T11" } ] }, { "id": "PMID-8657101_E4", "type": "Gene_expression", "trigger": { "text": [ "expression" ], "offsets": [ [ 858, 868 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "PMID-8657101_T12" } ] }, { "id": "PMID-8657101_E5", "type": "Positive_regulation", "trigger": { "text": [ "induced" ], "offsets": [ [ 873, 880 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "PMID-8657101_E4" }, { "role": "Cause", "ref_id": "PMID-8657101_E3" } ] }, { "id": "PMID-8657101_E6", "type": "Positive_regulation", "trigger": { "text": [ "induced" ], "offsets": [ [ 873, 880 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "PMID-8657101_E4" } ] }, { "id": "PMID-8657101_E7", "type": "Gene_expression", "trigger": { "text": [ "express" ], "offsets": [ [ 920, 927 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "PMID-8657101_T13" } ] }, { "id": "PMID-8657101_E8", "type": "Binding", "trigger": { "text": [ "binding" ], "offsets": [ [ 944, 951 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "PMID-8657101_T14" } ] }, { "id": "PMID-8657101_E9", "type": "Gene_expression", "trigger": { "text": [ "cotransfection" ], "offsets": [ [ 1326, 1340 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "PMID-8657101_T17" } ] }, { "id": "PMID-8657101_E10", "type": "Positive_regulation", "trigger": { "text": [ "cotransfection" ], "offsets": [ [ 1326, 1340 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "PMID-8657101_E9" } ] } ]

[ { "id": "PMID-8657101_1", "entity_ids": [ "PMID-8657101_T4", "PMID-8657101_T5" ] } ]

[]

[ { "id": "PMID-8659190__text", "type": "abstract", "text": [ "Transcription factors of T and B lymphocytes--basic research and clinical perspectives for gastroenterology. \nTissue specific regulation of gene expression by transcription factors is a fascinating new field in molecular immunology. This review summarizes data on specific regulation of promoters and enhancers by nuclear trans-acting factors in lymphocytes. The structural classes of transcription factors are described and basic methods for detection and analysis of transcription factors are detailed. Furthermore, the most important trans-acting factors of T and B lymphocytes (e.g. NF-kB, NF-AT and STAT families) and their functional importance are described. Several methods for specific down-regulation of transcription factors are shown that may be relevant to treatment of human disease. The data are discussed with regard to their potential clinical relevance for gastroenterology. " ], "offsets": [ [ 0, 893 ] ] } ]

[]

[]

[]

[]

[ { "id": "PMID-8662666__text", "type": "abstract", "text": [ "DNA triplex formation selectively inhibits granulocyte-macrophage colony-stimulating factor gene expression in human T cells. \nGranulocyte-macrophage colony-stimulating factor (GM-CSF) is a hemopoietic growth factor that is expressed in activated T cells, fibroblasts, macrophages, and endothelial cells. Although GM-CSF does not appear to be essential for normal hemopoiesis, overexpression of GM-CSF has been implicated in the pathogenesis of some diseases such as myeloid leukemia and chronic inflammation. An NF-kappaB/Rel binding site within the GM-CSF promoter, termed the kappaB element appears to be important for controlling expression in reporter gene assays in response to a number of stimuli in T cells. We investigated oligonucleotide-directed triple helix formation across this regulatory sequence as a potential tool to inhibit GM-CSF gene transcription. A 15-base oligonucleotide, GM3, was targeted to a purine-rich region in the GM-CSF proximal promoter, which overlaps the kappaB element. Gel mobility shift assays and DNase I footprinting demonstrated that GM3 formed a sequence-specific collinear triplex with its double-stranded DNA target. Triplex formation by GM3 blocked recombinant and nuclear NF-kappaB proteins binding to the GM-CSF element. GM3 also caused selective inhibition of the human T-cell lymphotrophic virus-1 Tax transactivator-induced luciferase activity from a reporter construct driven by the GM-CSF promoter in Jurkat T cells. Finally, GM3 greatly reduced the concentration of endogenous GM-CSF mRNA induced by different stimuli in Jurkat T cells but did not affect interleukin 3 mRNA levels in the same cells. We conclude that the kappaB element in the GM-CSF promoter plays a central role in the transcriptional activation of the endogenous GM-CSF gene. Colinear triplex formation acts as a selective transcriptional repressor of the GM-CSF gene and may have potential therapeutic application in cases of undesirable overexpression of this protein. " ], "offsets": [ [ 0, 1994 ] ] } ]

[ { "id": "PMID-8662666_T1", "type": "Protein", "text": [ "granulocyte-macrophage colony-stimulating factor" ], "offsets": [ [ 43, 91 ] ], "normalized": [] }, { "id": "PMID-8662666_T2", "type": "Protein", "text": [ "Granulocyte-macrophage colony-stimulating factor" ], "offsets": [ [ 127, 175 ] ], "normalized": [] }, { "id": "PMID-8662666_T3", "type": "Protein", "text": [ "GM-CSF" ], "offsets": [ [ 177, 183 ] ], "normalized": [] }, { "id": "PMID-8662666_T4", "type": "Protein", "text": [ "GM-CSF" ], "offsets": [ [ 314, 320 ] ], "normalized": [] }, { "id": "PMID-8662666_T5", "type": "Protein", "text": [ "GM-CSF" ], "offsets": [ [ 395, 401 ] ], "normalized": [] }, { "id": "PMID-8662666_T6", "type": "Protein", "text": [ "GM-CSF" ], "offsets": [ [ 551, 557 ] ], "normalized": [] }, { "id": "PMID-8662666_T7", "type": "Protein", "text": [ "GM-CSF" ], "offsets": [ [ 843, 849 ] ], "normalized": [] }, { "id": "PMID-8662666_T8", "type": "Protein", "text": [ "GM-CSF" ], "offsets": [ [ 946, 952 ] ], "normalized": [] }, { "id": "PMID-8662666_T9", "type": "Protein", "text": [ "DNase I" ], "offsets": [ [ 1037, 1044 ] ], "normalized": [] }, { "id": "PMID-8662666_T10", "type": "Protein", "text": [ "GM-CSF" ], "offsets": [ [ 1253, 1259 ] ], "normalized": [] }, { "id": "PMID-8662666_T11", "type": "Protein", "text": [ "Tax" ], "offsets": [ [ 1348, 1351 ] ], "normalized": [] }, { "id": "PMID-8662666_T12", "type": "Protein", "text": [ "GM-CSF" ], "offsets": [ [ 1435, 1441 ] ], "normalized": [] }, { "id": "PMID-8662666_T13", "type": "Protein", "text": [ "GM-CSF" ], "offsets": [ [ 1531, 1537 ] ], "normalized": [] }, { "id": "PMID-8662666_T14", "type": "Protein", "text": [ "interleukin 3" ], "offsets": [ [ 1609, 1622 ] ], "normalized": [] }, { "id": "PMID-8662666_T15", "type": "Protein", "text": [ "GM-CSF" ], "offsets": [ [ 1697, 1703 ] ], "normalized": [] }, { "id": "PMID-8662666_T16", "type": "Protein", "text": [ "GM-CSF" ], "offsets": [ [ 1786, 1792 ] ], "normalized": [] }, { "id": "PMID-8662666_T17", "type": "Protein", "text": [ "GM-CSF" ], "offsets": [ [ 1879, 1885 ] ], "normalized": [] }, { "id": "PMID-8662666_T26", "type": "Entity", "text": [ "proximal promoter" ], "offsets": [ [ 953, 970 ] ], "normalized": [] }, { "id": "PMID-8662666_T30", "type": "Entity", "text": [ "kappaB element" ], "offsets": [ [ 1675, 1689 ] ], "normalized": [] } ]

