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[ { "id": "PMID-1953785__text", "type": "abstract", "text": [ "Regulation of interleukin-1 beta production by glucocorticoids in human monocytes: the mechanism of action depends on the activation signal. \nGlucocorticoids are known to downregulate interleukin-1 beta production in monocytic cells by two different mechanims: direct inhibition of the gene transcription and destabilization of the preformed interleukin-1 beta mRNA. Now we have examined the effect of the nature of the monocyte activating signal on these two inhibitory mechanims. When human monocytes were preincubated with dexamethasone for 1 hour and then stimulated either with bacterial lipopolysaccharide or phorbol myristate, it was found that dexamethasone inhibited the lipopolysaccharide-induced interleukin-1 beta protein production, but the phorbol myristate-induced production was increased 3-10 fold. This difference was also seen at the mRNA level. When dexamethasone was added to the cultures 3 hours after the stimulators, it clearly decreased the interleukin-1 beta mRNA levels regardless of the stimulator used (although the effect was clearly weaker on the PMA-induced mRNA). Thus these data suggest that the phorbol myristate-induced signal (prolonged protein kinase C activation?) cannot be inhibited by prior incubation with dexamethasone and it also protects the induced mRNA for the degradative action of dexamethasone. " ], "offsets": [ [ 0, 1346 ] ] } ]

[ { "id": "PMID-1953785_T1", "type": "Protein", "text": [ "interleukin-1 beta" ], "offsets": [ [ 14, 32 ] ], "normalized": [] }, { "id": "PMID-1953785_T2", "type": "Protein", "text": [ "interleukin-1 beta" ], "offsets": [ [ 184, 202 ] ], "normalized": [] }, { "id": "PMID-1953785_T3", "type": "Protein", "text": [ "interleukin-1 beta" ], "offsets": [ [ 342, 360 ] ], "normalized": [] }, { "id": "PMID-1953785_T4", "type": "Protein", "text": [ "interleukin-1 beta" ], "offsets": [ [ 707, 725 ] ], "normalized": [] }, { "id": "PMID-1953785_T5", "type": "Protein", "text": [ "interleukin-1 beta" ], "offsets": [ [ 966, 984 ] ], "normalized": [] } ]

[ { "id": "PMID-1953785_E1", "type": "Regulation", "trigger": { "text": [ "Regulation" ], "offsets": [ [ 0, 10 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "PMID-1953785_E2" } ] }, { "id": "PMID-1953785_E2", "type": "Gene_expression", "trigger": { "text": [ "production" ], "offsets": [ [ 33, 43 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "PMID-1953785_T1" } ] }, { "id": "PMID-1953785_E3", "type": "Regulation", "trigger": { "text": [ "depends" ], "offsets": [ [ 107, 114 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "PMID-1953785_E1" } ] }, { "id": "PMID-1953785_E4", "type": "Negative_regulation", "trigger": { "text": [ "downregulate" ], "offsets": [ [ 171, 183 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "PMID-1953785_E6" } ] }, { "id": "PMID-1953785_E5", "type": "Negative_regulation", "trigger": { "text": [ "downregulate" ], "offsets": [ [ 171, 183 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "PMID-1953785_E6" }, { "role": "Cause", "ref_id": "PMID-1953785_E7" } ] }, { "id": "PMID-1953785_E6", "type": "Gene_expression", "trigger": { "text": [ "production" ], "offsets": [ [ 203, 213 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "PMID-1953785_T2" } ] }, { "id": "PMID-1953785_E7", "type": "Negative_regulation", "trigger": { "text": [ "destabilization" ], "offsets": [ [ 309, 324 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "PMID-1953785_T3" } ] }, { "id": "PMID-1953785_E8", "type": "Transcription", "trigger": { "text": [ "preformed" ], "offsets": [ [ 332, 341 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "PMID-1953785_T3" } ] }, { "id": "PMID-1953785_E9", "type": "Regulation", "trigger": { "text": [ "effect" ], "offsets": [ [ 392, 398 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "PMID-1953785_E7" } ] }, { "id": "PMID-1953785_E10", "type": "Negative_regulation", "trigger": { "text": [ "inhibited" ], "offsets": [ [ 666, 675 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "PMID-1953785_E11" } ] }, { "id": "PMID-1953785_E11", "type": "Positive_regulation", "trigger": { "text": [ "induced" ], "offsets": [ [ 699, 706 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "PMID-1953785_E12" } ] }, { "id": "PMID-1953785_E12", "type": "Gene_expression", "trigger": { "text": [ "production" ], "offsets": [ [ 734, 744 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "PMID-1953785_T4" } ] }, { "id": "PMID-1953785_E13", "type": "Positive_regulation", "trigger": { "text": [ "induced" ], "offsets": [ [ 772, 779 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "PMID-1953785_E12" } ] }, { "id": "PMID-1953785_E14", "type": "Positive_regulation", "trigger": { "text": [ "increased" ], "offsets": [ [ 795, 804 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "PMID-1953785_E13" } ] }, { "id": "PMID-1953785_E15", "type": "Negative_regulation", "trigger": { "text": [ "decreased" ], "offsets": [ [ 952, 961 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "PMID-1953785_E16" } ] }, { "id": "PMID-1953785_E16", "type": "Transcription", "trigger": { "text": [ "levels" ], "offsets": [ [ 990, 996 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "PMID-1953785_T5" } ] }, { "id": "PMID-1953785_E17", "type": "Regulation", "trigger": { "text": [ "regardless of" ], "offsets": [ [ 997, 1010 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "PMID-1953785_E15" } ] }, { "id": "PMID-1953785_E18", "type": "Positive_regulation", "trigger": { "text": [ "induced" ], "offsets": [ [ 1082, 1089 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "PMID-1953785_T5" } ] }, { "id": "PMID-1953785_E19", "type": "Positive_regulation", "trigger": { "text": [ "induced" ], "offsets": [ [ 1148, 1155 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "PMID-1953785_T5" } ] }, { "id": "PMID-1953785_E20", "type": "Negative_regulation", "trigger": { "text": [ "inhibited" ], "offsets": [ [ 1214, 1223 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "PMID-1953785_E19" } ] } ]

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[ { "id": "PMID-1956769__text", "type": "abstract", "text": [ "Identification of transcriptional suppressor proteins that bind to the negative regulatory element of the human immunodeficiency virus type 1. \nTwo different proteins which independently bound to neighboring sequences within the negative regulatory element (NRE) of human immunodeficiency virus type 1 (HIV-1) were detected in the nuclear extract of a virus-infected human T cell line. One of the factors bound to a novel dyad symmetrical sequence. This sequence is well conserved in various HIV-1 isolates and partial homology was found with the promoter region of the human retinoblastoma gene. Similar DNA binding activity was detected in a variety of virus-uninfected human T cell lines and HeLa cells by means of a gel mobility shift assay. The other factor bound to a putative AP-1 recognition sequence predicted for the HIV-1 NRE. However, this factor did not bind to a typical AP-1 site. The insertion of multiple copies of the binding site for the former or latter factor into a heterologous promoter reduced the promoter activity to one-tenth or one-third, respectively. Thus, each factor may function as a novel negative regulator of transcription. " ], "offsets": [ [ 0, 1160 ] ] } ]

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[ { "id": "PMID-1958222__text", "type": "abstract", "text": [ "Constitutive activation of NF-kB in human thymocytes. \nNF-kB is a eukaryotic transcription regulatory factor. In T cells and T cell lines, NF-kB is bound to a cytoplasmic proteic inhibitor, the IkB. Treatment of T cells with mitogens (phorbol esters) or cytokines (TNF alpha) induces NF-kB nuclear translocation and the subsequent expression of NF-kB dependent T cell genes. Here we examined the activation of NF-kB in human T cell thymic progenitors. We report differences in (Ca2+)i requirement for NF-kB activation in thymocytes as compared to mature T cells. Furthermore, our results indicated that thymocytes have a constitutively active form of NF-kB, suggesting that they are activated in vivo. " ], "offsets": [ [ 0, 702 ] ] } ]

[ { "id": "PMID-1958222_T1", "type": "Protein", "text": [ "TNF alpha" ], "offsets": [ [ 265, 274 ] ], "normalized": [] } ]

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[ { "id": "PMID-1964088__text", "type": "abstract", "text": [ "Suppression of signals required for activation of transcription factor NF-kappa B in cells constitutively expressing the HTLV-I Tax protein. \nTransient short-term expression of the Tax protein of human T-cell leukemia virus type-I (HTLV-I) leads to activation of the pleiotropic transcription factor NF-kappa B. Consistent with findings obtained with transient expression assays, we observed marked accumulation of the transcription factor NF-kappa B in the nucleus of Namalwa B lymphoid cells, which constitutively express Tax. In contrast, NF-kappa B activity was not detected in the nucleus following long-term expression of Tax in Jurkat T lymphocytes. The ability of both mitogens and cytokines to activate NF-kappa B was also blocked in Jurkat cells constitutively expressing Tax. However, the activation of other mitogen-inducible transcription factors, such as Fos and Jun, was unaffected. Thus, depending on the cellular environment, the short- and long-term effects of Tax expression can be quite different. Consequently, one function of Tax in cells infected with HTLV-I might involve cell-type-specific suppression, as opposed to activation, of distinct signal pathways. The cells lines described here should be useful for the delineation of signaling pathways utilized in the selective regulation of gene expression. " ], "offsets": [ [ 0, 1330 ] ] } ]

[ { "id": "PMID-1964088_T1", "type": "Protein", "text": [ "Tax" ], "offsets": [ [ 128, 131 ] ], "normalized": [] }, { "id": "PMID-1964088_T2", "type": "Protein", "text": [ "Tax" ], "offsets": [ [ 181, 184 ] ], "normalized": [] }, { "id": "PMID-1964088_T3", "type": "Protein", "text": [ "Tax" ], "offsets": [ [ 524, 527 ] ], "normalized": [] }, { "id": "PMID-1964088_T4", "type": "Protein", "text": [ "Tax" ], "offsets": [ [ 628, 631 ] ], "normalized": [] }, { "id": "PMID-1964088_T5", "type": "Protein", "text": [ "Tax" ], "offsets": [ [ 782, 785 ] ], "normalized": [] }, { "id": "PMID-1964088_T6", "type": "Protein", "text": [ "Fos" ], "offsets": [ [ 869, 872 ] ], "normalized": [] }, { "id": "PMID-1964088_T7", "type": "Protein", "text": [ "Jun" ], "offsets": [ [ 877, 880 ] ], "normalized": [] }, { "id": "PMID-1964088_T8", "type": "Protein", "text": [ "Tax" ], "offsets": [ [ 979, 982 ] ], "normalized": [] }, { "id": "PMID-1964088_T9", "type": "Protein", "text": [ "Tax" ], "offsets": [ [ 1048, 1051 ] ], "normalized": [] } ]

[ { "id": "PMID-1964088_E1", "type": "Gene_expression", "trigger": { "text": [ "expressing" ], "offsets": [ [ 106, 116 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "PMID-1964088_T1" } ] }, { "id": "PMID-1964088_E2", "type": "Gene_expression", "trigger": { "text": [ "expression" ], "offsets": [ [ 163, 173 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "PMID-1964088_T2" } ] }, { "id": "PMID-1964088_E3", "type": "Gene_expression", "trigger": { "text": [ "express" ], "offsets": [ [ 516, 523 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "PMID-1964088_T3" } ] }, { "id": "PMID-1964088_E4", "type": "Gene_expression", "trigger": { "text": [ "expression" ], "offsets": [ [ 614, 624 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "PMID-1964088_T4" } ] }, { "id": "PMID-1964088_E5", "type": "Gene_expression", "trigger": { "text": [ "expressing" ], "offsets": [ [ 771, 781 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "PMID-1964088_T5" } ] }, { "id": "PMID-1964088_E6", "type": "Positive_regulation", "trigger": { "text": [ "activation" ], "offsets": [ [ 800, 810 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "PMID-1964088_T6" } ] }, { "id": "PMID-1964088_E7", "type": "Positive_regulation", "trigger": { "text": [ "activation" ], "offsets": [ [ 800, 810 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "PMID-1964088_T7" } ] }, { "id": "PMID-1964088_E8", "type": "Negative_regulation", "trigger": { "text": [ "unaffected" ], "offsets": [ [ 886, 896 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "PMID-1964088_E7" }, { "role": "Cause", "ref_id": "PMID-1964088_E5" } ] }, { "id": "PMID-1964088_E9", "type": "Negative_regulation", "trigger": { "text": [ "unaffected" ], "offsets": [ [ 886, 896 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "PMID-1964088_E6" }, { "role": "Cause", "ref_id": "PMID-1964088_E5" } ] }, { "id": "PMID-1964088_E10", "type": "Regulation", "trigger": { "text": [ "depending" ], "offsets": [ [ 904, 913 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "PMID-1964088_E11" } ] }, { "id": "PMID-1964088_E11", "type": "Gene_expression", "trigger": { "text": [ "expression" ], "offsets": [ [ 983, 993 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "PMID-1964088_T8" } ] } ]

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[ { "id": "PMID-1972889__text", "type": "abstract", "text": [ "Stimulation of the human immunodeficiency virus type 2 (HIV-2) gene expression by the cytomegalovirus and HIV-2 transactivator gene. \nHuman immunodeficiency virus (HIV) often causes latent infection. Transactivation by some DNA viruses has been implicated in inducing HIV-1 replication and pathogenesis. The transactivator (IE-2) gene of the human cytomegalovirus (CMV) can enhance HIV-2 as well as HIV-1 gene expression in vitro. This inducer can act in concert with the HIV-2 tat gene and T-cell activation in enhancing gene expression in human CD4+ lymphocytes. While the HIV-2 and HIV-1 tat genes and T-cell activators apparently employ independent modes of action, the CMV transactivator in combination with the HIV-2 tat or T-cell activators may employ a gene activation pathway with some common and some distinct components. Both HIV-2 and CMV transactivators enhance HIV-2 gene expression by transcriptional activation involving transcript initiation as well as elongation, with CMV transactivator affecting elongation more than the initiation. A significant proportion of transcripts appear to terminate prematurely in the absence of transactivators. Deletion mutation analysis of the HIV-2 long terminal repeat (LTR) suggests that the element that responds to CMV transactivation in human CD4+ lymphocytes is either a diffuse one or located downstream of the HIV-2 enhancer element. " ], "offsets": [ [ 0, 1393 ] ] } ]

[ { "id": "PMID-1972889_T1", "type": "Protein", "text": [ "IE-2" ], "offsets": [ [ 324, 328 ] ], "normalized": [] }, { "id": "PMID-1972889_T2", "type": "Protein", "text": [ "tat" ], "offsets": [ [ 478, 481 ] ], "normalized": [] }, { "id": "PMID-1972889_T3", "type": "Protein", "text": [ "CD4" ], "offsets": [ [ 547, 550 ] ], "normalized": [] }, { "id": "PMID-1972889_T4", "type": "Protein", "text": [ "tat" ], "offsets": [ [ 591, 594 ] ], "normalized": [] }, { "id": "PMID-1972889_T5", "type": "Protein", "text": [ "tat" ], "offsets": [ [ 723, 726 ] ], "normalized": [] }, { "id": "PMID-1972889_T6", "type": "Protein", "text": [ "CD4" ], "offsets": [ [ 1299, 1302 ] ], "normalized": [] } ]

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[ { "id": "PMID-1981844__text", "type": "abstract", "text": [ "Human immunodeficiency virus type-2 gene expression: two enhancers and their activation by T-cell activators. \nThe human immunodeficiency viruses (HIVs) may include a spectrum of retroviruses with varying potential to infect their host, undergo long periods of latent infection, and induce pathology. Since expression of the viruses is in large part regulated by the sequence elements in their long terminal repeats (LTRs), this study was directed to an analysis of the regulatory elements in the HIV-2 LTR. The HIV-2 LTR was found to contain two enhancers. One of these enhancers is, in part, identical to the HIV-1 enhancer. This enhancer in HIV-1 is the T-cell activation response element; in HIV-2, however, it is the second enhancer that is mainly responsible for activation in response to T-cell activators. The second enhancer interacts with two nuclear binding proteins (85 kD and 27 kD mobility) that appear to be required for optimal enhancer function and activation. Observations such as these encourage the speculation that there may be subtle differences in the regulation of HIV-1 and HIV-2 expression that may be relevant to the possible longer latency and reduced pathogenicity of HIV-2. " ], "offsets": [ [ 0, 1204 ] ] } ]

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[ { "id": "PMID-1984449__text", "type": "abstract", "text": [ "Induction of NF-KB during monocyte differentiation by HIV type 1 infection. \nThe production of human immunodeficiency virus type 1 (HIV-1) progeny was followed in the U937 promonocytic cell line after stimulation either with retinoic acid or PMA, and in purified human monocytes and macrophages. Electrophoretic mobility shift assays and Southwestern blotting experiments were used to detect the binding of cellular transactivation factor NF-KB to the double repeat-KB enhancer sequence located in the long terminal repeat. PMA treatment, and not retinoic acid treatment of the U937 cells acts in inducing NF-KB expression in the nuclei. In nuclear extracts from monocytes or macrophages, induction of NF-KB occurred only if the cells were previously infected with HIV-1. When U937 cells were infected with HIV-1, no induction of NF-KB factor was detected, whereas high level of progeny virions was produced, suggesting that this factor was not required for viral replication. These results indicate that in monocytic cell lineage, HIV-1 could mimic some differentiation/activation stimuli allowing nuclear NF-KB expression. " ], "offsets": [ [ 0, 1125 ] ] } ]

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[ { "id": "PMID-1986254__text", "type": "abstract", "text": [ "Positive and negative regulation of immunoglobulin gene expression by a novel B-cell-specific enhancer element. \nA new B-cell-specific enhancer element has been identified 3' of E4 and the octamerlike motifs in the human immunoglobulin heavy-chain gene enhancer. Tandem copies of this 67-bp MnlI-AluI fragment, when fused to the chloramphenicol acetyltransferase gene driven by the conalbumin promoter, stimulated transcription in B cells but not in Jurkat T cells or HeLa cells. Footprinting analysis revealed that the identical sequence CCGAAACTGAAAAGG, designated E6, was protected by nuclear extracts from B cells, T cells, or HeLa cells. Gel mobility shift assays using a synthetic E6 motif detected a B-cell-specific complex in addition to a ubiquitous band found also in T cells and HeLa cells. In agreement with the results of gel retardation assays, tandem copies of the E6 motif stimulated transcription in ARH77 and Raji cells but not in Jurkat or HeLa cells. Furthermore, a mutant E6 motif lost both in vitro binding activity and in vivo enhancer activity. In striking contrast to the mouse Ig heavy-chain enhancer, in which the octamer motif acts as a B-cell-specific enhancer element, the human enhancer contains an octamerlike sequence with one base substitution which bound octamer-binding proteins with only very low affinity and showed no enhancer activity of its own. Interestingly, the MnlI-AluI fragment could suppress the basal-level activity of the conalbumin promoter in both Jurkat and HeLa cells. Moreover, simian virus 40 enhancer activity was blocked by the MnlI-AluI fragment in HeLa cells but not in B cells. Thus, the novel enhancer element identified in this study is probably a target site for both positive and negative factors. " ], "offsets": [ [ 0, 1763 ] ] } ]

[ { "id": "PMID-1986254_T1", "type": "Protein", "text": [ "chloramphenicol acetyltransferase" ], "offsets": [ [ 329, 362 ] ], "normalized": [] }, { "id": "PMID-1986254_T2", "type": "Protein", "text": [ "E6" ], "offsets": [ [ 567, 569 ] ], "normalized": [] }, { "id": "PMID-1986254_T3", "type": "Protein", "text": [ "E6" ], "offsets": [ [ 880, 882 ] ], "normalized": [] }, { "id": "PMID-1986254_T4", "type": "Protein", "text": [ "E6" ], "offsets": [ [ 993, 995 ] ], "normalized": [] } ]

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[ { "id": "PMID-1987353__text", "type": "abstract", "text": [ "The NF kappa B independent cis-acting sequences in HIV-1 LTR responsive to T-cell activation. \nThe rate of transcription initiation directed by the long terminal repeat (LTR) of HIV-1 increases in response to mitogenic stimuli of T cells. Here we show that the response of the HIV-1 LTR may be governed by two independent sequences located 5' to the site of transcription initiation sequences that bind either NFAT-1 or NF kappa B. The rate of LTR-directed gene expression increased in response to treatment with either a phorbol ester or tumor necrosis factor alpha if either the NFAT-1 or NF kappa B binding sites were deleted, but failed to respond to these mitogenic stimuli if both sequences were absent. The HIV-1 mutant virus containing both NF kappa B and NFAT-1 deletion was able to replicate although at a much decreased growth rate, while the deletion of NFAT-1 alone increased the viral growth rate in Jurkat cells. Neither deletion of NF kappa B nor deletion of NFAT-1 decreased activation of viral replication by phorbol ester. " ], "offsets": [ [ 0, 1042 ] ] } ]

[ { "id": "PMID-1987353_T1", "type": "Protein", "text": [ "NFAT-1" ], "offsets": [ [ 410, 416 ] ], "normalized": [] }, { "id": "PMID-1987353_T2", "type": "Protein", "text": [ "tumor necrosis factor alpha" ], "offsets": [ [ 539, 566 ] ], "normalized": [] }, { "id": "PMID-1987353_T3", "type": "Protein", "text": [ "NFAT-1" ], "offsets": [ [ 581, 587 ] ], "normalized": [] }, { "id": "PMID-1987353_T4", "type": "Protein", "text": [ "NFAT-1" ], "offsets": [ [ 764, 770 ] ], "normalized": [] }, { "id": "PMID-1987353_T5", "type": "Protein", "text": [ "NFAT-1" ], "offsets": [ [ 866, 872 ] ], "normalized": [] }, { "id": "PMID-1987353_T6", "type": "Protein", "text": [ "NFAT-1" ], "offsets": [ [ 975, 981 ] ], "normalized": [] } ]

[ { "id": "PMID-1987353_E1", "type": "Binding", "trigger": { "text": [ "bind" ], "offsets": [ [ 398, 402 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "PMID-1987353_T1" } ] } ]

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[ { "id": "PMID-2006151__text", "type": "abstract", "text": [ "Comparison of constitutive and inducible transcriptional enhancement mediated by kappa B-related sequences: modulation of activity in B cells by human T-cell leukemia virus type I tax gene. \nThe kappa B sequence (GGGACTTTCC) binds a factor, NF-kappa B, that is constitutively found in its functional, DNA binding form only in B lymphocytes. A factor with apparently indistinguishable sequence specificity can be induced in many other cell types, where it is used to regulate inducible gene expression. For example, kappa B-related sequences have been shown to be important for the transcription of a few inducible genes, such as the interleukin 2 receptor alpha-chain gene and the beta-interferon gene. However, these genes are not constitutively active in B lymphocytes, suggesting that other regulatory mechanisms must play a role in determining the patterns of expression. We have investigated the constitutive and inducible transcriptional activity mediated by five kappa B-related sequence elements in two different cell types. We show that in S194 plasma cells the activity of each element correlates well with the relative affinity of B-cell-derived NF-kappa B for that element. This leads to significantly lower transcription enhancement by sites derived from the interleukin 2 receptor or T-cell receptor genes in S194 cells. However, in either EL-4 (T) cells or S194 cells, both lower-affinity sites can be significantly induced by the tax gene product of human T-cell leukemia virus type I, showing that NF-kappa B activity can be modulated even in a B-cell line that constitutively expresses this factor. " ], "offsets": [ [ 0, 1617 ] ] } ]

[ { "id": "PMID-2006151_T1", "type": "Protein", "text": [ "tax" ], "offsets": [ [ 180, 183 ] ], "normalized": [] }, { "id": "PMID-2006151_T2", "type": "Protein", "text": [ "interleukin 2 receptor alpha-chain" ], "offsets": [ [ 633, 667 ] ], "normalized": [] }, { "id": "PMID-2006151_T3", "type": "Protein", "text": [ "beta-interferon" ], "offsets": [ [ 681, 696 ] ], "normalized": [] }, { "id": "PMID-2006151_T4", "type": "Protein", "text": [ "tax" ], "offsets": [ [ 1446, 1449 ] ], "normalized": [] } ]

[ { "id": "PMID-2006151_E1", "type": "Transcription", "trigger": { "text": [ "transcription" ], "offsets": [ [ 581, 594 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "PMID-2006151_T3" } ] }, { "id": "PMID-2006151_E2", "type": "Transcription", "trigger": { "text": [ "transcription" ], "offsets": [ [ 581, 594 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "PMID-2006151_T2" } ] }, { "id": "PMID-2006151_E3", "type": "Positive_regulation", "trigger": { "text": [ "active" ], "offsets": [ [ 747, 753 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "PMID-2006151_T3" } ] }, { "id": "PMID-2006151_E4", "type": "Positive_regulation", "trigger": { "text": [ "active" ], "offsets": [ [ 747, 753 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "PMID-2006151_T2" } ] } ]

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[ { "id": "PMID-2006423__text", "type": "abstract", "text": [ "Isolation of a rel-related human cDNA that potentially encodes the 65-kD subunit of NF-kappa B [published erratum appears in Science 1991 Oct 4;254(5028):11] \nA DNA probe that spanned a domain conserved among the proto-oncogene c-rel, the Drosophila morphogen dorsal, and the p50 DNA binding subunit of NF-kappa B was generated from Jurkat T cell complementary DNA with the polymerase chain reaction (PCR) and degenerate oligonucleotides. This probe was used to identify a rel-related complementary DNA that hybridized to a 2.6-kilobase messenger RNA present in human T and B lymphocytes. In vitro transcription and translation of the complementary DNA resulted in the synthesis of a protein with an apparent molecular size of 65 kilodaltons (kD). The translated protein showed weak DNA binding with a specificity for the kappa B binding motif. This protein-DNA complex comigrated with the complex obtained with the purified human p65 NF-kappa B subunit and binding was inhibited by I kappa B-alpha and -beta proteins. In addition, the 65-kD protein associated with the p50 subunit of NF-kappa B and the kappa B probe to form a complex with the same electrophoretic mobility as the NF-kappa B-DNA complex. Therefore the rel-related 65-kD protein may represent the p65 subunit of the active NF-kappa B transcription factor complex. " ], "offsets": [ [ 0, 1331 ] ] } ]

[ { "id": "PMID-2006423_T1", "type": "Protein", "text": [ "c-rel" ], "offsets": [ [ 228, 233 ] ], "normalized": [] }, { "id": "PMID-2006423_T2", "type": "Protein", "text": [ "p50" ], "offsets": [ [ 276, 279 ] ], "normalized": [] }, { "id": "PMID-2006423_T3", "type": "Protein", "text": [ "p65" ], "offsets": [ [ 931, 934 ] ], "normalized": [] }, { "id": "PMID-2006423_T4", "type": "Protein", "text": [ "I kappa B-alpha" ], "offsets": [ [ 983, 998 ] ], "normalized": [] }, { "id": "PMID-2006423_T5", "type": "Protein", "text": [ "-beta" ], "offsets": [ [ 1003, 1008 ] ], "normalized": [] }, { "id": "PMID-2006423_T6", "type": "Protein", "text": [ "p50" ], "offsets": [ [ 1070, 1073 ] ], "normalized": [] }, { "id": "PMID-2006423_T7", "type": "Protein", "text": [ "p65" ], "offsets": [ [ 1264, 1267 ] ], "normalized": [] } ]

[ { "id": "PMID-2006423_E1", "type": "Binding", "trigger": { "text": [ "associated" ], "offsets": [ [ 1050, 1060 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "PMID-2006423_T6" } ] } ]

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[ { "id": "PMID-2017177__text", "type": "abstract", "text": [ "Murine and human T-lymphocyte GATA-3 factors mediate transcription through a cis-regulatory element within the human T-cell receptor delta gene enhancer. \nA family of transcriptional activators has recently been identified in chickens; these transcriptional activators recognize a common consensus motif (WGATAR) through a conserved C4 zinc finger DNA-binding domain. One of the members of this multigene family, cGATA-3, is most abundantly expressed in the T-lymphocyte cell lineage. Analysis of human and murine GATA-3 factors shows a striking degree of amino acid sequence identity and similar patterns of tissue specificity of expression in these three organisms. The murine and human factors are abundantly expressed in a variety of human and murine T-cell lines and can activate transcription through a tissue-specific GATA-binding site identified within the human T-cell receptor delta gene enhancer. We infer that the murine and human GATA-3 proteins play a central and highly conserved role in vertebrate T-cell-specific transcriptional regulation. " ], "offsets": [ [ 0, 1058 ] ] } ]

[ { "id": "PMID-2017177_T1", "type": "Protein", "text": [ "GATA-3" ], "offsets": [ [ 30, 36 ] ], "normalized": [] }, { "id": "PMID-2017177_T2", "type": "Protein", "text": [ "cGATA-3" ], "offsets": [ [ 413, 420 ] ], "normalized": [] }, { "id": "PMID-2017177_T3", "type": "Protein", "text": [ "GATA-3" ], "offsets": [ [ 514, 520 ] ], "normalized": [] }, { "id": "PMID-2017177_T4", "type": "Protein", "text": [ "GATA-3" ], "offsets": [ [ 943, 949 ] ], "normalized": [] } ]

[ { "id": "PMID-2017177_E1", "type": "Binding", "trigger": { "text": [ "through" ], "offsets": [ [ 67, 74 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "PMID-2017177_T1" } ] }, { "id": "PMID-2017177_E2", "type": "Gene_expression", "trigger": { "text": [ "expressed" ], "offsets": [ [ 441, 450 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "PMID-2017177_T2" } ] }, { "id": "PMID-2017177_E3", "type": "Gene_expression", "trigger": { "text": [ "expression" ], "offsets": [ [ 631, 641 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "PMID-2017177_T3" } ] }, { "id": "PMID-2017177_E4", "type": "Gene_expression", "trigger": { "text": [ "expressed" ], "offsets": [ [ 712, 721 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "PMID-2017177_T3" } ] } ]

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[ { "id": "PMID-2017258__text", "type": "abstract", "text": [ "Processing of the precursor of NF-kappa B by the HIV-1 protease during acute infection. \nTranscription of the human immunodeficiency virus type-1 (HIV-1) genome is regulated in part by cellular factors and is stimulated by activation of latently infected T cells. T-cell activation also correlates with the induction of the factor NF-kappa B which binds to two adjacent sites in the HIV-1 long terminal repeat. This factor consists of two DNA-binding subunits of relative molecular mass 50,000 (50K) associated with two 65K subunits. It is located in the nucleus in mature B cells, but is present in other cell types as an inactive cytoplasmic complex. External stimuli, including those that activate T cells, result in nuclear translocation of active NF-kappa B. The cloning of the complementary DNA for the 50K subunit helped to identify an exclusively cytoplasmic 105K precursor (p105) (V.B., P.K. and A.I., manuscript submitted). The expression of active NF-kappa B might therefore also be regulated by the extent of processing of p105. Because HIV-1 requires active NF-kappa B for efficient transcription, we tested the effect of HIV-1 infection on the processing of the human 105K precursor. We show here that the HIV-1 protease can process p105 and increases levels of active nuclear NF-kappa B complex. " ], "offsets": [ [ 0, 1311 ] ] } ]

[ { "id": "PMID-2017258_T1", "type": "Protein", "text": [ "protease" ], "offsets": [ [ 55, 63 ] ], "normalized": [] }, { "id": "PMID-2017258_T2", "type": "Protein", "text": [ "50K subunit" ], "offsets": [ [ 809, 820 ] ], "normalized": [] }, { "id": "PMID-2017258_T3", "type": "Protein", "text": [ "p105" ], "offsets": [ [ 883, 887 ] ], "normalized": [] }, { "id": "PMID-2017258_T4", "type": "Protein", "text": [ "p105" ], "offsets": [ [ 1035, 1039 ] ], "normalized": [] }, { "id": "PMID-2017258_T5", "type": "Protein", "text": [ "protease" ], "offsets": [ [ 1226, 1234 ] ], "normalized": [] }, { "id": "PMID-2017258_T6", "type": "Protein", "text": [ "p105" ], "offsets": [ [ 1247, 1251 ] ], "normalized": [] } ]

[ { "id": "PMID-2017258_E1", "type": "Protein_catabolism", "trigger": { "text": [ "process" ], "offsets": [ [ 1239, 1246 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "PMID-2017258_T6" } ] }, { "id": "PMID-2017258_E2", "type": "Positive_regulation", "trigger": { "text": [ "process" ], "offsets": [ [ 1239, 1246 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "PMID-2017258_E1" }, { "role": "Cause", "ref_id": "PMID-2017258_T5" } ] } ]

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[ { "id": "PMID-2023633__text", "type": "abstract", "text": [ "HIV enhancer activity perpetuated by NF-kappa B induction on infection of monocytes [see comments] \nPermissiveness to replication of human immunodeficiency virus (HIV) differs in T lymphocytes and macrophages. In T cells, HIV transcription is poorly detected in vivo. Cloned, normal T lymphocytes show very little, if any, basal activity of the HIV enhancer and low nuclear expression of NF-kappa B, a potent transcriptional activator of the HIV enhancer. In contrast, fixed tissue macrophages express detectable HIV proteins, indicating permanent virus transcription. One explanation for the perpetuation of virus infection in macrophages could be sustained nuclear NF-kappa B expression. However, the U937 monocytic cell line, which is fully permissive to HIV replication, is known to express only low levels of nuclear NF-kappa B. We show here that chronic HIV infection results in both induction of a nuclear factor with antigenic properties indistinguishable from those of NF-kappa B and permanently increased HIV enhancer activity. This phenomenon, which is independent of tumour necrosis factor, is associated with HIV replication, and is thus likely to explain at least in part the perpetuation of HIV infection in monocytes. " ], "offsets": [ [ 0, 1234 ] ] } ]

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[ { "id": "PMID-2026605__text", "type": "abstract", "text": [ "Tissue-specific expression of the platelet GPIIb gene. \nOne of the major objectives in the study of thrombogenesis is to determine the mechanisms by which a hematopoietic progenitor is activated and committed to the megakaryocytic lineage. Recent development of primary cultures of human megakaryocytes and the molecular cloning of genes that are specific to this lineage offer the possibility of getting some insights into the genetic mechanisms that control megakaryocytopoiesis. One gene of interest is the glycoprotein IIb (GPIIb) gene; GPIIb, the alpha subunit of the platelet cytoadhesin GPIIb-IIIa, is produced in megakaryocytes at an early stage of the differentiation, whereas the other subunit of this complex, GPIIIa, is expressed in other cells. For these reasons, the 5'-flanking region of the GPIIb gene was used to identify the regions that interact with DNA-binding nuclear factors. A fragment extending from -643 to +33 is capable of controlling the tissue-specific expression of the CAT gene in transfection experiments. Within this region, we have identified several sequences that are implicated in DNA protein interactions as shown in DNAse I footprints and gel mobility shift assays. One region, centered at -54, is similar to a nuclear factor E1-binding site, and a region located at position -233 contains a CCAAT motif. Two domains centered at positions -345 and -540, respectively, bind proteins that are present in megakaryocytic cells and nonrelated cells as well. Finally, two other domains, located at positions -460 and -510, interact with proteins that are only present in megakaryocytic cells. In addition, deletion of the region containing these two domains results in a significant decrease of the promoter activity. It is very likely that these domains bind megakaryocyte-specific nuclear proteins acting as positive transcription factors. " ], "offsets": [ [ 0, 1876 ] ] } ]

[ { "id": "PMID-2026605_T1", "type": "Protein", "text": [ "GPIIb" ], "offsets": [ [ 43, 48 ] ], "normalized": [] }, { "id": "PMID-2026605_T2", "type": "Protein", "text": [ "glycoprotein IIb" ], "offsets": [ [ 510, 526 ] ], "normalized": [] }, { "id": "PMID-2026605_T3", "type": "Protein", "text": [ "GPIIb" ], "offsets": [ [ 528, 533 ] ], "normalized": [] }, { "id": "PMID-2026605_T4", "type": "Protein", "text": [ "GPIIb" ], "offsets": [ [ 541, 546 ] ], "normalized": [] }, { "id": "PMID-2026605_T5", "type": "Protein", "text": [ "GPIIIa" ], "offsets": [ [ 721, 727 ] ], "normalized": [] }, { "id": "PMID-2026605_T6", "type": "Protein", "text": [ "GPIIb" ], "offsets": [ [ 807, 812 ] ], "normalized": [] }, { "id": "PMID-2026605_T7", "type": "Protein", "text": [ "CAT" ], "offsets": [ [ 1001, 1004 ] ], "normalized": [] }, { "id": "PMID-2026605_T8", "type": "Protein", "text": [ "nuclear factor E1" ], "offsets": [ [ 1251, 1268 ] ], "normalized": [] }, { "id": "PMID-2026605_T12", "type": "Entity", "text": [ "5'-flanking region" ], "offsets": [ [ 781, 799 ] ], "normalized": [] } ]

[ { "id": "PMID-2026605_E1", "type": "Gene_expression", "trigger": { "text": [ "expression" ], "offsets": [ [ 16, 26 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "PMID-2026605_T1" } ] }, { "id": "PMID-2026605_E2", "type": "Gene_expression", "trigger": { "text": [ "produced" ], "offsets": [ [ 609, 617 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "PMID-2026605_T4" } ] }, { "id": "PMID-2026605_E3", "type": "Gene_expression", "trigger": { "text": [ "expressed" ], "offsets": [ [ 732, 741 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "PMID-2026605_T5" } ] }, { "id": "PMID-2026605_E4", "type": "Binding", "trigger": { "text": [ "interact" ], "offsets": [ [ 856, 864 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "PMID-2026605_T6" }, { "role": "Site", "ref_id": "PMID-2026605_T12" } ] }, { "id": "PMID-2026605_E5", "type": "Regulation", "trigger": { "text": [ "capable of controlling" ], "offsets": [ [ 940, 962 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "PMID-2026605_E6" } ] }, { "id": "PMID-2026605_E6", "type": "Gene_expression", "trigger": { "text": [ "expression" ], "offsets": [ [ 983, 993 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "PMID-2026605_T7" } ] } ]

[ { "id": "PMID-2026605_1", "entity_ids": [ "PMID-2026605_T2", "PMID-2026605_T3" ] } ]

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[ { "id": "PMID-2039752__text", "type": "abstract", "text": [ "Cortivazol mediated induction of glucocorticoid receptor messenger ribonucleic acid in wild-type and dexamethasone-resistant human leukemic (CEM) cells. \nCortivazol is a phenylpyrazolo glucocorticoid of high potency and unusual structure. In both wild-type and highly dexamethasone(dex)-resistant clones of the human leukemic cell line CEM, exposure to cortivazol leads to cell death. It has been shown recently that in wild-type CEM cells but not in a dex-resistant, glucocorticoid receptor(GR)-defective clone ICR-27 TK-3, dex induces GR mRNA. To test the hypothesis that cortivazol acts in dex-resistant cells by making use of the residual GR found there, wild-type and dex-resistant clones were treated with various concentrations of cortivazol and induction of GR mRNA was studied. Cortivazol significantly induced GR mRNA in the normal CEM-C7 as well as in two classes of dex-resistant clones, although the dex-resistant clones needed at least 10 times more cortivazol than the normal cells for significant GR mRNA induction. Increased levels of GR mRNA were noticed as early as 3 h after treatment. A general correlation between induction of GR mRNA and lysis of the normal and dex-resistant cells was found. Positive induction of GR mRNA might be one of the earliest crucial steps in the lysis of normal and dex-resistant CEM cells, or might serve as a marker for the process. However, the lysis pathway in the dex-resistant cells is defective in that dex-resistant clones needed significantly more cortivazol than the normal cells for lysis of the cells. " ], "offsets": [ [ 0, 1564 ] ] } ]

[ { "id": "PMID-2039752_T1", "type": "Protein", "text": [ "glucocorticoid receptor" ], "offsets": [ [ 33, 56 ] ], "normalized": [] }, { "id": "PMID-2039752_T2", "type": "Protein", "text": [ "glucocorticoid receptor" ], "offsets": [ [ 468, 491 ] ], "normalized": [] }, { "id": "PMID-2039752_T3", "type": "Protein", "text": [ "GR" ], "offsets": [ [ 492, 494 ] ], "normalized": [] }, { "id": "PMID-2039752_T4", "type": "Protein", "text": [ "GR" ], "offsets": [ [ 537, 539 ] ], "normalized": [] }, { "id": "PMID-2039752_T5", "type": "Protein", "text": [ "GR" ], "offsets": [ [ 643, 645 ] ], "normalized": [] }, { "id": "PMID-2039752_T6", "type": "Protein", "text": [ "GR" ], "offsets": [ [ 766, 768 ] ], "normalized": [] }, { "id": "PMID-2039752_T7", "type": "Protein", "text": [ "GR" ], "offsets": [ [ 820, 822 ] ], "normalized": [] }, { "id": "PMID-2039752_T8", "type": "Protein", "text": [ "GR" ], "offsets": [ [ 1013, 1015 ] ], "normalized": [] }, { "id": "PMID-2039752_T9", "type": "Protein", "text": [ "GR" ], "offsets": [ [ 1052, 1054 ] ], "normalized": [] }, { "id": "PMID-2039752_T10", "type": "Protein", "text": [ "GR" ], "offsets": [ [ 1149, 1151 ] ], "normalized": [] }, { "id": "PMID-2039752_T11", "type": "Protein", "text": [ "GR" ], "offsets": [ [ 1238, 1240 ] ], "normalized": [] } ]

[ { "id": "PMID-2039752_E1", "type": "Positive_regulation", "trigger": { "text": [ "induction" ], "offsets": [ [ 20, 29 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "PMID-2039752_T1" } ] }, { "id": "PMID-2039752_E2", "type": "Positive_regulation", "trigger": { "text": [ "induces" ], "offsets": [ [ 529, 536 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "PMID-2039752_T4" } ] }, { "id": "PMID-2039752_E3", "type": "Positive_regulation", "trigger": { "text": [ "induction" ], "offsets": [ [ 753, 762 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "PMID-2039752_T6" } ] }, { "id": "PMID-2039752_E4", "type": "Positive_regulation", "trigger": { "text": [ "induced" ], "offsets": [ [ 812, 819 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "PMID-2039752_T7" } ] }, { "id": "PMID-2039752_E5", "type": "Positive_regulation", "trigger": { "text": [ "induction" ], "offsets": [ [ 1021, 1030 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "PMID-2039752_T8" } ] }, { "id": "PMID-2039752_E6", "type": "Positive_regulation", "trigger": { "text": [ "Increased" ], "offsets": [ [ 1032, 1041 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "PMID-2039752_E7" } ] }, { "id": "PMID-2039752_E7", "type": "Transcription", "trigger": { "text": [ "levels" ], "offsets": [ [ 1042, 1048 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "PMID-2039752_T9" } ] }, { "id": "PMID-2039752_E8", "type": "Positive_regulation", "trigger": { "text": [ "induction" ], "offsets": [ [ 1136, 1145 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "PMID-2039752_T10" } ] }, { "id": "PMID-2039752_E9", "type": "Positive_regulation", "trigger": { "text": [ "Positive induction" ], "offsets": [ [ 1216, 1234 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "PMID-2039752_T11" } ] } ]

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[ { "id": "PMID-2056282__text", "type": "abstract", "text": [ "Human tumor necrosis factor alpha gene regulation in phorbol ester stimulated T and B cell lines. \nThe minimal region of the human tumor necrosis factor alpha (TNF-alpha) gene promoter necessary for its transcriptional induction by phorbol esters (PMA) in human T and B lymphocyte cell lines has been localized between -52 and +89 nucleotides (nt) relative to the gene's transcriptional start site. Comparison of these sequences to those required to mediate virus or lipopolysaccharide (LPS) induction of the gene reveal significant differences, and thus, the sequence requirements for PMA induction are distinct from those that mediate induction by virus or LPS. Although three sites in the TNF-alpha promoter (kappa 1, kappa 2, and kappa 3) specifically bind the transcription factor NF-kappa B in lymphoid nuclear extracts, TNF-alpha mRNA induction by PMA does not correlate with NF-kappa B binding activities displayed by different T and B cell lines. Moreover, kappa 1-kappa 3 can each be deleted from the TNF-alpha promoter with little effect on the gene's inducibility by PMA. Therefore, TNF-alpha mRNA induction by PMA, like its induction by virus and LPS, is not primarily mediated by NF-kappa B, but rather is mediated through other sequences and protein factors. Surprisingly, multimers of kappa 1-kappa 3 can confer PMA inducibility on a heterologous promoter in a B (Raji), but not a T (HUT78) cell line. However they are not functional on a truncated TNF-alpha promoter, indicating that promoter context and cell type specificity influence the PMA inducible function of these NF-kappa B binding sites. " ], "offsets": [ [ 0, 1616 ] ] } ]

[ { "id": "PMID-2056282_T1", "type": "Protein", "text": [ "tumor necrosis factor alpha" ], "offsets": [ [ 6, 33 ] ], "normalized": [] }, { "id": "PMID-2056282_T2", "type": "Protein", "text": [ "tumor necrosis factor alpha" ], "offsets": [ [ 131, 158 ] ], "normalized": [] }, { "id": "PMID-2056282_T3", "type": "Protein", "text": [ "TNF-alpha" ], "offsets": [ [ 160, 169 ] ], "normalized": [] }, { "id": "PMID-2056282_T4", "type": "Protein", "text": [ "TNF-alpha" ], "offsets": [ [ 692, 701 ] ], "normalized": [] }, { "id": "PMID-2056282_T5", "type": "Protein", "text": [ "TNF-alpha" ], "offsets": [ [ 827, 836 ] ], "normalized": [] }, { "id": "PMID-2056282_T6", "type": "Protein", "text": [ "TNF-alpha" ], "offsets": [ [ 1011, 1020 ] ], "normalized": [] }, { "id": "PMID-2056282_T7", "type": "Protein", "text": [ "TNF-alpha" ], "offsets": [ [ 1095, 1104 ] ], "normalized": [] }, { "id": "PMID-2056282_T8", "type": "Protein", "text": [ "TNF-alpha" ], "offsets": [ [ 1465, 1474 ] ], "normalized": [] }, { "id": "PMID-2056282_T10", "type": "Entity", "text": [ "promoter" ], "offsets": [ [ 176, 184 ] ], "normalized": [] }, { "id": "PMID-2056282_T18", "type": "Entity", "text": [ "kappa 1" ], "offsets": [ [ 712, 719 ] ], "normalized": [] }, { "id": "PMID-2056282_T19", "type": "Entity", "text": [ "kappa 2" ], "offsets": [ [ 721, 728 ] ], "normalized": [] }, { "id": "PMID-2056282_T20", "type": "Entity", "text": [ "kappa 3" ], "offsets": [ [ 734, 741 ] ], "normalized": [] } ]

[ { "id": "PMID-2056282_E1", "type": "Regulation", "trigger": { "text": [ "regulation" ], "offsets": [ [ 39, 49 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "PMID-2056282_T1" } ] }, { "id": "PMID-2056282_E2", "type": "Positive_regulation", "trigger": { "text": [ "necessary" ], "offsets": [ [ 185, 194 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "PMID-2056282_E3" }, { "role": "Cause", "ref_id": "PMID-2056282_T3" }, { "role": "CSite", "ref_id": "PMID-2056282_T10" } ] }, { "id": "PMID-2056282_E3", "type": "Positive_regulation", "trigger": { "text": [ "transcriptional induction" ], "offsets": [ [ 203, 228 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "PMID-2056282_T3" } ] }, { "id": "PMID-2056282_E4", "type": "Positive_regulation", "trigger": { "text": [ "mediate" ], "offsets": [ [ 450, 457 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "PMID-2056282_E5" } ] }, { "id": "PMID-2056282_E5", "type": "Positive_regulation", "trigger": { "text": [ "induction" ], "offsets": [ [ 492, 501 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "PMID-2056282_T3" } ] }, { "id": "PMID-2056282_E6", "type": "Positive_regulation", "trigger": { "text": [ "requirements" ], "offsets": [ [ 569, 581 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "PMID-2056282_E3" } ] }, { "id": "PMID-2056282_E7", "type": "Positive_regulation", "trigger": { "text": [ "mediate" ], "offsets": [ [ 629, 636 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "PMID-2056282_E8" } ] }, { "id": "PMID-2056282_E8", "type": "Positive_regulation", "trigger": { "text": [ "induction" ], "offsets": [ [ 637, 646 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "PMID-2056282_T3" } ] }, { "id": "PMID-2056282_E9", "type": "Binding", "trigger": { "text": [ "bind" ], "offsets": [ [ 756, 760 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "PMID-2056282_T4" }, { "role": "Site", "ref_id": "PMID-2056282_T20" } ] }, { "id": "PMID-2056282_E10", "type": "Binding", "trigger": { "text": [ "bind" ], "offsets": [ [ 756, 760 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "PMID-2056282_T4" }, { "role": "Site", "ref_id": "PMID-2056282_T18" } ] }, { "id": "PMID-2056282_E11", "type": "Binding", "trigger": { "text": [ "bind" ], "offsets": [ [ 756, 760 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "PMID-2056282_T4" }, { "role": "Site", "ref_id": "PMID-2056282_T19" } ] }, { "id": "PMID-2056282_E12", "type": "Positive_regulation", "trigger": { "text": [ "induction" ], "offsets": [ [ 842, 851 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "PMID-2056282_T5" } ] }, { "id": "PMID-2056282_E13", "type": "Positive_regulation", "trigger": { "text": [ "inducibility" ], "offsets": [ [ 1063, 1075 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "PMID-2056282_T6" } ] }, { "id": "PMID-2056282_E14", "type": "Positive_regulation", "trigger": { "text": [ "induction" ], "offsets": [ [ 1110, 1119 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "PMID-2056282_T7" } ] }, { "id": "PMID-2056282_E15", "type": "Positive_regulation", "trigger": { "text": [ "induction" ], "offsets": [ [ 1137, 1146 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "PMID-2056282_T7" } ] }, { "id": "PMID-2056282_E16", "type": "Positive_regulation", "trigger": { "text": [ "mediated" ], "offsets": [ [ 1182, 1190 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "PMID-2056282_E15" } ] }, { "id": "PMID-2056282_E17", "type": "Positive_regulation", "trigger": { "text": [ "mediated" ], "offsets": [ [ 1182, 1190 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "PMID-2056282_E14" } ] } ]

[ { "id": "PMID-2056282_1", "entity_ids": [ "PMID-2056282_T3", "PMID-2056282_T2" ] } ]

[]

[ { "id": "PMID-2065663__text", "type": "abstract", "text": [ "Reactive oxygen intermediates as apparently widely used messengers in the activation of the NF-kappa B transcription factor and HIV-1. \nHydrogen peroxide and oxygen radicals are agents commonly produced during inflammatory processes. In this study, we show that micromolar concentrations of H2O2 can induce the expression and replication of HIV-1 in a human T cell line. The effect is mediated by the NF-kappa B transcription factor which is potently and rapidly activated by an H2O2 treatment of cells from its inactive cytoplasmic form. N-acetyl-L-cysteine (NAC), a well characterized antioxidant which counteracts the effects of reactive oxygen intermediates (ROI) in living cells, prevented the activation of NF-kappa B by H2O2. NAC and other thiol compounds also blocked the activation of NF-kappa B by cycloheximide, double-stranded RNA, calcium ionophore, TNF-alpha, active phorbol ester, interleukin-1, lipopolysaccharide and lectin. This suggests that diverse agents thought to activate NF-kappa B by distinct intracellular pathways might all act through a common mechanism involving the synthesis of ROI. ROI appear to serve as messengers mediating directly or indirectly the release of the inhibitory subunit I kappa B from NF-kappa B. " ], "offsets": [ [ 0, 1247 ] ] } ]

[ { "id": "PMID-2065663_T1", "type": "Protein", "text": [ "TNF-alpha" ], "offsets": [ [ 863, 872 ] ], "normalized": [] } ]

[]

[]

[]

[ { "id": "PMID-2072454__text", "type": "abstract", "text": [ "Contribution of NF-kappa B and Sp1 binding motifs to the replicative capacity of human immunodeficiency virus type 1: distinct patterns of viral growth are determined by T-cell types. \nStarting with a replication-incompetent molecular clone of human immunodeficiency virus type 1, lacking all the NF-kappa B and Sp1 binding sites present in the native long terminal repeat (LTR), proviruses containing reconstructed LTRs with individual or combinations of NF-kappa B and Sp1 elements were generated and evaluated for their capacity to produce virus progeny following transfection-cocultivation. Virus stocks obtained from these experiments exhibited a continuum of replicative capacities in different human T-cell types depending on which element(s) was present in the LTR. For example, in experiments involving proviral clones with LTRs containing one or two NF-kappa B elements (and no Sp1 binding sites), a hierarchy of cellular permissivity to virus replication (peripheral blood lymphocytes = MT4 greater than H9 greater than CEM greater than Jurkat) was observed. Of note was the associated emergence of second-site LTR revertants which involved an alteration of the TATA box. These results suggest that the human immunodeficiency virus type 1 LTR possesses functional redundancy which ensures virus replication in different T-cell types and is capable of changing depending on the particular combination of transcriptional factors present. " ], "offsets": [ [ 0, 1447 ] ] } ]

[ { "id": "PMID-2072454_T1", "type": "Protein", "text": [ "Sp1" ], "offsets": [ [ 31, 34 ] ], "normalized": [] }, { "id": "PMID-2072454_T2", "type": "Protein", "text": [ "Sp1" ], "offsets": [ [ 312, 315 ] ], "normalized": [] }, { "id": "PMID-2072454_T3", "type": "Protein", "text": [ "Sp1" ], "offsets": [ [ 471, 474 ] ], "normalized": [] }, { "id": "PMID-2072454_T4", "type": "Protein", "text": [ "Sp1" ], "offsets": [ [ 888, 891 ] ], "normalized": [] } ]

[]

[]

[]

[ { "id": "PMID-2083253__text", "type": "abstract", "text": [ "Purification of TCF-1 alpha, a T-cell-specific transcription factor that activates the T-cell receptor C alpha gene enhancer in a context-dependent manner. \nThe differentiation of T cells into functionally diverse subpopulations is controlled in part, by transcriptional activation and silencing; however, little is known in detail about the proteins that influence this developmental process. We have purified a new T-cell-specific factor, TCF-1 alpha, that is implicated in the activation of genes encoding a major component of the human T-cell receptor (TCR). TCF-1 alpha, originally identified and purified through its binding sites on the HIV-1 promoter, was found to bind to the TCR alpha enhancer and to promoters for several genes expressed at significantly earlier stages of T-cell development than the TCR alpha gene (e.g., p56lck and CD3 delta). Sequences related to the TCF-1 alpha binding motif (5'-GGCACCCTTTGA-3') are also found in the human TCR delta (and possibly TCR beta) enhancers. Southwestern and gel renaturation experiments with the use of purified protein fractions revealed that TCF-1 alpha activity is derived from a family of 57- to 53-kD proteins that are abundantly expressed in mature and immature T-cell lines (Jurkat, CCRF-CEM) and not in mature B cells (JY, Namalwa) or nonlymphoid (HeLa) cell lines. A small 95-bp fragment of the TCR alpha control region that contains the TCF-1 alpha binding site juxtaposed between a cAMP-response element (the CRE or T alpha 1 motif) and the binding site for a distinct lymphoid-specific protein (TCF-2 alpha) behaved as a potent T-cell-specific enhancer in vivo. Tandem copies of this enhancer functioned synergistically in mature (Jurkat) T-cell lines as well as resting and activated immature (CCRF-CEM) T-cell lines. Mutation of the TCF-1 alpha binding site diminished enhancer activity and disrupted the synergism observed in vivo between tandem enhancer repeats. The TCF-1 alpha binding site was also required for TCR alpha enhancer activity in transcriptionally active extracts from Jurkat but not HeLa cells, confirming that TCF-1 alpha is a T-cell-specific transcription factor. Curiously, the TCF-1 alpha binding element was inactive in vivo when removed from its neighboring elements on the TCR alpha enhancer and positioned in one or more copies upstream of a heterologous promoter. Thus, the transcriptional activity of TCF-1 alpha appears to depend on the TCF-2 alpha and T alpha 1 (CREB) transcription factors and the context of its binding site within the TCR alpha enhancer. " ], "offsets": [ [ 0, 2563 ] ] } ]

[ { "id": "PMID-2083253_T1", "type": "Protein", "text": [ "TCF-1 alpha" ], "offsets": [ [ 16, 27 ] ], "normalized": [] }, { "id": "PMID-2083253_T2", "type": "Protein", "text": [ "T-cell receptor C alpha" ], "offsets": [ [ 87, 110 ] ], "normalized": [] }, { "id": "PMID-2083253_T3", "type": "Protein", "text": [ "TCF-1 alpha" ], "offsets": [ [ 441, 452 ] ], "normalized": [] }, { "id": "PMID-2083253_T4", "type": "Protein", "text": [ "TCF-1 alpha" ], "offsets": [ [ 563, 574 ] ], "normalized": [] }, { "id": "PMID-2083253_T5", "type": "Protein", "text": [ "TCR alpha" ], "offsets": [ [ 685, 694 ] ], "normalized": [] }, { "id": "PMID-2083253_T6", "type": "Protein", "text": [ "TCR alpha" ], "offsets": [ [ 812, 821 ] ], "normalized": [] }, { "id": "PMID-2083253_T7", "type": "Protein", "text": [ "p56lck" ], "offsets": [ [ 834, 840 ] ], "normalized": [] }, { "id": "PMID-2083253_T8", "type": "Protein", "text": [ "CD3 delta" ], "offsets": [ [ 845, 854 ] ], "normalized": [] }, { "id": "PMID-2083253_T9", "type": "Protein", "text": [ "TCF-1 alpha" ], "offsets": [ [ 882, 893 ] ], "normalized": [] }, { "id": "PMID-2083253_T10", "type": "Protein", "text": [ "TCR delta" ], "offsets": [ [ 957, 966 ] ], "normalized": [] }, { "id": "PMID-2083253_T11", "type": "Protein", "text": [ "TCR beta" ], "offsets": [ [ 981, 989 ] ], "normalized": [] }, { "id": "PMID-2083253_T12", "type": "Protein", "text": [ "TCF-1 alpha" ], "offsets": [ [ 1105, 1116 ] ], "normalized": [] }, { "id": "PMID-2083253_T13", "type": "Protein", "text": [ "TCR alpha" ], "offsets": [ [ 1365, 1374 ] ], "normalized": [] }, { "id": "PMID-2083253_T14", "type": "Protein", "text": [ "TCF-1 alpha" ], "offsets": [ [ 1408, 1419 ] ], "normalized": [] }, { "id": "PMID-2083253_T15", "type": "Protein", "text": [ "TCF-2 alpha" ], "offsets": [ [ 1568, 1579 ] ], "normalized": [] }, { "id": "PMID-2083253_T16", "type": "Protein", "text": [ "TCF-1 alpha" ], "offsets": [ [ 1808, 1819 ] ], "normalized": [] }, { "id": "PMID-2083253_T17", "type": "Protein", "text": [ "TCF-1 alpha" ], "offsets": [ [ 1944, 1955 ] ], "normalized": [] }, { "id": "PMID-2083253_T18", "type": "Protein", "text": [ "TCR alpha" ], "offsets": [ [ 1991, 2000 ] ], "normalized": [] }, { "id": "PMID-2083253_T19", "type": "Protein", "text": [ "TCF-1 alpha" ], "offsets": [ [ 2104, 2115 ] ], "normalized": [] }, { "id": "PMID-2083253_T20", "type": "Protein", "text": [ "TCF-1 alpha" ], "offsets": [ [ 2174, 2185 ] ], "normalized": [] }, { "id": "PMID-2083253_T21", "type": "Protein", "text": [ "TCR alpha" ], "offsets": [ [ 2273, 2282 ] ], "normalized": [] }, { "id": "PMID-2083253_T22", "type": "Protein", "text": [ "TCF-1 alpha" ], "offsets": [ [ 2404, 2415 ] ], "normalized": [] }, { "id": "PMID-2083253_T23", "type": "Protein", "text": [ "TCF-2 alpha" ], "offsets": [ [ 2441, 2452 ] ], "normalized": [] }, { "id": "PMID-2083253_T24", "type": "Protein", "text": [ "T alpha 1" ], "offsets": [ [ 2457, 2466 ] ], "normalized": [] }, { "id": "PMID-2083253_T25", "type": "Protein", "text": [ "CREB" ], "offsets": [ [ 2468, 2472 ] ], "normalized": [] }, { "id": "PMID-2083253_T26", "type": "Protein", "text": [ "TCR alpha" ], "offsets": [ [ 2543, 2552 ] ], "normalized": [] }, { "id": "PMID-2083253_T28", "type": "Entity", "text": [ "enhancer" ], "offsets": [ [ 116, 124 ] ], "normalized": [] }, { "id": "PMID-2083253_T30", "type": "Entity", "text": [ "enhancer" ], "offsets": [ [ 695, 703 ] ], "normalized": [] }, { "id": "PMID-2083253_T31", "type": "Entity", "text": [ "promoters" ], "offsets": [ [ 711, 720 ] ], "normalized": [] }, { "id": "PMID-2083253_T36", "type": "Entity", "text": [ "enhancer" ], "offsets": [ [ 2001, 2009 ] ], "normalized": [] }, { "id": "PMID-2083253_T39", "type": "Entity", "text": [ "enhancer" ], "offsets": [ [ 2553, 2561 ] ], "normalized": [] } ]

[ { "id": "PMID-2083253_E1", "type": "Positive_regulation", "trigger": { "text": [ "activates" ], "offsets": [ [ 73, 82 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "PMID-2083253_T2" }, { "role": "Cause", "ref_id": "PMID-2083253_T1" }, { "role": "Site", "ref_id": "PMID-2083253_T28" } ] }, { "id": "PMID-2083253_E2", "type": "Binding", "trigger": { "text": [ "bind" ], "offsets": [ [ 673, 677 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "PMID-2083253_T4" }, { "role": "Theme", "ref_id": "PMID-2083253_T5" }, { "role": "Site", "ref_id": "PMID-2083253_T31" } ] }, { "id": "PMID-2083253_E3", "type": "Binding", "trigger": { "text": [ "bind" ], "offsets": [ [ 673, 677 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "PMID-2083253_T4" }, { "role": "Theme", "ref_id": "PMID-2083253_T5" }, { "role": "Site", "ref_id": "PMID-2083253_T30" } ] }, { "id": "PMID-2083253_E4", "type": "Positive_regulation", "trigger": { "text": [ "promoters" ], "offsets": [ [ 711, 720 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "PMID-2083253_E5" } ] }, { "id": "PMID-2083253_E5", "type": "Gene_expression", "trigger": { "text": [ "expressed" ], "offsets": [ [ 739, 748 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "PMID-2083253_T7" } ] }, { "id": "PMID-2083253_E6", "type": "Gene_expression", "trigger": { "text": [ "expressed" ], "offsets": [ [ 739, 748 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "PMID-2083253_T8" } ] }, { "id": "PMID-2083253_E7", "type": "Gene_expression", "trigger": { "text": [ "expressed" ], "offsets": [ [ 739, 748 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "PMID-2083253_T6" } ] }, { "id": "PMID-2083253_E8", "type": "Positive_regulation", "trigger": { "text": [ "derived" ], "offsets": [ [ 1129, 1136 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "PMID-2083253_T12" } ] }, { "id": "PMID-2083253_E9", "type": "Positive_regulation", "trigger": { "text": [ "required" ], "offsets": [ [ 1978, 1986 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "PMID-2083253_T18" }, { "role": "Site", "ref_id": "PMID-2083253_T36" } ] }, { "id": "PMID-2083253_E10", "type": "Transcription", "trigger": { "text": [ "transcriptional activity" ], "offsets": [ [ 2376, 2400 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "PMID-2083253_T22" } ] }, { "id": "PMID-2083253_E11", "type": "Positive_regulation", "trigger": { "text": [ "depend" ], "offsets": [ [ 2427, 2433 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "PMID-2083253_E10" }, { "role": "Cause", "ref_id": "PMID-2083253_T23" } ] }, { "id": "PMID-2083253_E12", "type": "Positive_regulation", "trigger": { "text": [ "depend" ], "offsets": [ [ 2427, 2433 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "PMID-2083253_E10" }, { "role": "Cause", "ref_id": "PMID-2083253_T26" }, { "role": "CSite", "ref_id": "PMID-2083253_T39" } ] }, { "id": "PMID-2083253_E13", "type": "Positive_regulation", "trigger": { "text": [ "depend" ], "offsets": [ [ 2427, 2433 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "PMID-2083253_E10" }, { "role": "Cause", "ref_id": "PMID-2083253_T25" } ] } ]

[ { "id": "PMID-2083253_1", "entity_ids": [ "PMID-2083253_T25", "PMID-2083253_T24" ] } ]

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[ { "id": "PMID-2088505__text", "type": "abstract", "text": [ "A novel T-cell trans-activator that recognizes a phorbol ester-inducible element of the interleukin-2 promoter. \nThe interleukin 2 (IL-2) gene promoter is recognized by several cell-type-specific and ubiquitous transcriptional regulators that integrate information transmitted by various signaling systems leading to IL-2 production and T-cell activation. Using a combination of transfection, protein-DNA binding, and in vitro transcription methods, we have discovered the novel T-cell-specific transcriptional activator TCF-1 (for T-Cell Factor-1), which recognizes a T-cell-specific response element (TCE) located within the IL-2 promoter. Although the TCE is similar in sequence to a consensus NF kappa B site, several criteria indicate that TCF-1 is distinct from NF kappa B. However, like NF kappa B, TCF-1 activity is induced by phorbol esters and other T-cell activators. " ], "offsets": [ [ 0, 879 ] ] } ]

[ { "id": "PMID-2088505_T1", "type": "Protein", "text": [ "interleukin-2" ], "offsets": [ [ 88, 101 ] ], "normalized": [] }, { "id": "PMID-2088505_T2", "type": "Protein", "text": [ "interleukin 2" ], "offsets": [ [ 117, 130 ] ], "normalized": [] }, { "id": "PMID-2088505_T3", "type": "Protein", "text": [ "IL-2" ], "offsets": [ [ 132, 136 ] ], "normalized": [] }, { "id": "PMID-2088505_T4", "type": "Protein", "text": [ "IL-2" ], "offsets": [ [ 317, 321 ] ], "normalized": [] }, { "id": "PMID-2088505_T5", "type": "Protein", "text": [ "TCF-1" ], "offsets": [ [ 521, 526 ] ], "normalized": [] }, { "id": "PMID-2088505_T6", "type": "Protein", "text": [ "T-Cell Factor-1" ], "offsets": [ [ 532, 547 ] ], "normalized": [] }, { "id": "PMID-2088505_T7", "type": "Protein", "text": [ "IL-2" ], "offsets": [ [ 627, 631 ] ], "normalized": [] }, { "id": "PMID-2088505_T8", "type": "Protein", "text": [ "TCF-1" ], "offsets": [ [ 745, 750 ] ], "normalized": [] }, { "id": "PMID-2088505_T9", "type": "Protein", "text": [ "TCF-1" ], "offsets": [ [ 806, 811 ] ], "normalized": [] }, { "id": "PMID-2088505_T11", "type": "Entity", "text": [ "phorbol ester-inducible element" ], "offsets": [ [ 49, 80 ] ], "normalized": [] }, { "id": "PMID-2088505_T12", "type": "Entity", "text": [ "promoter" ], "offsets": [ [ 143, 151 ] ], "normalized": [] } ]

[ { "id": "PMID-2088505_E1", "type": "Binding", "trigger": { "text": [ "recognizes" ], "offsets": [ [ 36, 46 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "PMID-2088505_T1" }, { "role": "Site", "ref_id": "PMID-2088505_T11" } ] }, { "id": "PMID-2088505_E2", "type": "Binding", "trigger": { "text": [ "recognized" ], "offsets": [ [ 155, 165 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "PMID-2088505_T2" }, { "role": "Site", "ref_id": "PMID-2088505_T12" } ] }, { "id": "PMID-2088505_E3", "type": "Positive_regulation", "trigger": { "text": [ "leading" ], "offsets": [ [ 306, 313 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "PMID-2088505_E4" } ] }, { "id": "PMID-2088505_E4", "type": "Gene_expression", "trigger": { "text": [ "production" ], "offsets": [ [ 322, 332 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "PMID-2088505_T4" } ] }, { "id": "PMID-2088505_E5", "type": "Binding", "trigger": { "text": [ "recognizes" ], "offsets": [ [ 556, 566 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "PMID-2088505_T5" } ] }, { "id": "PMID-2088505_E6", "type": "Positive_regulation", "trigger": { "text": [ "induced" ], "offsets": [ [ 824, 831 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "PMID-2088505_T9" } ] } ]

[ { "id": "PMID-2088505_1", "entity_ids": [ "PMID-2088505_T2", "PMID-2088505_T3" ] } ]

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[ { "id": "PMID-2105528__text", "type": "abstract", "text": [ "Two distinct transcription factors that bind the immunoglobulin enhancer microE5/kappa 2 motif. \nActivity of the immunoglobulin heavy and kappa light chain gene enhancers depends on a complex interplay of ubiquitous and developmentally regulated proteins. Two complementary DNAs were isolated that encode proteins, denoted ITF-1 and ITF-2, that are expressed in a variety of cell types and bind the microE5/kappa 2 motif found in both heavy and kappa light chain enhancers. The complementary DNAs are the products of distinct genes, yet both ITF-1 and ITF-2 are structurally and functionally similar. The two proteins interact with one another through their putative helix-loop-helix motifs and each possesses a distinct domain that dictates transcription activation. " ], "offsets": [ [ 0, 768 ] ] } ]

[ { "id": "PMID-2105528_T1", "type": "Protein", "text": [ "ITF-1" ], "offsets": [ [ 323, 328 ] ], "normalized": [] }, { "id": "PMID-2105528_T2", "type": "Protein", "text": [ "ITF-2" ], "offsets": [ [ 333, 338 ] ], "normalized": [] }, { "id": "PMID-2105528_T3", "type": "Protein", "text": [ "ITF-1" ], "offsets": [ [ 542, 547 ] ], "normalized": [] }, { "id": "PMID-2105528_T4", "type": "Protein", "text": [ "ITF-2" ], "offsets": [ [ 552, 557 ] ], "normalized": [] } ]

[ { "id": "PMID-2105528_E1", "type": "Gene_expression", "trigger": { "text": [ "expressed" ], "offsets": [ [ 349, 358 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "PMID-2105528_T2" } ] }, { "id": "PMID-2105528_E2", "type": "Gene_expression", "trigger": { "text": [ "expressed" ], "offsets": [ [ 349, 358 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "PMID-2105528_T1" } ] }, { "id": "PMID-2105528_E3", "type": "Binding", "trigger": { "text": [ "bind" ], "offsets": [ [ 390, 394 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "PMID-2105528_T1" } ] }, { "id": "PMID-2105528_E4", "type": "Binding", "trigger": { "text": [ "bind" ], "offsets": [ [ 390, 394 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "PMID-2105528_T2" } ] }, { "id": "PMID-2105528_E5", "type": "Binding", "trigger": { "text": [ "interact" ], "offsets": [ [ 618, 626 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "PMID-2105528_T3" }, { "role": "Theme", "ref_id": "PMID-2105528_T4" } ] } ]

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[ { "id": "PMID-2105887__text", "type": "abstract", "text": [ "A factor known to bind to endogenous Ig heavy chain enhancer only in lymphocytes is a ubiquitously active transcription factor. \nThe transcriptional enhancer located in the first intron of the immunoglobulin heavy chain constant region is a major determinant of B-cell-specific expression of immunoglobulin genes. Like other enhancers, the Ig heavy chain enhancer contains several short sequence motifs that bind specific transcription factors. Each binding site contributes to the overall activity of the enhancer, however no single element seems absolutely required for activity. For a better understanding of the Ig heavy chain enhancer components, we have cloned and analyzed individual sequence elements. We find that the factor that binds to the E3 enhancer motif, CATGTGGC, is a ubiquitous transcription factor. It is present in an active form in both B cells and non-B cells, where it can mediate transcriptional activation in vitro and in vivo. However, despite its ability to activate transcription of a transfected reporter gene, the factor is apparently unable to bind to the endogenous Ig heavy chain enhancer in non-lymphoid cells: In previous experiments by others, the characteristic in vivo footprint of this factor, designated NF-muE3, was detected in B cells but not in non-B cells. From this and other findings the picture emerges that there are at least three categories of factors which mediate cell-type-specific transcription in B lymphocytes: (a) cell-specific factors such as Oct-2A and Oct-2B that are not expressed in most other cell types: (b) ubiquitous factors such as NF-kappa B that are constitutively active in B cells but are sequestered in an inactive form in other cells; (c) ubiquitously active factors, exemplified by the one binding to the E3 sequence motif. This factor is present in an active form in a variety of cell types but is apparently unable to bind to the endogenous Ig heavy chain enhancer in non-B cells, perhaps due to a non-permissive chromatin structure of the Ig heavy chain locus. " ], "offsets": [ [ 0, 2039 ] ] } ]

[ { "id": "PMID-2105887_T1", "type": "Protein", "text": [ "NF-muE3" ], "offsets": [ [ 1245, 1252 ] ], "normalized": [] }, { "id": "PMID-2105887_T2", "type": "Protein", "text": [ "Oct-2A" ], "offsets": [ [ 1502, 1508 ] ], "normalized": [] }, { "id": "PMID-2105887_T3", "type": "Protein", "text": [ "Oct-2B" ], "offsets": [ [ 1513, 1519 ] ], "normalized": [] } ]

[ { "id": "PMID-2105887_E1", "type": "Gene_expression", "trigger": { "text": [ "expressed" ], "offsets": [ [ 1533, 1542 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "PMID-2105887_T3" } ] }, { "id": "PMID-2105887_E2", "type": "Gene_expression", "trigger": { "text": [ "expressed" ], "offsets": [ [ 1533, 1542 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "PMID-2105887_T2" } ] }, { "id": "PMID-2105887_E3", "type": "Positive_regulation", "trigger": { "text": [ "active" ], "offsets": [ [ 1828, 1834 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "PMID-2105887_T1" } ] }, { "id": "PMID-2105887_E4", "type": "Binding", "trigger": { "text": [ "bind" ], "offsets": [ [ 1895, 1899 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "PMID-2105887_T1" } ] } ]

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[ { "id": "PMID-2105946__text", "type": "abstract", "text": [ "Transcriptional and post-transcriptional regulation of c-jun expression during monocytic differentiation of human myeloid leukemic cells. \nAP-1, the polypeptide product of c-jun, recognizes and binds to specific DNA sequences and stimulates transcription of genes responsive to certain growth factors and phorbol esters such as 12-O-tetradecanoylphorbol-13-acetate (TPA). We studied the effects of TPA on the regulation of c-jun gene expression in HL-60 cells during monocytic differentiation. Low levels of c-jun transcripts were detectable in untreated HL-60 leukemic cells, increased significantly by 6 h, and reached near maximal levels by 24 h of exposure to 32 nM TPA. Similar kinetics of c-jun induction by TPA were observed in human U-937 and THP-1 monocytic leukemia cells. Similar findings were obtained with bryostatin 1 (10 nM), another activator of protein kinase C and inducer of monocytic differentiation. Furthermore, 1,25-dihydroxyvitamin D3 (0.5 microM), a structurally distinct agent which also induces HL-60 monocytic differentiation, increased c-jun expression. TPA treatment of HL-60 cells in the presence of cycloheximide was associated with superinduction of c-jun transcripts. Run-on analysis demonstrated detectable levels of c-jun gene transcription in untreated HL-60 cells, and that exposure to TPA increases this rate 3.3-fold. Treatment of HL-60 cells with both TPA and cycloheximide had no effect on the rates of c-jun transcription. The half-life of c-jun RNA as determined by treating HL-60 cells with TPA and actinomycin D was 30 min. In contrast, the half-life of c-jun RNA in TPA-treated HL-60 cells exposed to cycloheximide and actinomycin D was greater than 2 h. These findings suggested that the increase in c-jun RNA observed during TPA-induced monocytic differentiation is mediated by both transcriptional and post-transcriptional mechanisms. " ], "offsets": [ [ 0, 1885 ] ] } ]

[ { "id": "PMID-2105946_T1", "type": "Protein", "text": [ "c-jun" ], "offsets": [ [ 55, 60 ] ], "normalized": [] }, { "id": "PMID-2105946_T2", "type": "Protein", "text": [ "c-jun" ], "offsets": [ [ 172, 177 ] ], "normalized": [] }, { "id": "PMID-2105946_T3", "type": "Protein", "text": [ "c-jun" ], "offsets": [ [ 423, 428 ] ], "normalized": [] }, { "id": "PMID-2105946_T4", "type": "Protein", "text": [ "c-jun" ], "offsets": [ [ 508, 513 ] ], "normalized": [] }, { "id": "PMID-2105946_T5", "type": "Protein", "text": [ "c-jun" ], "offsets": [ [ 695, 700 ] ], "normalized": [] }, { "id": "PMID-2105946_T6", "type": "Protein", "text": [ "c-jun" ], "offsets": [ [ 1065, 1070 ] ], "normalized": [] }, { "id": "PMID-2105946_T7", "type": "Protein", "text": [ "c-jun" ], "offsets": [ [ 1183, 1188 ] ], "normalized": [] }, { "id": "PMID-2105946_T8", "type": "Protein", "text": [ "c-jun" ], "offsets": [ [ 1252, 1257 ] ], "normalized": [] }, { "id": "PMID-2105946_T9", "type": "Protein", "text": [ "c-jun" ], "offsets": [ [ 1445, 1450 ] ], "normalized": [] }, { "id": "PMID-2105946_T10", "type": "Protein", "text": [ "c-jun" ], "offsets": [ [ 1483, 1488 ] ], "normalized": [] }, { "id": "PMID-2105946_T11", "type": "Protein", "text": [ "c-jun" ], "offsets": [ [ 1600, 1605 ] ], "normalized": [] }, { "id": "PMID-2105946_T12", "type": "Protein", "text": [ "c-jun" ], "offsets": [ [ 1748, 1753 ] ], "normalized": [] } ]

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[ { "id": "PMID-2109187__text", "type": "abstract", "text": [ "Identification of a novel factor that interacts with an immunoglobulin heavy-chain promoter and stimulates transcription in conjunction with the lymphoid cell-specific factor OTF2. \nThe tissue-specific expression of the MOPC 141 immunoglobulin heavy-chain gene was studied by using in vitro transcription. B-cell-specific transcription of this gene was dependent on the octamer element 5'-ATGCAAAG-3', located in the upstream region of this promoter and in the promoters of all other immunoglobulin heavy- and light-chain genes. The interaction of purified octamer transcription factors 1 and 2 (OTF1 and OTF2) with the MOPC 141 promoter was studied by using electrophoretic mobility shift assays and DNase I footprinting. Purified OTF1 from HeLa cells and OTF1 and OTF2 from B cells bound to identical sequences within the heavy-chain promoter. The OTF interactions we observed extended over the heptamer element 5'-CTCAGGA-3', and it seems likely that the binding of the purified factors involves cooperation between octamer and heptamer sites in this promoter. In addition to these elements, we identified a second regulatory element, the N element with the sequence 5'-GGAACCTCCCCC-3'. The N element could independently mediate low levels of transcription in both B-cell and HeLa-cell extracts, and, in conjunction with the octamer element, it can promote high levels of transcription in B-cell extracts. The N element bound a transcription factor, NTF, that is ubiquitous in cell-type distribution, and NTF was distinct from any of the previously described proteins that bind to similar sequences. Based on these results, we propose that NTF and OTF2 interactions (both with their cognate DNA elements and possibly at the protein-protein level) may be critical to B-cell-specific expression and that these interactions provide additional pathways for regulating gene expression. " ], "offsets": [ [ 0, 1884 ] ] } ]

[ { "id": "PMID-2109187_T1", "type": "Protein", "text": [ "OTF2" ], "offsets": [ [ 175, 179 ] ], "normalized": [] }, { "id": "PMID-2109187_T2", "type": "Protein", "text": [ "octamer transcription factors 1" ], "offsets": [ [ 557, 588 ] ], "normalized": [] }, { "id": "PMID-2109187_T3", "type": "Protein", "text": [ "2" ], "offsets": [ [ 593, 594 ] ], "normalized": [] }, { "id": "PMID-2109187_T4", "type": "Protein", "text": [ "OTF1" ], "offsets": [ [ 596, 600 ] ], "normalized": [] }, { "id": "PMID-2109187_T5", "type": "Protein", "text": [ "OTF2" ], "offsets": [ [ 605, 609 ] ], "normalized": [] }, { "id": "PMID-2109187_T6", "type": "Protein", "text": [ "OTF1" ], "offsets": [ [ 732, 736 ] ], "normalized": [] }, { "id": "PMID-2109187_T7", "type": "Protein", "text": [ "OTF1" ], "offsets": [ [ 757, 761 ] ], "normalized": [] }, { "id": "PMID-2109187_T8", "type": "Protein", "text": [ "OTF2" ], "offsets": [ [ 766, 770 ] ], "normalized": [] }, { "id": "PMID-2109187_T9", "type": "Protein", "text": [ "OTF2" ], "offsets": [ [ 1651, 1655 ] ], "normalized": [] } ]

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[ { "id": "PMID-2111447__text", "type": "abstract", "text": [ "Involvement of a second lymphoid-specific enhancer element in the regulation of immunoglobulin heavy-chain gene expression. \nTo determine whether enhancer elements in addition to the highly conserved octamer (OCTA)-nucleotide motif are important for lymphoid-specific expression of the immunoglobulin heavy-chain (IgH) gene, we have investigated the effect of mutating the binding site for a putative additional lymphoid-specific transcription factor, designated NF-microB, in the murine IgH enhancer. We demonstrate that the NF-microB-binding site plays a critical role in the IgH enhancer, because mutation of the microB DNA motif decreased transcriptional activity of the IgH enhancer in cells of the B-cell lineage but not in nonlymphoid cells. This effect was comparable to or even stronger than the effect of a mutation in the OCTA site. Moreover, combined mutation of both microB and OCTA sites further reduced enhancer activity in lymphoid cells. Interestingly, alteration of either the microB or E3 site in a 70-base-pair fragment of the IgH enhancer that lacks the binding site for OCTA abolished enhancer activity in lymphoid cells completely. Nevertheless, a multimer of the microB motif alone showed no enhancer activity. DNase footprinting analysis corroborated the functional data showing that a lymphoid-specific protein binds to the microB DNA motif. Our results suggest that the microB element is a new crucial element important for lymphoid-specific expression of the IgH gene but that interaction with another enhancer element is essential for its activity. " ], "offsets": [ [ 0, 1578 ] ] } ]

[ { "id": "PMID-2111447_T1", "type": "Protein", "text": [ "NF-microB" ], "offsets": [ [ 463, 472 ] ], "normalized": [] }, { "id": "PMID-2111447_T2", "type": "Protein", "text": [ "NF-microB" ], "offsets": [ [ 526, 535 ] ], "normalized": [] } ]