[ { "id": "PMID-8662666_E1", "type": "Negative_regulation", "trigger": { "text": [ "inhibits" ], "offsets": [ [ 34, 42 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "PMID-8662666_E2" } ] }, { "id": "PMID-8662666_E2", "type": "Gene_expression", "trigger": { "text": [ "expression" ], "offsets": [ [ 97, 107 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "PMID-8662666_T1" } ] }, { "id": "PMID-8662666_E3", "type": "Gene_expression", "trigger": { "text": [ "expressed" ], "offsets": [ [ 224, 233 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "PMID-8662666_T3" } ] }, { "id": "PMID-8662666_E4", "type": "Positive_regulation", "trigger": { "text": [ "overexpression" ], "offsets": [ [ 377, 391 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "PMID-8662666_E5" } ] }, { "id": "PMID-8662666_E5", "type": "Gene_expression", "trigger": { "text": [ "overexpression" ], "offsets": [ [ 377, 391 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "PMID-8662666_T5" } ] }, { "id": "PMID-8662666_E6", "type": "Negative_regulation", "trigger": { "text": [ "inhibit" ], "offsets": [ [ 835, 842 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "PMID-8662666_E7" } ] }, { "id": "PMID-8662666_E7", "type": "Transcription", "trigger": { "text": [ "transcription" ], "offsets": [ [ 855, 868 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "PMID-8662666_T7" } ] }, { "id": "PMID-8662666_E8", "type": "Binding", "trigger": { "text": [ "targeted" ], "offsets": [ [ 906, 914 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "PMID-8662666_T8" }, { "role": "Site", "ref_id": "PMID-8662666_T26" } ] }, { "id": "PMID-8662666_E9", "type": "Negative_regulation", "trigger": { "text": [ "reduced" ], "offsets": [ [ 1491, 1498 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "PMID-8662666_E10" } ] }, { "id": "PMID-8662666_E10", "type": "Positive_regulation", "trigger": { "text": [ "induced" ], "offsets": [ [ 1543, 1550 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "PMID-8662666_T13" } ] }, { "id": "PMID-8662666_E11", "type": "Regulation", "trigger": { "text": [ "affect" ], "offsets": [ [ 1602, 1608 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "PMID-8662666_T14" } ] }, { "id": "PMID-8662666_E12", "type": "Positive_regulation", "trigger": { "text": [ "central role" ], "offsets": [ [ 1721, 1733 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "PMID-8662666_E13" }, { "role": "Cause", "ref_id": "PMID-8662666_T15" }, { "role": "CSite", "ref_id": "PMID-8662666_T30" } ] }, { "id": "PMID-8662666_E13", "type": "Positive_regulation", "trigger": { "text": [ "transcriptional activation" ], "offsets": [ [ 1741, 1767 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "PMID-8662666_T16" } ] }, { "id": "PMID-8662666_E14", "type": "Negative_regulation", "trigger": { "text": [ "transcriptional repressor" ], "offsets": [ [ 1846, 1871 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "PMID-8662666_T17" } ] }, { "id": "PMID-8662666_E15", "type": "Positive_regulation", "trigger": { "text": [ "overexpression" ], "offsets": [ [ 1962, 1976 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "PMID-8662666_E16" } ] }, { "id": "PMID-8662666_E16", "type": "Gene_expression", "trigger": { "text": [ "overexpression" ], "offsets": [ [ 1962, 1976 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "PMID-8662666_T17" } ] } ]

[ { "id": "PMID-8662666_1", "entity_ids": [ "PMID-8662666_T3", "PMID-8662666_T2" ] } ]

[]

[ { "id": "PMID-8662845__text", "type": "abstract", "text": [ "Cooperation between core binding factor and adjacent promoter elements contributes to the tissue-specific expression of interleukin-3. \nTissue-specific expression of interleukin-3 (IL-3) is mediated via cis-acting elements located within 315 base pairs of the transcription start. This is achieved in part through the positive activities of the AP-1 and Elf-1 sites in the IL-3 promoter. The contribution to T cell-specific expression by other promoter sites was assessed in a transient expression assay with IL-3 promoter constructs linked to a luciferase gene, focusing initially on the core binding factor (CBF) site, which is footprinted in vivo upon T cell activation. Activity of the CBF site is shown to be critically dependent on the adjacent activator site Act-1. Together the Act-1 and CBF sites form a functional unit (AC unit) with dual activity. The AC unit is demonstrated to enhance basal activity of promoters both in fibroblasts and T cells. This activity is further inducible in activated T cells, but not in fibroblasts. In addition to the already identified NIP repressor site, evidence is presented for a second repressor region that restricts promoter activity in fibroblasts. Finally, a novel positive regulatory element has been mapped in the IL-3 promoter between nucleotide -180 and -210 that leads to increased expression in T cells. Together these results demonstrate that T cell expression of IL-3 is not specified by the activity of a single tissue-specific element, but instead involves multiple interacting elements that provide both specific positive regulation in T cells and specific negative regulation in fibroblasts. " ], "offsets": [ [ 0, 1655 ] ] } ]