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[ { "id": "PMID-2112575__text", "type": "abstract", "text": [ "The expression of c-fos, c-jun, and c-myc genes is regulated by heat shock in human lymphoid cells. \nThe effect of heat shock on the expression of the nuclear protooncogenes c-fos, c-jun, and c-myc was studied in human lymphoid cells. Heat shock caused an increase in c-fos and c-jun mRNA levels and a decrease in c-myc mRNA levels in pre-B (Hyon) and T (DND-41) cell lines as well as in freshly isolated normal human thymocytes. The changes in the mRNA levels of these protooncogenes in Hyon cells were most pronounced at 42 and 43 degrees C; kinetic analysis demonstrated that the changes could be detected within 30 min of heat shock. Altered transcription of c-fos and c-myc genes was the primary effect of heat shock. Secondarily, heat shock of Hyon cells stabilized the c-myc mRNA level by increasing its half-life from 24 to 45 min. The overall effect of heat shock on c-myc mRNA level, however, was a marked inhibition of its transcription. These results demonstrate that the transcription of nuclear protooncogenes is regulated by heat shock indicating a role for nuclear protooncogenes in the stress response of lymphoid cells. " ], "offsets": [ [ 0, 1138 ] ] } ]

[ { "id": "PMID-2112575_T1", "type": "Protein", "text": [ "c-fos" ], "offsets": [ [ 18, 23 ] ], "normalized": [] }, { "id": "PMID-2112575_T2", "type": "Protein", "text": [ "c-jun" ], "offsets": [ [ 25, 30 ] ], "normalized": [] }, { "id": "PMID-2112575_T3", "type": "Protein", "text": [ "c-myc" ], "offsets": [ [ 36, 41 ] ], "normalized": [] }, { "id": "PMID-2112575_T4", "type": "Protein", "text": [ "c-fos" ], "offsets": [ [ 174, 179 ] ], "normalized": [] }, { "id": "PMID-2112575_T5", "type": "Protein", "text": [ "c-jun" ], "offsets": [ [ 181, 186 ] ], "normalized": [] }, { "id": "PMID-2112575_T6", "type": "Protein", "text": [ "c-myc" ], "offsets": [ [ 192, 197 ] ], "normalized": [] }, { "id": "PMID-2112575_T7", "type": "Protein", "text": [ "c-fos" ], "offsets": [ [ 268, 273 ] ], "normalized": [] }, { "id": "PMID-2112575_T8", "type": "Protein", "text": [ "c-jun" ], "offsets": [ [ 278, 283 ] ], "normalized": [] }, { "id": "PMID-2112575_T9", "type": "Protein", "text": [ "c-myc" ], "offsets": [ [ 314, 319 ] ], "normalized": [] }, { "id": "PMID-2112575_T10", "type": "Protein", "text": [ "c-fos" ], "offsets": [ [ 663, 668 ] ], "normalized": [] }, { "id": "PMID-2112575_T11", "type": "Protein", "text": [ "c-myc" ], "offsets": [ [ 673, 678 ] ], "normalized": [] }, { "id": "PMID-2112575_T12", "type": "Protein", "text": [ "c-myc" ], "offsets": [ [ 776, 781 ] ], "normalized": [] }, { "id": "PMID-2112575_T13", "type": "Protein", "text": [ "c-myc" ], "offsets": [ [ 876, 881 ] ], "normalized": [] } ]

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143 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "PMID-2112575_T6" } ] }, { "id": "PMID-2112575_E12", "type": "Gene_expression", "trigger": { "text": [ "expression" ], "offsets": [ [ 133, 143 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "PMID-2112575_T4" } ] }, { "id": "PMID-2112575_E13", "type": "Positive_regulation", "trigger": { "text": [ "increase" ], "offsets": [ [ 256, 264 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "PMID-2112575_E16" } ] }, { "id": "PMID-2112575_E14", "type": "Positive_regulation", "trigger": { "text": [ "increase" ], "offsets": [ [ 256, 264 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "PMID-2112575_E15" } ] }, { "id": "PMID-2112575_E15", "type": "Transcription", "trigger": { "text": [ "levels" ], "offsets": [ [ 289, 295 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "PMID-2112575_T8" } ] }, { "id": "PMID-2112575_E16", "type": "Transcription", "trigger": { "text": [ "levels" ], "offsets": [ [ 289, 295 ] ] }, "arguments": [ { "role": 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"text": [ "inhibition" ], "offsets": [ [ 916, 926 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "PMID-2112575_E33" } ] }, { "id": "PMID-2112575_E33", "type": "Transcription", "trigger": { "text": [ "transcription" ], "offsets": [ [ 934, 947 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "PMID-2112575_T13" } ] } ]

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[ { "id": "PMID-2116990__text", "type": "abstract", "text": [ "Tandem AP-1-binding sites within the human beta-globin dominant control region function as an inducible enhancer in erythroid cells. \nA powerful enhancer has been mapped to an 18-bp DNA segment located 11 kb 5' to the human epsilon-globin gene within the dominant control or locus-activating region. This enhancer is inducible in K562 human erythroleukemia cells, increasing linked gamma-globin promoter/luciferase gene expression to 170-fold over an enhancerless construct. The enhancer consists of tandem AP-1-binding sites, phased 10 bp apart, which are both required for full activity. DNA-protein binding assays with nuclear extracts from induced cells demonstrate a high molecular weight complex on the enhancer. The formation of this complex also requires both AP-1 sites and correlates with maximal enhancer activity. Induction of the enhancer may have a role in the increase in globin gene transcription that characterizes erythroid maturation. Enhancer activity appears to be mediated by the binding of a complex of proteins from the jun and fos families to tandem AP-1 consensus sequences. " ], "offsets": [ [ 0, 1101 ] ] } ]

[ { "id": "PMID-2116990_T1", "type": "Protein", "text": [ "beta-globin" ], "offsets": [ [ 43, 54 ] ], "normalized": [] }, { "id": "PMID-2116990_T2", "type": "Protein", "text": [ "epsilon-globin" ], "offsets": [ [ 224, 238 ] ], "normalized": [] }, { "id": "PMID-2116990_T3", "type": "Protein", "text": [ "gamma-globin" ], "offsets": [ [ 382, 394 ] ], "normalized": [] }, { "id": "PMID-2116990_T4", "type": "Protein", "text": [ "luciferase" ], "offsets": [ [ 404, 414 ] ], "normalized": [] } ]

[ { "id": "PMID-2116990_E1", "type": "Positive_regulation", "trigger": { "text": [ "increasing" ], "offsets": [ [ 364, 374 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "PMID-2116990_E2" } ] }, { "id": "PMID-2116990_E2", "type": "Gene_expression", "trigger": { "text": [ "expression" ], "offsets": [ [ 420, 430 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "PMID-2116990_T4" } ] }, { "id": "PMID-2116990_E3", "type": "Positive_regulation", "trigger": { "text": [ "required" ], "offsets": [ [ 562, 570 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "PMID-2116990_E1" } ] } ]

[]

[]

[ { "id": "PMID-2121746__text", "type": "abstract", "text": [ "Adherence-dependent increase in human monocyte PDGF(B) mRNA is associated with increases in c-fos, c-jun, and EGR2 mRNA. \nAdherence is an important initial step in the transition of a circulating monocyte to a tissue macrophage. This differentiation is accompanied by an augmented capacity to generate growth factors. We hypothesized that adherence itself might be an important trigger for a sequence of gene activation culminating in cells with increased mRNA encoding profibrotic growth factors such as platelet-derived growth factor B subunit (PDGF[B]) and transforming growth factor-beta (TGF-beta). After in vitro adherence, human monocytes had a biphasic increase in PDGF(B) mRNA with peaks at 6 h and 13 d. No increase in TGF-beta mRNA was observed. The 6-h increase in PDGF(B) mRNA was adherence dependent, and in addition, was abrogated when the cytoskeletal integrity was compromised by cytochalasin D. The 6-h increase in PDGF(B) mRNA was unaltered by adherence in the presence of the monocyte stimulus lipopolysaccharide. Adherence to either fibronectin or collagen-coated plastic had little consistent effect on PDGF(B) mRNA accumulation. The increased PDGF(B) mRNA observed in adherent monocytes was accompanied by increases in mRNAs of the early growth response genes c-fos (maximal at 20 min), c-jun, and EGR2 (maximal at 6-24 h). The increase in c-jun and EGR2, but not c-fos, mRNA was also abrogated by cytochalasin D. These observations suggest that adherence results in increases of c-fos, c-jun, EGR2, and PDGF(B) mRNA. In addition, the increases in c-jun, EGR2, and PDGF(B) may depend on cytoskeletal rearrangement. Modulation of these events at the time of adherence offers a mechanism by which differential priming of the cells may be accomplished. " ], "offsets": [ [ 0, 1773 ] ] } ]

[ { "id": "PMID-2121746_T1", "type": "Protein", "text": [ "PDGF(B)" ], "offsets": [ [ 47, 54 ] ], "normalized": [] }, { "id": "PMID-2121746_T2", "type": "Protein", "text": [ "c-fos" ], "offsets": [ [ 92, 97 ] ], "normalized": [] }, { "id": "PMID-2121746_T3", "type": "Protein", "text": [ "c-jun" ], "offsets": [ [ 99, 104 ] ], "normalized": [] }, { "id": "PMID-2121746_T4", "type": "Protein", "text": [ "EGR2" ], "offsets": [ [ 110, 114 ] ], "normalized": [] }, { "id": "PMID-2121746_T5", "type": "Protein", "text": [ "platelet-derived growth factor B subunit" ], "offsets": [ [ 505, 545 ] ], "normalized": [] }, { "id": "PMID-2121746_T6", "type": "Protein", "text": [ "PDGF[B]" ], "offsets": [ [ 547, 554 ] ], "normalized": [] }, { "id": "PMID-2121746_T7", "type": "Protein", "text": [ "transforming growth factor-beta" ], "offsets": [ [ 560, 591 ] ], "normalized": [] }, { "id": "PMID-2121746_T8", "type": "Protein", "text": [ "TGF-beta" ], "offsets": [ [ 593, 601 ] ], "normalized": [] }, { "id": "PMID-2121746_T9", "type": "Protein", "text": [ "PDGF(B)" ], "offsets": [ [ 673, 680 ] ], "normalized": [] }, { "id": "PMID-2121746_T10", "type": "Protein", "text": [ "TGF-beta" ], "offsets": [ [ 729, 737 ] ], "normalized": [] }, { "id": "PMID-2121746_T11", "type": "Protein", "text": [ "PDGF(B)" ], "offsets": [ [ 777, 784 ] ], "normalized": [] }, { "id": "PMID-2121746_T12", "type": "Protein", "text": [ "PDGF(B)" ], "offsets": [ [ 933, 940 ] ], "normalized": [] }, { "id": "PMID-2121746_T13", "type": "Protein", "text": [ "fibronectin" ], "offsets": [ [ 1054, 1065 ] ], "normalized": [] }, { "id": "PMID-2121746_T14", "type": "Protein", "text": [ "PDGF(B)" ], "offsets": [ [ 1125, 1132 ] ], "normalized": [] }, { "id": "PMID-2121746_T15", "type": "Protein", "text": [ "PDGF(B)" ], "offsets": [ [ 1166, 1173 ] ], "normalized": [] }, { "id": "PMID-2121746_T16", "type": "Protein", "text": [ "c-fos" ], "offsets": [ [ 1283, 1288 ] ], "normalized": [] }, { "id": "PMID-2121746_T17", "type": "Protein", "text": [ "c-jun" ], "offsets": [ [ 1310, 1315 ] ], "normalized": [] }, { "id": "PMID-2121746_T18", "type": "Protein", "text": [ "EGR2" ], "offsets": [ [ 1321, 1325 ] ], "normalized": [] }, { "id": "PMID-2121746_T19", "type": "Protein", "text": [ "c-jun" ], "offsets": [ [ 1363, 1368 ] ], "normalized": [] }, { "id": "PMID-2121746_T20", "type": "Protein", "text": [ "EGR2" ], "offsets": [ [ 1373, 1377 ] ], "normalized": [] }, { "id": "PMID-2121746_T21", "type": "Protein", "text": [ "c-fos" ], "offsets": [ [ 1387, 1392 ] ], "normalized": [] }, { "id": "PMID-2121746_T22", "type": "Protein", "text": [ "c-fos" ], "offsets": [ [ 1503, 1508 ] ], "normalized": [] }, { "id": "PMID-2121746_T23", "type": "Protein", "text": [ "c-jun" ], "offsets": [ [ 1510, 1515 ] ], "normalized": [] }, { "id": "PMID-2121746_T24", "type": "Protein", "text": [ "EGR2" ], "offsets": [ [ 1517, 1521 ] ], "normalized": [] }, { "id": "PMID-2121746_T25", "type": "Protein", "text": [ "PDGF(B)" ], "offsets": [ [ 1527, 1534 ] ], "normalized": [] }, { "id": "PMID-2121746_T26", "type": "Protein", "text": [ "c-jun" ], "offsets": [ [ 1571, 1576 ] ], "normalized": [] }, { "id": "PMID-2121746_T27", "type": "Protein", "text": [ "EGR2" ], "offsets": [ [ 1578, 1582 ] ], "normalized": [] }, { "id": "PMID-2121746_T28", "type": "Protein", "text": [ "PDGF(B)" ], "offsets": [ [ 1588, 1595 ] ], "normalized": [] } ]

[ { "id": "PMID-2121746_E1", "type": "Positive_regulation", "trigger": { "text": [ "increase" ], "offsets": [ [ 20, 28 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "PMID-2121746_T1" } ] }, { "id": "PMID-2121746_E2", "type": "Positive_regulation", "trigger": { "text": [ "increases" ], "offsets": [ [ 79, 88 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "PMID-2121746_T4" } ] }, { "id": "PMID-2121746_E3", "type": "Positive_regulation", "trigger": { "text": [ "increases" ], "offsets": [ [ 79, 88 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "PMID-2121746_T2" } ] }, { "id": "PMID-2121746_E4", "type": "Positive_regulation", "trigger": { "text": [ "increases" ], "offsets": [ [ 79, 88 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "PMID-2121746_T3" } ] }, { "id": "PMID-2121746_E5", "type": "Positive_regulation", "trigger": { "text": [ "culminating" ], "offsets": [ [ 420, 431 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "PMID-2121746_E7" } ] }, { "id": "PMID-2121746_E6", "type": "Positive_regulation", "trigger": { "text": [ "culminating" ], "offsets": [ [ 420, 431 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "PMID-2121746_E8" } ] }, { "id": "PMID-2121746_E7", "type": "Positive_regulation", "trigger": { "text": [ "increased" ], "offsets": [ [ 446, 455 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "PMID-2121746_T8" } ] }, { "id": "PMID-2121746_E8", "type": "Positive_regulation", "trigger": { "text": [ "increased" ], "offsets": [ [ 446, 455 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "PMID-2121746_T6" } ] }, { "id": "PMID-2121746_E9", "type": "Positive_regulation", "trigger": { "text": [ "increase" ], "offsets": [ [ 661, 669 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "PMID-2121746_T9" } ] }, { "id": "PMID-2121746_E10", "type": "Positive_regulation", "trigger": { "text": [ "increase" ], "offsets": [ [ 717, 725 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "PMID-2121746_T10" } ] }, { "id": "PMID-2121746_E11", "type": "Positive_regulation", "trigger": { "text": [ "increase" ], "offsets": [ [ 765, 773 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "PMID-2121746_T11" } ] }, { "id": "PMID-2121746_E12", "type": "Regulation", "trigger": { "text": [ "dependent" ], "offsets": [ [ 804, 813 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "PMID-2121746_E11" } ] }, { "id": "PMID-2121746_E13", "type": "Negative_regulation", "trigger": { "text": [ "abrogated" ], "offsets": [ [ 836, 845 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "PMID-2121746_E11" } ] }, { "id": "PMID-2121746_E14", "type": "Positive_regulation", "trigger": { "text": [ "increase" ], "offsets": [ [ 921, 929 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "PMID-2121746_T12" } ] }, { "id": "PMID-2121746_E15", "type": "Regulation", "trigger": { "text": [ "unaltered" ], "offsets": [ [ 950, 959 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "PMID-2121746_E14" } ] }, { "id": "PMID-2121746_E16", "type": "Positive_regulation", "trigger": { "text": [ "in the presence of" ], "offsets": [ [ 973, 991 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "PMID-2121746_E15" } ] }, { "id": "PMID-2121746_E17", "type": "Regulation", "trigger": { "text": [ "effect" ], "offsets": [ [ 1115, 1121 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "PMID-2121746_E18" } ] }, { "id": "PMID-2121746_E18", "type": "Positive_regulation", "trigger": { "text": [ "accumulation" ], "offsets": [ [ 1138, 1150 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "PMID-2121746_T14" } ] }, { "id": "PMID-2121746_E19", "type": "Positive_regulation", "trigger": { "text": [ "increased" ], "offsets": [ [ 1156, 1165 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "PMID-2121746_T15" } ] }, { "id": "PMID-2121746_E20", "type": "Positive_regulation", "trigger": { "text": [ "increases" ], "offsets": [ [ 1229, 1238 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "PMID-2121746_T17" } ] }, { "id": "PMID-2121746_E21", "type": "Positive_regulation", "trigger": { "text": [ "increases" ], "offsets": [ [ 1229, 1238 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "PMID-2121746_T18" } ] }, { "id": "PMID-2121746_E22", "type": "Positive_regulation", "trigger": { "text": [ "increases" ], "offsets": [ [ 1229, 1238 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "PMID-2121746_T16" } ] }, { "id": "PMID-2121746_E23", "type": "Positive_regulation", "trigger": { "text": [ "increase" ], "offsets": [ [ 1351, 1359 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "PMID-2121746_T21" } ] }, { "id": "PMID-2121746_E24", "type": "Positive_regulation", "trigger": { "text": [ "increase" ], "offsets": [ [ 1351, 1359 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "PMID-2121746_T19" } ] }, { "id": "PMID-2121746_E25", "type": "Positive_regulation", "trigger": { "text": [ "increase" ], "offsets": [ [ 1351, 1359 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "PMID-2121746_T20" } ] }, { "id": "PMID-2121746_E26", "type": "Negative_regulation", "trigger": { "text": [ "abrogated" ], "offsets": [ [ 1408, 1417 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "PMID-2121746_E23" } ] }, { "id": "PMID-2121746_E27", "type": "Negative_regulation", "trigger": { "text": [ "abrogated" ], "offsets": [ [ 1408, 1417 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "PMID-2121746_E25" } ] }, { "id": "PMID-2121746_E28", "type": "Negative_regulation", "trigger": { "text": [ "abrogated" ], "offsets": [ [ 1408, 1417 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "PMID-2121746_E24" } ] }, { "id": "PMID-2121746_E29", "type": "Positive_regulation", "trigger": { "text": [ "results in increases" ], "offsets": [ [ 1479, 1499 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "PMID-2121746_T22" } ] }, { "id": "PMID-2121746_E30", "type": "Positive_regulation", "trigger": { "text": [ "results in increases" ], "offsets": [ [ 1479, 1499 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "PMID-2121746_T24" } ] }, { "id": "PMID-2121746_E31", "type": "Positive_regulation", "trigger": { "text": [ "results in increases" ], "offsets": [ [ 1479, 1499 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "PMID-2121746_T23" } ] }, { "id": "PMID-2121746_E32", "type": "Positive_regulation", "trigger": { "text": [ "results in increases" ], "offsets": [ [ 1479, 1499 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "PMID-2121746_T25" } ] }, { "id": "PMID-2121746_E33", "type": "Positive_regulation", "trigger": { "text": [ "increases" ], "offsets": [ [ 1558, 1567 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "PMID-2121746_T26" } ] }, { "id": "PMID-2121746_E34", "type": "Positive_regulation", "trigger": { "text": [ "increases" ], "offsets": [ [ 1558, 1567 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "PMID-2121746_T28" } ] }, { "id": "PMID-2121746_E35", "type": "Positive_regulation", "trigger": { "text": [ "increases" ], "offsets": [ [ 1558, 1567 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "PMID-2121746_T27" } ] }, { "id": "PMID-2121746_E36", "type": "Regulation", "trigger": { "text": [ "depend" ], "offsets": [ [ 1600, 1606 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "PMID-2121746_E33" } ] }, { "id": "PMID-2121746_E37", "type": "Regulation", "trigger": { "text": [ "depend" ], "offsets": [ [ 1600, 1606 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "PMID-2121746_E35" } ] }, { "id": "PMID-2121746_E38", "type": "Regulation", "trigger": { "text": [ "depend" ], "offsets": [ [ 1600, 1606 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "PMID-2121746_E34" } ] }, { "id": "PMID-2121746_E39", "type": "Regulation", "trigger": { "text": [ "Modulation" ], "offsets": [ [ 1638, 1648 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "PMID-2121746_E35" } ] }, { "id": "PMID-2121746_E40", "type": "Regulation", "trigger": { "text": [ "Modulation" ], "offsets": [ [ 1638, 1648 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "PMID-2121746_E33" } ] }, { "id": "PMID-2121746_E41", "type": "Regulation", "trigger": { "text": [ "Modulation" ], "offsets": [ [ 1638, 1648 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "PMID-2121746_E34" } ] } ]

[ { "id": "PMID-2121746_1", "entity_ids": [ "PMID-2121746_T6", "PMID-2121746_T5" ] }, { "id": "PMID-2121746_2", "entity_ids": [ "PMID-2121746_T8", "PMID-2121746_T7" ] } ]

[]

[ { "id": "PMID-2122173__text", "type": "abstract", "text": [ "Interferon-gamma and the sexual dimorphism of autoimmunity. \nThe sexual difference in the incidence of autoimmune diseases has remained an enigma for many years. In the examination of the induction of autoimmunity in transgenic mice, evidence has been obtained further implicating the lymphokine interferon-gamma in the etiology of autoimmunity. Sex steroid regulation of the production of this molecule, as well as other cytokines, may help explain the gender-specific differences in the immune system, including autoimmunity. " ], "offsets": [ [ 0, 528 ] ] } ]

[ { "id": "PMID-2122173_T1", "type": "Protein", "text": [ "Interferon-gamma" ], "offsets": [ [ 0, 16 ] ], "normalized": [] }, { "id": "PMID-2122173_T2", "type": "Protein", "text": [ "interferon-gamma" ], "offsets": [ [ 296, 312 ] ], "normalized": [] } ]

[ { "id": "PMID-2122173_E1", "type": "Regulation", "trigger": { "text": [ "regulation" ], "offsets": [ [ 358, 368 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "PMID-2122173_E2" } ] }, { "id": "PMID-2122173_E2", "type": "Gene_expression", "trigger": { "text": [ "production" ], "offsets": [ [ 376, 386 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "PMID-2122173_T2" } ] } ]

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[ { "id": "PMID-2123468__text", "type": "abstract", "text": [ "Single cell assay of a transcription factor reveals a threshold in transcription activated by signals emanating from the T-cell antigen receptor. \nStimulation of T lymphocytes through their antigen receptor leads to the appearance of several transcription factors, including NF-AT and NF-kappa B, which are involved in regulating genes required for immunologic activation. To investigate the activity of a single transcription factor in individual viable cells, we have applied an assay that uses the fluorescence-activated cell sorter to quantitate beta-galactosidase (beta-gal). We have analyzed the distribution of NF-AT transcriptional activity among T cells undergoing activation by using a construct in which three tandem copies of the NF-AT-binding site directs transcription of the lacZ gene. Unexpectedly, stimulation of cloned stably transfected Jurkat T cells leads to a bimodal pattern of beta-gal expression in which some cells express no beta-gal and others express high levels. This expression pattern cannot be accounted for by cell-cycle position or heritable variation. Further results, in which beta-gal activity is correlated with NF-AT-binding activity, indicate that the concentration of NF-AT must exceed a critical threshold before transcription initiates. This threshold likely reflects the NF-AT concentration-dependent assembly of transcription complexes at the promoter. Similar constructs controlled by NF-kappa B or the entire interleukin-2 enhancer show bimodal expression patterns during induction, suggesting that thresholds set by the concentration of transcription factors may be a common property of inducible genes. " ], "offsets": [ [ 0, 1653 ] ] } ]

[ { "id": "PMID-2123468_T1", "type": "Protein", "text": [ "beta-galactosidase" ], "offsets": [ [ 550, 568 ] ], "normalized": [] }, { "id": "PMID-2123468_T2", "type": "Protein", "text": [ "beta-gal" ], "offsets": [ [ 570, 578 ] ], "normalized": [] }, { "id": "PMID-2123468_T3", "type": "Protein", "text": [ "lacZ" ], "offsets": [ [ 790, 794 ] ], "normalized": [] }, { "id": "PMID-2123468_T4", "type": "Protein", "text": [ "beta-gal" ], "offsets": [ [ 901, 909 ] ], "normalized": [] }, { "id": "PMID-2123468_T5", "type": "Protein", "text": [ "beta-gal" ], "offsets": [ [ 952, 960 ] ], "normalized": [] }, { "id": "PMID-2123468_T6", "type": "Protein", "text": [ "beta-gal" ], "offsets": [ [ 1114, 1122 ] ], "normalized": [] }, { "id": "PMID-2123468_T7", "type": "Protein", "text": [ "interleukin-2" ], "offsets": [ [ 1457, 1470 ] ], "normalized": [] } ]

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[ { "id": "PMID-2123468_1", "entity_ids": [ "PMID-2123468_T1", "PMID-2123468_T2" ] } ]

[]

[ { "id": "PMID-2123553__text", "type": "abstract", "text": [ "Two distinct signal transmission pathways in T lymphocytes are inhibited by complexes formed between an immunophilin and either FK506 or rapamycin. \nProliferation and immunologic function of T lymphocytes are initiated by signals from the antigen receptor that are inhibited by the immunosuppressant FK506 but not by its structural analog, rapamycin. On the other hand, interleukin 2 (IL-2)-induced signals are blocked by rapamycin but not by FK506. Remarkably, these two drugs inhibit each other's actions, raising the possibility that both act by means of a common immunophilin (immunosuppressant binding protein). We find that the dissociation constant of rapamycin to the FK506 binding protein FKBP (Kd = 0.2 nM) is close to the dissociation constant of FK506 to FKBP (Kd = 0.4 nM) and to their effective biologic inhibitory concentrations. However, an excess of rapamycin is needed to revert FK506-mediated inhibition of IL-2 production, apoptosis, and transcriptional activation of NF-AT, a T-cell-specific transcription factor necessary for IL-2 gene activation. Similarly, an excess of FK506 is needed to revert rapamycin-mediated inhibition of IL-2-induced proliferation. The drug concentrations required for antagonism may be explained by the relative affinity of the drugs to, and by the abundance of, the immunophilin FKBP. FKBP has been shown to catalyze the interconversion of the cis- and trans-rotamers of the peptidyl-prolyl amide bond of peptide substrates; here we show that rapamycin, like FK506, is a potent inhibitor of the rotamase activity of FKBP (Ki = 0.2 nM). Neither FKBP binding nor inhibition of rotamase activity of FKBP alone is sufficient to explain the biologic actions of these drugs. Rather, these findings suggest that immunophilin bound to FK506 interferes with antigen receptor-induced signals, while rapamycin bound to the immunophilin interferes with IL-2-induced signals. " ], "offsets": [ [ 0, 1914 ] ] } ]

[ { "id": "PMID-2123553_T1", "type": "Protein", "text": [ "interleukin 2" ], "offsets": [ [ 370, 383 ] ], "normalized": [] }, { "id": "PMID-2123553_T2", "type": "Protein", "text": [ "IL-2" ], "offsets": [ [ 385, 389 ] ], "normalized": [] }, { "id": "PMID-2123553_T3", "type": "Protein", "text": [ "IL-2" ], "offsets": [ [ 926, 930 ] ], "normalized": [] }, { "id": "PMID-2123553_T4", "type": "Protein", "text": [ "IL-2" ], "offsets": [ [ 1048, 1052 ] ], "normalized": [] }, { "id": "PMID-2123553_T5", "type": "Protein", "text": [ "IL-2" ], "offsets": [ [ 1153, 1157 ] ], "normalized": [] }, { "id": "PMID-2123553_T6", "type": "Protein", "text": [ "IL-2" ], "offsets": [ [ 1892, 1896 ] ], "normalized": [] } ]

[ { "id": "PMID-2123553_E1", "type": "Negative_regulation", "trigger": { "text": [ "needed to revert" ], "offsets": [ [ 880, 896 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "PMID-2123553_E2" } ] }, { "id": "PMID-2123553_E2", "type": "Negative_regulation", "trigger": { "text": [ "inhibition" ], "offsets": [ [ 912, 922 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "PMID-2123553_E3" } ] }, { "id": "PMID-2123553_E3", "type": "Gene_expression", "trigger": { "text": [ "production" ], "offsets": [ [ 931, 941 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "PMID-2123553_T3" } ] }, { "id": "PMID-2123553_E4", "type": "Positive_regulation", "trigger": { "text": [ "necessary" ], "offsets": [ [ 1034, 1043 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "PMID-2123553_E5" } ] }, { "id": "PMID-2123553_E5", "type": "Positive_regulation", "trigger": { "text": [ "activation" ], "offsets": [ [ 1058, 1068 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "PMID-2123553_T4" } ] } ]

[ { "id": "PMID-2123553_1", "entity_ids": [ "PMID-2123553_T1", "PMID-2123553_T2" ] } ]

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[ { "id": "PMID-2127692__text", "type": "abstract", "text": [ "Transcriptional down-regulation of c-myc expression by protein synthesis-dependent and -independent pathways in a human T lymphoblastic tumor cell line. \nWe show that in the human T lymphoblastic tumor cell line Molt4 c-myc mRNA and protein expression is down-regulated after exposure to dimethyl sulfoxide, to phorbol myristate acetate, or to the calcium ionophore A23187, which raises the intracellular calcium concentration. A block to RNA elongation is largely responsible for decreased c-myc transcription. Although negative regulation by dimethyl sulfoxide takes place even when protein synthesis is inhibited by cycloheximide, the phorbol myristate acetate effect is blocked to some extent only by cycloheximide. The calcium ionophore-induced c-myc suppression, however, strictly requires de novo protein synthesis. Therefore, two different negative regulatory pathways are involved in c-myc regulation: one which is independent and one which depends on de novo protein synthesis. The latter one appears to be mediated by a rapidly calcium-dependent induced gene product. " ], "offsets": [ [ 0, 1079 ] ] } ]

[ { "id": "PMID-2127692_T1", "type": "Protein", "text": [ "c-myc" ], "offsets": [ [ 35, 40 ] ], "normalized": [] }, { "id": "PMID-2127692_T2", "type": "Protein", "text": [ "c-myc" ], "offsets": [ [ 218, 223 ] ], "normalized": [] }, { "id": "PMID-2127692_T3", "type": "Protein", "text": [ "c-myc" ], "offsets": [ [ 491, 496 ] ], "normalized": [] }, { "id": "PMID-2127692_T4", "type": "Protein", "text": [ "c-myc" ], "offsets": [ [ 750, 755 ] ], "normalized": [] }, { "id": "PMID-2127692_T5", "type": "Protein", "text": [ "c-myc" ], "offsets": [ [ 893, 898 ] ], "normalized": [] } ]

[ { "id": "PMID-2127692_E1", "type": "Negative_regulation", "trigger": { "text": [ "down-regulation" ], "offsets": [ [ 16, 31 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "PMID-2127692_E2" } ] }, { "id": "PMID-2127692_E2", "type": "Gene_expression", "trigger": { "text": [ "expression" ], "offsets": [ [ 41, 51 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "PMID-2127692_T1" } ] }, { "id": "PMID-2127692_E3", "type": "Transcription", "trigger": { "text": [ "expression" ], "offsets": [ [ 241, 251 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "PMID-2127692_T2" } ] }, { "id": "PMID-2127692_E4", "type": "Gene_expression", "trigger": { "text": [ "expression" ], "offsets": [ [ 241, 251 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "PMID-2127692_T2" } ] }, { "id": "PMID-2127692_E5", "type": "Negative_regulation", "trigger": { "text": [ "down-regulated" ], "offsets": [ [ 255, 269 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "PMID-2127692_E4" } ] }, { "id": "PMID-2127692_E6", "type": "Negative_regulation", "trigger": { "text": [ "down-regulated" ], "offsets": [ [ 255, 269 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "PMID-2127692_E3" } ] }, { "id": "PMID-2127692_E7", "type": "Regulation", "trigger": { "text": [ "responsible" ], "offsets": [ [ 465, 476 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "PMID-2127692_E8" } ] }, { "id": "PMID-2127692_E8", "type": "Negative_regulation", "trigger": { "text": [ "decreased" ], "offsets": [ [ 481, 490 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "PMID-2127692_E9" } ] }, { "id": "PMID-2127692_E9", "type": "Transcription", "trigger": { "text": [ "transcription" ], "offsets": [ [ 497, 510 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "PMID-2127692_T3" } ] }, { "id": "PMID-2127692_E10", "type": "Negative_regulation", "trigger": { "text": [ "negative regulation" ], "offsets": [ [ 521, 540 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "PMID-2127692_E3" } ] }, { "id": "PMID-2127692_E11", "type": "Negative_regulation", "trigger": { "text": [ "negative regulation" ], "offsets": [ [ 521, 540 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "PMID-2127692_E4" } ] }, { "id": "PMID-2127692_E12", "type": "Positive_regulation", "trigger": { "text": [ "when" ], "offsets": [ [ 580, 584 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "PMID-2127692_E10" } ] }, { "id": "PMID-2127692_E13", "type": "Positive_regulation", "trigger": { "text": [ "when" ], "offsets": [ [ 580, 584 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "PMID-2127692_E11" } ] }, { "id": "PMID-2127692_E14", "type": "Negative_regulation", "trigger": { "text": [ "effect" ], "offsets": [ [ 664, 670 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "PMID-2127692_E3" } ] }, { "id": "PMID-2127692_E15", "type": "Negative_regulation", "trigger": { "text": [ "effect" ], "offsets": [ [ 664, 670 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "PMID-2127692_E4" } ] }, { "id": "PMID-2127692_E16", "type": "Negative_regulation", "trigger": { "text": [ "blocked" ], "offsets": [ [ 674, 681 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "PMID-2127692_E14" } ] }, { "id": "PMID-2127692_E17", "type": "Negative_regulation", "trigger": { "text": [ "blocked" ], "offsets": [ [ 674, 681 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "PMID-2127692_E15" } ] }, { "id": "PMID-2127692_E18", "type": "Negative_regulation", "trigger": { "text": [ "suppression" ], "offsets": [ [ 756, 767 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "PMID-2127692_T4" } ] }, { "id": "PMID-2127692_E19", "type": "Positive_regulation", "trigger": { "text": [ "requires" ], "offsets": [ [ 787, 795 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "PMID-2127692_E18" } ] }, { "id": "PMID-2127692_E20", "type": "Regulation", "trigger": { "text": [ "regulation" ], "offsets": [ [ 899, 909 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "PMID-2127692_T5" } ] } ]

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[ { "id": "PMID-2144551__text", "type": "abstract", "text": [ "Induction of immediate early response genes by macrophage colony-stimulating factor in normal human monocytes. \nA group of coordinately induced protooncogenes, cytoskeletal, and extracellular matrix genes have been termed immediate early response genes, and their induction has been associated with growth factor-stimulated cell proliferation. We have investigated the induction of these genes by macrophage-CSF (M-CSF) in human monocytes that do not proliferate in response to M-CSF but require the factor for optimal cell differentiation. Normal human monocytes were isolated, carefully washed, and incubated for 36 to 48 h in fetal bovine serum-containing medium. At the end of this incubation the resting cells were stimulated with M-CSF, and RNA was isolated for analysis by Northern blotting. RNA from control resting cells contained low to undetectable levels of c-jun, fibronectin receptor, and actin mRNA. Within 15 to 30 min of addition of M-CSF, however, there was a dramatic coordinate induction of these genes. The c-jun gene expression was very transient and was not detectable by 60 min after M-CSF addition. In contrast, the expression of actin and fibronectin receptor mRNA was more sustained, and the expression of these genes remained elevated at 24 to 48 h after M-CSF addition. We also observed the induction of the myelomonocytic specific tyrosine kinase hck gene simultaneously with the other immediate early response genes. The protein synthesis inhibitor cycloheximide did not block the induction of any of these genes, and in fact, super-induced the expression of c-jun and hck. Nuclear run on transcription of the c-jun, hck, and actin genes. Therefore, in normal human monocytes M-CSF induces immediate early response genes without inducing cell proliferation. These genes may then play a role in altering the physiologic status of the cells in response to CSF. " ], "offsets": [ [ 0, 1890 ] ] } ]

[ { "id": "PMID-2144551_T1", "type": "Protein", "text": [ "macrophage-CSF" ], "offsets": [ [ 397, 411 ] ], "normalized": [] }, { "id": "PMID-2144551_T2", "type": "Protein", "text": [ "M-CSF" ], "offsets": [ [ 413, 418 ] ], "normalized": [] }, { "id": "PMID-2144551_T3", "type": "Protein", "text": [ "M-CSF" ], "offsets": [ [ 478, 483 ] ], "normalized": [] }, { "id": "PMID-2144551_T4", "type": "Protein", "text": [ "M-CSF" ], "offsets": [ [ 736, 741 ] ], "normalized": [] }, { "id": "PMID-2144551_T5", "type": "Protein", "text": [ "c-jun" ], "offsets": [ [ 870, 875 ] ], "normalized": [] }, { "id": "PMID-2144551_T6", "type": "Protein", "text": [ "M-CSF" ], "offsets": [ [ 950, 955 ] ], "normalized": [] }, { "id": "PMID-2144551_T7", "type": "Protein", "text": [ "c-jun" ], "offsets": [ [ 1028, 1033 ] ], "normalized": [] }, { "id": "PMID-2144551_T8", "type": "Protein", "text": [ "M-CSF" ], "offsets": [ [ 1108, 1113 ] ], "normalized": [] }, { "id": "PMID-2144551_T9", "type": "Protein", "text": [ "M-CSF" ], "offsets": [ [ 1283, 1288 ] ], "normalized": [] }, { "id": "PMID-2144551_T10", "type": "Protein", "text": [ "hck" ], "offsets": [ [ 1377, 1380 ] ], "normalized": [] }, { "id": "PMID-2144551_T11", "type": "Protein", "text": [ "c-jun" ], "offsets": [ [ 1590, 1595 ] ], "normalized": [] }, { "id": "PMID-2144551_T12", "type": "Protein", "text": [ "hck" ], "offsets": [ [ 1600, 1603 ] ], "normalized": [] }, { "id": "PMID-2144551_T13", "type": "Protein", "text": [ "c-jun" ], "offsets": [ [ 1641, 1646 ] ], "normalized": [] }, { "id": "PMID-2144551_T14", "type": "Protein", "text": [ "hck" ], "offsets": [ [ 1648, 1651 ] ], "normalized": [] }, { "id": "PMID-2144551_T15", "type": "Protein", "text": [ "M-CSF" ], "offsets": [ [ 1707, 1712 ] ], "normalized": [] } ]

[ { "id": "PMID-2144551_E1", "type": "Transcription", "trigger": { "text": [ "levels" ], "offsets": [ [ 860, 866 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "PMID-2144551_T5" } ] }, { "id": "PMID-2144551_E2", "type": "Positive_regulation", "trigger": { "text": [ "induction" ], "offsets": [ [ 998, 1007 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "PMID-2144551_T5" } ] }, { "id": "PMID-2144551_E3", "type": "Gene_expression", "trigger": { "text": [ "expression" ], "offsets": [ [ 1039, 1049 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "PMID-2144551_T7" } ] }, { "id": "PMID-2144551_E4", "type": "Positive_regulation", "trigger": { "text": [ "after" ], "offsets": [ [ 1102, 1107 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "PMID-2144551_E3" }, { "role": "Cause", "ref_id": "PMID-2144551_T8" } ] }, { "id": "PMID-2144551_E5", "type": "Positive_regulation", "trigger": { "text": [ "induction" ], "offsets": [ [ 1320, 1329 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "PMID-2144551_T10" } ] }, { "id": "PMID-2144551_E6", "type": "Positive_regulation", "trigger": { "text": [ "super-induced" ], "offsets": [ [ 1558, 1571 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "PMID-2144551_E8" } ] }, { "id": "PMID-2144551_E7", "type": "Gene_expression", "trigger": { "text": [ "expression" ], "offsets": [ [ 1576, 1586 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "PMID-2144551_T12" } ] }, { "id": "PMID-2144551_E8", "type": "Gene_expression", "trigger": { "text": [ "expression" ], "offsets": [ [ 1576, 1586 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "PMID-2144551_T11" } ] }, { "id": "PMID-2144551_E9", "type": "Transcription", "trigger": { "text": [ "transcription" ], "offsets": [ [ 1620, 1633 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "PMID-2144551_T13" } ] }, { "id": "PMID-2144551_E10", "type": "Transcription", "trigger": { "text": [ "transcription" ], "offsets": [ [ 1620, 1633 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "PMID-2144551_T14" } ] } ]

[ { "id": "PMID-2144551_1", "entity_ids": [ "PMID-2144551_T1", "PMID-2144551_T2" ] } ]

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[ { "id": "PMID-2146676__text", "type": "abstract", "text": [ "Stimulation of a human T-cell clone with anti-CD3 or tumor necrosis factor induces NF-kappa B translocation but not human immunodeficiency virus 1 enhancer-dependent transcription. \nThe expression of transiently transfected expression vectors under the control of the long terminal repeat (LTR) of the human immunodeficiency virus (HIV) or its enhancer sequence and the translocation of the HIV enhancer-binding protein NF-kappa B were analyzed in two human T-cell clones stimulated through their T-cell receptor complex or by tumor necrosis factor or phorbol 12-myristate 13-acetate. We found a dissociation of NF-kappa B translocation from transactivation of either the HIV LTR or the HIV enhancer. Interleukin 2 induced proliferation but not NF-kappa B translocation or LTR transactivation. Phorbol ester or specific antigen recognition induced HIV LTR transactivation, whereas stimulation with tumor necrosis factor or antibody to CD3 did not. The two latter signals were nevertheless able to induce NF-kappa B translocation with a pattern in the band-shift assay indistinguishable from that observed using phorbol ester. Our finding that induction of NF-kappa B by tumor necrosis factor or antibody to CD3 is not sufficient to induce HIV enhancer-dependent transcription in cloned T cells contrasts with results obtained in most lymphoblastoid T-cell lines and indicates that normal T lymphocytes differ from tumoral T cells in terms of requirements for HIV LTR activation. Furthermore, our results suggest that events linked to T-cell activation, in addition to NF-kappa B translocation per se, induce functional interactions of the NF-kappa B complex with the HIV enhancer. " ], "offsets": [ [ 0, 1681 ] ] } ]

[ { "id": "PMID-2146676_T1", "type": "Protein", "text": [ "Interleukin 2" ], "offsets": [ [ 701, 714 ] ], "normalized": [] } ]

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[ { "id": "PMID-2148290__text", "type": "abstract", "text": [ "Lymphoid specific gene expression of the adenovirus early region 3 promoter is mediated by NF-kappa B binding motifs. \nA primary site of infection by human adenoviruses is lymphoid cells. However, analysis of the viral control elements and the cellular factors that regulate adenoviral gene expression in lymphocytes has not been reported. The adenovirus early region 3 (ES) gene products are involved in the maintenance of viral persistence by complexing with the class I MHC antigens, thus preventing their cell surface expression with a resultant decrease in host immunologic destruction. To determine whether different cellular factors were involved in E3 regulation in lymphocytes as compared with HeLa cells, both DNA binding and transfection analysis with the E3 promoter in both cell types were performed. These studies detected two novel domains referred to as L1 and L2 with a variety of lymphoid but not HeLa extracts. Each of these domains possessed strong homology to motifs previously found to bind the cellular factor NF-kappa B. Transfections of E3 constructs linked to the chloramphenicol acetyltransferase gene revealed that mutagenesis of the distal NF-kappa B motif (L2) had minimal effects on promoter expression in HeLa cells, but resulted in dramatic decreases in expression by lymphoid cells. In contrast, mutagenesis of proximal NF-kappa B motif (L1) had minimal effects on gene expression in both HeLa cells and lymphoid cells but resulted in a small, but reproducible, increase in gene expression in lymphoid cells when coupled to the L2 mutation. Reversing the position and subsequent mutagenesis of the L1 and L2 domains indicated that the primary sequence of these motifs rather than their position in the E3 promoter was critical for regulating gene expression. (ABSTRACT TRUNCATED AT 250 WORDS) " ], "offsets": [ [ 0, 1827 ] ] } ]

[ { "id": "PMID-2148290_T1", "type": "Protein", "text": [ "chloramphenicol acetyltransferase" ], "offsets": [ [ 1090, 1123 ] ], "normalized": [] } ]

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[ { "id": "PMID-2172166__text", "type": "abstract", "text": [ "Characterization of defensin resistance phenotypes associated with mutations in the phoP virulence regulon of Salmonella typhimurium. \nThe defensin sensitivities of Salmonella typhimurium strains with mutations in the phoP/phoQ two-component virulence regulon were tested by using purified defensins NP-1 and NP-2. Strains with mutations in either gene of the regulatory pair (phoP [transcriptional activator] or phoQ [membrane sensor kinase]) had increased sensitivities to defensin. The predicted periplasmic domain of the PhoQ protein contained a markedly anionic domain that could interact with cationic proteins and that could be responsible for resistance to defensin. Because insertion mutations in phoP are polar on phoQ, we constructed strains that expressed the PhoQ protein in the absence of PhoP to test whether resistance to defensin requires only the phoQ gene product. We found that resistance to defensin requires the function of both components of this regulatory system, because strains expressing PhoQ without PhoP were still markedly sensitive to defensins. This implied that a pag (phoP-activated gene) product is responsible for defensin resistance. We also tested for the ability of defensins NP-1, NP-5, and HNP-1 to activate pag expression and found that these peptides have no effect. Defensin resistance is not the only virulence characteristic controlled by the PhoP-PhoQ regulon because mutations in pagC, as well as ones in the phoP locus that resulted in constitutive pag activation (phenotype PhoPc), had no effect on defensin resistance, even though they rendered the organism avirulent and deficient in survival within macrophages. The virulence defect conferred by mutations in the phoP-phoQ two-component regulatory system is not completely explained by alterations in resistance to cationic proteins and involves the control of other proteins necessary for S. typhimurium survival within macrophages. " ], "offsets": [ [ 0, 1938 ] ] } ]

[ { "id": "PMID-2172166_T1", "type": "Protein", "text": [ "phoP" ], "offsets": [ [ 218, 222 ] ], "normalized": [] }, { "id": "PMID-2172166_T2", "type": "Protein", "text": [ "phoQ" ], "offsets": [ [ 223, 227 ] ], "normalized": [] }, { "id": "PMID-2172166_T3", "type": "Protein", "text": [ "NP-1" ], "offsets": [ [ 300, 304 ] ], "normalized": [] }, { "id": "PMID-2172166_T4", "type": "Protein", "text": [ "NP-2" ], "offsets": [ [ 309, 313 ] ], "normalized": [] }, { "id": "PMID-2172166_T5", "type": "Protein", "text": [ "phoP" ], "offsets": [ [ 377, 381 ] ], "normalized": [] }, { "id": "PMID-2172166_T6", "type": "Protein", "text": [ "phoQ" ], "offsets": [ [ 413, 417 ] ], "normalized": [] }, { "id": "PMID-2172166_T7", "type": "Protein", "text": [ "PhoQ" ], "offsets": [ [ 525, 529 ] ], "normalized": [] }, { "id": "PMID-2172166_T8", "type": "Protein", "text": [ "phoP" ], "offsets": [ [ 706, 710 ] ], "normalized": [] }, { "id": "PMID-2172166_T9", "type": "Protein", "text": [ "phoQ" ], "offsets": [ [ 724, 728 ] ], "normalized": [] }, { "id": "PMID-2172166_T10", "type": "Protein", "text": [ "PhoQ" ], "offsets": [ [ 772, 776 ] ], "normalized": [] }, { "id": "PMID-2172166_T11", "type": "Protein", "text": [ "PhoP" ], "offsets": [ [ 803, 807 ] ], "normalized": [] }, { "id": "PMID-2172166_T12", "type": "Protein", "text": [ "phoQ" ], "offsets": [ [ 865, 869 ] ], "normalized": [] }, { "id": "PMID-2172166_T13", "type": "Protein", "text": [ "PhoQ" ], "offsets": [ [ 1016, 1020 ] ], "normalized": [] }, { "id": "PMID-2172166_T14", "type": "Protein", "text": [ "PhoP" ], "offsets": [ [ 1029, 1033 ] ], "normalized": [] }, { "id": "PMID-2172166_T15", "type": "Protein", "text": [ "NP-1" ], "offsets": [ [ 1216, 1220 ] ], "normalized": [] }, { "id": "PMID-2172166_T16", "type": "Protein", "text": [ "NP-5" ], "offsets": [ [ 1222, 1226 ] ], "normalized": [] }, { "id": "PMID-2172166_T17", "type": "Protein", "text": [ "HNP-1" ], "offsets": [ [ 1232, 1237 ] ], "normalized": [] }, { "id": "PMID-2172166_T18", "type": "Protein", "text": [ "PhoP" ], "offsets": [ [ 1390, 1394 ] ], "normalized": [] }, { "id": "PMID-2172166_T19", "type": "Protein", "text": [ "PhoQ" ], "offsets": [ [ 1395, 1399 ] ], "normalized": [] }, { "id": "PMID-2172166_T20", "type": "Protein", "text": [ "pagC" ], "offsets": [ [ 1429, 1433 ] ], "normalized": [] }, { "id": "PMID-2172166_T21", "type": "Protein", "text": [ "phoP" ], "offsets": [ [ 1458, 1462 ] ], "normalized": [] }, { "id": "PMID-2172166_T22", "type": "Protein", "text": [ "phoP" ], "offsets": [ [ 1717, 1721 ] ], "normalized": [] }, { "id": "PMID-2172166_T23", "type": "Protein", "text": [ "phoQ" ], "offsets": [ [ 1722, 1726 ] ], "normalized": [] } ]

[ { "id": "PMID-2172166_E1", "type": "Gene_expression", "trigger": { "text": [ "expressed" ], "offsets": [ [ 758, 767 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "PMID-2172166_T10" } ] }, { "id": "PMID-2172166_E2", "type": "Gene_expression", "trigger": { "text": [ "expressing" ], "offsets": [ [ 1005, 1015 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "PMID-2172166_T14" } ] }, { "id": "PMID-2172166_E3", "type": "Gene_expression", "trigger": { "text": [ "expressing" ], "offsets": [ [ 1005, 1015 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "PMID-2172166_T13" } ] } ]

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[ { "id": "PMID-2192264__text", "type": "abstract", "text": [ "Involvement of cyclic AMP-dependent protein kinases in the signal transduction pathway for interleukin-1. \nExpression of a highly specific protein inhibitor for cyclic AMP-dependent protein kinases in interleukin-1 (IL-1)-responsive cells blocked IL-1-induced gene transcription that was driven by the kappa immunoglobulin enhancer or the human immunodeficiency virus long terminal repeat. This inhibitor did not affect protein kinase C-mediated gene transcription, suggesting that cyclic AMP-dependent protein kinases are involved in the signal transduction pathway for IL-1 in a number of responsive cell types. " ], "offsets": [ [ 0, 614 ] ] } ]

[ { "id": "PMID-2192264_T1", "type": "Protein", "text": [ "interleukin-1" ], "offsets": [ [ 91, 104 ] ], "normalized": [] }, { "id": "PMID-2192264_T2", "type": "Protein", "text": [ "interleukin-1" ], "offsets": [ [ 201, 214 ] ], "normalized": [] }, { "id": "PMID-2192264_T3", "type": "Protein", "text": [ "IL-1" ], "offsets": [ [ 216, 220 ] ], "normalized": [] }, { "id": "PMID-2192264_T4", "type": "Protein", "text": [ "IL-1" ], "offsets": [ [ 247, 251 ] ], "normalized": [] }, { "id": "PMID-2192264_T5", "type": "Protein", "text": [ "kappa immunoglobulin" ], "offsets": [ [ 302, 322 ] ], "normalized": [] }, { "id": "PMID-2192264_T6", "type": "Protein", "text": [ "IL-1" ], "offsets": [ [ 571, 575 ] ], "normalized": [] } ]

[]

[ { "id": "PMID-2192264_1", "entity_ids": [ "PMID-2192264_T2", "PMID-2192264_T3" ] } ]

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[ { "id": "PMID-2193097__text", "type": "abstract", "text": [ "Lipopolysaccharide is a potent monocyte/macrophage-specific stimulator of human immunodeficiency virus type 1 expression. \nLipopolysaccharide (LPS) potently stimulates human immunodeficiency virus type 1-long terminal repeat (HIV-1-LTR) CAT constructs transfected into monocyte/macrophage-like cell lines but not a T cell line. This effect appears to be mediated through the induction of nuclear factor kappa B (NF-kappa B). Electrophoretic mobility shift assays demonstrate that LPS induces a DNA binding activity indistinguishable from NF-kappa B in U937 and THP-1 cells. LPS is also shown to dramatically increase HIV-1 production from a chronically infected monocyte/macrophage-like cloned cell line, U1, which produces very low levels of HIV-1 at baseline. The stimulation of viral production from this cell line occurs only if these cells are treated with granulocyte/macrophage colony-stimulating factor (GM-CSF) before treatment with LPS. This stimulation of HIV-1 production is correlated with an increase in the level of HIV-1 RNA and and activation of NF-kappa B. LPS is not able to induce HIV-1 production in a cloned T cell line. The effect of LPS on HIV-1 replication occurs at picogram per milliliter concentrations and may be clinically significant in understanding the variability of the natural history of HIV-1 infection. " ], "offsets": [ [ 0, 1341 ] ] } ]

[ { "id": "PMID-2193097_T1", "type": "Protein", "text": [ "CAT" ], "offsets": [ [ 237, 240 ] ], "normalized": [] }, { "id": "PMID-2193097_T2", "type": "Protein", "text": [ "granulocyte/macrophage colony-stimulating factor" ], "offsets": [ [ 862, 910 ] ], "normalized": [] }, { "id": "PMID-2193097_T3", "type": "Protein", "text": [ "GM-CSF" ], "offsets": [ [ 912, 918 ] ], "normalized": [] } ]

[]

[ { "id": "PMID-2193097_1", "entity_ids": [ "PMID-2193097_T2", "PMID-2193097_T3" ] } ]

[]

[ { "id": "PMID-2196387__text", "type": "abstract", "text": [ "Inducible nuclear factor binding to the kappa B elements of the human immunodeficiency virus enhancer in T cells can be blocked by cyclosporin A in a signal-dependent manner. \nCyclosporin A (CsA) is thought to exert its immunosuppressive effects by inhibiting the expression of a distinct set of lymphokine genes which are induced upon T-cell activation, among them the gene coding for interleukin-2. In addition, the activation of the human immunodeficiency virus (HIV) is partially suppressed. To better understand the molecular mechanisms underlying suppression by CsA, we have investigated the effects of this drug on transcription factors in T cells. Here we report that the formation of two distinct mitogen-inducible DNA-binding complexes, the kappa B complex within the HIV enhancer and the NFAT-1 complex within the interleukin-2 enhancer, is inhibited in the presence of CsA. The kappa B-binding activity with the HIV enhancer is inhibited only if it is activated via the mitogen phytohemagglutinin whereas phorbol myristate acetate-mediated activation is completely insensitive to the drug. This suggests a model in which functionally indistinguishable kappa B complexes can be activated via two separate pathways of signal transduction distinguishable by CsA. " ], "offsets": [ [ 0, 1272 ] ] } ]

[ { "id": "PMID-2196387_T1", "type": "Protein", "text": [ "interleukin-2" ], "offsets": [ [ 386, 399 ] ], "normalized": [] }, { "id": "PMID-2196387_T2", "type": "Protein", "text": [ "NFAT-1" ], "offsets": [ [ 799, 805 ] ], "normalized": [] }, { "id": "PMID-2196387_T3", "type": "Protein", "text": [ "interleukin-2" ], "offsets": [ [ 825, 838 ] ], "normalized": [] }, { "id": "PMID-2196387_T7", "type": "Entity", "text": [ "enhancer" ], "offsets": [ [ 839, 847 ] ], "normalized": [] } ]

[ { "id": "PMID-2196387_E1", "type": "Negative_regulation", "trigger": { "text": [ "inhibiting" ], "offsets": [ [ 249, 259 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "PMID-2196387_E2" } ] }, { "id": "PMID-2196387_E2", "type": "Gene_expression", "trigger": { "text": [ "expression" ], "offsets": [ [ 264, 274 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "PMID-2196387_T1" } ] }, { "id": "PMID-2196387_E3", "type": "Binding", "trigger": { "text": [ "formation" ], "offsets": [ [ 680, 689 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "PMID-2196387_T2" }, { "role": "Theme", "ref_id": "PMID-2196387_T3" }, { "role": "Site", "ref_id": "PMID-2196387_T7" } ] }, { "id": "PMID-2196387_E4", "type": "Negative_regulation", "trigger": { "text": [ "inhibited" ], "offsets": [ [ 852, 861 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "PMID-2196387_E3" } ] } ]

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[ { "id": "PMID-2204723__text", "type": "abstract", "text": [ "Cell-specific differences in activation of NF-kappa B regulatory elements of human immunodeficiency virus and beta interferon promoters by tumor necrosis factor. \nThree aspects of the involvement of tumor necrosis factor in human immunodeficiency virus (HIV) pathogenesis were examined. Tumor necrosis factor alpha (TNF-alpha) mRNA production was analyzed by polymerase chain reaction amplification in monocytic U937 cells and in a chronically HIV infected U937 cell line (U9-IIIB). TNF-alpha RNA was undetectable in U937 cells, whereas a low constitutive level was detected in U9-IIIB cells. Paramyxovirus infection induced a 5- to 10-fold increase in the steady-state level of TNF-alpha RNA in U9-IIIB cells compared with U937 cells, suggesting that HIV-infected monocytic cells produced higher levels of TNF-alpha than did normal cells after a secondary virus infection. The effects of TNF-alpha on gene expression were examined by transient expression assays using reporter chloramphenicol acetyltransferase plasmids linked to regulatory elements from the HIV long terminal repeat (LTR) and the beta interferon promoter. In U937 and Jurkat T lymphoid cells, the inducibility of the different hybrid promoters by TNF-alpha or phorbol ester varied in a cell type- and promoter context-specific manner; the levels of gene activity of NF-kappa B-containing plasmids correlated directly with induction of NF-kappa B DNA-binding activity. Although the intact beta interferon promoter was only weakly stimulated by phorbol ester or TNF-alpha, multimers of the PRDII NF-kappa B-binding domain were inducible by both agents. TNF-alpha was able to increase expression of the HIV LTR in T cells, but in monocytic cells, TNF-alpha did not induce the HIV LTR above a constitutive level of activity. This level of NF-kappa B-independent activity appears to be sufficient for virus multiplication, since TNF-alpha treatment had no effect on the kinetics of de novo HIV type 1 (HIV-1) infection and viral RNA production in U937 cells. However, in Jurkat cells, TNF-alpha dramatically enhanced the spread of HIV-1 through the cell population and increased viral RNA synthesis, indicating that in T cells HIV-1 multiplication was stimulated by TNF-alpha treatment. " ], "offsets": [ [ 0, 2251 ] ] } ]

[ { "id": "PMID-2204723_T1", "type": "Protein", "text": [ "tumor necrosis factor" ], "offsets": [ [ 139, 160 ] ], "normalized": [] }, { "id": "PMID-2204723_T2", "type": "Protein", "text": [ "tumor necrosis factor" ], "offsets": [ [ 199, 220 ] ], "normalized": [] }, { "id": "PMID-2204723_T3", "type": "Protein", "text": [ "Tumor necrosis factor alpha" ], "offsets": [ [ 287, 314 ] ], "normalized": [] }, { "id": "PMID-2204723_T4", "type": "Protein", "text": [ "TNF-alpha" ], "offsets": [ [ 316, 325 ] ], "normalized": [] }, { "id": "PMID-2204723_T5", "type": "Protein", "text": [ "TNF-alpha" ], "offsets": [ [ 483, 492 ] ], "normalized": [] }, { "id": "PMID-2204723_T6", "type": "Protein", "text": [ "TNF-alpha" ], "offsets": [ [ 679, 688 ] ], "normalized": [] }, { "id": "PMID-2204723_T7", "type": "Protein", "text": [ "TNF-alpha" ], "offsets": [ [ 807, 816 ] ], "normalized": [] }, { "id": "PMID-2204723_T8", "type": "Protein", "text": [ "TNF-alpha" ], "offsets": [ [ 889, 898 ] ], "normalized": [] }, { "id": "PMID-2204723_T9", "type": "Protein", "text": [ "chloramphenicol acetyltransferase" ], "offsets": [ [ 978, 1011 ] ], "normalized": [] }, { "id": "PMID-2204723_T10", "type": "Protein", "text": [ "beta interferon" ], "offsets": [ [ 1099, 1114 ] ], "normalized": [] }, { "id": "PMID-2204723_T11", "type": "Protein", "text": [ "TNF-alpha" ], "offsets": [ [ 1216, 1225 ] ], "normalized": [] }, { "id": "PMID-2204723_T12", "type": "Protein", "text": [ "beta interferon" ], "offsets": [ [ 1457, 1472 ] ], "normalized": [] }, { "id": "PMID-2204723_T13", "type": "Protein", "text": [ "TNF-alpha" ], "offsets": [ [ 1529, 1538 ] ], "normalized": [] }, { "id": "PMID-2204723_T14", "type": "Protein", "text": [ "TNF-alpha" ], "offsets": [ [ 1620, 1629 ] ], "normalized": [] }, { "id": "PMID-2204723_T15", "type": "Protein", "text": [ "TNF-alpha" ], "offsets": [ [ 1713, 1722 ] ], "normalized": [] }, { "id": "PMID-2204723_T16", "type": "Protein", "text": [ "TNF-alpha" ], "offsets": [ [ 1893, 1902 ] ], "normalized": [] }, { "id": "PMID-2204723_T17", "type": "Protein", "text": [ "TNF-alpha" ], "offsets": [ [ 2049, 2058 ] ], "normalized": [] }, { "id": "PMID-2204723_T18", "type": "Protein", "text": [ "TNF-alpha" ], "offsets": [ [ 2230, 2239 ] ], "normalized": [] }, { "id": "PMID-2204723_T26", "type": "Entity", "text": [ "promoter" ], "offsets": [ [ 1473, 1481 ] ], "normalized": [] } ]

[ { "id": "PMID-2204723_E1", "type": "Transcription", "trigger": { "text": [ "production" ], "offsets": [ [ 332, 342 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "PMID-2204723_T4" } ] }, { "id": "PMID-2204723_E2", "type": "Transcription", "trigger": { "text": [ "undetectable" ], "offsets": [ [ 501, 513 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "PMID-2204723_T5" } ] }, { "id": "PMID-2204723_E3", "type": "Transcription", "trigger": { "text": [ "detected" ], "offsets": [ [ 566, 574 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "PMID-2204723_T5" } ] }, { "id": "PMID-2204723_E4", "type": "Positive_regulation", "trigger": { "text": [ "induced" ], "offsets": [ [ 617, 624 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "PMID-2204723_E5" } ] }, { "id": "PMID-2204723_E5", "type": "Positive_regulation", "trigger": { "text": [ "increase" ], "offsets": [ [ 641, 649 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "PMID-2204723_T6" } ] }, { "id": "PMID-2204723_E6", "type": "Gene_expression", "trigger": { "text": [ "produced" ], "offsets": [ [ 781, 789 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "PMID-2204723_T7" } ] }, { "id": "PMID-2204723_E7", "type": "Positive_regulation", "trigger": { "text": [ "higher levels" ], "offsets": [ [ 790, 803 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "PMID-2204723_E6" } ] }, { "id": "PMID-2204723_E8", "type": "Positive_regulation", "trigger": { "text": [ "stimulated" ], "offsets": [ [ 1498, 1508 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "PMID-2204723_T12" }, { "role": "Site", "ref_id": "PMID-2204723_T26" } ] }, { "id": "PMID-2204723_E9", "type": "Positive_regulation", "trigger": { "text": [ "stimulated" ], "offsets": [ [ 1498, 1508 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "PMID-2204723_T12" }, { "role": "Cause", "ref_id": "PMID-2204723_T13" }, { "role": "Site", "ref_id": "PMID-2204723_T26" } ] } ]

[ { "id": "PMID-2204723_1", "entity_ids": [ "PMID-2204723_T4", "PMID-2204723_T3" ] } ]

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[ { "id": "PMID-2216722__text", "type": "abstract", "text": [ "Astrocytes and glioblastoma cells express novel octamer-DNA binding proteins distinct from the ubiquitous Oct-1 and B cell type Oct-2 proteins. \nThe 'octamer' sequence, ATGCAAAT or its complement ATTTGCAT, is a key element for the transcriptional regulation of immunoglobulin genes in B-lymphocytes as well as a number of housekeeping genes in all cell types. In lymphocytes, the octamer-binding protein Oct-2A and variants thereof are thought to contribute to the B-cell specific gene expression, while the ubiquitous protein Oct-1 seems to control general octamer site-dependent transcription. Various other genes, for example interleukin-1 and MHC class II genes, contain an octamer sequence in the promoter and are expressed in cells of both the immune and nervous systems. This prompted us to analyze the octamer-binding proteins in the latter cells. Using the electrophoretic mobility shift assay, at least six novel octamer binding proteins were detected in nuclear extracts of cultured mouse astrocytes. These proteins are differentially expressed in human glioblastoma and neuroblastoma cell lines. The nervous system-derived (N-Oct) proteins bound to the octamer DNA sequence in a manner which is indistinguishable from the Oct-1 and Oct-2A proteins. The relationship of the N-Oct proteins to Oct-1 and Oct-2A was analyzed by proteolytic clipping bandshift assays and by their reactivity towards antisera raised against recombinant Oct-1 and Oct-2A proteins. On the basis of these assays, all N-Oct-factors were found to be distinct from the ubiquitous Oct-1 and the lymphoid-specific Oct-2A proteins. In melanoma cells that contain the N-Oct-3 factor, a transfected lymphocyte-specific promoter was neither activated nor was it repressed upon contransfection with an Oct-2A expression vector. We therefore speculate that N-Oct-3 and other N-Oct factors have a specific role in gene expression in cells of the nervous system. " ], "offsets": [ [ 0, 1936 ] ] } ]

[ { "id": "PMID-2216722_T1", "type": "Protein", "text": [ "Oct-1" ], "offsets": [ [ 106, 111 ] ], "normalized": [] }, { "id": "PMID-2216722_T2", "type": "Protein", "text": [ "Oct-2" ], "offsets": [ [ 128, 133 ] ], "normalized": [] }, { "id": "PMID-2216722_T3", "type": "Protein", "text": [ "Oct-2A" ], "offsets": [ [ 404, 410 ] ], "normalized": [] }, { "id": "PMID-2216722_T4", "type": "Protein", "text": [ "Oct-1" ], "offsets": [ [ 527, 532 ] ], "normalized": [] }, { "id": "PMID-2216722_T5", "type": "Protein", "text": [ "Oct-1" ], "offsets": [ [ 1234, 1239 ] ], "normalized": [] }, { "id": "PMID-2216722_T6", "type": "Protein", "text": [ "Oct-2A" ], "offsets": [ [ 1244, 1250 ] ], "normalized": [] }, { "id": "PMID-2216722_T7", "type": "Protein", "text": [ "Oct-1" ], "offsets": [ [ 1303, 1308 ] ], "normalized": [] }, { "id": "PMID-2216722_T8", "type": "Protein", "text": [ "Oct-2A" ], "offsets": [ [ 1313, 1319 ] ], "normalized": [] }, { "id": "PMID-2216722_T9", "type": "Protein", "text": [ "Oct-1" ], "offsets": [ [ 1442, 1447 ] ], "normalized": [] }, { "id": "PMID-2216722_T10", "type": "Protein", "text": [ "Oct-2A" ], "offsets": [ [ 1452, 1458 ] ], "normalized": [] }, { "id": "PMID-2216722_T11", "type": "Protein", "text": [ "Oct-1" ], "offsets": [ [ 1563, 1568 ] ], "normalized": [] }, { "id": "PMID-2216722_T12", "type": "Protein", "text": [ "Oct-2A" ], "offsets": [ [ 1595, 1601 ] ], "normalized": [] }, { "id": "PMID-2216722_T13", "type": "Protein", "text": [ "N-Oct-3" ], "offsets": [ [ 1647, 1654 ] ], "normalized": [] }, { "id": "PMID-2216722_T14", "type": "Protein", "text": [ "Oct-2A" ], "offsets": [ [ 1778, 1784 ] ], "normalized": [] }, { "id": "PMID-2216722_T15", "type": "Protein", "text": [ "N-Oct-3" ], "offsets": [ [ 1832, 1839 ] ], "normalized": [] } ]

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[ { "id": "PMID-2234062__text", "type": "abstract", "text": [ "Cloning of a mitogen-inducible gene encoding a kappa B DNA-binding protein with homology to the rel oncogene and to cell-cycle motifs. \nWe have cloned and characterized a mitogen-inducible gene isolated from human T cells that predicts a protein of 968 amino acids. The amino-terminal domain has regions homologous to the oncogene rel and to the developmentally important gene dorsal of Drosophila. The carboxy-terminal domain contains repeat structures found in a variety of proteins that are involved in cell-cycle control of yeast and in tissue differentiation in Drosophila and Ceanorhabditis elegans, as well as in the putative human oncogene bcl-3 and in the ankyrin protein. A truncated form of the product of this gene translated in vitro is a DNA-binding protein which interacts specifically with the kappa B binding site found in many inducible genes, including the enhancer in human immunodeficiency virus. This gene is yet another in a growing list of important regulatory molecules whose expression is transcriptionally induced upon cellular activation. " ], "offsets": [ [ 0, 1067 ] ] } ]

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[ { "id": "PMID-2237444__text", "type": "abstract", "text": [ "Regulation of gene expression with double-stranded phosphorothioate oligonucleotides. \nAlteration of gene transcription by inhibition of specific transcriptional regulatory proteins is necessary for determining how these factors participate in cellular differentiation. The functions of these proteins can be antagonized by several methods, each with specific limitations. Inhibition of sequence-specific DNA-binding proteins was achieved with double-stranded (ds) phosphorothioate oligonucleotides that contained octamer or kappa B consensus sequences. The phosphorothioate oligonucleotides specifically bound either octamer transcription factor or nuclear factor (NF)-kappa B. The modified oligonucleotides accumulated in cells more effectively than standard ds oligonucleotides and modulated gene expression in a specific manner. Octamer-dependent activation of a reporter plasmid or NF-kappa B-dependent activation of the human immunodeficiency virus (HIV) enhancer was inhibited when the appropriate phosphorothioate oligonucleotide was added to a transiently transfected B cell line. Addition of phosphorothioate oligonucleotides that contained the octamer consensus to Jurkat T leukemia cells inhibited interleukin-2 (IL-2) secretion to a degree similar to that observed with a mutated octamer site in the IL-2 enhancer. The ds phosphorothioate oligonucleotides probably compete for binding of specific transcription factors and may provide anti-viral, immunosuppressive, or other therapeutic effects. " ], "offsets": [ [ 0, 1509 ] ] } ]

[ { "id": "PMID-2237444_T1", "type": "Protein", "text": [ "interleukin-2" ], "offsets": [ [ 1210, 1223 ] ], "normalized": [] }, { "id": "PMID-2237444_T2", "type": "Protein", "text": [ "IL-2" ], "offsets": [ [ 1225, 1229 ] ], "normalized": [] }, { "id": "PMID-2237444_T3", "type": "Protein", "text": [ "IL-2" ], "offsets": [ [ 1313, 1317 ] ], "normalized": [] }, { "id": "PMID-2237444_T6", "type": "Entity", "text": [ "mutated octamer site" ], "offsets": [ [ 1285, 1305 ] ], "normalized": [] } ]

[ { "id": "PMID-2237444_E1", "type": "Negative_regulation", "trigger": { "text": [ "inhibited" ], "offsets": [ [ 1200, 1209 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "PMID-2237444_E3" }, { "role": "Cause", "ref_id": "PMID-2237444_T3" }, { "role": "CSite", "ref_id": "PMID-2237444_T6" } ] }, { "id": "PMID-2237444_E2", "type": "Negative_regulation", "trigger": { "text": [ "inhibited" ], "offsets": [ [ 1200, 1209 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "PMID-2237444_E3" } ] }, { "id": "PMID-2237444_E3", "type": "Localization", "trigger": { "text": [ "secretion" ], "offsets": [ [ 1231, 1240 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "PMID-2237444_T2" } ] } ]

[ { "id": "PMID-2237444_1", "entity_ids": [ "PMID-2237444_T2", "PMID-2237444_T1" ] } ]

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[ { "id": "PMID-2258623__text", "type": "abstract", "text": [ "Differences in transcriptional enhancers of HIV-1 and HIV-2. Response to T cell activation signals. \nT cell activation results in high levels of HIV replication and is thought to be one mechanism leading to the conversion from latent to active viral infection. In HIV-1, the sequences that respond to these signaling events are found in the long terminal repeat (LTR) and comprise the transcriptional enhancer, which contains two conserved binding sites for the nuclear factor kappa B (NF kappa B). The corresponding region in the second AIDS retrovirus, HIV-2, contains a conserved and a divergent NF kappa B binding site. We demonstrate that the HIV-1 LTR responds better than the HIV-2 LTR to T cell activation signals. These qualitative differences in the response to T cell activation are reproduced not only when HIV-1 or HIV-2 enhancers are placed upstream of a heterologous promoter but also when these enhancers are switched between their respective LTR. In electrophoretic mobility shift assays, NF kappa B binds to both conserved sites in the HIV-1 transcriptional enhancer and only to the single conserved site in the HIV-2 transcriptional enhancer. Instead of NF kappa B, the activator protein 3 binds to the divergent site in HIV-2. In conclusion, HIV-1 and HIV-2 are differentially regulated by T cell activation signals, and this difference may account for the longer period of viral latency observed with HIV-2 than with HIV-1 infection. " ], "offsets": [ [ 0, 1455 ] ] } ]

[ { "id": "PMID-2258623_T1", "type": "Protein", "text": [ "activator protein 3" ], "offsets": [ [ 1189, 1208 ] ], "normalized": [] } ]

[ { "id": "PMID-2258623_E1", "type": "Binding", "trigger": { "text": [ "binds" ], "offsets": [ [ 1209, 1214 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "PMID-2258623_T1" } ] } ]

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[ { "id": "PMID-2269427__text", "type": "abstract", "text": [ "An in vitro globin gene switching model based on differentiated embryonic stem cells. \nWe used mouse embryonic stem (ES) cells to study globin gene expression and switching in vitro. We show that ES-derived embryoid bodies express the full complement of mouse embryonic globin genes in the correct temporal order and that on further differentiation, a switch occurs to the fetal/adult genes. In addition, the erythroid-specific transcription factor NF-E1 was shown to be expressed coordinately with that of globin in embryoid bodies. We conclude from these experiments that the ES cell system provides a good model to study hematopoietic development. When the human epsilon- or beta-globin genes driven by the dominant control region (DCR) are introduced into this system, the human epsilon-globin gene, in contrast to the beta-globin gene, is not deregulated by the presence of the DCR and is expressed strictly as an embryonic gene. We conclude from this that the epsilon-globin gene is not regulated by competition with other genes in the human beta-globin locus. " ], "offsets": [ [ 0, 1067 ] ] } ]

[ { "id": "PMID-2269427_T1", "type": "Protein", "text": [ "NF-E1" ], "offsets": [ [ 449, 454 ] ], "normalized": [] }, { "id": "PMID-2269427_T2", "type": "Protein", "text": [ "epsilon-globin" ], "offsets": [ [ 783, 797 ] ], "normalized": [] }, { "id": "PMID-2269427_T3", "type": "Protein", "text": [ "beta-globin" ], "offsets": [ [ 823, 834 ] ], "normalized": [] }, { "id": "PMID-2269427_T4", "type": "Protein", "text": [ "epsilon-globin" ], "offsets": [ [ 966, 980 ] ], "normalized": [] }, { "id": "PMID-2269427_T5", "type": "Protein", "text": [ "beta-globin" ], "offsets": [ [ 1048, 1059 ] ], "normalized": [] } ]

[ { "id": "PMID-2269427_E1", "type": "Gene_expression", "trigger": { "text": [ "expressed" ], "offsets": [ [ 471, 480 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "PMID-2269427_T1" } ] }, { "id": "PMID-2269427_E2", "type": "Regulation", "trigger": { "text": [ "deregulated" ], "offsets": [ [ 848, 859 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "PMID-2269427_T3" } ] }, { "id": "PMID-2269427_E3", "type": "Negative_regulation", "trigger": { "text": [ "deregulated" ], "offsets": [ [ 848, 859 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "PMID-2269427_T2" } ] }, { "id": "PMID-2269427_E4", "type": "Gene_expression", "trigger": { "text": [ "expressed" ], "offsets": [ [ 894, 903 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "PMID-2269427_T2" } ] }, { "id": "PMID-2269427_E5", "type": "Regulation", "trigger": { "text": [ "regulated" ], "offsets": [ [ 993, 1002 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "PMID-2269427_T4" } ] } ]

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[ { "id": "PMID-2278044__text", "type": "abstract", "text": [ "Functional analysis of cis-linked regulatory sequences in the HLA DRA promoter by transcription in vitro. \nTwo consensus sequences, called X and Y boxes, capable of binding nuclear proteins and regulating expression in B cells have been defined within the immediate upstream region of major histocompatibility complex (MHC) class II promoters. Unlike other class II promoters, the HLA-DR alpha (DRA) promoter also contains one element identical to the \"octamer\" motif of immunoglobulin variable region promoters that is responsible for B cell-specific transcription. This \"octamer\" in the context of DRA appears capable of binding both the ubiquitous (OTF-1) and lymphoid-specific (OTF-2) \"octamer\" binding proteins, but at least one other distinct \"octamer\" complex was found. In order to characterize the function of cis-acting elements, we have developed an in vitro system in which a DRA promoter construct is transcribed more efficiently in extracts from B cells than in extracts from class II-negative HeLa cells. 5' deletion constructs which lacked the Y box, but retained the \"octamer\" motif and TATA box were completely inactive, and internal deletion of the Y box reduced transcription by 95%. Using supercoiled, but not linear templates, we observed differences in transcription efficiencies from templates lacking or disrupting the X consensus element that reflect effects of random replacement of X box sequences in transient expression assays. Demonstration of the complete dependence on the Y box in this system suggests that, despite its demonstrated importance in the DRA promoter, the DRA \"octamer\" does not utilize OTF-2 in a manner analogous to immunoglobulin promoters in B cells. " ], "offsets": [ [ 0, 1702 ] ] } ]

[ { "id": "PMID-2278044_T1", "type": "Protein", "text": [ "OTF-1" ], "offsets": [ [ 652, 657 ] ], "normalized": [] }, { "id": "PMID-2278044_T2", "type": "Protein", "text": [ "OTF-2" ], "offsets": [ [ 682, 687 ] ], "normalized": [] }, { "id": "PMID-2278044_T3", "type": "Protein", "text": [ "OTF-2" ], "offsets": [ [ 1634, 1639 ] ], "normalized": [] } ]

[ { "id": "PMID-2278044_E1", "type": "Binding", "trigger": { "text": [ "binding" ], "offsets": [ [ 623, 630 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "PMID-2278044_T2" } ] }, { "id": "PMID-2278044_E2", "type": "Binding", "trigger": { "text": [ "binding" ], "offsets": [ [ 623, 630 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "PMID-2278044_T1" } ] }, { "id": "PMID-2278044_E3", "type": "Regulation", "trigger": { "text": [ "utilize" ], "offsets": [ [ 1626, 1633 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "PMID-2278044_T3" } ] } ]

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[ { "id": "PMID-2302185__text", "type": "abstract", "text": [ "Characterization of the human immunodeficiency virus type 1 enhancer-binding proteins from the human T-cell line Jurkat. \nThe transcription of the human immunodeficiency virus type 1 (HIV-1) is under the control of cellular proteins that bind to the viral long terminal repeat (LTR). Among the protein-binding regions of the HIV-1 LTR is the transcription-enhancer region. We show that at least one inducible, C1, and one constitutive, C2, protein can bind to the HIV enhancer in Jurkat cells. The two proteins differ in their surface charge, since they are separable by anion-exchange chromatography. Bivalent cations such as Mg2+ and Zn2+ differentially affect their binding to oligonucleotides which contain the HIV-enhancer domain. Both C1 and C2 proteins also bind to a similar sequence found in the interleukin-2-receptor alpha-subunit enhancer. The inducible C1 protein was partially purified by three chromatographic steps and characterized by u.v. cross-linking as a 47 kDa protein. " ], "offsets": [ [ 0, 992 ] ] } ]

[ { "id": "PMID-2302185_T1", "type": "Protein", "text": [ "C1" ], "offsets": [ [ 410, 412 ] ], "normalized": [] }, { "id": "PMID-2302185_T2", "type": "Protein", "text": [ "C2" ], "offsets": [ [ 436, 438 ] ], "normalized": [] }, { "id": "PMID-2302185_T3", "type": "Protein", "text": [ "C1" ], "offsets": [ [ 741, 743 ] ], "normalized": [] }, { "id": "PMID-2302185_T4", "type": "Protein", "text": [ "C2" ], "offsets": [ [ 748, 750 ] ], "normalized": [] }, { "id": "PMID-2302185_T5", "type": "Protein", "text": [ "interleukin-2-receptor alpha-subunit" ], "offsets": [ [ 805, 841 ] ], "normalized": [] }, { "id": "PMID-2302185_T6", "type": "Protein", "text": [ "C1" ], "offsets": [ [ 866, 868 ] ], "normalized": [] }, { "id": "PMID-2302185_T11", "type": "Entity", "text": [ "enhancer" ], "offsets": [ [ 842, 850 ] ], "normalized": [] } ]

[ { "id": "PMID-2302185_E1", "type": "Binding", "trigger": { "text": [ "bind" ], "offsets": [ [ 452, 456 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "PMID-2302185_T1" } ] }, { "id": "PMID-2302185_E2", "type": "Binding", "trigger": { "text": [ "bind" ], "offsets": [ [ 452, 456 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "PMID-2302185_T2" } ] }, { "id": "PMID-2302185_E3", "type": "Regulation", "trigger": { "text": [ "affect" ], "offsets": [ [ 656, 662 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "PMID-2302185_E6" } ] }, { "id": "PMID-2302185_E4", "type": "Regulation", "trigger": { "text": [ "affect" ], "offsets": [ [ 656, 662 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "PMID-2302185_E5" } ] }, { "id": "PMID-2302185_E5", "type": "Binding", "trigger": { "text": [ "binding" ], "offsets": [ [ 669, 676 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "PMID-2302185_T2" } ] }, { "id": "PMID-2302185_E6", "type": "Binding", "trigger": { "text": [ "binding" ], "offsets": [ [ 669, 676 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "PMID-2302185_T1" } ] }, { "id": "PMID-2302185_E7", "type": "Binding", "trigger": { "text": [ "bind" ], "offsets": [ [ 765, 769 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "PMID-2302185_T4" }, { "role": "Theme", "ref_id": "PMID-2302185_T5" }, { "role": "Site", "ref_id": "PMID-2302185_T11" } ] }, { "id": "PMID-2302185_E8", "type": "Binding", "trigger": { "text": [ "bind" ], "offsets": [ [ 765, 769 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "PMID-2302185_T3" }, { "role": "Theme", "ref_id": "PMID-2302185_T5" }, { "role": "Site", "ref_id": "PMID-2302185_T11" } ] } ]