[ { "id": "PMID-8662845_T1", "type": "Protein", "text": [ "interleukin-3" ], "offsets": [ [ 120, 133 ] ], "normalized": [] }, { "id": "PMID-8662845_T2", "type": "Protein", "text": [ "interleukin-3" ], "offsets": [ [ 166, 179 ] ], "normalized": [] }, { "id": "PMID-8662845_T3", "type": "Protein", "text": [ "IL-3" ], "offsets": [ [ 181, 185 ] ], "normalized": [] }, { "id": "PMID-8662845_T4", "type": "Protein", "text": [ "IL-3" ], "offsets": [ [ 373, 377 ] ], "normalized": [] }, { "id": "PMID-8662845_T5", "type": "Protein", "text": [ "IL-3" ], "offsets": [ [ 509, 513 ] ], "normalized": [] }, { "id": "PMID-8662845_T6", "type": "Protein", "text": [ "IL-3" ], "offsets": [ [ 1267, 1271 ] ], "normalized": [] }, { "id": "PMID-8662845_T7", "type": "Protein", "text": [ "IL-3" ], "offsets": [ [ 1422, 1426 ] ], "normalized": [] } ]

[ { "id": "PMID-8662845_E1", "type": "Positive_regulation", "trigger": { "text": [ "contributes" ], "offsets": [ [ 71, 82 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "PMID-8662845_E2" } ] }, { "id": "PMID-8662845_E2", "type": "Gene_expression", "trigger": { "text": [ "expression" ], "offsets": [ [ 106, 116 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "PMID-8662845_T1" } ] }, { "id": "PMID-8662845_E3", "type": "Gene_expression", "trigger": { "text": [ "expression" ], "offsets": [ [ 152, 162 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "PMID-8662845_T3" } ] }, { "id": "PMID-8662845_E4", "type": "Positive_regulation", "trigger": { "text": [ "mediated" ], "offsets": [ [ 190, 198 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "PMID-8662845_E3" } ] }, { "id": "PMID-8662845_E5", "type": "Gene_expression", "trigger": { "text": [ "expression" ], "offsets": [ [ 1408, 1418 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "PMID-8662845_T7" } ] }, { "id": "PMID-8662845_E6", "type": "Positive_regulation", "trigger": { "text": [ "specified" ], "offsets": [ [ 1434, 1443 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "PMID-8662845_E5" } ] } ]

[ { "id": "PMID-8662845_1", "entity_ids": [ "PMID-8662845_T3", "PMID-8662845_T2" ] } ]

[]

[ { "id": "PMID-8663022__text", "type": "abstract", "text": [ "Octamer binding factors and their coactivator can activate the murine PU.1 (spi-1) promoter. \nPU.1 (spi-1), a member of the Ets transcription factor family, is predominantly expressed in myeloid and B cells, activates many B cell and myeloid genes, and is critical for development of both of these lineages. Our previous studies (Chen, H.M., Ray-Gallet, D., Zhang, P., Hetherington, C.J., Gonzalez, D.A., Zhang, D.-E., Moreau-Gachelin, F., and Tenen, D.G.(1995) Oncogene 11, 1549-1560) demonstrate that the PU.1 promoter directs cell type-specific reporter gene expression in myeloid cell lines, and that PU.1 activates its own promoter in an autoregulatory loop. Here we show that the murine PU.1 promoter is also specifically and highly functional in B cell lines as well. Oct-1 and Oct-2 can bind specifically to a site at base pair -55 in vitro, and this site is specifically protected in B cells in vivo. We also demonstrate that two other sites contribute to promoter activity in B cells; an Sp1 binding site adjacent to the octamer site, and the PU.1 autoregulatory site. Finally, we show that the B cell coactivator OBF-1/Bob1/OCA-B is only expressed in B cells and not in myeloid cells, and that OBF-1/Bob1/OCA-B can transactivate the PU.1 promoter in HeLa and myeloid cells. This B cell restricted coactivator may be responsible for the B cell specific expression of PU.1 mediated by the octamer site. " ], "offsets": [ [ 0, 1412 ] ] } ]

[ { "id": "PMID-8663022_T1", "type": "Protein", "text": [ "PU.1" ], "offsets": [ [ 70, 74 ] ], "normalized": [] }, { "id": "PMID-8663022_T2", "type": "Protein", "text": [ "spi-1" ], "offsets": [ [ 76, 81 ] ], "normalized": [] }, { "id": "PMID-8663022_T3", "type": "Protein", "text": [ "PU.1" ], "offsets": [ [ 94, 98 ] ], "normalized": [] }, { "id": "PMID-8663022_T4", "type": "Protein", "text": [ "spi-1" ], "offsets": [ [ 100, 105 ] ], "normalized": [] }, { "id": "PMID-8663022_T5", "type": "Protein", "text": [ "PU.1" ], "offsets": [ [ 507, 511 ] ], "normalized": [] }, { "id": "PMID-8663022_T6", "type": "Protein", "text": [ "PU.1" ], "offsets": [ [ 605, 609 ] ], "normalized": [] }, { "id": "PMID-8663022_T7", "type": "Protein", "text": [ "PU.1" ], "offsets": [ [ 693, 697 ] ], "normalized": [] }, { "id": "PMID-8663022_T8", "type": "Protein", "text": [ "Oct-1" ], "offsets": [ [ 775, 780 ] ], "normalized": [] }, { "id": "PMID-8663022_T9", "type": "Protein", "text": [ "Oct-2" ], "offsets": [ [ 785, 790 ] ], "normalized": [] }, { "id": "PMID-8663022_T10", "type": "Protein", "text": [ "Sp1" ], "offsets": [ [ 998, 1001 ] ], "normalized": [] }, { "id": "PMID-8663022_T11", "type": "Protein", "text": [ "PU.1" ], "offsets": [ [ 1053, 1057 ] ], "normalized": [] }, { "id": "PMID-8663022_T12", "type": "Protein", "text": [ "OBF-1" ], "offsets": [ [ 1124, 1129 ] ], "normalized": [] }, { "id": "PMID-8663022_T13", "type": "Protein", "text": [ "Bob1" ], "offsets": [ [ 1130, 1134 ] ], "normalized": [] }, { "id": "PMID-8663022_T14", "type": "Protein", "text": [ "OCA-B" ], "offsets": [ [ 1135, 1140 ] ], "normalized": [] }, { "id": "PMID-8663022_T15", "type": "Protein", "text": [ "OBF-1" ], "offsets": [ [ 1205, 1210 ] ], "normalized": [] }, { "id": "PMID-8663022_T16", "type": "Protein", "text": [ "Bob1" ], "offsets": [ [ 1211, 1215 ] ], "normalized": [] }, { "id": "PMID-8663022_T17", "type": "Protein", "text": [ "OCA-B" ], "offsets": [ [ 1216, 1221 ] ], "normalized": [] }, { "id": "PMID-8663022_T18", "type": "Protein", "text": [ "PU.1" ], "offsets": [ [ 1244, 1248 ] ], "normalized": [] }, { "id": "PMID-8663022_T19", "type": "Protein", "text": [ "PU.1" ], "offsets": [ [ 1377, 1381 ] ], "normalized": [] }, { "id": "PMID-8663022_T21", "type": "Entity", "text": [ "promoter" ], "offsets": [ [ 83, 91 ] ], "normalized": [] }, { "id": "PMID-8663022_T23", "type": "Entity", "text": [ "promoter" ], "offsets": [ [ 512, 520 ] ], "normalized": [] }, { "id": "PMID-8663022_T28", "type": "Entity", "text": [ "promoter" ], "offsets": [ [ 1249, 1257 ] ], "normalized": [] } ]