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[ { "id": "PMID-2304473__text", "type": "abstract", "text": [ "The ubiquitous octamer-binding protein(s) is sufficient for transcription of immunoglobulin genes. \nAll immunoglobulin genes contain a conserved octanucleotide promoter element, ATGCAAAT, which has been shown to be required for their normal B-cell-specific transcription. Proteins that bind this octamer have been purified, and cDNAs encoding octamer-binding proteins have been cloned. Some of these proteins (referred to as OTF-2) are lymphoid specific, whereas at least one other, and possibly more (referred to as OTF-1), is found ubiquitously in all cell types. The exact role of these different proteins in directing the tissue-specific expression of immunoglobulin genes is unclear. We have identified two human pre-B-cell lines that contain extremely low levels of OTF-2 yet still express high levels of steady-state immunoglobulin heavy-chain mRNA in vivo and efficiently transcribe an immunoglobulin gene in vitro. Addition of a highly enriched preparation of OTF-1 made from one of these pre-B cells or from HeLa cells specifically stimulated in vitro transcription of an immunoglobulin gene. Furthermore, OFT-1 appeared to have approximately the same transactivation ability as OTF-2 when normalized for binding activity. These results suggest that OTF-1, without OTF-2, is sufficient for transcription of immunoglobulin genes and that OTF-2 alone is not responsible for the B-cell-specific regulation of immunoglobulin gene expression. " ], "offsets": [ [ 0, 1448 ] ] } ]

[ { "id": "PMID-2304473_T1", "type": "Protein", "text": [ "OTF-2" ], "offsets": [ [ 425, 430 ] ], "normalized": [] }, { "id": "PMID-2304473_T2", "type": "Protein", "text": [ "OTF-1" ], "offsets": [ [ 517, 522 ] ], "normalized": [] }, { "id": "PMID-2304473_T3", "type": "Protein", "text": [ "OTF-2" ], "offsets": [ [ 772, 777 ] ], "normalized": [] }, { "id": "PMID-2304473_T4", "type": "Protein", "text": [ "OTF-1" ], "offsets": [ [ 969, 974 ] ], "normalized": [] }, { "id": "PMID-2304473_T5", "type": "Protein", "text": [ "OFT-1" ], "offsets": [ [ 1116, 1121 ] ], "normalized": [] }, { "id": "PMID-2304473_T6", "type": "Protein", "text": [ "OTF-2" ], "offsets": [ [ 1189, 1194 ] ], "normalized": [] }, { "id": "PMID-2304473_T7", "type": "Protein", "text": [ "OTF-1" ], "offsets": [ [ 1260, 1265 ] ], "normalized": [] }, { "id": "PMID-2304473_T8", "type": "Protein", "text": [ "OTF-2" ], "offsets": [ [ 1275, 1280 ] ], "normalized": [] }, { "id": "PMID-2304473_T9", "type": "Protein", "text": [ "OTF-2" ], "offsets": [ [ 1347, 1352 ] ], "normalized": [] } ]

[ { "id": "PMID-2304473_E1", "type": "Gene_expression", "trigger": { "text": [ "made" ], "offsets": [ [ 975, 979 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "PMID-2304473_T4" } ] }, { "id": "PMID-2304473_E2", "type": "Positive_regulation", "trigger": { "text": [ "transactivation" ], "offsets": [ [ 1162, 1177 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "PMID-2304473_T5" } ] }, { "id": "PMID-2304473_E3", "type": "Positive_regulation", "trigger": { "text": [ "transactivation" ], "offsets": [ [ 1162, 1177 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "PMID-2304473_T6" } ] } ]

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[ { "id": "PMID-2314899__text", "type": "abstract", "text": [ "Tax-independent binding of multiple cellular factors to Tax-response element DNA of HTLV-I. \nThe human T-cell leukemia virus type I (HTLV-I) promoter contains three copies of imperfect repeats of a 21-base pair sequence designated here as TRE (Tax-response element) that is responsive to the virally encoded transactivator protein Tax. We have identified and separated four nuclear proteins from C81-66-45 cells, an HTLV-I immortalized Tax-expressing human T-lymphocyte line (Salahuddin et al., 1983), that interact with the TRE-DNA, none of which are identical with the Tax-protein. The proteins identified have molecular weights of about 32, 36 to 42, 50 and 110 kD. Four different methods were used to identify the proteins. First, from different cell lines three or all four of the nuclear proteins were specifically cross-linked by UV irradiation to the radioactively labeled TRE-DNA fragment. Second, TRE-DNA binding proteins sedimented through a glycerol density gradient at rates corresponding to proteins of native molecular weights of 35 to 50 kD and 110 kD. Third, only the 50 kD protein was retained on a biotinylated DNA-streptavidin matrix when the DNA fragment contained the TRE-DNA. Fourth, extensive purification by several cycles of TRE-DNA affinity chromatography resulted in the 32, 36 to 42 and 110 kD proteins and to less extent the 50 kD factor. Two abundant proteins of 75 and 80 kD were competed out by poly[d(I-C)] in all reactions. The cAMP-response element CRE, TGACGTCA, present in the 21 base-pair sequence, appears to be essential for specific protein-TRE-DNA interactions because mutation of the two G's destroys this complex. This result suggests that the cAMP response element binding protein, CREB, is involved in the protein-TRE-DNA complex and in mediating the Tax response. " ], "offsets": [ [ 0, 1812 ] ] } ]

[ { "id": "PMID-2314899_T1", "type": "Protein", "text": [ "Tax" ], "offsets": [ [ 0, 3 ] ], "normalized": [] }, { "id": "PMID-2314899_T2", "type": "Protein", "text": [ "Tax" ], "offsets": [ [ 56, 59 ] ], "normalized": [] }, { "id": "PMID-2314899_T3", "type": "Protein", "text": [ "Tax" ], "offsets": [ [ 331, 334 ] ], "normalized": [] }, { "id": "PMID-2314899_T4", "type": "Protein", "text": [ "Tax" ], "offsets": [ [ 436, 439 ] ], "normalized": [] }, { "id": "PMID-2314899_T5", "type": "Protein", "text": [ "Tax" ], "offsets": [ [ 571, 574 ] ], "normalized": [] }, { "id": "PMID-2314899_T6", "type": "Protein", "text": [ "CREB" ], "offsets": [ [ 1728, 1732 ] ], "normalized": [] }, { "id": "PMID-2314899_T7", "type": "Protein", "text": [ "Tax" ], "offsets": [ [ 1798, 1801 ] ], "normalized": [] } ]

[ { "id": "PMID-2314899_E1", "type": "Gene_expression", "trigger": { "text": [ "expressing" ], "offsets": [ [ 440, 450 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "PMID-2314899_T4" } ] }, { "id": "PMID-2314899_E2", "type": "Regulation", "trigger": { "text": [ "involved" ], "offsets": [ [ 1737, 1745 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "PMID-2314899_E3" }, { "role": "Cause", "ref_id": "PMID-2314899_T6" } ] }, { "id": "PMID-2314899_E3", "type": "Regulation", "trigger": { "text": [ "mediating" ], "offsets": [ [ 1784, 1793 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "PMID-2314899_E4" }, { "role": "Cause", "ref_id": "PMID-2314899_T6" } ] }, { "id": "PMID-2314899_E4", "type": "Regulation", "trigger": { "text": [ "response" ], "offsets": [ [ 1802, 1810 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "PMID-2314899_T7" } ] } ]

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[ { "id": "PMID-2394747__text", "type": "abstract", "text": [ "Cell type specificity and activation requirements for NFAT-1 (nuclear factor of activated T-cells) transcriptional activity determined by a new method using transgenic mice to assay transcriptional activity of an individual nuclear factor. \nNuclear factor of activated T-cells (NFAT-1) is a transcription factor which is considered to be an important regulator in early T-cell activation. We have developed a system to monitor the transcriptional activity of NFAT-1 at the single cell level in whole animals. The system is based on the use of an oligomerized NFAT-1 binding motif that directs transcription of SV40 T-antigen in transgenic mice. This report represents the first demonstration that a multimerized short binding motif can function appropriately in transgenic mice. NFAT-1 activity had previously been thought to be confined to activated T-lymphocytes upon release of intracellular calcium. By targeting NFAT-1-dependent gene expression in transgenic mice we discovered new sites of NFAT-1 activity. Besides in T-lymphocytes NFAT-1 activity could also be induced in T-lymphocyte-depleted spleen cells and purified B-lymphocytes and requires agents that both release intracellular calcium and activate protein kinase C. A difference in the time course of appearance of NFAT-1 activity between T-lymphocytes and non-T-lymphocytes was revealed. Constitutive expression was observed in a small population of cells in the dermis and some mice have developed skin lesions. Interestingly, the tissue pattern of expression of the NFAT-1 activity resembles the expression pattern described for HIV-LTR/tat transgenic mice (Vogel, J., Hinrichs, S. H., Reynolds, R. K., Luciw, P. A., and Jay, G. (1988) Nature 335, 606-611). This similarity in expression and the fact that NFAT-1 has been shown to bind functional sequences in HIV-LTR suggest a role for NFAT-1 in dermal activation of the HIV-LTR. " ], "offsets": [ [ 0, 1900 ] ] } ]

[ { "id": "PMID-2394747_T1", "type": "Protein", "text": [ "NFAT-1" ], "offsets": [ [ 54, 60 ] ], "normalized": [] }, { "id": "PMID-2394747_T2", "type": "Protein", "text": [ "NFAT-1" ], "offsets": [ [ 278, 284 ] ], "normalized": [] }, { "id": "PMID-2394747_T3", "type": "Protein", "text": [ "NFAT-1" ], "offsets": [ [ 459, 465 ] ], "normalized": [] }, { "id": "PMID-2394747_T4", "type": "Protein", "text": [ "NFAT-1" ], "offsets": [ [ 559, 565 ] ], "normalized": [] }, { "id": "PMID-2394747_T5", "type": "Protein", "text": [ "NFAT-1" ], "offsets": [ [ 779, 785 ] ], "normalized": [] }, { "id": "PMID-2394747_T6", "type": "Protein", "text": [ "NFAT-1" ], "offsets": [ [ 917, 923 ] ], "normalized": [] }, { "id": "PMID-2394747_T7", "type": "Protein", "text": [ "NFAT-1" ], "offsets": [ [ 996, 1002 ] ], "normalized": [] }, { "id": "PMID-2394747_T8", "type": "Protein", "text": [ "NFAT-1" ], "offsets": [ [ 1038, 1044 ] ], "normalized": [] }, { "id": "PMID-2394747_T9", "type": "Protein", "text": [ "NFAT-1" ], "offsets": [ [ 1281, 1287 ] ], "normalized": [] }, { "id": "PMID-2394747_T10", "type": "Protein", "text": [ "NFAT-1" ], "offsets": [ [ 1535, 1541 ] ], "normalized": [] }, { "id": "PMID-2394747_T11", "type": "Protein", "text": [ "NFAT-1" ], "offsets": [ [ 1775, 1781 ] ], "normalized": [] }, { "id": "PMID-2394747_T12", "type": "Protein", "text": [ "NFAT-1" ], "offsets": [ [ 1856, 1862 ] ], "normalized": [] }, { "id": "PMID-2394747_T16", "type": "Entity", "text": [ "tissue" ], "offsets": [ [ 1499, 1505 ] ], "normalized": [] }, { "id": "PMID-2394747_T19", "type": "Entity", "text": [ "HIV-LTR/tat transgenic mice" ], "offsets": [ [ 1598, 1625 ] ], "normalized": [] } ]

[ { "id": "PMID-2394747_E1", "type": "Positive_regulation", "trigger": { "text": [ "induced" ], "offsets": [ [ 1068, 1075 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "PMID-2394747_T8" } ] }, { "id": "PMID-2394747_E2", "type": "Positive_regulation", "trigger": { "text": [ "requires" ], "offsets": [ [ 1145, 1153 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "PMID-2394747_T8" } ] }, { "id": "PMID-2394747_E3", "type": "Positive_regulation", "trigger": { "text": [ "appearance" ], "offsets": [ [ 1267, 1277 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "PMID-2394747_T9" } ] }, { "id": "PMID-2394747_E4", "type": "Localization", "trigger": { "text": [ "expression" ], "offsets": [ [ 1517, 1527 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "PMID-2394747_T10" }, { "role": "AtLoc", "ref_id": "PMID-2394747_T16" } ] }, { "id": "PMID-2394747_E5", "type": "Localization", "trigger": { "text": [ "expression" ], "offsets": [ [ 1565, 1575 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "PMID-2394747_T10" }, { "role": "AtLoc", "ref_id": "PMID-2394747_T19" } ] }, { "id": "PMID-2394747_E6", "type": "Binding", "trigger": { "text": [ "bind" ], "offsets": [ [ 1800, 1804 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "PMID-2394747_T11" } ] } ]

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[ { "id": "PMID-2407588__text", "type": "abstract", "text": [ "Octamer transcription factors and the cell type-specificity of immunoglobulin gene expression. \nAntibodies are produced exclusively in B lymphocytes. The expression of the antibody-encoding genes, the immunoglobulin (Ig) genes, is also restricted to B cells. The octamer sequence ATGCAAAT is present in the promoter and the enhancer of Ig genes, and plays an important role in its tissue-specific expression. This sequence motif is a binding site for nuclear proteins, the so-called octamer transcription factors (Oct or OTF factors). The Oct-1 protein is present in all cell types analyzed so far, whereas Oct-2A and Oct-2B are found mainly in B lymphocytes. All three proteins show the same sequence specificity and binding affinity. It appears that the B cell-specific expression of Ig genes is mediated at least in part by cell type-specific Oct factors, and that there are both quantitative and qualitative differences between Oct-1 and Oct-2 factors. Recently, a number of other octamer factor variants were identified. Many of these may be created by alternative splicing of a primary transcript of one Oct factor gene and may serve a specific function in the fine tuning of gene expression. " ], "offsets": [ [ 0, 1199 ] ] } ]

[ { "id": "PMID-2407588_T1", "type": "Protein", "text": [ "Oct-1" ], "offsets": [ [ 539, 544 ] ], "normalized": [] }, { "id": "PMID-2407588_T2", "type": "Protein", "text": [ "Oct-2A" ], "offsets": [ [ 607, 613 ] ], "normalized": [] }, { "id": "PMID-2407588_T3", "type": "Protein", "text": [ "Oct-2B" ], "offsets": [ [ 618, 624 ] ], "normalized": [] }, { "id": "PMID-2407588_T4", "type": "Protein", "text": [ "Oct-1" ], "offsets": [ [ 932, 937 ] ], "normalized": [] }, { "id": "PMID-2407588_T5", "type": "Protein", "text": [ "Oct-2" ], "offsets": [ [ 942, 947 ] ], "normalized": [] } ]

[ { "id": "PMID-2407588_E1", "type": "Gene_expression", "trigger": { "text": [ "present" ], "offsets": [ [ 556, 563 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "PMID-2407588_T1" } ] }, { "id": "PMID-2407588_E2", "type": "Gene_expression", "trigger": { "text": [ "found" ], "offsets": [ [ 629, 634 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "PMID-2407588_T3" } ] }, { "id": "PMID-2407588_E3", "type": "Gene_expression", "trigger": { "text": [ "found" ], "offsets": [ [ 629, 634 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "PMID-2407588_T2" } ] } ]

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[ { "id": "PMID-7510689__text", "type": "abstract", "text": [ "Thrombin and thrombin receptor agonist peptide induce early events of T cell activation and synergize with TCR cross-linking for CD69 expression and interleukin 2 production. \nThrombin stimulation of the T leukemic cell line Jurkat induced a transient increase in [Ca2+]i. Proteolytic activity of the enzyme was required for this effect since diisopropyl fluorophosphate-thrombin failed to increase [Ca2+]i. Furthermore, hirudin and anti-thrombin III inhibited the thrombin-induced [Ca2+]i rise in Jurkat T cells. A synthetic thrombin receptor agonist peptide (TRP) of 7 residues (SFLLRNP) was found to be as effective as thrombin for [Ca2+]i mobilization, and both agonists induced Ca2+ release exclusively from internal stores. Thrombin stimulated tyrosine phosphorylation of several proteins of molecular mass 40, 42, 70, 120, and 130 kDa. There was a good correlation between thrombin-induced tyrosine phosphorylation of the latter three proteins and Ca2+ mobilization. Thrombin and TRP also caused translocation of protein kinase C from the cytosol to the plasma membrane. As a likely consequence of these events, thrombin activated the nuclear factor NF-kB. Several cell lines of hematopoietic origin including the leukemic T cell line HPB.ALL and the erythroleukemic cell line K562 were responsive to thrombin, whereas others such as THP1, a myelomonocytic cell line, and BL2, a Burkitt lymphoma were refractory to thrombin or TRP stimulation. The magnitude of the thrombin response in the different cell types paralleled the expression of the thrombin receptor mRNA. We found that activation of Jurkat T cells by a combination of phytohemagglutinin and phorbol 12-myristate 13-acetate led to a dramatic inhibition of thrombin receptor mRNA expression and to a concomitant loss of the thrombin response. Finally, we demonstrate that thrombin and TRP enhanced CD69 expression and interleukin 2 production induced by T cell receptor cross-linking in both Jurkat T cells and peripheral blood lymphocytes. These findings highlight the role of thrombin as a potential regulator of T lymphocyte activation. " ], "offsets": [ [ 0, 2108 ] ] } ]

[ { "id": "PMID-7510689_T1", "type": "Protein", "text": [ "Thrombin" ], "offsets": [ [ 0, 8 ] ], "normalized": [] }, { "id": "PMID-7510689_T2", "type": "Protein", "text": [ "CD69" ], "offsets": [ [ 129, 133 ] ], "normalized": [] }, { "id": "PMID-7510689_T3", "type": "Protein", "text": [ "interleukin 2" ], "offsets": [ [ 149, 162 ] ], "normalized": [] }, { "id": "PMID-7510689_T4", "type": "Protein", "text": [ "Thrombin" ], "offsets": [ [ 176, 184 ] ], "normalized": [] }, { "id": "PMID-7510689_T5", "type": "Protein", "text": [ "thrombin" ], "offsets": [ [ 371, 379 ] ], "normalized": [] }, { "id": "PMID-7510689_T6", "type": "Protein", "text": [ "thrombin III" ], "offsets": [ [ 438, 450 ] ], "normalized": [] }, { "id": "PMID-7510689_T7", "type": "Protein", "text": [ "thrombin" ], "offsets": [ [ 465, 473 ] ], "normalized": [] }, { "id": "PMID-7510689_T8", "type": "Protein", "text": [ "thrombin" ], "offsets": [ [ 622, 630 ] ], "normalized": [] }, { "id": "PMID-7510689_T9", "type": "Protein", "text": [ "Thrombin" ], "offsets": [ [ 730, 738 ] ], "normalized": [] }, { "id": "PMID-7510689_T10", "type": "Protein", "text": [ "thrombin" ], "offsets": [ [ 880, 888 ] ], "normalized": [] }, { "id": "PMID-7510689_T11", "type": "Protein", "text": [ "Thrombin" ], "offsets": [ [ 974, 982 ] ], "normalized": [] }, { "id": "PMID-7510689_T12", "type": "Protein", "text": [ "thrombin" ], "offsets": [ [ 1119, 1127 ] ], "normalized": [] }, { "id": "PMID-7510689_T13", "type": "Protein", "text": [ "thrombin" ], "offsets": [ [ 1308, 1316 ] ], "normalized": [] }, { "id": "PMID-7510689_T14", "type": "Protein", "text": [ "thrombin" ], "offsets": [ [ 1422, 1430 ] ], "normalized": [] }, { "id": "PMID-7510689_T15", "type": "Protein", "text": [ "thrombin" ], "offsets": [ [ 1472, 1480 ] ], "normalized": [] }, { "id": "PMID-7510689_T16", "type": "Protein", "text": [ "thrombin receptor" ], "offsets": [ [ 1551, 1568 ] ], "normalized": [] }, { "id": "PMID-7510689_T17", "type": "Protein", "text": [ "phytohemagglutinin" ], "offsets": [ [ 1638, 1656 ] ], "normalized": [] }, { "id": "PMID-7510689_T18", "type": "Protein", "text": [ "thrombin receptor" ], "offsets": [ [ 1725, 1742 ] ], "normalized": [] }, { "id": "PMID-7510689_T19", "type": "Protein", "text": [ "thrombin" ], "offsets": [ [ 1792, 1800 ] ], "normalized": [] }, { "id": "PMID-7510689_T20", "type": "Protein", "text": [ "thrombin" ], "offsets": [ [ 1840, 1848 ] ], "normalized": [] }, { "id": "PMID-7510689_T21", "type": "Protein", "text": [ "CD69" ], "offsets": [ [ 1866, 1870 ] ], "normalized": [] }, { "id": "PMID-7510689_T22", "type": "Protein", "text": [ "interleukin 2" ], "offsets": [ [ 1886, 1899 ] ], "normalized": [] }, { "id": "PMID-7510689_T23", "type": "Protein", "text": [ "thrombin" ], "offsets": [ [ 2046, 2054 ] ], "normalized": [] } ]

[ { "id": "PMID-7510689_E1", "type": "Positive_regulation", "trigger": { "text": [ "synergize" ], "offsets": [ [ 92, 101 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "PMID-7510689_E5" } ] }, { "id": "PMID-7510689_E2", "type": "Positive_regulation", "trigger": { "text": [ "synergize" ], "offsets": [ [ 92, 101 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "PMID-7510689_E6" }, { "role": "Cause", "ref_id": "PMID-7510689_T1" } ] }, { "id": "PMID-7510689_E3", "type": "Positive_regulation", "trigger": { "text": [ "synergize" ], "offsets": [ [ 92, 101 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "PMID-7510689_E5" }, { "role": "Cause", "ref_id": "PMID-7510689_T1" } ] }, { "id": "PMID-7510689_E4", "type": "Positive_regulation", "trigger": { "text": [ "synergize" ], "offsets": [ [ 92, 101 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "PMID-7510689_E6" } ] }, { "id": "PMID-7510689_E5", "type": "Gene_expression", "trigger": { "text": [ "expression" ], "offsets": [ [ 134, 144 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "PMID-7510689_T2" } ] }, { "id": "PMID-7510689_E6", "type": "Gene_expression", "trigger": { "text": [ "production" ], "offsets": [ [ 163, 173 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "PMID-7510689_T3" } ] }, { "id": "PMID-7510689_E7", "type": "Transcription", "trigger": { "text": [ "expression" ], "offsets": [ [ 1533, 1543 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "PMID-7510689_T16" } ] }, { "id": "PMID-7510689_E8", "type": "Negative_regulation", "trigger": { "text": [ "inhibition" ], "offsets": [ [ 1711, 1721 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "PMID-7510689_E9" } ] }, { "id": "PMID-7510689_E9", "type": "Transcription", "trigger": { "text": [ "expression" ], "offsets": [ [ 1748, 1758 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "PMID-7510689_T18" } ] }, { "id": "PMID-7510689_E10", "type": "Positive_regulation", "trigger": { "text": [ "enhanced" ], "offsets": [ [ 1857, 1865 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "PMID-7510689_E15" }, { "role": "Cause", "ref_id": "PMID-7510689_T20" } ] }, { "id": "PMID-7510689_E11", "type": "Positive_regulation", "trigger": { "text": [ "enhanced" ], "offsets": [ [ 1857, 1865 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "PMID-7510689_E14" } ] }, { "id": "PMID-7510689_E12", "type": "Gene_expression", "trigger": { "text": [ "expression" ], "offsets": [ [ 1871, 1881 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "PMID-7510689_T21" } ] }, { "id": "PMID-7510689_E13", "type": "Gene_expression", "trigger": { "text": [ "production" ], "offsets": [ [ 1900, 1910 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "PMID-7510689_T22" } ] }, { "id": "PMID-7510689_E14", "type": "Positive_regulation", "trigger": { "text": [ "induced" ], "offsets": [ [ 1911, 1918 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "PMID-7510689_E13" } ] }, { "id": "PMID-7510689_E15", "type": "Positive_regulation", "trigger": { "text": [ "induced" ], "offsets": [ [ 1911, 1918 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "PMID-7510689_E12" } ] } ]

[]

[]

[ { "id": "PMID-7512565__text", "type": "abstract", "text": [ "Sp1 is a critical factor for the monocytic specific expression of human CD14. \nCD14 is a membrane glycoprotein expressed specifically on monocytes and macrophages, and its expression is markedly increased during the process of monocyte differentiation. In order to study CD14 gene regulation, the human CD14 gene was cloned from a partial EcoRI digested chromosome 5 library. A 5.5-kilobase genomic clone contained the full-length CD14 coding sequence and 4.2 kilobases of 5'-upstream sequence. One major and one minor transcription start site were identified 101 and 130 base pairs (bp) upstream, respectively, from the protein translation start ATG. A DNA fragment containing 128 bp of upstream sequence had strong, monocyte-specific promoter activity in the CD14 positive monocytic cell line Mono Mac 6 as compared to the nonmonocytic cell lines HeLa and REX. Four regions in this DNA fragment interact with nuclear proteins isolated from monocytic cells. The Sp1 transcription factor bound to three different regions in the CD14 promoter. Mutation of the major Sp1 binding site (-110 bp) decreased tissue-specific promoter activity, and these results, together with transactivation experiments, demonstrate that Sp1 plays a critical role in the tissue-specific expression of CD14 in monocytic cells. CD14 Sp1 site oligonucleotides bound preferentially to a 105-kDa Sp1 species, which is present in higher relative levels in monocytic than non-monocytic cells, suggesting that modification of Sp1, such as phosphorylation, may explain how the Sp1 site mediates monocytic specific promoter activity. " ], "offsets": [ [ 0, 1602 ] ] } ]

[ { "id": "PMID-7512565_T1", "type": "Protein", "text": [ "Sp1" ], "offsets": [ [ 0, 3 ] ], "normalized": [] }, { "id": "PMID-7512565_T2", "type": "Protein", "text": [ "CD14" ], "offsets": [ [ 72, 76 ] ], "normalized": [] }, { "id": "PMID-7512565_T3", "type": "Protein", "text": [ "CD14" ], "offsets": [ [ 79, 83 ] ], "normalized": [] }, { "id": "PMID-7512565_T4", "type": "Protein", "text": [ "CD14" ], "offsets": [ [ 271, 275 ] ], "normalized": [] }, { "id": "PMID-7512565_T5", "type": "Protein", "text": [ "CD14" ], "offsets": [ [ 303, 307 ] ], "normalized": [] }, { "id": "PMID-7512565_T6", "type": "Protein", "text": [ "EcoRI" ], "offsets": [ [ 339, 344 ] ], "normalized": [] }, { "id": "PMID-7512565_T7", "type": "Protein", "text": [ "CD14" ], "offsets": [ [ 431, 435 ] ], "normalized": [] }, { "id": "PMID-7512565_T8", "type": "Protein", "text": [ "CD14" ], "offsets": [ [ 761, 765 ] ], "normalized": [] }, { "id": "PMID-7512565_T9", "type": "Protein", "text": [ "Sp1" ], "offsets": [ [ 963, 966 ] ], "normalized": [] }, { "id": "PMID-7512565_T10", "type": "Protein", "text": [ "CD14" ], "offsets": [ [ 1028, 1032 ] ], "normalized": [] }, { "id": "PMID-7512565_T11", "type": "Protein", "text": [ "Sp1" ], "offsets": [ [ 1065, 1068 ] ], "normalized": [] }, { "id": "PMID-7512565_T12", "type": "Protein", "text": [ "Sp1" ], "offsets": [ [ 1216, 1219 ] ], "normalized": [] }, { "id": "PMID-7512565_T13", "type": "Protein", "text": [ "CD14" ], "offsets": [ [ 1279, 1283 ] ], "normalized": [] }, { "id": "PMID-7512565_T14", "type": "Protein", "text": [ "CD14" ], "offsets": [ [ 1304, 1308 ] ], "normalized": [] }, { "id": "PMID-7512565_T15", "type": "Protein", "text": [ "Sp1" ], "offsets": [ [ 1309, 1312 ] ], "normalized": [] }, { "id": "PMID-7512565_T16", "type": "Protein", "text": [ "Sp1" ], "offsets": [ [ 1369, 1372 ] ], "normalized": [] }, { "id": "PMID-7512565_T17", "type": "Protein", "text": [ "Sp1" ], "offsets": [ [ 1496, 1499 ] ], "normalized": [] }, { "id": "PMID-7512565_T18", "type": "Protein", "text": [ "Sp1" ], "offsets": [ [ 1546, 1549 ] ], "normalized": [] }, { "id": "PMID-7512565_T25", "type": "Entity", "text": [ "promoter" ], "offsets": [ [ 1033, 1041 ] ], "normalized": [] } ]

[ { "id": "PMID-7512565_E1", "type": "Regulation", "trigger": { "text": [ "critical" ], "offsets": [ [ 9, 17 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "PMID-7512565_E2" }, { "role": "Cause", "ref_id": "PMID-7512565_T1" } ] }, { "id": "PMID-7512565_E2", "type": "Gene_expression", "trigger": { "text": [ "expression" ], "offsets": [ [ 52, 62 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "PMID-7512565_T2" } ] }, { "id": "PMID-7512565_E3", "type": "Gene_expression", "trigger": { "text": [ "expressed" ], "offsets": [ [ 111, 120 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "PMID-7512565_T3" } ] }, { "id": "PMID-7512565_E4", "type": "Positive_regulation", "trigger": { "text": [ "increased" ], "offsets": [ [ 195, 204 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "PMID-7512565_E3" } ] }, { "id": "PMID-7512565_E5", "type": "Regulation", "trigger": { "text": [ "regulation" ], "offsets": [ [ 281, 291 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "PMID-7512565_T4" } ] }, { "id": "PMID-7512565_E6", "type": "Binding", "trigger": { "text": [ "bound" ], "offsets": [ [ 988, 993 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "PMID-7512565_T9" }, { "role": "Theme", "ref_id": "PMID-7512565_T10" }, { "role": "Site", "ref_id": "PMID-7512565_T25" } ] }, { "id": "PMID-7512565_E7", "type": "Regulation", "trigger": { "text": [ "role" ], "offsets": [ [ 1237, 1241 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "PMID-7512565_E8" }, { "role": "Cause", "ref_id": "PMID-7512565_T12" } ] }, { "id": "PMID-7512565_E8", "type": "Gene_expression", "trigger": { "text": [ "expression" ], "offsets": [ [ 1265, 1275 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "PMID-7512565_T13" } ] }, { "id": "PMID-7512565_E9", "type": "Binding", "trigger": { "text": [ "bound" ], "offsets": [ [ 1335, 1340 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "PMID-7512565_T16" } ] }, { "id": "PMID-7512565_E10", "type": "Phosphorylation", "trigger": { "text": [ "phosphorylation" ], "offsets": [ [ 1509, 1524 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "PMID-7512565_T17" } ] } ]

[]

[]

[ { "id": "PMID-7516328__text", "type": "abstract", "text": [ "Tolerance to lipopolysaccharide involves mobilization of nuclear factor kappa B with predominance of p50 homodimers. \nStimulation of the human monocytic cell line Mono Mac 6 with lipopolysaccharide (LPS) leads to rapid and transient expression of cytokines like tumor necrosis factor (TNF). When such cells are precultured for 2 days with a low dose of LPS (20 ng/ml) followed by stimulation with a high dose of LPS (1 microgram/ml), expression of the TNF gene is minimal, i.e. the cells are tolerant. In nuclear run-on analysis, such tolerant cells show only a low degree of transcription, indicating that tolerance operates at or upstream of the transcription level. The CD14 LPS receptor is, however, up-regulated (not down-regulated) in tolerant cells, and LPS can, in fact, still lead to activation of tolerant cells as evidenced by mobilization of the transcription factor nuclear factor kappa B (NF-kappa B). Resolution of the NF-kappa B complex in gel shift analysis shows that the binding protein, mobilized in naive Mono Mac 6 cells, consists mainly of p50-p65 heterodimers, while in tolerant cells, the p50 homodimer is predominant. This increase in p50 homodimers coincides with an increase in p105 mRNA, suggestive of a transcriptional up-regulation of p50. Reporter gene analysis reveals that the NF-kappa B complex mobilized in tolerant cells is functionally inactive in that NF-kappa B-dependent luciferase constructs containing the human immunodeficiency virus long terminal repeat or the TNF 5'-region show only minimal transactivation after LPS stimulation. Similar to Mono Mac 6 cells, primary blood monocytes, when precultured with a low dose of LPS, also become tolerant and produce little TNF after LPS stimulation. The tolerant blood monocytes also up-regulate CD14, and they mobilize NF-kappa B with a predominance of p50 homodimers. Taken together, these results demonstrate that tolerance to LPS is determined by post-receptor mechanisms that involve an altered composition of the NF-kappa B complex. " ], "offsets": [ [ 0, 2028 ] ] } ]

[ { "id": "PMID-7516328_T1", "type": "Protein", "text": [ "p50" ], "offsets": [ [ 101, 104 ] ], "normalized": [] }, { "id": "PMID-7516328_T2", "type": "Protein", "text": [ "CD14" ], "offsets": [ [ 673, 677 ] ], "normalized": [] }, { "id": "PMID-7516328_T3", "type": "Protein", "text": [ "p50" ], "offsets": [ [ 1063, 1066 ] ], "normalized": [] }, { "id": "PMID-7516328_T4", "type": "Protein", "text": [ "p65" ], "offsets": [ [ 1067, 1070 ] ], "normalized": [] }, { "id": "PMID-7516328_T5", "type": "Protein", "text": [ "p50" ], "offsets": [ [ 1114, 1117 ] ], "normalized": [] }, { "id": "PMID-7516328_T6", "type": "Protein", "text": [ "p50" ], "offsets": [ [ 1161, 1164 ] ], "normalized": [] }, { "id": "PMID-7516328_T7", "type": "Protein", "text": [ "p105" ], "offsets": [ [ 1206, 1210 ] ], "normalized": [] }, { "id": "PMID-7516328_T8", "type": "Protein", "text": [ "p50" ], "offsets": [ [ 1266, 1269 ] ], "normalized": [] }, { "id": "PMID-7516328_T9", "type": "Protein", "text": [ "CD14" ], "offsets": [ [ 1785, 1789 ] ], "normalized": [] }, { "id": "PMID-7516328_T10", "type": "Protein", "text": [ "p50" ], "offsets": [ [ 1843, 1846 ] ], "normalized": [] }, { "id": "PMID-7516328_T13", "type": "Entity", "text": [ "naive Mono Mac 6 cells" ], "offsets": [ [ 1020, 1042 ] ], "normalized": [] } ]

[ { "id": "PMID-7516328_E1", "type": "Localization", "trigger": { "text": [ "mobilization" ], "offsets": [ [ 41, 53 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "PMID-7516328_T1" } ] }, { "id": "PMID-7516328_E2", "type": "Localization", "trigger": { "text": [ "mobilized" ], "offsets": [ [ 1007, 1016 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "PMID-7516328_T3" }, { "role": "AtLoc", "ref_id": "PMID-7516328_T13" } ] }, { "id": "PMID-7516328_E3", "type": "Localization", "trigger": { "text": [ "mobilized" ], "offsets": [ [ 1007, 1016 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "PMID-7516328_T5" } ] }, { "id": "PMID-7516328_E4", "type": "Localization", "trigger": { "text": [ "mobilized" ], "offsets": [ [ 1007, 1016 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "PMID-7516328_T4" }, { "role": "AtLoc", "ref_id": "PMID-7516328_T13" } ] }, { "id": "PMID-7516328_E5", "type": "Positive_regulation", "trigger": { "text": [ "increase" ], "offsets": [ [ 1149, 1157 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "PMID-7516328_T6" } ] }, { "id": "PMID-7516328_E6", "type": "Positive_regulation", "trigger": { "text": [ "increase" ], "offsets": [ [ 1194, 1202 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "PMID-7516328_T7" } ] }, { "id": "PMID-7516328_E7", "type": "Positive_regulation", "trigger": { "text": [ "transcriptional up-regulation" ], "offsets": [ [ 1233, 1262 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "PMID-7516328_T8" } ] }, { "id": "PMID-7516328_E8", "type": "Positive_regulation", "trigger": { "text": [ "up-regulate" ], "offsets": [ [ 1773, 1784 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "PMID-7516328_T9" } ] } ]

[]

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[ { "id": "PMID-7518803__text", "type": "abstract", "text": [ "Evidence for a trans-acting activator function regulating the expression of the human CD5 antigen. \nInterspecies somatic cell hybrids were generated by fusing the mouse T-lymphoma cell line, BW5147, with normal human T lymphocytes at different stages of differentiation. Thymocytes, activated peripheral T lymphocytes, or an activated T-cell clone were used as human partners, respectively, in three independent fusions. Irrespective of the human cell partner used for fusion, a certain number of hybrids lost CD5 surface expression over a period of time in culture. Analysis at the phenotype and genetic level showed that lack of CD5 expression was due neither to segregation of human autosome 11, on which the CD5 gene has been mapped, nor to deletion of the CD5 structural gene. Furthermore, loss of CD5 surface expression correlated with the absence of specific mRNA. Since these hybrids preferentially segregate human chromosomes, these results indicate the existence of a non-syntenic trans-active locus, or loci, positively controlling the expression of the human CD5 gene. " ], "offsets": [ [ 0, 1081 ] ] } ]

[ { "id": "PMID-7518803_T1", "type": "Protein", "text": [ "CD5" ], "offsets": [ [ 86, 89 ] ], "normalized": [] }, { "id": "PMID-7518803_T2", "type": "Protein", "text": [ "CD5" ], "offsets": [ [ 510, 513 ] ], "normalized": [] }, { "id": "PMID-7518803_T3", "type": "Protein", "text": [ "CD5" ], "offsets": [ [ 631, 634 ] ], "normalized": [] }, { "id": "PMID-7518803_T4", "type": "Protein", "text": [ "CD5" ], "offsets": [ [ 712, 715 ] ], "normalized": [] }, { "id": "PMID-7518803_T5", "type": "Protein", "text": [ "CD5" ], "offsets": [ [ 761, 764 ] ], "normalized": [] }, { "id": "PMID-7518803_T6", "type": "Protein", "text": [ "CD5" ], "offsets": [ [ 803, 806 ] ], "normalized": [] }, { "id": "PMID-7518803_T7", "type": "Protein", "text": [ "CD5" ], "offsets": [ [ 1071, 1074 ] ], "normalized": [] } ]

[ { "id": "PMID-7518803_E1", "type": "Regulation", "trigger": { "text": [ "regulating" ], "offsets": [ [ 47, 57 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "PMID-7518803_E2" } ] }, { "id": "PMID-7518803_E2", "type": "Gene_expression", "trigger": { "text": [ "expression" ], "offsets": [ [ 62, 72 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "PMID-7518803_T1" } ] }, { "id": "PMID-7518803_E3", "type": "Negative_regulation", "trigger": { "text": [ "lost" ], "offsets": [ [ 505, 509 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "PMID-7518803_E4" } ] }, { "id": "PMID-7518803_E4", "type": "Gene_expression", "trigger": { "text": [ "expression" ], "offsets": [ [ 522, 532 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "PMID-7518803_T2" } ] }, { "id": "PMID-7518803_E5", "type": "Gene_expression", "trigger": { "text": [ "expression" ], "offsets": [ [ 635, 645 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "PMID-7518803_T3" } ] }, { "id": "PMID-7518803_E6", "type": "Positive_regulation", "trigger": { "text": [ "due" ], "offsets": [ [ 650, 653 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "PMID-7518803_E5" } ] }, { "id": "PMID-7518803_E7", "type": "Negative_regulation", "trigger": { "text": [ "loss" ], "offsets": [ [ 795, 799 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "PMID-7518803_E8" } ] }, { "id": "PMID-7518803_E8", "type": "Gene_expression", "trigger": { "text": [ "expression" ], "offsets": [ [ 815, 825 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "PMID-7518803_T6" } ] }, { "id": "PMID-7518803_E9", "type": "Transcription", "trigger": { "text": [ "absence" ], "offsets": [ [ 846, 853 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "PMID-7518803_T6" } ] }, { "id": "PMID-7518803_E10", "type": "Positive_regulation", "trigger": { "text": [ "positively controlling" ], "offsets": [ [ 1020, 1042 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "PMID-7518803_E11" } ] }, { "id": "PMID-7518803_E11", "type": "Gene_expression", "trigger": { "text": [ "expression" ], "offsets": [ [ 1047, 1057 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "PMID-7518803_T7" } ] } ]

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[ { "id": "PMID-7518838__text", "type": "abstract", "text": [ "Alpha-tocopherol inhibits agonist-induced monocytic cell adhesion to cultured human endothelial cells. \nAntioxidants have been proposed to be anti-atherosclerotic agents; however, the mechanisms underlying their beneficial effects are poorly understood. We have examined the effect of alpha-tocopherol (alpha-tcp) on one cellular event in atherosclerotic plaque development, monocyte adhesion to stimulated endothelial cells (ECs). Human umbilical vein ECs were pretreated with alpha-tcp before stimulation with known agonists of monocyte adhesion: IL-1 (10 ng/ml), LPS (10 ng/ml), thrombin (30 U/ml), or PMA (10 nM). Agonist-induced monocytic cell adhesion, but not basal adhesion, was inhibited in a time- and concentration-dependent manner by alpha-tcp. The IC50 of alpha-tcp on an IL-1-induced response was 45 microM. The inhibition correlated with a decrease in steady state levels of E-selectin mRNA and cell surface expression of E-selectin which is consistent with the ability of a monoclonal antibody to E-selectin to inhibit monocytic cell adhesion in this system. Probucol (50 microM) and N-acetylcysteine (20 mM) also inhibited agonist-induced monocytic cell adhesion; whereas, several other antioxidants had no significant effect. Protein kinase C (PKC) does not appear to play a role in the alpha-tcp effect since no suppression of phosphorylation of PKC substrates was observed. Activation of the transcription factor NF-kappa B is reported to be necessary but not sufficient for E-selectin expression in EC. Electrophoretic mobility shift assays failed to show an alpha-tcp-induced decrease in activation of this transcription factor after cytokine stimulation. It has been hypothesized that alpha-tcp acts as an anti-atherosclerotic molecule by inhibiting generation of oxidized LDL--a putative triggering molecule in the atherosclerotic process. Our results point to a novel alternative mechanism of action of alpha-tcp. " ], "offsets": [ [ 0, 1939 ] ] } ]