[ { "id": "PMID-8663022_E1", "type": "Positive_regulation", "trigger": { "text": [ "activate" ], "offsets": [ [ 50, 58 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "PMID-8663022_T1" }, { "role": "Site", "ref_id": "PMID-8663022_T21" } ] }, { "id": "PMID-8663022_E2", "type": "Gene_expression", "trigger": { "text": [ "expressed" ], "offsets": [ [ 174, 183 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "PMID-8663022_T4" } ] }, { "id": "PMID-8663022_E3", "type": "Positive_regulation", "trigger": { "text": [ "activates" ], "offsets": [ [ 610, 619 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "PMID-8663022_T5" }, { "role": "Cause", "ref_id": "PMID-8663022_T6" }, { "role": "Site", "ref_id": "PMID-8663022_T23" } ] }, { "id": "PMID-8663022_E4", "type": "Binding", "trigger": { "text": [ "bind" ], "offsets": [ [ 795, 799 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "PMID-8663022_T8" } ] }, { "id": "PMID-8663022_E5", "type": "Binding", "trigger": { "text": [ "bind" ], "offsets": [ [ 795, 799 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "PMID-8663022_T9" } ] }, { "id": "PMID-8663022_E6", "type": "Gene_expression", "trigger": { "text": [ "expressed" ], "offsets": [ [ 1149, 1158 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "PMID-8663022_T12" } ] }, { "id": "PMID-8663022_E7", "type": "Positive_regulation", "trigger": { "text": [ "transactivate" ], "offsets": [ [ 1226, 1239 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "PMID-8663022_T18" }, { "role": "Cause", "ref_id": "PMID-8663022_T15" }, { "role": "Site", "ref_id": "PMID-8663022_T28" } ] }, { "id": "PMID-8663022_E8", "type": "Positive_regulation", "trigger": { "text": [ "responsible" ], "offsets": [ [ 1327, 1338 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "PMID-8663022_E10" }, { "role": "Cause", "ref_id": "PMID-8663022_T15" } ] }, { "id": "PMID-8663022_E9", "type": "Gene_expression", "trigger": { "text": [ "expression" ], "offsets": [ [ 1363, 1373 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "PMID-8663022_T19" } ] }, { "id": "PMID-8663022_E10", "type": "Positive_regulation", "trigger": { "text": [ "mediated" ], "offsets": [ [ 1382, 1390 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "PMID-8663022_E9" } ] } ]

[ { "id": "PMID-8663022_1", "entity_ids": [ "PMID-8663022_T1", "PMID-8663022_T2" ] }, { "id": "PMID-8663022_2", "entity_ids": [ "PMID-8663022_T4", "PMID-8663022_T3" ] }, { "id": "PMID-8663022_3", "entity_ids": [ "PMID-8663022_T12", "PMID-8663022_T13", "PMID-8663022_T14" ] }, { "id": "PMID-8663022_4", "entity_ids": [ "PMID-8663022_T15", "PMID-8663022_T16", "PMID-8663022_T17" ] } ]

[]

[ { "id": "PMID-8663060__text", "type": "abstract", "text": [ "Tissue-specific activity of the gammac chain gene promoter depends upon an Ets binding site and is regulated by GA-binding protein. \nThe gammac chain is a subunit of multiple cytokine receptors (interleukin (IL)-2, IL-4, IL-7, IL-9, and IL-15), the expression of which is restricted to hematopoietic lineages. A defect in gammac leads to the X-linked severe combined immunodeficiency characterized by a block in T cell differentiation. In order to better characterize the human gammac promoter and define the minimal tissue-specific promoter region, progressive 5'-deletion constructs of a segment extending 1053 base pairs upstream of the major transcription start site were generated and tested for promoter activity in various hematopoietic and nonhematopoietic cell types. The -1053/+34 construct allowed promoter activity only in cells of hematopoietic origin, and tissue specificity was conserved in all other constructs tested. The region downstream of -90 appeared critical for basal promoter activity. It contains two potential Ets binding sites conserved in the murine gammac promoter gene, one of which was found essential for functional promoter activity as determined by mutational analysis. The functional Ets binding site was found to bind Ets family proteins, principally GA-binding protein and Elf-1 and could be transactivated by GABPalpha and -beta synergistically. These results indicate that, as already reported for the IL2Rbeta promoter, GA-binding protein is an essential component of gammac basal promoter activity. Although GABP expression is not restricted to the hematopoietic lineage, its interaction with other specific factors may contribute to the tissue-specific expression of the gammac gene. " ], "offsets": [ [ 0, 1727 ] ] } ]

[ { "id": "PMID-8663060_T1", "type": "Protein", "text": [ "gammac" ], "offsets": [ [ 137, 143 ] ], "normalized": [] }, { "id": "PMID-8663060_T2", "type": "Protein", "text": [ "interleukin (IL)-2" ], "offsets": [ [ 195, 213 ] ], "normalized": [] }, { "id": "PMID-8663060_T3", "type": "Protein", "text": [ "IL-4" ], "offsets": [ [ 215, 219 ] ], "normalized": [] }, { "id": "PMID-8663060_T4", "type": "Protein", "text": [ "IL-7" ], "offsets": [ [ 221, 225 ] ], "normalized": [] }, { "id": "PMID-8663060_T5", "type": "Protein", "text": [ "IL-9" ], "offsets": [ [ 227, 231 ] ], "normalized": [] }, { "id": "PMID-8663060_T6", "type": "Protein", "text": [ "IL-15" ], "offsets": [ [ 237, 242 ] ], "normalized": [] }, { "id": "PMID-8663060_T7", "type": "Protein", "text": [ "gammac" ], "offsets": [ [ 322, 328 ] ], "normalized": [] }, { "id": "PMID-8663060_T8", "type": "Protein", "text": [ "gammac" ], "offsets": [ [ 478, 484 ] ], "normalized": [] }, { "id": "PMID-8663060_T9", "type": "Protein", "text": [ "gammac" ], "offsets": [ [ 1079, 1085 ] ], "normalized": [] }, { "id": "PMID-8663060_T10", "type": "Protein", "text": [ "Elf-1" ], "offsets": [ [ 1311, 1316 ] ], "normalized": [] }, { "id": "PMID-8663060_T11", "type": "Protein", "text": [ "IL2Rbeta" ], "offsets": [ [ 1442, 1450 ] ], "normalized": [] }, { "id": "PMID-8663060_T12", "type": "Protein", "text": [ "gammac" ], "offsets": [ [ 1509, 1515 ] ], "normalized": [] }, { "id": "PMID-8663060_T13", "type": "Protein", "text": [ "GABP" ], "offsets": [ [ 1550, 1554 ] ], "normalized": [] }, { "id": "PMID-8663060_T14", "type": "Protein", "text": [ "gammac" ], "offsets": [ [ 1714, 1720 ] ], "normalized": [] } ]

[ { "id": "PMID-8663060_E1", "type": "Negative_regulation", "trigger": { "text": [ "defect" ], "offsets": [ [ 312, 318 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "PMID-8663060_T7" } ] }, { "id": "PMID-8663060_E2", "type": "Binding", "trigger": { "text": [ "bind" ], "offsets": [ [ 1250, 1254 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "PMID-8663060_T10" } ] }, { "id": "PMID-8663060_E3", "type": "Gene_expression", "trigger": { "text": [ "expression" ], "offsets": [ [ 1555, 1565 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "PMID-8663060_T13" } ] }, { "id": "PMID-8663060_E4", "type": "Binding", "trigger": { "text": [ "interaction" ], "offsets": [ [ 1618, 1629 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "PMID-8663060_T13" } ] }, { "id": "PMID-8663060_E5", "type": "Positive_regulation", "trigger": { "text": [ "contribute" ], "offsets": [ [ 1662, 1672 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "PMID-8663060_E6" }, { "role": "Cause", "ref_id": "PMID-8663060_E4" } ] }, { "id": "PMID-8663060_E6", "type": "Gene_expression", "trigger": { "text": [ "expression" ], "offsets": [ [ 1696, 1706 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "PMID-8663060_T14" } ] } ]

[]

[]

[ { "id": "PMID-8663174__text", "type": "abstract", "text": [ "Multiple transcription factors are required for activation of human interleukin 9 gene in T cells. \nThe genetic elements and regulatory mechanisms responsible for human interleukin 9 (IL-9) gene expression in a human T cell leukemia virus type I-transformed human T cell line, C5MJ2, were investigated. We demonstrated that IL-9 gene expression is controlled, at least in part, by transcriptional activation. Transient expression of the luciferase reporter gene linked to serially deleted sequences of the 5'-flanking region of the IL-9 gene has revealed several positive and negative regulatory elements involved in the basal and inducible expression of the IL-9 gene in C5MJ2 cells. An AP-1 site at -146 to -140 was shown to be involved in the expression of the IL-9 gene. A proximal region between -46 and -80 was identified as the minimum sequence for the basal and inducible expression of the IL-9 gene in C5MJ2 cells. Within this region, an NF-kappaB site at -59 to -50 and its adjacent 20-base pair upstream sequence were demonstrated to play a critical role for the IL-9 promoter activity. DNA-protein binding studies indicated that NF-kappaB, c-Jun, and potentially novel proteins (around 35 kDa) can bind to this important sequence. Mutations at different sites within this proximal promoter region abolished the promoter activity as well as the DNA binding. Taken together, these results suggest that the cooperation of different transcription factors is essential for IL-9 gene expression in T cells. " ], "offsets": [ [ 0, 1513 ] ] } ]

[ { "id": "PMID-8663174_T1", "type": "Protein", "text": [ "interleukin 9" ], "offsets": [ [ 68, 81 ] ], "normalized": [] }, { "id": "PMID-8663174_T2", "type": "Protein", "text": [ "interleukin 9" ], "offsets": [ [ 169, 182 ] ], "normalized": [] }, { "id": "PMID-8663174_T3", "type": "Protein", "text": [ "IL-9" ], "offsets": [ [ 184, 188 ] ], "normalized": [] }, { "id": "PMID-8663174_T4", "type": "Protein", "text": [ "IL-9" ], "offsets": [ [ 324, 328 ] ], "normalized": [] }, { "id": "PMID-8663174_T5", "type": "Protein", "text": [ "IL-9" ], "offsets": [ [ 532, 536 ] ], "normalized": [] }, { "id": "PMID-8663174_T6", "type": "Protein", "text": [ "IL-9" ], "offsets": [ [ 659, 663 ] ], "normalized": [] }, { "id": "PMID-8663174_T7", "type": "Protein", "text": [ "IL-9" ], "offsets": [ [ 764, 768 ] ], "normalized": [] }, { "id": "PMID-8663174_T8", "type": "Protein", "text": [ "IL-9" ], "offsets": [ [ 898, 902 ] ], "normalized": [] }, { "id": "PMID-8663174_T9", "type": "Protein", "text": [ "IL-9" ], "offsets": [ [ 1074, 1078 ] ], "normalized": [] }, { "id": "PMID-8663174_T10", "type": "Protein", "text": [ "c-Jun" ], "offsets": [ [ 1152, 1157 ] ], "normalized": [] }, { "id": "PMID-8663174_T11", "type": "Protein", "text": [ "IL-9" ], "offsets": [ [ 1480, 1484 ] ], "normalized": [] }, { "id": "PMID-8663174_T23", "type": "Entity", "text": [ "promoter" ], "offsets": [ [ 1079, 1087 ] ], "normalized": [] } ]