[ { "id": "PMID-7518838_T1", "type": "Protein", "text": [ "E-selectin" ], "offsets": [ [ 890, 900 ] ], "normalized": [] }, { "id": "PMID-7518838_T2", "type": "Protein", "text": [ "E-selectin" ], "offsets": [ [ 937, 947 ] ], "normalized": [] }, { "id": "PMID-7518838_T3", "type": "Protein", "text": [ "E-selectin" ], "offsets": [ [ 1013, 1023 ] ], "normalized": [] }, { "id": "PMID-7518838_T4", "type": "Protein", "text": [ "E-selectin" ], "offsets": [ [ 1495, 1505 ] ], "normalized": [] } ]

[ { "id": "PMID-7518838_E1", "type": "Negative_regulation", "trigger": { "text": [ "decrease" ], "offsets": [ [ 855, 863 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "PMID-7518838_T1" } ] }, { "id": "PMID-7518838_E2", "type": "Negative_regulation", "trigger": { "text": [ "decrease" ], "offsets": [ [ 855, 863 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "PMID-7518838_E3" } ] }, { "id": "PMID-7518838_E3", "type": "Gene_expression", "trigger": { "text": [ "expression" ], "offsets": [ [ 923, 933 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "PMID-7518838_T2" } ] }, { "id": "PMID-7518838_E4", "type": "Positive_regulation", "trigger": { "text": [ "necessary" ], "offsets": [ [ 1462, 1471 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "PMID-7518838_E5" } ] }, { "id": "PMID-7518838_E5", "type": "Gene_expression", "trigger": { "text": [ "expression" ], "offsets": [ [ 1506, 1516 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "PMID-7518838_T4" } ] } ]

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[ { "id": "PMID-7520093__text", "type": "abstract", "text": [ "Upregulation of bcl-2 by the Epstein-Barr virus latent membrane protein LMP1: a B-cell-specific response that is delayed relative to NF-kappa B activation and to induction of cell surface markers. \nAn ability of the Epstein-Barr virus latent membrane protein LMP1 to enhance the survival of infected B cells through upregulation of the bcl-2 oncogene was first suggested by experiments involving gene transfection and the selection of stable LMP1+ clones (S.Henderson, M. Rowe, C.Gregory, F.Wang, E.Kieff, and A.Rickinson, Cell 65:1107-1115, 1991). However, it was not possible to ascertain whether Bcl-2 upregulation was a specific consequence of LMP1 expression or an artifact of the selection procedure whereby rare Bcl-2+ cells already present in the starting population might best be able to tolerate the potentially toxic effects of LMP1. We therefore reexamined this issue by using two different experimental approaches that allowed LMP1- induced effects to be monitored immediately following expression of the viral protein and in the absence of selective pressures; activation of the NF-kappa B transcription factor and upregulation of the cell adhesion molecule ICAM-1 were used as early indices of LMP1 function. In the first approach, stable clones of two B-cell lines carrying an LMP1 gene under the control of an inducible metallothionein promoter were induced to express LMP1 in all cells. Activation of NK-kappa B and upregulation of ICAM-1 occurred within 24 h and were followed at 48 to 72 h by upregulation of Bcl-2. In the second approach, we tested the generality of this phenomenon by transiently expressing LMP1 from a strong constitutively active promoter in a range of different cell types. All six B-cell lines tested showed NF-kappa B activation in response to LMP1 expression, and this was followed in five of six lines by expression of ICAM-1 and Bcl-2. In the same experiments, all three non-B-cell lines showed NF-kappa B activation and ICAM-1 upregulation but never any effect upon Bcl-2. We therefore conclude that Bcl-2 upregulation is part of the panoply of cellular changes induced by LMP1 but that the effect is cell type specific. Our data also suggest that whilst NF-kappa B may be an essential component of LMP1 signal transduction, other cell-specific factors may be required to effect some functions of the viral protein. " ], "offsets": [ [ 0, 2364 ] ] } ]

[ { "id": "PMID-7520093_T1", "type": "Protein", "text": [ "bcl-2" ], "offsets": [ [ 16, 21 ] ], "normalized": [] }, { "id": "PMID-7520093_T2", "type": "Protein", "text": [ "LMP1" ], "offsets": [ [ 72, 76 ] ], "normalized": [] }, { "id": "PMID-7520093_T3", "type": "Protein", "text": [ "LMP1" ], "offsets": [ [ 259, 263 ] ], "normalized": [] }, { "id": "PMID-7520093_T4", "type": "Protein", "text": [ "bcl-2" ], "offsets": [ [ 336, 341 ] ], "normalized": [] }, { "id": "PMID-7520093_T5", "type": "Protein", "text": [ "LMP1" ], "offsets": [ [ 442, 446 ] ], "normalized": [] }, { "id": "PMID-7520093_T6", "type": "Protein", "text": [ "Bcl-2" ], "offsets": [ [ 599, 604 ] ], "normalized": [] }, { "id": "PMID-7520093_T7", "type": "Protein", "text": [ "LMP1" ], "offsets": [ [ 648, 652 ] ], "normalized": [] }, { "id": "PMID-7520093_T8", "type": "Protein", "text": [ "Bcl-2" ], "offsets": [ [ 719, 724 ] ], "normalized": [] }, { "id": "PMID-7520093_T9", "type": "Protein", "text": [ "LMP1" ], "offsets": [ [ 839, 843 ] ], "normalized": [] }, { "id": "PMID-7520093_T10", "type": "Protein", "text": [ "LMP1" ], "offsets": [ [ 940, 944 ] ], "normalized": [] }, { "id": "PMID-7520093_T11", "type": "Protein", "text": [ "ICAM-1" ], "offsets": [ [ 1172, 1178 ] ], "normalized": [] }, { "id": "PMID-7520093_T12", "type": "Protein", "text": [ "LMP1" ], "offsets": [ [ 1209, 1213 ] ], "normalized": [] }, { "id": "PMID-7520093_T13", "type": "Protein", "text": [ "LMP1" ], "offsets": [ [ 1293, 1297 ] ], "normalized": [] }, { "id": "PMID-7520093_T14", "type": "Protein", "text": [ "LMP1" ], "offsets": [ [ 1386, 1390 ] ], "normalized": [] }, { "id": "PMID-7520093_T15", "type": "Protein", "text": [ "ICAM-1" ], "offsets": [ [ 1450, 1456 ] ], "normalized": [] }, { "id": "PMID-7520093_T16", "type": "Protein", "text": [ "Bcl-2" ], "offsets": [ [ 1529, 1534 ] ], "normalized": [] }, { "id": "PMID-7520093_T17", "type": "Protein", "text": [ "LMP1" ], "offsets": [ [ 1630, 1634 ] ], "normalized": [] }, { "id": "PMID-7520093_T18", "type": "Protein", "text": [ "LMP1" ], "offsets": [ [ 1788, 1792 ] ], "normalized": [] }, { "id": "PMID-7520093_T19", "type": "Protein", "text": [ "ICAM-1" ], "offsets": [ [ 1865, 1871 ] ], "normalized": [] }, { "id": "PMID-7520093_T20", "type": "Protein", "text": [ "Bcl-2" ], "offsets": [ [ 1876, 1881 ] ], "normalized": [] }, { "id": "PMID-7520093_T21", "type": "Protein", "text": [ "ICAM-1" ], "offsets": [ [ 1968, 1974 ] ], "normalized": [] }, { "id": "PMID-7520093_T22", "type": "Protein", "text": [ "Bcl-2" ], "offsets": [ [ 2014, 2019 ] ], "normalized": [] }, { "id": "PMID-7520093_T23", "type": "Protein", "text": [ "Bcl-2" ], "offsets": [ [ 2048, 2053 ] ], "normalized": [] }, { "id": "PMID-7520093_T24", "type": "Protein", "text": [ "LMP1" ], "offsets": [ [ 2121, 2125 ] ], "normalized": [] }, { "id": "PMID-7520093_T25", "type": "Protein", "text": [ "LMP1" ], "offsets": [ [ 2247, 2251 ] ], "normalized": [] } ]

[ { "id": "PMID-7520093_E1", "type": "Positive_regulation", "trigger": { "text": [ "Upregulation" ], "offsets": [ [ 0, 12 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "PMID-7520093_T1" }, { "role": "Cause", "ref_id": "PMID-7520093_T2" } ] }, { "id": "PMID-7520093_E2", "type": "Positive_regulation", "trigger": { "text": [ "upregulation" ], "offsets": [ [ 316, 328 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "PMID-7520093_T4" }, { "role": "Cause", "ref_id": "PMID-7520093_T3" } ] }, { "id": "PMID-7520093_E3", "type": "Positive_regulation", "trigger": { "text": [ "upregulation" ], "offsets": [ [ 605, 617 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "PMID-7520093_T6" }, { "role": "Cause", "ref_id": "PMID-7520093_E4" } ] }, { "id": "PMID-7520093_E4", "type": "Gene_expression", "trigger": { "text": [ "expression" ], "offsets": [ [ 653, 663 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "PMID-7520093_T7" } ] }, { "id": "PMID-7520093_E5", "type": "Positive_regulation", "trigger": { "text": [ "induced" ], "offsets": [ [ 946, 953 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "PMID-7520093_T9" }, { "role": "Cause", "ref_id": "PMID-7520093_T10" } ] }, { "id": "PMID-7520093_E6", "type": "Gene_expression", "trigger": { "text": [ "expression" ], "offsets": [ [ 1000, 1010 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "PMID-7520093_T10" } ] }, { "id": "PMID-7520093_E7", "type": "Positive_regulation", "trigger": { "text": [ "upregulation" ], "offsets": [ [ 1129, 1141 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "PMID-7520093_T11" } ] }, { "id": "PMID-7520093_E8", "type": "Positive_regulation", "trigger": { "text": [ "induced" ], "offsets": [ [ 1367, 1374 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "PMID-7520093_E9" } ] }, { "id": "PMID-7520093_E9", "type": "Gene_expression", "trigger": { "text": [ "express" ], "offsets": [ [ 1378, 1385 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "PMID-7520093_T14" } ] }, { "id": "PMID-7520093_E10", "type": "Positive_regulation", "trigger": { "text": [ "upregulation" ], "offsets": [ [ 1434, 1446 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "PMID-7520093_T15" } ] }, { "id": "PMID-7520093_E11", "type": "Positive_regulation", "trigger": { "text": [ "upregulation" ], "offsets": [ [ 1513, 1525 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "PMID-7520093_T16" } ] }, { "id": "PMID-7520093_E12", "type": "Gene_expression", "trigger": { "text": [ "expressing" ], "offsets": [ [ 1619, 1629 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "PMID-7520093_T17" } ] }, { "id": "PMID-7520093_E13", "type": "Gene_expression", "trigger": { "text": [ "expression" ], "offsets": [ [ 1793, 1803 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "PMID-7520093_T18" } ] }, { "id": "PMID-7520093_E14", "type": "Gene_expression", "trigger": { "text": [ "expression" ], "offsets": [ [ 1851, 1861 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "PMID-7520093_T20" } ] }, { "id": "PMID-7520093_E15", "type": "Gene_expression", "trigger": { "text": [ "expression" ], "offsets": [ [ 1851, 1861 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "PMID-7520093_T19" } ] }, { "id": "PMID-7520093_E16", "type": "Positive_regulation", "trigger": { "text": [ "upregulation" ], "offsets": [ [ 1975, 1987 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "PMID-7520093_T21" }, { "role": "Cause", "ref_id": "PMID-7520093_E13" } ] }, { "id": "PMID-7520093_E17", "type": "Positive_regulation", "trigger": { "text": [ "effect" ], "offsets": [ [ 2002, 2008 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "PMID-7520093_T22" }, { "role": "Cause", "ref_id": "PMID-7520093_E13" } ] }, { "id": "PMID-7520093_E18", "type": "Positive_regulation", "trigger": { "text": [ "upregulation" ], "offsets": [ [ 2054, 2066 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "PMID-7520093_T23" } ] } ]

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[ { "id": "PMID-7520914__text", "type": "abstract", "text": [ "CD14-mediated translocation of nuclear factor-kappa B induced by lipopolysaccharide does not require tyrosine kinase activity. \nDuring the course of serious bacterial infections, lipopolysaccharide (LPS) is believed to interact with macrophage receptors, resulting in the generation of inflammatory mediators and systemic symptoms including hemodynamic instability and shock. CD14, a glycosylphosphatidylinositol-linked antigen, functions as an LPS signaling receptor. A critical issue concerns the mechanism by which CD14, which has no transmembrane domain, transduces its signal following LPS binding. Recently, investigators have hypothesized that CD14-mediated signaling is effected through a receptor-associated tyrosine kinase (TK), suggesting a multicomponent receptor model of LPS signaling. Wild-type Chinese hamster ovary (CHO)-K1 cells can be activated by endotoxin to release arachidonate following transfection with human CD14 (CHO/CD14). Nuclear translocation of cytosolic NF-kappa B is correlated with a number of LPS-inducible responses. We sought to determine if this pathway were present in CHO/CD14 cells and to elucidate the relationship of NF-kappa B activation to the CD14 receptor system. LPS-stimulated translocation of NF-kappa B in CHO/CD14 cells resembled the same response in the murine macrophage-like cell line RAW 264.7. Protein synthesis inhibitors and corticosteroids, which suppress arachidonate release and the synthesis of proinflammatory cytokines, had no effect on translocation of NF-kappa B in CHO/CD14 or RAW 264.7 cells, demonstrating that NF-kappa B translocation is an early event. Although TK activity was consistently observed by immunoblotting extracts from activated RAW 264.7 cells, LPS-induced phosphotyrosine residues were not observed from similarly treated CHO/CD14 cells. Furthermore, the TK inhibitors herbimycin A and genistein failed to inhibit translocation of NF-kappa B in CHO/CD14 or RAW 264.7 cells, although both of these agents inhibited LPS-induced TK activity in RAW 264.7 cells. These results imply that TK activity is not obligatory for CD14-mediated signal transduction to occur in response to LPS. " ], "offsets": [ [ 0, 2168 ] ] } ]

[ { "id": "PMID-7520914_T1", "type": "Protein", "text": [ "CD14" ], "offsets": [ [ 0, 4 ] ], "normalized": [] }, { "id": "PMID-7520914_T2", "type": "Protein", "text": [ "CD14" ], "offsets": [ [ 376, 380 ] ], "normalized": [] }, { "id": "PMID-7520914_T3", "type": "Protein", "text": [ "CD14" ], "offsets": [ [ 518, 522 ] ], "normalized": [] }, { "id": "PMID-7520914_T4", "type": "Protein", "text": [ "CD14" ], "offsets": [ [ 651, 655 ] ], "normalized": [] }, { "id": "PMID-7520914_T5", "type": "Protein", "text": [ "CD14" ], "offsets": [ [ 935, 939 ] ], "normalized": [] }, { "id": "PMID-7520914_T6", "type": "Protein", "text": [ "CD14" ], "offsets": [ [ 945, 949 ] ], "normalized": [] }, { "id": "PMID-7520914_T7", "type": "Protein", "text": [ "CD14" ], "offsets": [ [ 1113, 1117 ] ], "normalized": [] }, { "id": "PMID-7520914_T8", "type": "Protein", "text": [ "CD14" ], "offsets": [ [ 1190, 1194 ] ], "normalized": [] }, { "id": "PMID-7520914_T9", "type": "Protein", "text": [ "CD14" ], "offsets": [ [ 1262, 1266 ] ], "normalized": [] }, { "id": "PMID-7520914_T10", "type": "Protein", "text": [ "CD14" ], "offsets": [ [ 1538, 1542 ] ], "normalized": [] }, { "id": "PMID-7520914_T11", "type": "Protein", "text": [ "CD14" ], "offsets": [ [ 1814, 1818 ] ], "normalized": [] }, { "id": "PMID-7520914_T12", "type": "Protein", "text": [ "CD14" ], "offsets": [ [ 1937, 1941 ] ], "normalized": [] }, { "id": "PMID-7520914_T13", "type": "Protein", "text": [ "CD14" ], "offsets": [ [ 2105, 2109 ] ], "normalized": [] } ]

[ { "id": "PMID-7520914_E1", "type": "Regulation", "trigger": { "text": [ "receptor" ], "offsets": [ [ 459, 467 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "PMID-7520914_T2" } ] }, { "id": "PMID-7520914_E2", "type": "Binding", "trigger": { "text": [ "binding" ], "offsets": [ [ 595, 602 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "PMID-7520914_T3" } ] }, { "id": "PMID-7520914_E3", "type": "Gene_expression", "trigger": { "text": [ "transfection" ], "offsets": [ [ 911, 923 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "PMID-7520914_T5" } ] }, { "id": "PMID-7520914_E4", "type": "Positive_regulation", "trigger": { "text": [ "transfection" ], "offsets": [ [ 911, 923 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "PMID-7520914_E3" } ] } ]

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[]

[ { "id": "PMID-7522257__text", "type": "abstract", "text": [ "Regulation of CD14 expression during monocytic differentiation induced with 1 alpha,25-dihydroxyvitamin D3. \nCD14, a monocyte/macrophage receptor for the complex of LPS and LPS binding protein, is a differentiation marker for the monocyte/macrophage lineage. We have analyzed the regulation of CD14 expression during 1 alpha,25-dihydroxyvitamin D3 (VitD3)-induced monocytic differentiation. Using FACS, Northern blotting, and nuclear run-on analyses, we demonstrate that the up-regulation of CD14 expression during monocytic cell maturation is regulated mainly at the level of gene transcription, and that new protein synthesis is required for CD14 induction. We have recently cloned the CD14 5' upstream sequence and demonstrated its tissue-specific promoter activity. Using stable transfection of the monocytoid U937 cell line with a series of deletion mutants of the CD14 5' upstream sequence coupled to a reporter gene construct, we show that bp -128 to -70 is the critical region for the induction of CD14 expression. This region contains two binding sites for the Sp1 transcription factor. A 3-bp mutation at the distal Sp1-binding site not only eliminates Sp1 interaction, but also abolishes most of the VitD3 induction of CD14 expression. Electrophoretic mobility shift analysis does not detect a direct interaction of the CD14 distal Sp1-binding site with the vitamin D3 receptor and its partner, the retinoid X receptor. These data demonstrate that VitD3 induces CD14 indirectly through some intermediary factor, and suggest a critical role for Sp1 in this process. " ], "offsets": [ [ 0, 1576 ] ] } ]

[ { "id": "PMID-7522257_T1", "type": "Protein", "text": [ "CD14" ], "offsets": [ [ 14, 18 ] ], "normalized": [] }, { "id": "PMID-7522257_T2", "type": "Protein", "text": [ "CD14" ], "offsets": [ [ 109, 113 ] ], "normalized": [] }, { "id": "PMID-7522257_T3", "type": "Protein", "text": [ "CD14" ], "offsets": [ [ 294, 298 ] ], "normalized": [] }, { "id": "PMID-7522257_T4", "type": "Protein", "text": [ "CD14" ], "offsets": [ [ 492, 496 ] ], "normalized": [] }, { "id": "PMID-7522257_T5", "type": "Protein", "text": [ "CD14" ], "offsets": [ [ 644, 648 ] ], "normalized": [] }, { "id": "PMID-7522257_T6", "type": "Protein", "text": [ "CD14" ], "offsets": [ [ 688, 692 ] ], "normalized": [] }, { "id": "PMID-7522257_T7", "type": "Protein", "text": [ "CD14" ], "offsets": [ [ 870, 874 ] ], "normalized": [] }, { "id": "PMID-7522257_T8", "type": "Protein", "text": [ "CD14" ], "offsets": [ [ 1006, 1010 ] ], "normalized": [] }, { "id": "PMID-7522257_T9", "type": "Protein", "text": [ "Sp1" ], "offsets": [ [ 1070, 1073 ] ], "normalized": [] }, { "id": "PMID-7522257_T10", "type": "Protein", "text": [ "Sp1" ], "offsets": [ [ 1126, 1129 ] ], "normalized": [] }, { "id": "PMID-7522257_T11", "type": "Protein", "text": [ "Sp1" ], "offsets": [ [ 1163, 1166 ] ], "normalized": [] }, { "id": "PMID-7522257_T12", "type": "Protein", "text": [ "CD14" ], "offsets": [ [ 1230, 1234 ] ], "normalized": [] }, { "id": "PMID-7522257_T13", "type": "Protein", "text": [ "CD14" ], "offsets": [ [ 1331, 1335 ] ], "normalized": [] }, { "id": "PMID-7522257_T14", "type": "Protein", "text": [ "Sp1" ], "offsets": [ [ 1343, 1346 ] ], "normalized": [] }, { "id": "PMID-7522257_T15", "type": "Protein", "text": [ "vitamin D3 receptor" ], "offsets": [ [ 1369, 1388 ] ], "normalized": [] }, { "id": "PMID-7522257_T16", "type": "Protein", "text": [ "CD14" ], "offsets": [ [ 1473, 1477 ] ], "normalized": [] }, { "id": "PMID-7522257_T17", "type": "Protein", "text": [ "Sp1" ], "offsets": [ [ 1555, 1558 ] ], "normalized": [] } ]

[ { "id": "PMID-7522257_E1", "type": "Regulation", "trigger": { "text": [ "Regulation" ], "offsets": [ [ 0, 10 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "PMID-7522257_E2" } ] }, { "id": "PMID-7522257_E2", "type": "Gene_expression", "trigger": { "text": [ "expression" ], "offsets": [ [ 19, 29 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "PMID-7522257_T1" } ] }, { "id": "PMID-7522257_E3", "type": "Regulation", "trigger": { "text": [ "regulation" ], "offsets": [ [ 280, 290 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "PMID-7522257_E4" } ] }, { "id": "PMID-7522257_E4", "type": "Gene_expression", "trigger": { "text": [ "expression" ], "offsets": [ [ 299, 309 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "PMID-7522257_T3" } ] }, { "id": "PMID-7522257_E5", "type": "Positive_regulation", "trigger": { "text": [ "up-regulation" ], "offsets": [ [ 475, 488 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "PMID-7522257_E6" } ] }, { "id": "PMID-7522257_E6", "type": "Gene_expression", "trigger": { "text": [ "expression" ], "offsets": [ [ 497, 507 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "PMID-7522257_T4" } ] }, { "id": "PMID-7522257_E7", "type": "Regulation", "trigger": { "text": [ "regulated" ], "offsets": [ [ 544, 553 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "PMID-7522257_E5" }, { "role": "Cause", "ref_id": "PMID-7522257_E8" } ] }, { "id": "PMID-7522257_E8", "type": "Positive_regulation", "trigger": { "text": [ "level" ], "offsets": [ [ 568, 573 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "PMID-7522257_E9" } ] }, { "id": "PMID-7522257_E9", "type": "Transcription", "trigger": { "text": [ "transcription" ], "offsets": [ [ 582, 595 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "PMID-7522257_T4" } ] }, { "id": "PMID-7522257_E10", "type": "Positive_regulation", "trigger": { "text": [ "required" ], "offsets": [ [ 631, 639 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "PMID-7522257_E11" } ] }, { "id": "PMID-7522257_E11", "type": "Positive_regulation", "trigger": { "text": [ "induction" ], "offsets": [ [ 649, 658 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "PMID-7522257_T5" } ] }, { "id": "PMID-7522257_E12", "type": "Positive_regulation", "trigger": { "text": [ "induction" ], "offsets": [ [ 993, 1002 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "PMID-7522257_E13" } ] }, { "id": "PMID-7522257_E13", "type": "Gene_expression", "trigger": { "text": [ "expression" ], "offsets": [ [ 1011, 1021 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "PMID-7522257_T8" } ] }, { "id": "PMID-7522257_E14", "type": "Binding", "trigger": { "text": [ "binding" ], "offsets": [ [ 1048, 1055 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "PMID-7522257_T9" } ] }, { "id": "PMID-7522257_E15", "type": "Negative_regulation", "trigger": { "text": [ "eliminates" ], "offsets": [ [ 1152, 1162 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "PMID-7522257_E16" } ] }, { "id": "PMID-7522257_E16", "type": "Binding", "trigger": { "text": [ "interaction" ], "offsets": [ [ 1167, 1178 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "PMID-7522257_T11" } ] }, { "id": "PMID-7522257_E17", "type": "Negative_regulation", "trigger": { "text": [ "abolishes" ], "offsets": [ [ 1189, 1198 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "PMID-7522257_E18" } ] }, { "id": "PMID-7522257_E18", "type": "Positive_regulation", "trigger": { "text": [ "induction" ], "offsets": [ [ 1217, 1226 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "PMID-7522257_E19" } ] }, { "id": "PMID-7522257_E19", "type": "Gene_expression", "trigger": { "text": [ "expression" ], "offsets": [ [ 1235, 1245 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "PMID-7522257_T12" } ] }, { "id": "PMID-7522257_E20", "type": "Binding", "trigger": { "text": [ "interaction" ], "offsets": [ [ 1312, 1323 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "PMID-7522257_T15" } ] }, { "id": "PMID-7522257_E21", "type": "Positive_regulation", "trigger": { "text": [ "through" ], "offsets": [ [ 1489, 1496 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "PMID-7522257_T16" } ] }, { "id": "PMID-7522257_E22", "type": "Positive_regulation", "trigger": { "text": [ "critical role" ], "offsets": [ [ 1537, 1550 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "PMID-7522257_T17" } ] } ]

[]

[]

[ { "id": "PMID-7522304__text", "type": "abstract", "text": [ "Calcium signalling in T cells stimulated by a cyclophilin B-binding protein. \nThe immunosuppressant drug cyclosporin A blocks a calcium-dependent signal from the T-cell receptor (TCR) that normally leads to T-cell activation. When bound to cyclophilin, cyclosporin A binds and inactivates the key signalling intermediate calcineurin. To identify potential cellular homologues of cyclosporin A that might regulate calcium signalling, we have cloned human genes encoding cyclophilin B-binding-proteins using the yeast two-hybrid system. One gene product, when overexpressed in Jurkat T cells, specifically induced transcription from the interleukin-2 enhancer, by activating the T-cell-specific transcription factors NF-AT and NF-IL2A. This protein, termed calcium-signal modulating cyclophilin ligand (CAML), acts downstream of the TCR and upstream of calcineurin by causing an influx of calcium. CAML appears to be a new participant in the calcium-signal transduction pathway, implicating cyclophilin B in calcium signalling, even in the absence of cyclosporin. " ], "offsets": [ [ 0, 1062 ] ] } ]

[ { "id": "PMID-7522304_T1", "type": "Protein", "text": [ "cyclophilin B" ], "offsets": [ [ 46, 59 ] ], "normalized": [] }, { "id": "PMID-7522304_T2", "type": "Protein", "text": [ "cyclophilin B" ], "offsets": [ [ 469, 482 ] ], "normalized": [] }, { "id": "PMID-7522304_T3", "type": "Protein", "text": [ "interleukin-2" ], "offsets": [ [ 635, 648 ] ], "normalized": [] }, { "id": "PMID-7522304_T4", "type": "Protein", "text": [ "calcium-signal modulating cyclophilin ligand" ], "offsets": [ [ 755, 799 ] ], "normalized": [] }, { "id": "PMID-7522304_T5", "type": "Protein", "text": [ "CAML" ], "offsets": [ [ 801, 805 ] ], "normalized": [] }, { "id": "PMID-7522304_T6", "type": "Protein", "text": [ "CAML" ], "offsets": [ [ 896, 900 ] ], "normalized": [] }, { "id": "PMID-7522304_T7", "type": "Protein", "text": [ "cyclophilin B" ], "offsets": [ [ 989, 1002 ] ], "normalized": [] } ]

[ { "id": "PMID-7522304_E1", "type": "Positive_regulation", "trigger": { "text": [ "induced" ], "offsets": [ [ 604, 611 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "PMID-7522304_E2" } ] }, { "id": "PMID-7522304_E2", "type": "Transcription", "trigger": { "text": [ "transcription" ], "offsets": [ [ 612, 625 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "PMID-7522304_T3" } ] } ]

[ { "id": "PMID-7522304_1", "entity_ids": [ "PMID-7522304_T4", "PMID-7522304_T5" ] } ]

[]

[ { "id": "PMID-7522548__text", "type": "abstract", "text": [ "Antioxidants inhibit monocyte adhesion by suppressing nuclear factor-kappa B mobilization and induction of vascular cell adhesion molecule-1 in endothelial cells stimulated to generate radicals. \nCell adhesion to endothelial cells stimulated by tumor necrosis factor-alpha (TNF) is due to induction of surface receptors, such as vascular cell adhesion molecule-1 (VCAM-1). The antioxidant pyrrolidine dithiocarbamate (PDTC) specifically inhibits activation of nuclear factor-kappa B (NF-kappa B). Since kappa B motifs are present in VCAM-1 and intercellular adhesion molecule-1 (ICAM-1) promoters, we used PDTC to study the regulatory mechanisms of VCAM-1 and ICAM-1 induction and subsequent monocyte adhesion in TNF-treated human umbilical vein endothelial cells (HUVECs). PDTC or N-acetylcysteine dose dependently reduced TNF-induced VCAM-1 but not ICAM-1 surface protein (also in human umbilical arterial endothelial cells) and mRNA expression (by 70% at 100 mumol/L PDTC) in HUVECs as assessed by flow cytometry and polymerase chain reaction. Gel-shift analysis in HUVECs demonstrated that PDTC prevented NF-kappa B mobilization by TNF, suggesting that only VCAM-1 induction was controlled by NF-kappa B. Since HUVECs released superoxide anions in response to TNF, and H2O2 induces VCAM-1, PDTC may act as a radical scavenger. Although ICAM-1 induction was unaffected, inhibitors of NADPH oxidase (apocynin) or cytochrome P-450 (SKF525a) suppressed VCAM-1 induction by TNF, revealing that several radical-generating systems are involved in its regulation. PDTC, apocynin, or SKF525a decreased adhesion of monocytic U937 cells to TNF-treated HUVECs (by 75% at 100 mumol/L PDTC). Inhibition by anti-VCAM-1 monoclonal antibody 1G11 indicated that U937 adhesion was VCAM-1 dependent and suppression by antioxidants was due to reduced VCAM-1 induction. (ABSTRACT TRUNCATED AT 250 WORDS) " ], "offsets": [ [ 0, 1886 ] ] } ]

[ { "id": "PMID-7522548_T1", "type": "Protein", "text": [ "vascular cell adhesion molecule-1" ], "offsets": [ [ 107, 140 ] ], "normalized": [] }, { "id": "PMID-7522548_T2", "type": "Protein", "text": [ "tumor necrosis factor-alpha" ], "offsets": [ [ 245, 272 ] ], "normalized": [] }, { "id": "PMID-7522548_T3", "type": "Protein", "text": [ "TNF" ], "offsets": [ [ 274, 277 ] ], "normalized": [] }, { "id": "PMID-7522548_T4", "type": "Protein", "text": [ "vascular cell adhesion molecule-1" ], "offsets": [ [ 329, 362 ] ], "normalized": [] }, { "id": "PMID-7522548_T5", "type": "Protein", "text": [ "VCAM-1" ], "offsets": [ [ 364, 370 ] ], "normalized": [] }, { "id": "PMID-7522548_T6", "type": "Protein", "text": [ "VCAM-1" ], "offsets": [ [ 533, 539 ] ], "normalized": [] }, { "id": "PMID-7522548_T7", "type": "Protein", "text": [ "ntercellular adhesion molecule-1" ], "offsets": [ [ 545, 577 ] ], "normalized": [] }, { "id": "PMID-7522548_T8", "type": "Protein", "text": [ "ICAM-1" ], "offsets": [ [ 579, 585 ] ], "normalized": [] }, { "id": "PMID-7522548_T9", "type": "Protein", "text": [ "VCAM-1" ], "offsets": [ [ 649, 655 ] ], "normalized": [] }, { "id": "PMID-7522548_T10", "type": "Protein", "text": [ "ICAM-1" ], "offsets": [ [ 660, 666 ] ], "normalized": [] }, { "id": "PMID-7522548_T11", "type": "Protein", "text": [ "TNF" ], "offsets": [ [ 713, 716 ] ], "normalized": [] }, { "id": "PMID-7522548_T12", "type": "Protein", "text": [ "TNF" ], "offsets": [ [ 824, 827 ] ], "normalized": [] }, { "id": "PMID-7522548_T13", "type": "Protein", "text": [ "VCAM-1" ], "offsets": [ [ 836, 842 ] ], "normalized": [] }, { "id": "PMID-7522548_T14", "type": "Protein", "text": [ "ICAM-1" ], "offsets": [ [ 851, 857 ] ], "normalized": [] }, { "id": "PMID-7522548_T15", "type": "Protein", "text": [ "TNF" ], "offsets": [ [ 1136, 1139 ] ], "normalized": [] }, { "id": "PMID-7522548_T16", "type": "Protein", "text": [ "VCAM-1" ], "offsets": [ [ 1162, 1168 ] ], "normalized": [] }, { "id": "PMID-7522548_T17", "type": "Protein", "text": [ "TNF" ], "offsets": [ [ 1264, 1267 ] ], "normalized": [] }, { "id": "PMID-7522548_T18", "type": "Protein", "text": [ "VCAM-1" ], "offsets": [ [ 1286, 1292 ] ], "normalized": [] }, { "id": "PMID-7522548_T19", "type": "Protein", "text": [ "ICAM-1" ], "offsets": [ [ 1340, 1346 ] ], "normalized": [] }, { "id": "PMID-7522548_T20", "type": "Protein", "text": [ "VCAM-1" ], "offsets": [ [ 1453, 1459 ] ], "normalized": [] }, { "id": "PMID-7522548_T21", "type": "Protein", "text": [ "TNF" ], "offsets": [ [ 1473, 1476 ] ], "normalized": [] }, { "id": "PMID-7522548_T22", "type": "Protein", "text": [ "TNF" ], "offsets": [ [ 1633, 1636 ] ], "normalized": [] }, { "id": "PMID-7522548_T23", "type": "Protein", "text": [ "VCAM-1" ], "offsets": [ [ 1701, 1707 ] ], "normalized": [] }, { "id": "PMID-7522548_T24", "type": "Protein", "text": [ "VCAM-1" ], "offsets": [ [ 1766, 1772 ] ], "normalized": [] }, { "id": "PMID-7522548_T25", "type": "Protein", "text": [ "VCAM-1" ], "offsets": [ [ 1834, 1840 ] ], "normalized": [] } ]

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"Positive_regulation", "trigger": { "text": [ "induction" ], "offsets": [ [ 667, 676 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "PMID-7522548_T10" }, { "role": "Cause", "ref_id": "PMID-7522548_T11" } ] }, { "id": "PMID-7522548_E7", "type": "Positive_regulation", "trigger": { "text": [ "induction" ], "offsets": [ [ 667, 676 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "PMID-7522548_T9" }, { "role": "Cause", "ref_id": "PMID-7522548_T11" } ] }, { "id": "PMID-7522548_E8", "type": "Negative_regulation", "trigger": { "text": [ "reduced" ], "offsets": [ [ 816, 823 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "PMID-7522548_E15" } ] }, { "id": "PMID-7522548_E9", "type": "Negative_regulation", "trigger": { "text": [ "reduced" ], "offsets": [ [ 816, 823 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "PMID-7522548_E13" } ] }, { "id": "PMID-7522548_E10", "type": "Negative_regulation", "trigger": { "text": [ "reduced" ], "offsets": [ [ 816, 823 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "PMID-7522548_E14" } ] }, { "id": "PMID-7522548_E11", "type": "Negative_regulation", "trigger": { "text": [ "reduced" ], "offsets": [ [ 816, 823 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "PMID-7522548_E12" } ] }, { "id": "PMID-7522548_E12", "type": "Positive_regulation", "trigger": { "text": [ "induced" ], "offsets": [ [ 828, 835 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "PMID-7522548_E19" }, { "role": "Cause", "ref_id": "PMID-7522548_T12" } ] }, { "id": "PMID-7522548_E13", "type": "Positive_regulation", "trigger": { "text": [ "induced" ], "offsets": [ [ 828, 835 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "PMID-7522548_E16" }, { "role": "Cause", "ref_id": "PMID-7522548_T12" } ] }, { "id": "PMID-7522548_E14", "type": "Positive_regulation", "trigger": { "text": [ "induced" ], "offsets": [ [ 828, 835 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "PMID-7522548_E17" }, { "role": "Cause", "ref_id": "PMID-7522548_T12" } ] }, { "id": "PMID-7522548_E15", "type": "Positive_regulation", "trigger": { "text": [ "induced" ], "offsets": [ [ 828, 835 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "PMID-7522548_E18" }, { "role": "Cause", "ref_id": "PMID-7522548_T12" } ] }, { "id": "PMID-7522548_E16", "type": "Transcription", "trigger": { "text": [ "expression" ], "offsets": [ [ 936, 946 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "PMID-7522548_T13" } ] }, { "id": "PMID-7522548_E17", "type": "Gene_expression", "trigger": { "text": [ "expression" ], "offsets": [ [ 936, 946 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "PMID-7522548_T13" } ] }, { "id": "PMID-7522548_E18", "type": "Transcription", "trigger": { "text": [ "expression" ], "offsets": [ [ 936, 946 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "PMID-7522548_T14" } ] }, { "id": "PMID-7522548_E19", "type": "Gene_expression", "trigger": { "text": [ "expression" ], "offsets": [ [ 936, 946 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "PMID-7522548_T14" } ] }, { "id": "PMID-7522548_E20", "type": "Positive_regulation", "trigger": { "text": [ "induction" ], "offsets": [ [ 1169, 1178 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "PMID-7522548_T16" } ] }, { "id": "PMID-7522548_E21", "type": "Regulation", "trigger": { "text": [ "controlled" ], "offsets": [ [ 1183, 1193 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "PMID-7522548_E20" } ] }, { "id": "PMID-7522548_E22", "type": "Positive_regulation", "trigger": { "text": [ "induces" ], "offsets": [ [ 1278, 1285 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "PMID-7522548_T18" } ] }, { "id": "PMID-7522548_E23", "type": "Positive_regulation", "trigger": { "text": [ "induction" ], "offsets": [ [ 1347, 1356 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "PMID-7522548_T19" }, { "role": "Cause", "ref_id": "PMID-7522548_T12" } ] }, { "id": "PMID-7522548_E24", "type": "Negative_regulation", "trigger": { "text": [ "unaffected" ], "offsets": [ [ 1361, 1371 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "PMID-7522548_E23" } ] }, { "id": "PMID-7522548_E25", "type": "Negative_regulation", "trigger": { "text": [ "suppressed" ], "offsets": [ [ 1442, 1452 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "PMID-7522548_E26" } ] }, { "id": "PMID-7522548_E26", "type": "Positive_regulation", "trigger": { "text": [ "induction" ], "offsets": [ [ 1460, 1469 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "PMID-7522548_T20" }, { "role": "Cause", "ref_id": "PMID-7522548_T21" } ] }, { "id": "PMID-7522548_E27", "type": "Regulation", "trigger": { "text": [ "regulation" ], "offsets": [ [ 1548, 1558 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "PMID-7522548_E26" } ] }, { "id": "PMID-7522548_E28", "type": "Negative_regulation", "trigger": { "text": [ "reduced" ], "offsets": [ [ 1826, 1833 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "PMID-7522548_E29" } ] }, { "id": "PMID-7522548_E29", "type": "Positive_regulation", "trigger": { "text": [ "induction" ], "offsets": [ [ 1841, 1850 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "PMID-7522548_T25" }, { "role": "Cause", "ref_id": "PMID-7522548_T12" } ] } ]

[ { "id": "PMID-7522548_1", "entity_ids": [ "PMID-7522548_T2", "PMID-7522548_T3" ] }, { "id": "PMID-7522548_2", "entity_ids": [ "PMID-7522548_T7", "PMID-7522548_T8" ] }, { "id": "PMID-7522548_3", "entity_ids": [ "PMID-7522548_T5", "PMID-7522548_T4" ] } ]

[]

[ { "id": "PMID-7523507__text", "type": "abstract", "text": [ "Inducible binding to the c-fos serum response element during T cell activation is regulated by a phosphotyrosine-containing protein. \nThe proto-oncogene c-fos is an immediate-early gene, and one of the first genes transcribed after stimulation of most cells with a variety of ligands. Fos expression may be a pivotal event in converting ligand-receptor interactions at the membrane into functional modulation of cell phenotype. The serum response element (SRE) in the c-fos regulatory region participates in induction of transcription by various growth factors and by phorbol esters and subsequent squelching of transcription. We show that an inducible protein complex (Band A) binds to SRE DNA within 10 min after mitogenic stimulation of human PBL-T, and becomes nondetectable by 60 min. Band A contains the serum response factor plus additional factor(s). A protein that is phosphorylated on a tyrosine residue in resting PBL-T suppresses binding of a component of Band A to the SRE motif. Upon stimulation of the cells, this protein no longer prevents binding of DNA by Band A, and suppression of binding is restored within 30 min. The phosphorylated tyrosine residue itself is important for the protein-protein interaction. " ], "offsets": [ [ 0, 1229 ] ] } ]

[ { "id": "PMID-7523507_T1", "type": "Protein", "text": [ "c-fos" ], "offsets": [ [ 25, 30 ] ], "normalized": [] }, { "id": "PMID-7523507_T2", "type": "Protein", "text": [ "c-fos" ], "offsets": [ [ 153, 158 ] ], "normalized": [] }, { "id": "PMID-7523507_T3", "type": "Protein", "text": [ "Fos" ], "offsets": [ [ 285, 288 ] ], "normalized": [] }, { "id": "PMID-7523507_T4", "type": "Protein", "text": [ "c-fos" ], "offsets": [ [ 468, 473 ] ], "normalized": [] } ]

[ { "id": "PMID-7523507_E1", "type": "Transcription", "trigger": { "text": [ "transcribed" ], "offsets": [ [ 214, 225 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "PMID-7523507_T2" } ] }, { "id": "PMID-7523507_E2", "type": "Positive_regulation", "trigger": { "text": [ "after" ], "offsets": [ [ 226, 231 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "PMID-7523507_E1" } ] }, { "id": "PMID-7523507_E3", "type": "Gene_expression", "trigger": { "text": [ "expression" ], "offsets": [ [ 289, 299 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "PMID-7523507_T3" } ] } ]

[]

[]

[ { "id": "PMID-7524762__text", "type": "abstract", "text": [ "Steel factor affects SCL expression during normal erythroid differentiation. \nSteel factor is one of the growth factors that controls the proliferation and differentiation of hematopoietic cells and SCL, also known as Tcl-5 or Tal-1, is a transcription factor involved in erythropoiesis. In this report, we studied the role of SCL in the proliferation of human peripheral blood burst-forming unit-erythroid (BFU-E) and the effects of Steel factor on SCL expression in proliferating erythroid cells. BFU-E-derived colonies increase progressively in size, as determined by cell number, from day 7 to day 14 of culture, with the greatest increase in colony size (10-fold expansion) occurring between day 7 and day 10. SCL protein levels in BFU-E-derived cells were highest in day 7 cells and decreased progressively from day 7 to day 14 of culture, suggesting an association of SCL with erythroid proliferation. In contrast, SCL mRNA levels did not decrease significantly between day 7 and day 14 cells, suggesting that posttranscriptional mechanisms are largely responsible for the decrease in SCL protein observed. The role of SCL in Steel factor-induced erythroid proliferation was then examined. In BFU-E-derived colonies cultured with Steel factor, colony size was significantly increased compared to control. In day 7 and day 10 erythroid precursors cultured with Steel factor, SCL protein was increased significantly compared to control. The increase in SCL protein levels in early erythroid precursors stimulated with Steel factor suggests one mechanism through which Steel factor may enhance normal erythroid proliferation. SCL mRNA levels assessed by Northern blot in day 7 cells did not increase significantly in response to Steel factor stimulation, suggesting that posttranscriptional mechanisms may also be important in the increase in SCL protein observed in response to Steel. " ], "offsets": [ [ 0, 1890 ] ] } ]

[ { "id": "PMID-7524762_T1", "type": "Protein", "text": [ "Steel factor" ], "offsets": [ [ 0, 12 ] ], "normalized": [] }, { "id": "PMID-7524762_T2", "type": "Protein", "text": [ "SCL" ], "offsets": [ [ 21, 24 ] ], "normalized": [] }, { "id": "PMID-7524762_T3", "type": "Protein", "text": [ "Steel factor" ], "offsets": [ [ 78, 90 ] ], "normalized": [] }, { "id": "PMID-7524762_T4", "type": "Protein", "text": [ "SCL" ], "offsets": [ [ 199, 202 ] ], "normalized": [] }, { "id": "PMID-7524762_T5", "type": "Protein", "text": [ "Tcl-5" ], "offsets": [ [ 218, 223 ] ], "normalized": [] }, { "id": "PMID-7524762_T6", "type": "Protein", "text": [ "Tal-1" ], "offsets": [ [ 227, 232 ] ], "normalized": [] }, { "id": "PMID-7524762_T7", "type": "Protein", "text": [ "SCL" ], "offsets": [ [ 327, 330 ] ], "normalized": [] }, { "id": "PMID-7524762_T8", "type": "Protein", "text": [ "Steel factor" ], "offsets": [ [ 434, 446 ] ], "normalized": [] }, { "id": "PMID-7524762_T9", "type": "Protein", "text": [ "SCL" ], "offsets": [ [ 450, 453 ] ], "normalized": [] }, { "id": "PMID-7524762_T10", "type": "Protein", "text": [ "SCL" ], "offsets": [ [ 715, 718 ] ], "normalized": [] }, { "id": "PMID-7524762_T11", "type": "Protein", "text": [ "SCL" ], "offsets": [ [ 875, 878 ] ], "normalized": [] }, { "id": "PMID-7524762_T12", "type": "Protein", "text": [ "SCL" ], "offsets": [ [ 922, 925 ] ], "normalized": [] }, { "id": "PMID-7524762_T13", "type": "Protein", "text": [ "SCL" ], "offsets": [ [ 1092, 1095 ] ], "normalized": [] }, { "id": "PMID-7524762_T14", "type": "Protein", "text": [ "SCL" ], "offsets": [ [ 1126, 1129 ] ], "normalized": [] }, { "id": "PMID-7524762_T15", "type": "Protein", "text": [ "Steel factor" ], "offsets": [ [ 1133, 1145 ] ], "normalized": [] }, { "id": "PMID-7524762_T16", "type": "Protein", "text": [ "Steel factor" ], "offsets": [ [ 1237, 1249 ] ], "normalized": [] }, { "id": "PMID-7524762_T17", "type": "Protein", "text": [ "Steel factor" ], "offsets": [ [ 1367, 1379 ] ], "normalized": [] }, { "id": "PMID-7524762_T18", "type": "Protein", "text": [ "SCL" ], "offsets": [ [ 1381, 1384 ] ], "normalized": [] }, { "id": "PMID-7524762_T19", "type": "Protein", "text": [ "SCL" ], "offsets": [ [ 1458, 1461 ] ], "normalized": [] }, { "id": "PMID-7524762_T20", "type": "Protein", "text": [ "Steel factor" ], "offsets": [ [ 1523, 1535 ] ], "normalized": [] }, { "id": "PMID-7524762_T21", "type": "Protein", "text": [ "Steel factor" ], "offsets": [ [ 1573, 1585 ] ], "normalized": [] }, { "id": "PMID-7524762_T22", "type": "Protein", "text": [ "SCL" ], "offsets": [ [ 1630, 1633 ] ], "normalized": [] }, { "id": "PMID-7524762_T23", "type": "Protein", "text": [ "Steel factor" ], "offsets": [ [ 1733, 1745 ] ], "normalized": [] }, { "id": "PMID-7524762_T24", "type": "Protein", "text": [ "SCL" ], "offsets": [ [ 1847, 1850 ] ], "normalized": [] }, { "id": "PMID-7524762_T25", "type": "Protein", "text": [ "Steel" ], "offsets": [ [ 1883, 1888 ] ], "normalized": [] } ]

[ { "id": "PMID-7524762_E1", "type": "Regulation", "trigger": { "text": [ "affects" ], "offsets": [ [ 13, 20 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "PMID-7524762_E2" }, { "role": "Cause", "ref_id": "PMID-7524762_T1" } ] }, { "id": "PMID-7524762_E2", "type": "Gene_expression", "trigger": { "text": [ "expression" ], "offsets": [ [ 25, 35 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "PMID-7524762_T2" } ] }, { "id": "PMID-7524762_E3", "type": "Regulation", "trigger": { "text": [ "effects" ], "offsets": [ [ 423, 430 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "PMID-7524762_E4" }, { "role": "Cause", "ref_id": "PMID-7524762_T8" } ] }, { "id": "PMID-7524762_E4", "type": "Gene_expression", "trigger": { "text": [ "expression" ], "offsets": [ [ 454, 464 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "PMID-7524762_T9" } ] }, { "id": "PMID-7524762_E5", "type": "Negative_regulation", "trigger": { "text": [ "decreased" ], "offsets": [ [ 789, 798 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "PMID-7524762_T10" } ] }, { "id": "PMID-7524762_E6", "type": "Negative_regulation", "trigger": { "text": [ "decrease" ], "offsets": [ [ 946, 954 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "PMID-7524762_T12" } ] }, { "id": "PMID-7524762_E7", "type": "Regulation", "trigger": { "text": [ "responsible" ], "offsets": [ [ 1060, 1071 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "PMID-7524762_E8" } ] }, { "id": "PMID-7524762_E8", "type": "Negative_regulation", "trigger": { "text": [ "decrease" ], "offsets": [ [ 1080, 1088 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "PMID-7524762_T13" } ] }, { "id": "PMID-7524762_E9", "type": "Positive_regulation", "trigger": { "text": [ "increased" ], "offsets": [ [ 1397, 1406 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "PMID-7524762_T18" } ] }, { "id": "PMID-7524762_E10", "type": "Positive_regulation", "trigger": { "text": [ "increase" ], "offsets": [ [ 1446, 1454 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "PMID-7524762_T19" } ] }, { "id": "PMID-7524762_E11", "type": "Transcription", "trigger": { "text": [ "levels" ], "offsets": [ [ 1639, 1645 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "PMID-7524762_T22" } ] }, { "id": "PMID-7524762_E12", "type": "Positive_regulation", "trigger": { "text": [ "increase" ], "offsets": [ [ 1695, 1703 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "PMID-7524762_E11" }, { "role": "Cause", "ref_id": "PMID-7524762_T23" } ] }, { "id": "PMID-7524762_E13", "type": "Regulation", "trigger": { "text": [ "important" ], "offsets": [ [ 1818, 1827 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "PMID-7524762_E14" } ] }, { "id": "PMID-7524762_E14", "type": "Positive_regulation", "trigger": { "text": [ "increase" ], "offsets": [ [ 1835, 1843 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "PMID-7524762_T24" }, { "role": "Cause", "ref_id": "PMID-7524762_T25" } ] } ]

[ { "id": "PMID-7524762_1", "entity_ids": [ "PMID-7524762_T4", "PMID-7524762_T5", "PMID-7524762_T6" ] } ]

[]

[ { "id": "PMID-7525701__text", "type": "abstract", "text": [ "Cross-linking CD40 on B cells rapidly activates nuclear factor-kappa B. \nThe B cell-associated surface molecule CD40 functions to regulate B cell responses. Cross-linking CD40 on B cells can lead to homotypic cell adhesion, IL-6 production, and, in combination with cytokines, to Ig isotype switching. Tyrosine kinase activity is increased shortly after engagement of this receptor. Little is known about how the very early events induced by CD40 cross-linking link to cellular responses. In this study, we demonstrate that nuclear factor (NF)-kappa B and NF-kappa B-like transcription factors are activated after cross-linking CD40 on resting human tonsillar B cells and on B cell lines. The activation is rapid and is mediated through a tyrosine kinase-dependent pathway. The complexes detected in electrophoretic mobility shift assays contain p50, p65 (RelA), c-Rel, and most likely other components. By using transient transfection assays, we found that cross-linking CD40 supports NF-kappa B-dependent gene expression. Our results define the NF-kappa B system as an intermediate event in CD40 signaling and suggest that the CD40 pathway can influence the expression of B cell-associated genes with NF-kappa B consensus sites. " ], "offsets": [ [ 0, 1231 ] ] } ]

[ { "id": "PMID-7525701_T1", "type": "Protein", "text": [ "CD40" ], "offsets": [ [ 14, 18 ] ], "normalized": [] }, { "id": "PMID-7525701_T2", "type": "Protein", "text": [ "CD40" ], "offsets": [ [ 112, 116 ] ], "normalized": [] }, { "id": "PMID-7525701_T3", "type": "Protein", "text": [ "CD40" ], "offsets": [ [ 171, 175 ] ], "normalized": [] }, { "id": "PMID-7525701_T4", "type": "Protein", "text": [ "IL-6" ], "offsets": [ [ 224, 228 ] ], "normalized": [] }, { "id": "PMID-7525701_T5", "type": "Protein", "text": [ "CD40" ], "offsets": [ [ 442, 446 ] ], "normalized": [] }, { "id": "PMID-7525701_T6", "type": "Protein", "text": [ "CD40" ], "offsets": [ [ 628, 632 ] ], "normalized": [] }, { "id": "PMID-7525701_T7", "type": "Protein", "text": [ "p50" ], "offsets": [ [ 846, 849 ] ], "normalized": [] }, { "id": "PMID-7525701_T8", "type": "Protein", "text": [ "p65" ], "offsets": [ [ 851, 854 ] ], "normalized": [] }, { "id": "PMID-7525701_T9", "type": "Protein", "text": [ "RelA" ], "offsets": [ [ 856, 860 ] ], "normalized": [] }, { "id": "PMID-7525701_T10", "type": "Protein", "text": [ "c-Rel" ], "offsets": [ [ 863, 868 ] ], "normalized": [] }, { "id": "PMID-7525701_T11", "type": "Protein", "text": [ "CD40" ], "offsets": [ [ 972, 976 ] ], "normalized": [] }, { "id": "PMID-7525701_T12", "type": "Protein", "text": [ "CD40" ], "offsets": [ [ 1093, 1097 ] ], "normalized": [] }, { "id": "PMID-7525701_T13", "type": "Protein", "text": [ "CD40" ], "offsets": [ [ 1129, 1133 ] ], "normalized": [] } ]

[ { "id": "PMID-7525701_E1", "type": "Binding", "trigger": { "text": [ "Cross-linking" ], "offsets": [ [ 0, 13 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "PMID-7525701_T1" } ] }, { "id": "PMID-7525701_E2", "type": "Binding", "trigger": { "text": [ "Cross-linking" ], "offsets": [ [ 157, 170 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "PMID-7525701_T3" } ] }, { "id": "PMID-7525701_E3", "type": "Positive_regulation", "trigger": { "text": [ "lead" ], "offsets": [ [ 191, 195 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "PMID-7525701_E4" }, { "role": "Cause", "ref_id": "PMID-7525701_E2" } ] }, { "id": "PMID-7525701_E4", "type": "Gene_expression", "trigger": { "text": [ "production" ], "offsets": [ [ 229, 239 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "PMID-7525701_T4" } ] }, { "id": "PMID-7525701_E5", "type": "Binding", "trigger": { "text": [ "engagement" ], "offsets": [ [ 354, 364 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "PMID-7525701_T3" } ] }, { "id": "PMID-7525701_E6", "type": "Binding", "trigger": { "text": [ "cross-linking" ], "offsets": [ [ 447, 460 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "PMID-7525701_T5" } ] }, { "id": "PMID-7525701_E7", "type": "Binding", "trigger": { "text": [ "cross-linking" ], "offsets": [ [ 614, 627 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "PMID-7525701_T6" } ] }, { "id": "PMID-7525701_E8", "type": "Binding", "trigger": { "text": [ "cross-linking" ], "offsets": [ [ 958, 971 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "PMID-7525701_T11" } ] } ]

[ { "id": "PMID-7525701_1", "entity_ids": [ "PMID-7525701_T8", "PMID-7525701_T9" ] } ]

[]

[ { "id": "PMID-7526398__text", "type": "abstract", "text": [ "Separation of oxidant-initiated and redox-regulated steps in the NF-kappa B signal transduction pathway. \nStudies presented here show that overall NF-kappa B signal transduction begins with a parallel series of stimuli-specific pathways through which cytokines (tumor necrosis factor alpha), oxidants (hydrogen peroxide and mitomycin C), and phorbol ester (phorbol 12-myristate 13-acetate) individually initiate signaling. These initial pathways culminate in a common pathway through which all of the stimulating agents ultimately signal NF-kappa B activation. We distinguish the stimuli-specific pathways by showing that the oxidative stimuli trigger NF-kappa B activation in only one of two human T-cell lines (Wurzburg but not Jurkat), whereas tumor necrosis factor alpha and phorbol 12-myristate 13-acetate readily stimulate in both lines. We propose the common pathway as the simplest way of accounting for the common requirements and properties of the signaling pathway. We include a redox-regulatory mechanism(s) in this common pathway to account for the previously demonstrated redox regulation of NF-kappa B activation in Jurkat cells (in which oxidants don't activate NF-kappa B); we put tyrosine phosphorylation in the common pathway by showing that kinase activity (inhibitable by herbimycin A and tyrphostin 47) is required for NF-kappa B activation by all stimuli tested in both cell lines. Since internal sites of oxidant production have been shown to play a key role in the cytokine-stimulated activation of NF-kappa B, and since tyrosine kinase and phosphatase activities are known to be altered by oxidants, these findings suggest that intracellular redox status controls NF-kappa B activation by regulating tyrosine phosphorylation event(s) within the common step of the NF-kappa B signal transduction pathway. " ], "offsets": [ [ 0, 1830 ] ] } ]

[ { "id": "PMID-7526398_T1", "type": "Protein", "text": [ "tumor necrosis factor alpha" ], "offsets": [ [ 262, 289 ] ], "normalized": [] }, { "id": "PMID-7526398_T2", "type": "Protein", "text": [ "tumor necrosis factor alpha" ], "offsets": [ [ 747, 774 ] ], "normalized": [] } ]

[]

[]

[]

[ { "id": "PMID-7532282__text", "type": "abstract", "text": [ "Transcription-independent turnover of I kappa B alpha during monocyte adherence: implications for a translational component regulating I kappa B alpha/MAD-3 mRNA levels. \nWe identified I kappa B alpha/MAD-3 as an immediate-early gene in human monocytes that is expressed in response to a variety of signals, including adhesion, lipopolysaccharide, and phorbol myristate acetate. Within 5 min of monocyte adhesion, the level of the I kappa B alpha protein is markedly diminished but is rapidly replaced in a cycloheximide-sensitive manner within 20 min. Accompanying the rapid turnover of the I kappa B alpha protein is simultaneous translocation of NF-kappa B-related transcription factors to nuclei of adhered monocytes. The demonstration that NF-kappa B can regulate I kappa B alpha/MAD-3 gene transcription in other cell types suggested that the rapid increase in steady-state I kappa B alpha/MAD-3 mRNA levels we observed within 30 min of monocyte adherence would result from NF-kappa B-dependent transcriptional stimulation of the I kappa B alpha/MAD-3 gene. Nuclear run-on analyses indicated that, instead, while several immediate-early cytokine genes, such as the interleukin 1 beta (IL-1 beta) gene, were transcriptionally activated during monocyte adhesion, the rate of I kappa B alpha/MAD-3 gene transcription remained constant. The adherence-dependent increase in I kappa B alpha/MAD-3 mRNA levels was also not a consequence of mRNA stabilization events. Interestingly, while increases in both IL-1 beta and I kappa B alpha/MAD-3 mRNA levels were detected in nuclei of adherent monocytes, cytoplasmic levels of IL-1 beta mRNA increased during adherence whereas those of I kappa B alpha/MAD-3 mRNA did not. Taken together, our data suggest that two interactive mechanisms regulate monocytic I kappa B alpha/MAD-3 mRNA levels. We propose that adherent monocytes regulate nuclear processing (or decay) of I kappa B alpha/MAD-3 mRNA, thereby increasing mRNA levels without stimulating I kappa B alpha/MAD-3 gene transcription. Moreover, since inhibition of protein synthesis leads to accumulation of I kappa B alpha/MAD-3 mRNA without stimulating I kappa B alpha/MAD-3 gene transcription, we suggest that low cytoplasmic levels of I kappa B alpha/MAD-3 mRNA are maintained by a translation-dependent degradation mechanism. " ], "offsets": [ [ 0, 2330 ] ] } ]

[ { "id": "PMID-7532282_T1", "type": "Protein", "text": [ "I kappa B alpha" ], "offsets": [ [ 38, 53 ] ], "normalized": [] }, { "id": "PMID-7532282_T2", "type": "Protein", "text": [ "I kappa B alpha" ], "offsets": [ [ 135, 150 ] ], "normalized": [] }, { "id": "PMID-7532282_T3", "type": "Protein", "text": [ "MAD-3" ], "offsets": [ [ 151, 156 ] ], "normalized": [] }, { "id": "PMID-7532282_T4", "type": "Protein", "text": [ "I kappa B alpha" ], "offsets": [ [ 185, 200 ] ], "normalized": [] }, { "id": "PMID-7532282_T5", "type": "Protein", "text": [ "MAD-3" ], "offsets": [ [ 201, 206 ] ], "normalized": [] }, { "id": "PMID-7532282_T6", "type": "Protein", "text": [ "I kappa B alpha" ], "offsets": [ [ 431, 446 ] ], "normalized": [] }, { "id": "PMID-7532282_T7", "type": "Protein", "text": [ "I kappa B alpha" ], "offsets": [ [ 592, 607 ] ], "normalized": [] }, { "id": "PMID-7532282_T8", "type": "Protein", "text": [ "I kappa B alpha" ], "offsets": [ [ 769, 784 ] ], "normalized": [] }, { "id": "PMID-7532282_T9", "type": "Protein", "text": [ "MAD-3" ], "offsets": [ [ 785, 790 ] ], "normalized": [] }, { "id": "PMID-7532282_T10", "type": "Protein", "text": [ "I kappa B alpha" ], "offsets": [ [ 880, 895 ] ], "normalized": [] }, { "id": "PMID-7532282_T11", "type": "Protein", "text": [ "MAD-3" ], "offsets": [ [ 896, 901 ] ], "normalized": [] }, { "id": "PMID-7532282_T12", "type": "Protein", "text": [ "I kappa B alpha" ], "offsets": [ [ 1036, 1051 ] ], "normalized": [] }, { "id": "PMID-7532282_T13", "type": "Protein", "text": [ "MAD-3" ], "offsets": [ [ 1052, 1057 ] ], "normalized": [] }, { "id": "PMID-7532282_T14", "type": "Protein", "text": [ "interleukin 1 beta" ], "offsets": [ [ 1171, 1189 ] ], "normalized": [] }, { "id": "PMID-7532282_T15", "type": "Protein", "text": [ "IL-1 beta" ], "offsets": [ [ 1191, 1200 ] ], "normalized": [] }, { "id": "PMID-7532282_T16", "type": "Protein", "text": [ "I kappa B alpha" ], "offsets": [ [ 1279, 1294 ] ], "normalized": [] }, { "id": "PMID-7532282_T17", "type": "Protein", "text": [ "MAD-3" ], "offsets": [ [ 1295, 1300 ] ], "normalized": [] }, { "id": "PMID-7532282_T18", "type": "Protein", "text": [ "I kappa B alpha" ], "offsets": [ [ 1375, 1390 ] ], "normalized": [] }, { "id": "PMID-7532282_T19", "type": "Protein", "text": [ "MAD-3" ], "offsets": [ [ 1391, 1396 ] ], "normalized": [] }, { "id": "PMID-7532282_T20", "type": "Protein", "text": [ "IL-1 beta" ], "offsets": [ [ 1505, 1514 ] ], "normalized": [] }, { "id": "PMID-7532282_T21", "type": "Protein", "text": [ "I kappa B alpha" ], "offsets": [ [ 1519, 1534 ] ], "normalized": [] }, { "id": "PMID-7532282_T22", "type": "Protein", "text": [ "MAD-3" ], "offsets": [ [ 1535, 1540 ] ], "normalized": [] }, { "id": "PMID-7532282_T23", "type": "Protein", "text": [ "IL-1 beta" ], "offsets": [ [ 1622, 1631 ] ], "normalized": [] }, { "id": "PMID-7532282_T24", "type": "Protein", "text": [ "I kappa B alpha" ], "offsets": [ [ 1681, 1696 ] ], "normalized": [] }, { "id": "PMID-7532282_T25", "type": "Protein", "text": [ "MAD-3" ], "offsets": [ [ 1697, 1702 ] ], "normalized": [] }, { "id": "PMID-7532282_T26", "type": "Protein", "text": [ "I kappa B alpha" ], "offsets": [ [ 1801, 1816 ] ], "normalized": [] }, { "id": "PMID-7532282_T27", "type": "Protein", "text": [ "MAD-3" ], "offsets": [ [ 1817, 1822 ] ], "normalized": [] }, { "id": "PMID-7532282_T28", "type": "Protein", "text": [ "I kappa B alpha" ], "offsets": [ [ 1913, 1928 ] ], "normalized": [] }, { "id": "PMID-7532282_T29", "type": "Protein", "text": [ "MAD-3" ], "offsets": [ [ 1929, 1934 ] ], "normalized": [] }, { "id": "PMID-7532282_T30", "type": "Protein", "text": [ "I kappa B alpha" ], "offsets": [ [ 1992, 2007 ] ], "normalized": [] }, { "id": "PMID-7532282_T31", "type": "Protein", "text": [ "MAD-3" ], "offsets": [ [ 2008, 2013 ] ], "normalized": [] }, { "id": "PMID-7532282_T32", "type": "Protein", "text": [ "I kappa B alpha" ], "offsets": [ [ 2107, 2122 ] ], "normalized": [] }, { "id": "PMID-7532282_T33", "type": "Protein", "text": [ "MAD-3" ], "offsets": [ [ 2123, 2128 ] ], "normalized": [] }, { "id": "PMID-7532282_T34", "type": "Protein", "text": [ "I kappa B alpha" ], "offsets": [ [ 2154, 2169 ] ], "normalized": [] }, { "id": "PMID-7532282_T35", "type": "Protein", "text": [ "MAD-3" ], "offsets": [ [ 2170, 2175 ] ], "normalized": [] }, { "id": "PMID-7532282_T36", "type": "Protein", "text": [ "I kappa B alpha" ], "offsets": [ [ 2238, 2253 ] ], "normalized": [] }, { "id": "PMID-7532282_T37", "type": "Protein", "text": [ "MAD-3" ], "offsets": [ [ 2254, 2259 ] ], "normalized": [] } ]

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"PMID-7532282_E6", "type": "Regulation", "trigger": { "text": [ "sensitive" ], "offsets": [ [ 521, 530 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "PMID-7532282_E5" } ] }, { "id": "PMID-7532282_E7", "type": "Regulation", "trigger": { "text": [ "regulate" ], "offsets": [ [ 760, 768 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "PMID-7532282_E8" } ] }, { "id": "PMID-7532282_E8", "type": "Transcription", "trigger": { "text": [ "transcription" ], "offsets": [ [ 796, 809 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "PMID-7532282_T8" } ] }, { "id": "PMID-7532282_E9", "type": "Positive_regulation", "trigger": { "text": [ "increase" ], "offsets": [ [ 855, 863 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "PMID-7532282_T10" } ] }, { "id": "PMID-7532282_E10", "type": "Positive_regulation", "trigger": { "text": [ "transcriptional stimulation" ], "offsets": [ [ 1001, 1028 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "PMID-7532282_T12" } ] }, { "id": "PMID-7532282_E11", "type": "Positive_regulation", "trigger": { "text": [ "transcriptionally activated" ], "offsets": [ [ 1213, 1240 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "PMID-7532282_T15" } ] }, { "id": "PMID-7532282_E12", "type": "Transcription", "trigger": { "text": [ "transcription" ], "offsets": [ [ 1306, 1319 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "PMID-7532282_T16" } ] }, { "id": "PMID-7532282_E13", "type": "Positive_regulation", "trigger": { "text": [ "remained constant" ], "offsets": [ [ 1320, 1337 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "PMID-7532282_E12" } ] }, { "id": "PMID-7532282_E14", "type": "Positive_regulation", "trigger": { "text": [ "increase" ], "offsets": [ [ 1363, 1371 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "PMID-7532282_T18" } ] }, { "id": "PMID-7532282_E15", "type": "Positive_regulation", "trigger": { "text": [ "consequence" ], "offsets": [ [ 1424, 1435 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "PMID-7532282_E14" }, { "role": "Cause", "ref_id": "PMID-7532282_E16" } ] }, { "id": "PMID-7532282_E16", "type": "Positive_regulation", "trigger": { "text": [ "stabilization" ], "offsets": [ [ 1444, 1457 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "PMID-7532282_T18" } ] }, { "id": "PMID-7532282_E17", "type": "Positive_regulation", "trigger": { "text": [ "increases" ], "offsets": [ [ 1487, 1496 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "PMID-7532282_T21" } ] }, { "id": "PMID-7532282_E18", "type": "Positive_regulation", "trigger": { "text": [ "increases" ], "offsets": [ [ 1487, 1496 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "PMID-7532282_T20" } ] }, { "id": "PMID-7532282_E19", "type": "Positive_regulation", "trigger": { "text": [ "increased" ], "offsets": [ [ 1637, 1646 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "PMID-7532282_T23" } ] }, { "id": "PMID-7532282_E20", "type": "Positive_regulation", "trigger": { "text": [ "increased" ], "offsets": [ [ 1637, 1646 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "PMID-7532282_T24" } ] }, { "id": "PMID-7532282_E21", "type": "Regulation", "trigger": { "text": [ "regulate" ], "offsets": [ [ 1782, 1790 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "PMID-7532282_T26" } ] }, { "id": "PMID-7532282_E22", "type": "Positive_regulation", "trigger": { "text": [ "increasing" ], "offsets": [ [ 1949, 1959 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "PMID-7532282_T28" } ] }, { "id": "PMID-7532282_E23", "type": "Positive_regulation", "trigger": { "text": [ "without stimulating" ], "offsets": [ [ 1972, 1991 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "PMID-7532282_E24" } ] }, { "id": "PMID-7532282_E24", "type": "Transcription", "trigger": { "text": [ "transcription" ], "offsets": [ [ 2019, 2032 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "PMID-7532282_T30" } ] }, { "id": "PMID-7532282_E25", "type": "Positive_regulation", "trigger": { "text": [ "leads" ], "offsets": [ [ 2082, 2087 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "PMID-7532282_E26" } ] }, { "id": "PMID-7532282_E26", "type": "Positive_regulation", "trigger": { "text": [ "accumulation" ], "offsets": [ [ 2091, 2103 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "PMID-7532282_T32" } ] }, { "id": "PMID-7532282_E27", "type": "Positive_regulation", "trigger": { "text": [ "stimulating" ], "offsets": [ [ 2142, 2153 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "PMID-7532282_E28" } ] }, { "id": "PMID-7532282_E28", "type": "Transcription", "trigger": { "text": [ "transcription" ], "offsets": [ [ 2181, 2194 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "PMID-7532282_T34" } ] }, { "id": "PMID-7532282_E29", "type": "Negative_regulation", "trigger": { "text": [ "maintained" ], "offsets": [ [ 2269, 2279 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "PMID-7532282_T36" } ] } ]

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[]

[ { "id": "PMID-7534293__text", "type": "abstract", "text": [ "E2F-1 and a cyclin-like DNA repair enzyme, uracil-DNA glycosylase, provide evidence for an autoregulatory mechanism for transcription. \nThe cell cycle-dependent transcription factor, E2F-1, regulates the cyclin-like species of the DNA repair enzyme uracil-DNA glycosylase (UDG) gene in human osteosarcoma (Saos-2) cells. We demonstrate, through the deletion of the human UDG promoter sequences, that expression of E2F-1 activates the UDG promoter through several E2F sites. The major putative downstream site for E2F, located in the first exon, serves as a target for E2F-1/DP1 complex binding in vitro. We also provide evidence for the functional relationship between the cyclin-like UDG gene product and E2F. High levels of UDG expression in a transient transfection assay result in the down-regulation of transcriptional activity through elements specific for E2F-mediated transcription. Overexpression of UDG in Saos 2 cells was observed to delay growth late in G1 phase and transiently arrest these cells from progressing into the S phase. This hypothetical model integrates one mechanism of DNA repair with the cell cycle control of gene transcription, likely through E2F. This implicates E2F as a multifunctional target for proteins and enzymes, possibly, responsive to DNA damage through the negative effect of UDG on E2F-mediated transcriptional activity. " ], "offsets": [ [ 0, 1365 ] ] } ]

[ { "id": "PMID-7534293_T1", "type": "Protein", "text": [ "E2F-1" ], "offsets": [ [ 0, 5 ] ], "normalized": [] }, { "id": "PMID-7534293_T2", "type": "Protein", "text": [ "uracil-DNA glycosylase" ], "offsets": [ [ 43, 65 ] ], "normalized": [] }, { "id": "PMID-7534293_T3", "type": "Protein", "text": [ "E2F-1" ], "offsets": [ [ 183, 188 ] ], "normalized": [] }, { "id": "PMID-7534293_T4", "type": "Protein", "text": [ "uracil-DNA glycosylase" ], "offsets": [ [ 249, 271 ] ], "normalized": [] }, { "id": "PMID-7534293_T5", "type": "Protein", "text": [ "UDG" ], "offsets": [ [ 273, 276 ] ], "normalized": [] }, { "id": "PMID-7534293_T6", "type": "Protein", "text": [ "UDG" ], "offsets": [ [ 371, 374 ] ], "normalized": [] }, { "id": "PMID-7534293_T7", "type": "Protein", "text": [ "E2F-1" ], "offsets": [ [ 414, 419 ] ], "normalized": [] }, { "id": "PMID-7534293_T8", "type": "Protein", "text": [ "UDG" ], "offsets": [ [ 434, 437 ] ], "normalized": [] }, { "id": "PMID-7534293_T9", "type": "Protein", "text": [ "E2F-1" ], "offsets": [ [ 568, 573 ] ], "normalized": [] }, { "id": "PMID-7534293_T10", "type": "Protein", "text": [ "DP1" ], "offsets": [ [ 574, 577 ] ], "normalized": [] }, { "id": "PMID-7534293_T11", "type": "Protein", "text": [ "UDG" ], "offsets": [ [ 685, 688 ] ], "normalized": [] }, { "id": "PMID-7534293_T12", "type": "Protein", "text": [ "UDG" ], "offsets": [ [ 726, 729 ] ], "normalized": [] }, { "id": "PMID-7534293_T13", "type": "Protein", "text": [ "UDG" ], "offsets": [ [ 909, 912 ] ], "normalized": [] }, { "id": "PMID-7534293_T14", "type": "Protein", "text": [ "UDG" ], "offsets": [ [ 1319, 1322 ] ], "normalized": [] }, { "id": "PMID-7534293_T18", "type": "Entity", "text": [ "promoter" ], "offsets": [ [ 438, 446 ] ], "normalized": [] } ]

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[]

[ { "id": "PMID-7534663__text", "type": "abstract", "text": [ "Aspirin inhibits nuclear factor-kappa B mobilization and monocyte adhesion in stimulated human endothelial cells. \nBACKGROUND: The induction of vascular cell adhesion molecule-1 (VCAM-1) and E-selectin by tumor necrosis factor-alpha (TNF) is mediated by mobilization of the transcription factor nuclear factor-kappa B (NF-kappa B). Since salicylates have been reported to inhibit NF-kappa B activation by preventing the degradation of its inhibitor I kappa B, we studied a potential inhibition of this pathway by acetylsalicylate (aspirin) in human umbilical vein endothelial cells (HUVECs). METHODS AND RESULTS: Gel-shift analyses demonstrated dose-dependent inhibition of TNF-induced NF-kappa B mobilization by aspirin at concentrations ranging from 1 to 10 mmol/L. Induction of VCAM-1 and E-selectin surface expression by TNF was dose-dependently reduced by aspirin over the same range, while induction of intercellular adhesion molecule-1 (ICAM-1) was hardly affected. Aspirin appeared to prevent VCAM-1 transcription, since it dose-dependently inhibited induction of VCAM-1 mRNA by TNF. As a functional consequence, adhesion of U937 monocytes to TNF-stimulated HUVECs was markedly reduced by aspirin due to suppression of VCAM-1 and E-selectin upregulation. These effects of aspirin were not related to the inhibition of cyclooxygenase activity, since indomethacin was ineffective. CONCLUSIONS: Our data suggest that aspirin inhibits NF-kappa B mobilization, induction of VCAM-1 and E-selectin, and subsequent monocyte adhesion in endothelial cells stimulated by TNF, thereby providing an additional mechanism for therapeutic effects of aspirin. " ], "offsets": [ [ 0, 1651 ] ] } ]

[ { "id": "PMID-7534663_T1", "type": "Protein", "text": [ "vascular cell adhesion molecule-1" ], "offsets": [ [ 144, 177 ] ], "normalized": [] }, { "id": "PMID-7534663_T2", "type": "Protein", "text": [ "VCAM-1" ], "offsets": [ [ 179, 185 ] ], "normalized": [] }, { "id": "PMID-7534663_T3", "type": "Protein", "text": [ "E-selectin" ], "offsets": [ [ 191, 201 ] ], "normalized": [] }, { "id": "PMID-7534663_T4", "type": "Protein", "text": [ "tumor necrosis factor-alpha" ], "offsets": [ [ 205, 232 ] ], "normalized": [] }, { "id": "PMID-7534663_T5", "type": "Protein", "text": [ "TNF" ], "offsets": [ [ 234, 237 ] ], "normalized": [] }, { "id": "PMID-7534663_T6", "type": "Protein", "text": [ "TNF" ], "offsets": [ [ 674, 677 ] ], "normalized": [] }, { "id": "PMID-7534663_T7", "type": "Protein", "text": [ "VCAM-1" ], "offsets": [ [ 781, 787 ] ], "normalized": [] }, { "id": "PMID-7534663_T8", "type": "Protein", "text": [ "E-selectin" ], "offsets": [ [ 792, 802 ] ], "normalized": [] }, { "id": "PMID-7534663_T9", "type": "Protein", "text": [ "TNF" ], "offsets": [ [ 825, 828 ] ], "normalized": [] }, { "id": "PMID-7534663_T10", "type": "Protein", "text": [ "intercellular adhesion molecule-1" ], "offsets": [ [ 909, 942 ] ], "normalized": [] }, { "id": "PMID-7534663_T11", "type": "Protein", "text": [ "ICAM-1" ], "offsets": [ [ 944, 950 ] ], "normalized": [] }, { "id": "PMID-7534663_T12", "type": "Protein", "text": [ "VCAM-1" ], "offsets": [ [ 1001, 1007 ] ], "normalized": [] }, { "id": "PMID-7534663_T13", "type": "Protein", "text": [ "VCAM-1" ], "offsets": [ [ 1072, 1078 ] ], "normalized": [] }, { "id": "PMID-7534663_T14", "type": "Protein", "text": [ "TNF" ], "offsets": [ [ 1087, 1090 ] ], "normalized": [] }, { "id": "PMID-7534663_T15", "type": "Protein", "text": [ "TNF" ], "offsets": [ [ 1151, 1154 ] ], "normalized": [] }, { "id": "PMID-7534663_T16", "type": "Protein", "text": [ "VCAM-1" ], "offsets": [ [ 1227, 1233 ] ], "normalized": [] }, { "id": "PMID-7534663_T17", "type": "Protein", "text": [ "E-selectin" ], "offsets": [ [ 1238, 1248 ] ], "normalized": [] }, { "id": "PMID-7534663_T18", "type": "Protein", "text": [ "VCAM-1" ], "offsets": [ [ 1477, 1483 ] ], "normalized": [] }, { "id": "PMID-7534663_T19", "type": "Protein", "text": [ "E-selectin" ], "offsets": [ [ 1488, 1498 ] ], "normalized": [] }, { "id": "PMID-7534663_T20", "type": "Protein", "text": [ "TNF" ], "offsets": [ [ 1568, 1571 ] ], "normalized": [] }, { "id": "PMID-7534663_T24", "type": "Entity", "text": [ "surface" ], "offsets": [ [ 803, 810 ] ], "normalized": [] } ]

[ { "id": "PMID-7534663_E1", "type": "Positive_regulation", "trigger": { "text": [ "induction" ], "offsets": [ [ 131, 140 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "PMID-7534663_T3" }, { "role": "Cause", "ref_id": "PMID-7534663_T5" } ] }, { "id": "PMID-7534663_E2", "type": "Positive_regulation", "trigger": { "text": [ "induction" ], "offsets": [ [ 131, 140 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "PMID-7534663_T2" }, { "role": "Cause", "ref_id": "PMID-7534663_T5" } ] }, { "id": "PMID-7534663_E3", "type": "Positive_regulation", "trigger": { "text": [ "mediated" ], "offsets": [ [ 242, 250 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "PMID-7534663_E2" } ] }, { "id": "PMID-7534663_E4", "type": "Positive_regulation", "trigger": { "text": [ "mediated" ], "offsets": [ [ 242, 250 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "PMID-7534663_E1" } ] }, { "id": "PMID-7534663_E5", "type": "Positive_regulation", "trigger": { "text": [ "Induction" ], "offsets": [ [ 768, 777 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "PMID-7534663_E8" }, { "role": "Cause", "ref_id": "PMID-7534663_T9" } ] }, { "id": "PMID-7534663_E6", "type": "Positive_regulation", "trigger": { "text": [ "Induction" ], "offsets": [ [ 768, 777 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "PMID-7534663_E7" }, { "role": "Cause", "ref_id": "PMID-7534663_T9" } ] }, { "id": "PMID-7534663_E7", "type": "Localization", "trigger": { "text": [ "expression" ], "offsets": [ [ 811, 821 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "PMID-7534663_T8" }, { "role": "AtLoc", "ref_id": "PMID-7534663_T24" } ] }, { "id": "PMID-7534663_E8", "type": "Localization", "trigger": { "text": [ "expression" ], "offsets": [ [ 811, 821 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "PMID-7534663_T7" }, { "role": "AtLoc", "ref_id": "PMID-7534663_T24" } ] }, { "id": "PMID-7534663_E9", "type": "Negative_regulation", "trigger": { "text": [ "reduced" ], "offsets": [ [ 850, 857 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "PMID-7534663_E6" } ] }, { "id": "PMID-7534663_E10", "type": "Negative_regulation", "trigger": { "text": [ "reduced" ], "offsets": [ [ 850, 857 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "PMID-7534663_E5" } ] }, { "id": "PMID-7534663_E11", "type": "Positive_regulation", "trigger": { "text": [ "induction" ], "offsets": [ [ 896, 905 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "PMID-7534663_T11" } ] }, { "id": "PMID-7534663_E12", "type": "Regulation", "trigger": { "text": [ "affected" ], "offsets": [ [ 963, 971 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "PMID-7534663_E11" } ] }, { "id": "PMID-7534663_E13", "type": "Negative_regulation", "trigger": { "text": [ "prevent" ], "offsets": [ [ 993, 1000 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "PMID-7534663_E14" } ] }, { "id": "PMID-7534663_E14", "type": "Transcription", "trigger": { "text": [ "transcription" ], "offsets": [ [ 1008, 1021 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "PMID-7534663_T12" } ] }, { "id": "PMID-7534663_E15", "type": "Negative_regulation", "trigger": { "text": [ "inhibited" ], "offsets": [ [ 1049, 1058 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "PMID-7534663_E16" } ] }, { "id": "PMID-7534663_E16", "type": "Positive_regulation", "trigger": { "text": [ "induction" ], "offsets": [ [ 1059, 1068 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "PMID-7534663_T13" }, { "role": "Cause", "ref_id": "PMID-7534663_T14" } ] }, { "id": "PMID-7534663_E17", "type": "Negative_regulation", "trigger": { "text": [ "suppression" ], "offsets": [ [ 1212, 1223 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "PMID-7534663_E19" } ] }, { "id": "PMID-7534663_E18", "type": "Negative_regulation", "trigger": { "text": [ "suppression" ], "offsets": [ [ 1212, 1223 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "PMID-7534663_E20" } ] }, { "id": "PMID-7534663_E19", "type": "Positive_regulation", "trigger": { "text": [ "upregulation" ], "offsets": [ [ 1249, 1261 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "PMID-7534663_T16" } ] }, { "id": "PMID-7534663_E20", "type": "Positive_regulation", "trigger": { "text": [ "upregulation" ], "offsets": [ [ 1249, 1261 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "PMID-7534663_T17" } ] }, { "id": "PMID-7534663_E21", "type": "Regulation", "trigger": { "text": [ "ineffective" ], "offsets": [ [ 1374, 1385 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "PMID-7534663_E17" } ] }, { "id": "PMID-7534663_E22", "type": "Regulation", "trigger": { "text": [ "ineffective" ], "offsets": [ [ 1374, 1385 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "PMID-7534663_E18" } ] }, { "id": "PMID-7534663_E23", "type": "Negative_regulation", "trigger": { "text": [ "inhibits" ], "offsets": [ [ 1430, 1438 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "PMID-7534663_E25" } ] }, { "id": "PMID-7534663_E24", "type": "Negative_regulation", "trigger": { "text": [ "inhibits" ], "offsets": [ [ 1430, 1438 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "PMID-7534663_E26" } ] }, { "id": "PMID-7534663_E25", "type": "Positive_regulation", "trigger": { "text": [ "induction" ], "offsets": [ [ 1464, 1473 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "PMID-7534663_T18" } ] }, { "id": "PMID-7534663_E26", "type": "Positive_regulation", "trigger": { "text": [ "induction" ], "offsets": [ [ 1464, 1473 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "PMID-7534663_T19" } ] } ]