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[ { "id": "PMID-8663174_1", "entity_ids": [ "PMID-8663174_T2", "PMID-8663174_T3" ] } ]

[]

[ { "id": "PMID-8663230__text", "type": "abstract", "text": [ "Mapping of the transcriptional repression domain of the lymphoid-specific transcription factor oct-2A. \nThe lymphoid-specific transcription factor Oct-2a is implicated in B cell-specific transcriptional activity via the octamer motif. Structure/function analysis of various Oct-2a effector regions in the context of the GAL4 DNA-binding domain revealed that Oct-2a contains two functionally different activation domains at the N and the C termini. The transcriptional activity of both domains is strongly potentiated by interactions with distinct B cell-specific coactivators. Recently, we have identified a repression domain located within the N terminus of Oct-2a (amino acids 2-99). When this domain was transferred to a potent activator, transcription was strongly inhibited. In this study we present a deletion analysis of the N-terminal region of Oct-2a to determine the minimal repression domain. We identified a stretch of 23 amino acids, rich in serine and threonine residues, which was responsible for most of the repression activity. We show that repression is strongly dependent on the type of enhancer present in the reporter plasmid as well as on the cell line tested. The possibility that Oct-2a can act as an activator and/or a repressor may have important consequences for the function of Oct-2a in B cell differentiation and other developmental processes. " ], "offsets": [ [ 0, 1374 ] ] } ]

[ { "id": "PMID-8663230_T1", "type": "Protein", "text": [ "oct-2A" ], "offsets": [ [ 95, 101 ] ], "normalized": [] }, { "id": "PMID-8663230_T2", "type": "Protein", "text": [ "Oct-2a" ], "offsets": [ [ 147, 153 ] ], "normalized": [] }, { "id": "PMID-8663230_T3", "type": "Protein", "text": [ "Oct-2a" ], "offsets": [ [ 274, 280 ] ], "normalized": [] }, { "id": "PMID-8663230_T4", "type": "Protein", "text": [ "GAL4" ], "offsets": [ [ 320, 324 ] ], "normalized": [] }, { "id": "PMID-8663230_T5", "type": "Protein", "text": [ "Oct-2a" ], "offsets": [ [ 358, 364 ] ], "normalized": [] }, { "id": "PMID-8663230_T6", "type": "Protein", "text": [ "Oct-2a" ], "offsets": [ [ 659, 665 ] ], "normalized": [] }, { "id": "PMID-8663230_T7", "type": "Protein", "text": [ "Oct-2a" ], "offsets": [ [ 853, 859 ] ], "normalized": [] }, { "id": "PMID-8663230_T8", "type": "Protein", "text": [ "Oct-2a" ], "offsets": [ [ 1204, 1210 ] ], "normalized": [] }, { "id": "PMID-8663230_T9", "type": "Protein", "text": [ "Oct-2a" ], "offsets": [ [ 1306, 1312 ] ], "normalized": [] }, { "id": "PMID-8663230_T10", "type": "Entity", "text": [ "N" ], "offsets": [ [ 427, 428 ] ], "normalized": [] }, { "id": "PMID-8663230_T11", "type": "Entity", "text": [ "termini" ], "offsets": [ [ 439, 446 ] ], "normalized": [] } ]

[ { "id": "PMID-8663230_E1", "type": "Positive_regulation", "trigger": { "text": [ "potentiated" ], "offsets": [ [ 505, 516 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "PMID-8663230_T5" }, { "role": "Cause", "ref_id": "PMID-8663230_E4" }, { "role": "Site", "ref_id": "PMID-8663230_T11" } ] }, { "id": "PMID-8663230_E2", "type": "Positive_regulation", "trigger": { "text": [ "potentiated" ], "offsets": [ [ 505, 516 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "PMID-8663230_T5" }, { "role": "Cause", "ref_id": "PMID-8663230_E3" }, { "role": "Site", "ref_id": "PMID-8663230_T10" } ] }, { "id": "PMID-8663230_E3", "type": "Binding", "trigger": { "text": [ "interactions" ], "offsets": [ [ 520, 532 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "PMID-8663230_T5" }, { "role": "Site", "ref_id": "PMID-8663230_T10" } ] }, { "id": "PMID-8663230_E4", "type": "Binding", "trigger": { "text": [ "interactions" ], "offsets": [ [ 520, 532 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "PMID-8663230_T5" }, { "role": "Site", "ref_id": "PMID-8663230_T11" } ] } ]

[]

[]

[ { "id": "PMID-8664547__text", "type": "abstract", "text": [ "The role of BSAP (Pax-5) in B-cell development. \nThe hierarchy of transcriptional control in B-cell development has recently been analyzed by targeted gene inactivation in the mouse. In this manner, the paired box containing gene Pax-5, encoding the B cell specific transcription factor BSAP, has been shown to play a key role in early B lymphopoiesis. Other experimental strategies have implicated BSAP in the control of cell proliferation, isotype switching and transcription of the immunoglobulin heavy-chain gene at late stages of B-cell differentiation. " ], "offsets": [ [ 0, 559 ] ] } ]

[ { "id": "PMID-8664547_T1", "type": "Protein", "text": [ "BSAP" ], "offsets": [ [ 12, 16 ] ], "normalized": [] }, { "id": "PMID-8664547_T2", "type": "Protein", "text": [ "Pax-5" ], "offsets": [ [ 18, 23 ] ], "normalized": [] }, { "id": "PMID-8664547_T3", "type": "Protein", "text": [ "Pax-5" ], "offsets": [ [ 230, 235 ] ], "normalized": [] }, { "id": "PMID-8664547_T4", "type": "Protein", "text": [ "B cell specific transcription factor" ], "offsets": [ [ 250, 286 ] ], "normalized": [] }, { "id": "PMID-8664547_T5", "type": "Protein", "text": [ "BSAP" ], "offsets": [ [ 287, 291 ] ], "normalized": [] }, { "id": "PMID-8664547_T6", "type": "Protein", "text": [ "BSAP" ], "offsets": [ [ 399, 403 ] ], "normalized": [] } ]

[]

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[ { "id": "PMID-8666783__text", "type": "abstract", "text": [ "Modulation of the expression of the IFN-gamma receptor beta-chain controls responsiveness to IFN-gamma in human peripheral blood T cells. \nIFN-gamma has potent antiproliferative and apoptotic effects in T cells that are important in determining T cell development and polarized differentiation. Therefore, any event that enables T cells to become less responsive to IFN- gamma may potentially alter immune responsiveness to Ag. In this work, we show that human peripheral blood T cells that are stimulated through the TCR and expanded with IL-2 are unresponsive to IFN-gamma, as determined by a lack of activation of jak kinases and the transcription factor, STAT1(alpha), a signal transducer and activator of transcription. This nonresponsiveness occurs because of a lack of expression of the beta- chain (accessory factor) of the IFN-gamma receptor, while at the same time maintaining IFN-gamma receptor alpha-chain expression. Expression of the beta-chain can be restored by secondary TCR ligation or PMA treatment. T cell blasts treated with PMA are now responsive to IFN-gamma. When freshly isolated, highly enriched (>98%) T cells are examined for IFN-gamma responsiveness; these cells can respond to IFN-gamma and express beta-chain. Therefore, as T cells progress from primary TCR activation through IL-2-dependent proliferation, followed by secondary TCR stimulation, their responsiveness to IFN-gamma varies, and this may affect their ability to participate in an ongoing immune response. " ], "offsets": [ [ 0, 1499 ] ] } ]

[ { "id": "PMID-8666783_T1", "type": "Protein", "text": [ "IFN-gamma receptor beta-chain" ], "offsets": [ [ 36, 65 ] ], "normalized": [] }, { "id": "PMID-8666783_T2", "type": "Protein", "text": [ "IFN-gamma" ], "offsets": [ [ 93, 102 ] ], "normalized": [] }, { "id": "PMID-8666783_T3", "type": "Protein", "text": [ "IFN-gamma" ], "offsets": [ [ 139, 148 ] ], "normalized": [] }, { "id": "PMID-8666783_T4", "type": "Protein", "text": [ "IFN- gamma" ], "offsets": [ [ 366, 376 ] ], "normalized": [] }, { "id": "PMID-8666783_T5", "type": "Protein", "text": [ "IL-2" ], "offsets": [ [ 540, 544 ] ], "normalized": [] }, { "id": "PMID-8666783_T6", "type": "Protein", "text": [ "IFN-gamma" ], "offsets": [ [ 565, 574 ] ], "normalized": [] }, { "id": "PMID-8666783_T7", "type": "Protein", "text": [ "STAT1(alpha)" ], "offsets": [ [ 659, 671 ] ], "normalized": [] }, { "id": "PMID-8666783_T8", "type": "Protein", "text": [ "IFN-gamma receptor alpha-chain" ], "offsets": [ [ 887, 917 ] ], "normalized": [] }, { "id": "PMID-8666783_T9", "type": "Protein", "text": [ "IFN-gamma" ], "offsets": [ [ 1072, 1081 ] ], "normalized": [] }, { "id": "PMID-8666783_T10", "type": "Protein", "text": [ "IFN-gamma" ], "offsets": [ [ 1154, 1163 ] ], "normalized": [] }, { "id": "PMID-8666783_T11", "type": "Protein", "text": [ "IFN-gamma" ], "offsets": [ [ 1207, 1216 ] ], "normalized": [] }, { "id": "PMID-8666783_T12", "type": "Protein", "text": [ "IL-2" ], "offsets": [ [ 1308, 1312 ] ], "normalized": [] }, { "id": "PMID-8666783_T13", "type": "Protein", "text": [ "IFN-gamma" ], "offsets": [ [ 1401, 1410 ] ], "normalized": [] } ]

[ { "id": "PMID-8666783_E1", "type": "Regulation", "trigger": { "text": [ "Modulation" ], "offsets": [ [ 0, 10 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "PMID-8666783_E2" } ] }, { "id": "PMID-8666783_E2", "type": "Gene_expression", "trigger": { "text": [ "expression" ], "offsets": [ [ 18, 28 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "PMID-8666783_T1" } ] }, { "id": "PMID-8666783_E3", "type": "Positive_regulation", "trigger": { "text": [ "activation" ], "offsets": [ [ 603, 613 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "PMID-8666783_T7" } ] }, { "id": "PMID-8666783_E4", "type": "Gene_expression", "trigger": { "text": [ "expression" ], "offsets": [ [ 918, 928 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "PMID-8666783_T8" } ] } ]

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[ { "id": "PMID-8666795__text", "type": "abstract", "text": [ "Induction of CIITA and modification of in vivo HLA-DR promoter occupancy in normal thymic epithelial cells treated with IFN-gamma: similarities and distinctions with respect to HLA-DR-constitutive B cells. \nIn this study, the IFN-gamma induction of MHC class II gene expression in primary cultures of thymic epithelial cells (TEC) was analyzed. This cellular system offers the advantage that MHC class II induction is studied in a \"physiologic\" cell lineage that, as a result of this expression within the thymus, is thought to participate to the selection and maturation of the T cells. It was found that the MHC class II gene expression was associated with the de novo transcription of the gene encoding the CIITA trans-activator, a crucial MHC class II gene regulatory factor. Furthermore, the anatomy of interaction between the MHC class II DRA promoter and corresponding binding factors was analyzed by in vivo DNAse I footprint. It was found that treatment with IFN-gamma induces changes in the occupancy of the DRA gene regulatory sequences by nuclear factors. The resulting occupancy displays strong similarities with the one observed in the MHC class II-constitutive B cells, represented by both the Burkitt lymphoma line Raji and normal tonsil- derived B cells. However, some peculiar differences were observed between the TEC, either IFN-gamma-induced or not, and the constitutive B cells. These results suggest that both common mechanisms, such as the one mediated by the CIITA trans-activator, and distinct tissue-specific constraints contribute to the transcriptional control of constitutive and IFN-gamma-induced MHC class II gene expression. " ], "offsets": [ [ 0, 1658 ] ] } ]

[ { "id": "PMID-8666795_T1", "type": "Protein", "text": [ "CIITA" ], "offsets": [ [ 13, 18 ] ], "normalized": [] }, { "id": "PMID-8666795_T2", "type": "Protein", "text": [ "IFN-gamma" ], "offsets": [ [ 120, 129 ] ], "normalized": [] }, { "id": "PMID-8666795_T3", "type": "Protein", "text": [ "IFN-gamma" ], "offsets": [ [ 226, 235 ] ], "normalized": [] }, { "id": "PMID-8666795_T4", "type": "Protein", "text": [ "CIITA" ], "offsets": [ [ 710, 715 ] ], "normalized": [] }, { "id": "PMID-8666795_T5", "type": "Protein", "text": [ "IFN-gamma" ], "offsets": [ [ 968, 977 ] ], "normalized": [] }, { "id": "PMID-8666795_T6", "type": "Protein", "text": [ "IFN-gamma" ], "offsets": [ [ 1345, 1354 ] ], "normalized": [] }, { "id": "PMID-8666795_T7", "type": "Protein", "text": [ "CIITA" ], "offsets": [ [ 1484, 1489 ] ], "normalized": [] }, { "id": "PMID-8666795_T8", "type": "Protein", "text": [ "IFN-gamma" ], "offsets": [ [ 1610, 1619 ] ], "normalized": [] } ]

[ { "id": "PMID-8666795_E1", "type": "Positive_regulation", "trigger": { "text": [ "Induction" ], "offsets": [ [ 0, 9 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "PMID-8666795_T1" } ] }, { "id": "PMID-8666795_E2", "type": "Transcription", "trigger": { "text": [ "transcription" ], "offsets": [ [ 671, 684 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "PMID-8666795_T4" } ] } ]

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[ { "id": "PMID-8668213__text", "type": "abstract", "text": [ "Recombinant NFAT1 (NFATp) is regulated by calcineurin in T cells and mediates transcription of several cytokine genes. \nTranscription factors of the NFAT family play a key role in the transcription of cytokine genes and other genes during the immune response. We have identified two new isoforms of the transcription factor NFAT1 (previously termed NFATp) that are the predominant isoforms expressed in murine and human T cells. When expressed in Jurkat T cells, recombinant NFAT1 is regulated, as expected, by the calmodulin-dependent phosphatase calcineurin, and its function is inhibited by the immunosuppressive agent cyclosporin A (CsA). Transactivation by recombinant NFAT1 in Jurkat T cells requires dual stimulation with ionomycin and phorbol 12-myristate 13-acetate; this activity is potentiated by coexpression of constitutively active calcineurin and is inhibited by CsA. Immunocytochemical analysis indicates that recombinant NFAT1 localizes in the cytoplasm of transiently transfected T cells and translocates into the nucleus in a CsA-sensitive manner following ionomycin stimulation. When expressed in COS cells, however, NFAT1 is capable of transactivation, but it is not regulated correctly: its subcellular localization and transcriptional function are not affected by stimulation of the COS cells with ionomycin and phorbol 12-myristate 13-acetate. Recombinant NFAT1 can mediate transcription of the interleukin-2, interleukin-4, tumor necrosis factor alpha, and granulocyte-macrophage colony-stimulating factor promoters in T cells, suggesting that NFAT1 contributes to the CsA-sensitive transcription of these genes during the immune response. " ], "offsets": [ [ 0, 1665 ] ] } ]

[ { "id": "PMID-8668213_T1", "type": "Protein", "text": [ "NFAT1" ], "offsets": [ [ 12, 17 ] ], "normalized": [] }, { "id": "PMID-8668213_T2", "type": "Protein", "text": [ "NFATp" ], "offsets": [ [ 19, 24 ] ], "normalized": [] }, { "id": "PMID-8668213_T3", "type": "Protein", "text": [ "NFAT1" ], "offsets": [ [ 324, 329 ] ], "normalized": [] }, { "id": "PMID-8668213_T4", "type": "Protein", "text": [ "NFATp" ], "offsets": [ [ 349, 354 ] ], "normalized": [] }, { "id": "PMID-8668213_T5", "type": "Protein", "text": [ "NFAT1" ], "offsets": [ [ 475, 480 ] ], "normalized": [] }, { "id": "PMID-8668213_T6", "type": "Protein", "text": [ "calmodulin" ], "offsets": [ [ 515, 525 ] ], "normalized": [] }, { "id": "PMID-8668213_T7", "type": "Protein", "text": [ "NFAT1" ], "offsets": [ [ 674, 679 ] ], "normalized": [] }, { "id": "PMID-8668213_T8", "type": "Protein", "text": [ "NFAT1" ], "offsets": [ [ 938, 943 ] ], "normalized": [] }, { "id": "PMID-8668213_T9", "type": "Protein", "text": [ "NFAT1" ], "offsets": [ [ 1137, 1142 ] ], "normalized": [] }, { "id": "PMID-8668213_T10", "type": "Protein", "text": [ "NFAT1" ], "offsets": [ [ 1380, 1385 ] ], "normalized": [] }, { "id": "PMID-8668213_T11", "type": "Protein", "text": [ "interleukin-2" ], "offsets": [ [ 1419, 1432 ] ], "normalized": [] }, { "id": "PMID-8668213_T12", "type": "Protein", "text": [ "interleukin-4" ], "offsets": [ [ 1434, 1447 ] ], "normalized": [] }, { "id": "PMID-8668213_T13", "type": "Protein", "text": [ "tumor necrosis factor alpha" ], "offsets": [ [ 1449, 1476 ] ], "normalized": [] }, { "id": "PMID-8668213_T14", "type": "Protein", "text": [ "granulocyte-macrophage colony-stimulating factor" ], "offsets": [ [ 1482, 1530 ] ], "normalized": [] }, { "id": "PMID-8668213_T15", "type": "Protein", "text": [ "NFAT1" ], "offsets": [ [ 1569, 1574 ] ], "normalized": [] } ]

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[ { "id": "PMID-8668213_1", "entity_ids": [ "PMID-8668213_T1", "PMID-8668213_T2" ] } ]

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