[ { "id": "PMID-7534663_1", "entity_ids": [ "PMID-7534663_T2", "PMID-7534663_T1" ] }, { "id": "PMID-7534663_2", "entity_ids": [ "PMID-7534663_T5", "PMID-7534663_T4" ] }, { "id": "PMID-7534663_3", "entity_ids": [ "PMID-7534663_T11", "PMID-7534663_T10" ] } ]

[]

[ { "id": "PMID-7540578__text", "type": "abstract", "text": [ "Danazol decreases transcription of estrogen receptor gene in human monocytes. \n1. Administration of danazol for over one month reduced the levels of estrogen receptor (ER) and its mRNA to approximately 50 and 20%, respectively in monocytes. 2. Danazol did not alter the degradation rate of ER mRNA in monocytes. 3. Danazol decreased the transcription rate of ER gene to approximately 50% in monocytes in a run-on assay. 4. Danazol may release estrogen predominance via the reduction of transcription for ER gene, which leads to the reduction of ER mRNA and ER expressions in monocytes. " ], "offsets": [ [ 0, 586 ] ] } ]

[ { "id": "PMID-7540578_T1", "type": "Protein", "text": [ "estrogen receptor" ], "offsets": [ [ 35, 52 ] ], "normalized": [] }, { "id": "PMID-7540578_T2", "type": "Protein", "text": [ "estrogen receptor" ], "offsets": [ [ 149, 166 ] ], "normalized": [] }, { "id": "PMID-7540578_T3", "type": "Protein", "text": [ "ER" ], "offsets": [ [ 168, 170 ] ], "normalized": [] }, { "id": "PMID-7540578_T4", "type": "Protein", "text": [ "ER" ], "offsets": [ [ 290, 292 ] ], "normalized": [] }, { "id": "PMID-7540578_T5", "type": "Protein", "text": [ "ER" ], "offsets": [ [ 359, 361 ] ], "normalized": [] }, { "id": "PMID-7540578_T6", "type": "Protein", "text": [ "ER" ], "offsets": [ [ 504, 506 ] ], "normalized": [] }, { "id": "PMID-7540578_T7", "type": "Protein", "text": [ "ER" ], "offsets": [ [ 545, 547 ] ], "normalized": [] }, { "id": "PMID-7540578_T8", "type": "Protein", "text": [ "ER" ], "offsets": [ [ 557, 559 ] ], "normalized": [] } ]

[ { "id": "PMID-7540578_E1", "type": "Negative_regulation", "trigger": { "text": [ "decreases" ], "offsets": [ [ 8, 17 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "PMID-7540578_E2" } ] }, { "id": "PMID-7540578_E2", "type": "Transcription", "trigger": { "text": [ "transcription" ], "offsets": [ [ 18, 31 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "PMID-7540578_T1" } ] }, { "id": "PMID-7540578_E3", "type": "Negative_regulation", "trigger": { "text": [ "reduced the levels" ], "offsets": [ [ 127, 145 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "PMID-7540578_T3" } ] }, { "id": "PMID-7540578_E4", "type": "Regulation", "trigger": { "text": [ "alter" ], "offsets": [ [ 260, 265 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "PMID-7540578_E5" } ] }, { "id": "PMID-7540578_E5", "type": "Protein_catabolism", "trigger": { "text": [ "degradation" ], "offsets": [ [ 270, 281 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "PMID-7540578_T4" } ] }, { "id": "PMID-7540578_E6", "type": "Negative_regulation", "trigger": { "text": [ "decreased" ], "offsets": [ [ 323, 332 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "PMID-7540578_E7" } ] }, { "id": "PMID-7540578_E7", "type": "Transcription", "trigger": { "text": [ "transcription" ], "offsets": [ [ 337, 350 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "PMID-7540578_T5" } ] }, { "id": "PMID-7540578_E8", "type": "Negative_regulation", "trigger": { "text": [ "reduction" ], "offsets": [ [ 473, 482 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "PMID-7540578_E9" } ] }, { "id": "PMID-7540578_E9", "type": "Transcription", "trigger": { "text": [ "transcription" ], "offsets": [ [ 486, 499 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "PMID-7540578_T6" } ] }, { "id": "PMID-7540578_E10", "type": "Positive_regulation", "trigger": { "text": [ "leads" ], "offsets": [ [ 519, 524 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "PMID-7540578_E12" }, { "role": "Cause", "ref_id": "PMID-7540578_E8" } ] }, { "id": "PMID-7540578_E11", "type": "Positive_regulation", "trigger": { "text": [ "leads" ], "offsets": [ [ 519, 524 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "PMID-7540578_E13" }, { "role": "Cause", "ref_id": "PMID-7540578_E8" } ] }, { "id": "PMID-7540578_E12", "type": "Negative_regulation", "trigger": { "text": [ "reduction" ], "offsets": [ [ 532, 541 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "PMID-7540578_E15" } ] }, { "id": "PMID-7540578_E13", "type": "Negative_regulation", "trigger": { "text": [ "reduction" ], "offsets": [ [ 532, 541 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "PMID-7540578_E14" } ] }, { "id": "PMID-7540578_E14", "type": "Gene_expression", "trigger": { "text": [ "expressions" ], "offsets": [ [ 560, 571 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "PMID-7540578_T8" } ] }, { "id": "PMID-7540578_E15", "type": "Transcription", "trigger": { "text": [ "expressions" ], "offsets": [ [ 560, 571 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "PMID-7540578_T7" } ] } ]

[ { "id": "PMID-7540578_1", "entity_ids": [ "PMID-7540578_T3", "PMID-7540578_T2" ] } ]

[]

[ { "id": "PMID-7540942__text", "type": "abstract", "text": [ "Cross-linking of CD30 induces HIV expression in chronically infected T cells. \nCD30, a member of the tumor necrosis factor (TNF) receptor family, is expressed constitutively on the surface of the human T cell line ACH-2, which is chronically infected with human immunodeficiency virus type-1 (HIV)-1. We demonstrate that cross-linking CD30 with an anti-CD30-specific monoclonal antibody, which mimics the described biological activities of the CD30 ligand (CD30L), results in HIV expression. CD30 cross-linking does not alter proliferation of ACH-2 cells and the induction of HIV expression is not mediated by endogenous TNF alpha/beta. Furthermore, cross-linking of CD30 leads to NF-kappa B activation and enhanced HIV transcription. Thus, CD30-CD30L interactions mediate the induction of HIV expression by a kappa B-dependent pathway that is independent of TNF. This mechanism may be important in the activation of HIV expression from latently infected CD4+ T cells, especially in lymphoid organs where cell to cell contact is conducive to receptor-ligand interactions. " ], "offsets": [ [ 0, 1072 ] ] } ]

[ { "id": "PMID-7540942_T1", "type": "Protein", "text": [ "CD30" ], "offsets": [ [ 17, 21 ] ], "normalized": [] }, { "id": "PMID-7540942_T2", "type": "Protein", "text": [ "CD30" ], "offsets": [ [ 79, 83 ] ], "normalized": [] }, { "id": "PMID-7540942_T3", "type": "Protein", "text": [ "CD30" ], "offsets": [ [ 335, 339 ] ], "normalized": [] }, { "id": "PMID-7540942_T4", "type": "Protein", "text": [ "CD30" ], "offsets": [ [ 353, 357 ] ], "normalized": [] }, { "id": "PMID-7540942_T5", "type": "Protein", "text": [ "CD30 ligand" ], "offsets": [ [ 444, 455 ] ], "normalized": [] }, { "id": "PMID-7540942_T6", "type": "Protein", "text": [ "CD30L" ], "offsets": [ [ 457, 462 ] ], "normalized": [] }, { "id": "PMID-7540942_T7", "type": "Protein", "text": [ "CD30" ], "offsets": [ [ 492, 496 ] ], "normalized": [] }, { "id": "PMID-7540942_T8", "type": "Protein", "text": [ "TNF alpha" ], "offsets": [ [ 621, 630 ] ], "normalized": [] }, { "id": "PMID-7540942_T9", "type": "Protein", "text": [ "beta" ], "offsets": [ [ 631, 635 ] ], "normalized": [] }, { "id": "PMID-7540942_T10", "type": "Protein", "text": [ "CD30" ], "offsets": [ [ 667, 671 ] ], "normalized": [] }, { "id": "PMID-7540942_T11", "type": "Protein", "text": [ "CD30" ], "offsets": [ [ 741, 745 ] ], "normalized": [] }, { "id": "PMID-7540942_T12", "type": "Protein", "text": [ "CD30L" ], "offsets": [ [ 746, 751 ] ], "normalized": [] }, { "id": "PMID-7540942_T13", "type": "Protein", "text": [ "CD4" ], "offsets": [ [ 955, 958 ] ], "normalized": [] } ]

[ { "id": "PMID-7540942_E1", "type": "Binding", "trigger": { "text": [ "Cross-linking" ], "offsets": [ [ 0, 13 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "PMID-7540942_T1" } ] }, { "id": "PMID-7540942_E2", "type": "Gene_expression", "trigger": { "text": [ "expressed" ], "offsets": [ [ 149, 158 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "PMID-7540942_T2" } ] }, { "id": "PMID-7540942_E3", "type": "Binding", "trigger": { "text": [ "cross-linking" ], "offsets": [ [ 321, 334 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "PMID-7540942_T3" }, { "role": "Theme", "ref_id": "PMID-7540942_T6" } ] }, { "id": "PMID-7540942_E4", "type": "Binding", "trigger": { "text": [ "cross-linking" ], "offsets": [ [ 321, 334 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "PMID-7540942_T3" } ] }, { "id": "PMID-7540942_E5", "type": "Binding", "trigger": { "text": [ "cross-linking" ], "offsets": [ [ 497, 510 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "PMID-7540942_T7" } ] }, { "id": "PMID-7540942_E6", "type": "Binding", "trigger": { "text": [ "cross-linking" ], "offsets": [ [ 650, 663 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "PMID-7540942_T10" } ] }, { "id": "PMID-7540942_E7", "type": "Binding", "trigger": { "text": [ "interactions" ], "offsets": [ [ 752, 764 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "PMID-7540942_T11" }, { "role": "Theme", "ref_id": "PMID-7540942_T12" } ] }, { "id": "PMID-7540942_E8", "type": "Binding", "trigger": { "text": [ "interactions" ], "offsets": [ [ 1058, 1070 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "PMID-7540942_T11" }, { "role": "Theme", "ref_id": "PMID-7540942_T12" } ] } ]

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[]

[ { "id": "PMID-7541794__text", "type": "abstract", "text": [ "Integrin-mediated tyrosine phosphorylation and cytokine message induction in monocytic cells. A possible signaling role for the Syk tyrosine kinase. \nActivation of cytoplasmic tyrosine kinases is an important aspect of signal transduction mediated by integrins. In the human monocytic cell line THP-1, either integrin-dependent cell adhesion to fibronectin or ligation of beta 1 integrins with antibodies causes a rapid and intense tyrosine phosphorylation of two sets of proteins of about 65-75 and 120-125 kDa. In addition, integrin ligation leads to nuclear translocation of the p50 and p65 subunits of the NF-kappa B transcription factor, to activation of a reporter gene driven by a promoter containing NF-kappa B sites, and to increased levels of mRNAs for immediate-early genes, including the cytokine interleukin (IL)-1 beta. The tyrosine kinase inhibitors genistein and herbimycin A block both integrin-mediated tyrosine phosphorylation and increases in IL-1 beta message levels, indicating a causal relationship between the two events. The components tyrosine phosphorylated subsequent to cell adhesion include paxillin, pp125FAK, and the SH2 domain containing tyrosine kinase Syk. In contrast, integrin ligation with antibodies induces tyrosine phosphorylation of Syk but not of FAK or paxillin. In adhering cells, pre-treatment with cytochalasin D suppresses tyrosine phosphorylation of FAK and paxillin but not of Syk, while IL-1 beta message induction is unaffected. These observations indicate that the Syk tyrosine kinase may be an important component of an integrin signaling pathway in monocytic cells, leading to activation of NF-kappa B and to increased levels of cytokine messages. " ], "offsets": [ [ 0, 1703 ] ] } ]

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"Theme", "ref_id": "PMID-7541794_T6" } ] }, { "id": "PMID-7541794_E11", "type": "Phosphorylation", "trigger": { "text": [ "phosphorylated" ], "offsets": [ [ 1070, 1084 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "PMID-7541794_T8" }, { "role": "Site", "ref_id": "PMID-7541794_T24" } ] }, { "id": "PMID-7541794_E12", "type": "Phosphorylation", "trigger": { "text": [ "phosphorylated" ], "offsets": [ [ 1070, 1084 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "PMID-7541794_T7" }, { "role": "Site", "ref_id": "PMID-7541794_T24" } ] }, { "id": "PMID-7541794_E13", "type": "Phosphorylation", "trigger": { "text": [ "phosphorylated" ], "offsets": [ [ 1070, 1084 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "PMID-7541794_T9" }, { "role": "Site", "ref_id": "PMID-7541794_T24" } ] }, { "id": "PMID-7541794_E14", "type": "Positive_regulation", "trigger": { "text": [ "subsequent to" ], "offsets": [ [ 1085, 1098 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "PMID-7541794_E17" } ] }, { "id": "PMID-7541794_E15", "type": "Positive_regulation", "trigger": { "text": [ "subsequent to" ], "offsets": [ [ 1085, 1098 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "PMID-7541794_E12" } ] }, { "id": "PMID-7541794_E16", "type": "Positive_regulation", "trigger": { "text": [ "induces" ], "offsets": [ [ 1239, 1246 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "PMID-7541794_E19" } ] }, { "id": "PMID-7541794_E17", "type": "Positive_regulation", "trigger": { "text": [ "induces" ], "offsets": [ [ 1239, 1246 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "PMID-7541794_E21" } ] }, { "id": "PMID-7541794_E18", "type": "Positive_regulation", "trigger": { "text": [ "induces" ], "offsets": [ [ 1239, 1246 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "PMID-7541794_E20" } ] }, { "id": "PMID-7541794_E19", "type": "Phosphorylation", "trigger": { "text": [ "phosphorylation" ], "offsets": [ [ 1256, 1271 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "PMID-7541794_T11" }, { "role": "Site", "ref_id": "PMID-7541794_T28" } ] }, { "id": "PMID-7541794_E20", "type": "Phosphorylation", "trigger": { "text": [ "phosphorylation" ], "offsets": [ [ 1256, 1271 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "PMID-7541794_T8" }, { "role": "Site", "ref_id": "PMID-7541794_T28" } ] }, { "id": "PMID-7541794_E21", "type": "Phosphorylation", "trigger": { "text": [ "phosphorylation" ], "offsets": [ [ 1256, 1271 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "PMID-7541794_T10" }, { "role": "Site", "ref_id": "PMID-7541794_T28" } ] }, { "id": "PMID-7541794_E22", "type": "Negative_regulation", "trigger": { "text": [ "suppresses" ], "offsets": [ [ 1360, 1370 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "PMID-7541794_E27" } ] }, { "id": "PMID-7541794_E23", "type": "Negative_regulation", "trigger": { "text": [ "suppresses" ], "offsets": [ [ 1360, 1370 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "PMID-7541794_E25" } ] }, { "id": "PMID-7541794_E24", "type": "Negative_regulation", "trigger": { "text": [ "suppresses" ], "offsets": [ [ 1360, 1370 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "PMID-7541794_E26" } ] }, { "id": "PMID-7541794_E25", "type": "Phosphorylation", "trigger": { "text": [ "phosphorylation" ], "offsets": [ [ 1380, 1395 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "PMID-7541794_T12" }, { "role": "Site", "ref_id": "PMID-7541794_T31" } ] }, { "id": "PMID-7541794_E26", "type": "Phosphorylation", "trigger": { "text": [ "phosphorylation" ], "offsets": [ [ 1380, 1395 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "PMID-7541794_T8" }, { "role": "Site", "ref_id": "PMID-7541794_T31" } ] }, { "id": "PMID-7541794_E27", "type": "Phosphorylation", "trigger": { "text": [ "phosphorylation" ], "offsets": [ [ 1380, 1395 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "PMID-7541794_T13" }, { "role": "Site", "ref_id": "PMID-7541794_T31" } ] }, { "id": "PMID-7541794_E28", "type": "Positive_regulation", "trigger": { "text": [ "induction" ], "offsets": [ [ 1456, 1465 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "PMID-7541794_T14" } ] }, { "id": "PMID-7541794_E29", "type": "Regulation", "trigger": { "text": [ "unaffected" ], "offsets": [ [ 1469, 1479 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "PMID-7541794_E28" } ] } ]

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[ { "id": "PMID-7542286__text", "type": "abstract", "text": [ "Nitric oxide decreases cytokine-induced endothelial activation. Nitric oxide selectively reduces endothelial expression of adhesion molecules and proinflammatory cytokines. \nTo test the hypothesis that nitric oxide (NO) limits endothelial activation, we treated cytokine-stimulated human saphenous vein endothelial cells with several NO donors and assessed their effects on the inducible expression of vascular cell adhesion molecule-1 (VCAM-1). In a concentration-dependent manner, NO inhibited interleukin (IL)-1 alpha-stimulated VCAM-1 expression by 35-55% as determined by cell surface enzyme immunoassays and flow cytometry. This inhibition was paralleled by reduced monocyte adhesion to endothelial monolayers in nonstatic assays, was unaffected by cGMP analogues, and was quantitatively similar after stimulation by either IL-1 alpha, IL-1 beta, IL-4, tumor necrosis factor (TNF alpha), or bacterial lipopolysaccharide. NO also decreased the endothelial expression of other leukocyte adhesion molecules (E-selectin and to a lesser extent, intercellular adhesion molecule-1) and secretable cytokines (IL-6 and IL-8). Inhibition of endogenous NO production by L-N-monomethyl-arginine also induced the expression of VCAM-1, but did not augment cytokine-induced VCAM-1 expression. Nuclear run-on assays, transfection studies using various VCAM-1 promoter reporter gene constructs, and electrophoretic mobility shift assays indicated that NO represses VCAM-1 gene transcription, in part, by inhibiting NF-kappa B. We propose that NO's ability to limit endothelial activation and inhibit monocyte adhesion may contribute to some of its antiatherogenic and antiinflammatory properties within the vessel wall. " ], "offsets": [ [ 0, 1709 ] ] } ]

[ { "id": "PMID-7542286_T1", "type": "Protein", "text": [ "vascular cell adhesion molecule-1" ], "offsets": [ [ 402, 435 ] ], "normalized": [] }, { "id": "PMID-7542286_T2", "type": "Protein", "text": [ "VCAM-1" ], "offsets": [ [ 437, 443 ] ], "normalized": [] }, { "id": "PMID-7542286_T3", "type": "Protein", "text": [ "interleukin (IL)-1 alpha" ], "offsets": [ [ 496, 520 ] ], "normalized": [] }, { "id": "PMID-7542286_T4", "type": "Protein", "text": [ "VCAM-1" ], "offsets": [ [ 532, 538 ] ], "normalized": [] }, { "id": "PMID-7542286_T5", "type": "Protein", "text": [ "IL-1 alpha" ], "offsets": [ [ 830, 840 ] ], "normalized": [] }, { "id": "PMID-7542286_T6", "type": "Protein", "text": [ "IL-1 beta" ], "offsets": [ [ 842, 851 ] ], "normalized": [] }, { "id": "PMID-7542286_T7", "type": "Protein", "text": [ "IL-4" ], "offsets": [ [ 853, 857 ] ], "normalized": [] }, { "id": "PMID-7542286_T8", "type": "Protein", "text": [ "tumor necrosis factor" ], "offsets": [ [ 859, 880 ] ], "normalized": [] }, { "id": "PMID-7542286_T9", "type": "Protein", "text": [ "TNF alpha" ], "offsets": [ [ 882, 891 ] ], "normalized": [] }, { "id": "PMID-7542286_T10", "type": "Protein", "text": [ "E-selectin" ], "offsets": [ [ 1011, 1021 ] ], "normalized": [] }, { "id": "PMID-7542286_T11", "type": "Protein", "text": [ "intercellular adhesion molecule-1" ], "offsets": [ [ 1046, 1079 ] ], "normalized": [] }, { "id": "PMID-7542286_T12", "type": "Protein", "text": [ "IL-6" ], "offsets": [ [ 1107, 1111 ] ], "normalized": [] }, { "id": "PMID-7542286_T13", "type": "Protein", "text": [ "IL-8" ], "offsets": [ [ 1116, 1120 ] ], "normalized": [] }, { "id": "PMID-7542286_T14", "type": "Protein", "text": [ "VCAM-1" ], "offsets": [ [ 1220, 1226 ] ], "normalized": [] }, { "id": "PMID-7542286_T15", "type": "Protein", "text": [ "VCAM-1" ], "offsets": [ [ 1265, 1271 ] ], "normalized": [] }, { "id": "PMID-7542286_T16", "type": "Protein", "text": [ "VCAM-1" ], "offsets": [ [ 1342, 1348 ] ], "normalized": [] }, { "id": "PMID-7542286_T17", "type": "Protein", "text": [ "VCAM-1" ], "offsets": [ [ 1454, 1460 ] ], "normalized": [] } ]

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"PMID-7542286_E17" } ] }, { "id": "PMID-7542286_E11", "type": "Negative_regulation", "trigger": { "text": [ "inhibition" ], "offsets": [ [ 635, 645 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "PMID-7542286_E14" } ] }, { "id": "PMID-7542286_E12", "type": "Regulation", "trigger": { "text": [ "unaffected" ], "offsets": [ [ 741, 751 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "PMID-7542286_E4" } ] }, { "id": "PMID-7542286_E13", "type": "Positive_regulation", "trigger": { "text": [ "stimulation" ], "offsets": [ [ 808, 819 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "PMID-7542286_E6" }, { "role": "Cause", "ref_id": "PMID-7542286_T9" } ] }, { "id": "PMID-7542286_E14", "type": "Positive_regulation", "trigger": { "text": [ "stimulation" ], "offsets": [ [ 808, 819 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "PMID-7542286_E6" }, { "role": "Cause", "ref_id": "PMID-7542286_T7" } ] }, { "id": "PMID-7542286_E15", "type": "Positive_regulation", "trigger": { "text": [ 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} ] }, { "id": "PMID-7542286_E25", "type": "Gene_expression", "trigger": { "text": [ "expression" ], "offsets": [ [ 961, 971 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "PMID-7542286_T13" } ] }, { "id": "PMID-7542286_E26", "type": "Positive_regulation", "trigger": { "text": [ "induced" ], "offsets": [ [ 1194, 1201 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "PMID-7542286_E27" } ] }, { "id": "PMID-7542286_E27", "type": "Gene_expression", "trigger": { "text": [ "expression" ], "offsets": [ [ 1206, 1216 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "PMID-7542286_T14" } ] }, { "id": "PMID-7542286_E28", "type": "Positive_regulation", "trigger": { "text": [ "augment" ], "offsets": [ [ 1240, 1247 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "PMID-7542286_E29" } ] }, { "id": "PMID-7542286_E29", "type": "Positive_regulation", "trigger": { "text": [ "induced" ], "offsets": [ [ 1257, 1264 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "PMID-7542286_E30" } ] }, { "id": "PMID-7542286_E30", "type": "Gene_expression", "trigger": { "text": [ "expression" ], "offsets": [ [ 1272, 1282 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "PMID-7542286_T15" } ] }, { "id": "PMID-7542286_E31", "type": "Negative_regulation", "trigger": { "text": [ "represses" ], "offsets": [ [ 1444, 1453 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "PMID-7542286_E32" } ] }, { "id": "PMID-7542286_E32", "type": "Transcription", "trigger": { "text": [ "transcription" ], "offsets": [ [ 1466, 1479 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "PMID-7542286_T17" } ] } ]

[ { "id": "PMID-7542286_1", "entity_ids": [ "PMID-7542286_T9", "PMID-7542286_T8" ] }, { "id": "PMID-7542286_2", "entity_ids": [ "PMID-7542286_T2", "PMID-7542286_T1" ] } ]

[]

[ { "id": "PMID-7542591__text", "type": "abstract", "text": [ "Distinct signaling properties identify functionally different CD4 epitopes. \nThe CD4 coreceptor interacts with non-polymorphic regions of major histocompatibility complex class II molecules on antigen-presenting cells and contributes to T cell activation. We have investigated the effect of CD4 triggering on T cell activating signals in a lymphoma model using monoclonal antibodies (mAb) which recognize different CD4 epitopes. We demonstrate that CD4 triggering delivers signals capable of activating the NF-AT transcription factor which is required for interleukin-2 gene expression. Whereas different anti-CD4 mAb or HIV-1 gp120 could all trigger activation of the protein tyrosine kinases p56lck and p59fyn and phosphorylation of the Shc adaptor protein, which mediates signals to Ras, they differed significantly in their ability to activate NF-AT. Lack of full activation of NF-AT could be correlated to a dramatically reduced capacity to induce calcium flux and could be complemented with a calcium ionophore. The results identify functionally distinct epitopes on the CD4 coreceptor involved in activation of the Ras/protein kinase C and calcium pathways. " ], "offsets": [ [ 0, 1165 ] ] } ]

[ { "id": "PMID-7542591_T1", "type": "Protein", "text": [ "CD4" ], "offsets": [ [ 62, 65 ] ], "normalized": [] }, { "id": "PMID-7542591_T2", "type": "Protein", "text": [ "CD4" ], "offsets": [ [ 81, 84 ] ], "normalized": [] }, { "id": "PMID-7542591_T3", "type": "Protein", "text": [ "CD4" ], "offsets": [ [ 291, 294 ] ], "normalized": [] }, { "id": "PMID-7542591_T4", "type": "Protein", "text": [ "CD4" ], "offsets": [ [ 415, 418 ] ], "normalized": [] }, { "id": "PMID-7542591_T5", "type": "Protein", "text": [ "CD4" ], "offsets": [ [ 449, 452 ] ], "normalized": [] }, { "id": "PMID-7542591_T6", "type": "Protein", "text": [ "interleukin-2" ], "offsets": [ [ 556, 569 ] ], "normalized": [] }, { "id": "PMID-7542591_T7", "type": "Protein", "text": [ "CD4" ], "offsets": [ [ 610, 613 ] ], "normalized": [] }, { "id": "PMID-7542591_T8", "type": "Protein", "text": [ "gp120" ], "offsets": [ [ 627, 632 ] ], "normalized": [] }, { "id": "PMID-7542591_T9", "type": "Protein", "text": [ "p56lck" ], "offsets": [ [ 694, 700 ] ], "normalized": [] }, { "id": "PMID-7542591_T10", "type": "Protein", "text": [ "p59fyn" ], "offsets": [ [ 705, 711 ] ], "normalized": [] }, { "id": "PMID-7542591_T11", "type": "Protein", "text": [ "CD4" ], "offsets": [ [ 1077, 1080 ] ], "normalized": [] }, { "id": "PMID-7542591_T15", "type": "Entity", "text": [ "epitopes" ], "offsets": [ [ 419, 427 ] ], "normalized": [] } ]

[ { "id": "PMID-7542591_E1", "type": "Binding", "trigger": { "text": [ "interacts" ], "offsets": [ [ 96, 105 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "PMID-7542591_T2" } ] }, { "id": "PMID-7542591_E2", "type": "Positive_regulation", "trigger": { "text": [ "triggering" ], "offsets": [ [ 295, 305 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "PMID-7542591_T3" } ] }, { "id": "PMID-7542591_E3", "type": "Binding", "trigger": { "text": [ "recognize" ], "offsets": [ [ 395, 404 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "PMID-7542591_T4" }, { "role": "Site", "ref_id": "PMID-7542591_T15" } ] }, { "id": "PMID-7542591_E4", "type": "Positive_regulation", "trigger": { "text": [ "triggering" ], "offsets": [ [ 453, 463 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "PMID-7542591_T5" } ] }, { "id": "PMID-7542591_E5", "type": "Positive_regulation", "trigger": { "text": [ "required" ], "offsets": [ [ 543, 551 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "PMID-7542591_E6" } ] }, { "id": "PMID-7542591_E6", "type": "Gene_expression", "trigger": { "text": [ "expression" ], "offsets": [ [ 575, 585 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "PMID-7542591_T6" } ] }, { "id": "PMID-7542591_E7", "type": "Positive_regulation", "trigger": { "text": [ "trigger" ], "offsets": [ [ 643, 650 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "PMID-7542591_E11" } ] }, { "id": "PMID-7542591_E8", "type": "Positive_regulation", "trigger": { "text": [ "trigger" ], "offsets": [ [ 643, 650 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "PMID-7542591_E12" } ] }, { "id": "PMID-7542591_E9", "type": "Positive_regulation", "trigger": { "text": [ "trigger" ], "offsets": [ [ 643, 650 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "PMID-7542591_E12" }, { "role": "Cause", "ref_id": "PMID-7542591_T8" } ] }, { "id": "PMID-7542591_E10", "type": "Positive_regulation", "trigger": { "text": [ "trigger" ], "offsets": [ [ 643, 650 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "PMID-7542591_E11" }, { "role": "Cause", "ref_id": "PMID-7542591_T8" } ] }, { "id": "PMID-7542591_E11", "type": "Positive_regulation", "trigger": { "text": [ "activation" ], "offsets": [ [ 651, 661 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "PMID-7542591_T10" } ] }, { "id": "PMID-7542591_E12", "type": "Positive_regulation", "trigger": { "text": [ "activation" ], "offsets": [ [ 651, 661 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "PMID-7542591_T9" } ] } ]

[]

[]

[ { "id": "PMID-7543076__text", "type": "abstract", "text": [ "Lipopolysaccharide-induced E-selectin expression requires continuous presence of LPS and is inhibited by bactericidal/permeability-increasing protein. \nEndothelial cells stimulated by LPS express E-selectin, which plays an important role in mediating neutrophil adhesion during inflammation. E-selectin is induced within 1-2 h, peaks at 4-6 h, and gradually returns to basal level by 24 h. rBPI21, a recombinant N-terminal fragment of human bactericidal/permeability-increasing protein (BPI), inhibited LPS-induced E-selectin expression when added at the same time as, and up to 6 h after, LPS. Delayed administration of rBPI21 also affected LPS-mediated activation of the nuclear factor, NF-kappa B. Two to 4 h following LPS addition to endothelial cells, when NF-kappa B was already activated, addition of rBPI21 resulted in marked reduction of NF-kappa B detectable at 4 or 6 h. These results indicate that endothelial activation requires continuous presence of LPS, and rBPI21 acts to reverse LPS-mediated endothelial activation by interrupting the on-going LPS signal. " ], "offsets": [ [ 0, 1074 ] ] } ]

[ { "id": "PMID-7543076_T1", "type": "Protein", "text": [ "E-selectin" ], "offsets": [ [ 27, 37 ] ], "normalized": [] }, { "id": "PMID-7543076_T2", "type": "Protein", "text": [ "E-selectin" ], "offsets": [ [ 196, 206 ] ], "normalized": [] }, { "id": "PMID-7543076_T3", "type": "Protein", "text": [ "E-selectin" ], "offsets": [ [ 292, 302 ] ], "normalized": [] }, { "id": "PMID-7543076_T4", "type": "Protein", "text": [ "bactericidal/permeability-increasing protein" ], "offsets": [ [ 441, 485 ] ], "normalized": [] }, { "id": "PMID-7543076_T5", "type": "Protein", "text": [ "BPI" ], "offsets": [ [ 487, 490 ] ], "normalized": [] }, { "id": "PMID-7543076_T6", "type": "Protein", "text": [ "E-selectin" ], "offsets": [ [ 515, 525 ] ], "normalized": [] } ]

[ { "id": "PMID-7543076_E1", "type": "Positive_regulation", "trigger": { "text": [ "induced" ], "offsets": [ [ 19, 26 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "PMID-7543076_E2" } ] }, { "id": "PMID-7543076_E2", "type": "Gene_expression", "trigger": { "text": [ "expression" ], "offsets": [ [ 38, 48 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "PMID-7543076_T1" } ] }, { "id": "PMID-7543076_E3", "type": "Positive_regulation", "trigger": { "text": [ "requires" ], "offsets": [ [ 49, 57 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "PMID-7543076_E1" } ] }, { "id": "PMID-7543076_E4", "type": "Negative_regulation", "trigger": { "text": [ "inhibited" ], "offsets": [ [ 92, 101 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "PMID-7543076_E1" } ] }, { "id": "PMID-7543076_E5", "type": "Gene_expression", "trigger": { "text": [ "express" ], "offsets": [ [ 188, 195 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "PMID-7543076_T2" } ] }, { "id": "PMID-7543076_E6", "type": "Positive_regulation", "trigger": { "text": [ "induced" ], "offsets": [ [ 306, 313 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "PMID-7543076_T3" } ] }, { "id": "PMID-7543076_E7", "type": "Negative_regulation", "trigger": { "text": [ "inhibited" ], "offsets": [ [ 493, 502 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "PMID-7543076_E8" } ] }, { "id": "PMID-7543076_E8", "type": "Positive_regulation", "trigger": { "text": [ "induced" ], "offsets": [ [ 507, 514 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "PMID-7543076_E9" } ] }, { "id": "PMID-7543076_E9", "type": "Gene_expression", "trigger": { "text": [ "expression" ], "offsets": [ [ 526, 536 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "PMID-7543076_T6" } ] } ]

[ { "id": "PMID-7543076_1", "entity_ids": [ "PMID-7543076_T4", "PMID-7543076_T5" ] } ]

[]

[ { "id": "PMID-7543515__text", "type": "abstract", "text": [ "Costimulation of human CD4+ T cells with LFA-3 and B7 induce distinct effects on AP-1 and NF-kappa B transcription factors. \nWe have earlier shown that stimulation of human CD4+ T cells with SEA presented on Chinese hamster ovary (CHO)-DR transfectants coexpressing either B7 or LFA-3 resulted in distinct cytokine profiles. We now demonstrate that B7, but not LFA-3, strongly costimulated IL-2 transcription and mRNA expression in CD4+ T cells. Maximal increase in IL-2 transcription was recorded with CHO-DR/B7/LFA-3, suggesting a cooperative effect of B7 and LFA-3 at the transcriptional level. Gel-shift analysis demonstrated that stimulation of CD4+ T cells with CHO-DR and staphylococcal enterotoxin A was sufficient to induce significant amounts of NF-kappa B binding proteins, whereas induction of AP-1 binding proteins required costimulation. LFA-3 induced moderate levels of AP-1, but did not influence the levels of NF-kappa B, while B7 costimulation strongly induced both AP-1 and substantially enhanced NF-kappa B binding proteins. The CHO-DR/B7/LFA-3 triple transfectant induced a further increase in AP-1 and NF-kappa B binding proteins compared with the double transfectants. The level of Oct-1 binding proteins remained similar in all samples. Super-shift analysis revealed that the NF-kappa B complex of costimulated CD4+ T cells contained large amounts of p50, substantial amounts of p65, and marginal levels of c-Rel proteins. The AP-1 binding proteins contained c-Jun, Jun-D, and Fra-1, but marginal amounts of Jun-B and c-Fos. Our results indicate distinct effects of B7 and LFA-3 costimulation on the activity of AP-1 and NF-kappa B. These may partly account for the differential effects of B7 and LFA-3 costimulation on IL-2 expression. " ], "offsets": [ [ 0, 1761 ] ] } ]

[ { "id": "PMID-7543515_T1", "type": "Protein", "text": [ "CD4" ], "offsets": [ [ 23, 26 ] ], "normalized": [] }, { "id": "PMID-7543515_T2", "type": "Protein", "text": [ "LFA-3" ], "offsets": [ [ 41, 46 ] ], "normalized": [] }, { "id": "PMID-7543515_T3", "type": "Protein", "text": [ "B7" ], "offsets": [ [ 51, 53 ] ], "normalized": [] }, { "id": "PMID-7543515_T4", "type": "Protein", "text": [ "CD4" ], "offsets": [ [ 173, 176 ] ], "normalized": [] }, { "id": "PMID-7543515_T5", "type": "Protein", "text": [ "B7" ], "offsets": [ [ 273, 275 ] ], "normalized": [] }, { "id": "PMID-7543515_T6", "type": "Protein", "text": [ "LFA-3" ], "offsets": [ [ 279, 284 ] ], "normalized": [] }, { "id": "PMID-7543515_T7", "type": "Protein", "text": [ "B7" ], "offsets": [ [ 349, 351 ] ], "normalized": [] }, { "id": "PMID-7543515_T8", "type": "Protein", "text": [ "LFA-3" ], "offsets": [ [ 361, 366 ] ], "normalized": [] }, { "id": "PMID-7543515_T9", "type": "Protein", "text": [ "IL-2" ], "offsets": [ [ 390, 394 ] ], "normalized": [] }, { "id": "PMID-7543515_T10", "type": "Protein", "text": [ "CD4" ], "offsets": [ [ 432, 435 ] ], "normalized": [] }, { "id": "PMID-7543515_T11", "type": "Protein", "text": [ "IL-2" ], "offsets": [ [ 466, 470 ] ], "normalized": [] }, { "id": "PMID-7543515_T12", "type": "Protein", "text": [ "B7" ], "offsets": [ [ 510, 512 ] ], "normalized": [] }, { "id": "PMID-7543515_T13", "type": "Protein", "text": [ "LFA-3" ], "offsets": [ [ 513, 518 ] ], "normalized": [] }, { "id": "PMID-7543515_T14", "type": "Protein", "text": [ "B7" ], "offsets": [ [ 555, 557 ] ], "normalized": [] }, { "id": "PMID-7543515_T15", "type": "Protein", "text": [ "LFA-3" ], "offsets": [ [ 562, 567 ] ], "normalized": [] }, { "id": "PMID-7543515_T16", "type": "Protein", "text": [ "CD4" ], "offsets": [ [ 650, 653 ] ], "normalized": [] }, { "id": "PMID-7543515_T17", "type": "Protein", "text": [ "LFA-3" ], "offsets": [ [ 852, 857 ] ], "normalized": [] }, { "id": "PMID-7543515_T18", "type": "Protein", "text": [ "B7" ], "offsets": [ [ 945, 947 ] ], "normalized": [] }, { "id": "PMID-7543515_T19", "type": "Protein", "text": [ "B7" ], "offsets": [ [ 1056, 1058 ] ], "normalized": [] }, { "id": "PMID-7543515_T20", "type": "Protein", "text": [ "LFA-3" ], "offsets": [ [ 1059, 1064 ] ], "normalized": [] }, { "id": "PMID-7543515_T21", "type": "Protein", "text": [ "CD4" ], "offsets": [ [ 1335, 1338 ] ], "normalized": [] }, { "id": "PMID-7543515_T22", "type": "Protein", "text": [ "p50" ], "offsets": [ [ 1375, 1378 ] ], "normalized": [] }, { "id": "PMID-7543515_T23", "type": "Protein", "text": [ "p65" ], "offsets": [ [ 1403, 1406 ] ], "normalized": [] }, { "id": "PMID-7543515_T24", "type": "Protein", "text": [ "c-Rel" ], "offsets": [ [ 1431, 1436 ] ], "normalized": [] }, { "id": "PMID-7543515_T25", "type": "Protein", "text": [ "c-Jun" ], "offsets": [ [ 1483, 1488 ] ], "normalized": [] }, { "id": "PMID-7543515_T26", "type": "Protein", "text": [ "Jun-D" ], "offsets": [ [ 1490, 1495 ] ], "normalized": [] }, { "id": "PMID-7543515_T27", "type": "Protein", "text": [ "Fra-1" ], "offsets": [ [ 1501, 1506 ] ], "normalized": [] }, { "id": "PMID-7543515_T28", "type": "Protein", "text": [ "Jun-B" ], "offsets": [ [ 1532, 1537 ] ], "normalized": [] }, { "id": "PMID-7543515_T29", "type": "Protein", "text": [ "c-Fos" ], "offsets": [ [ 1542, 1547 ] ], "normalized": [] }, { "id": "PMID-7543515_T30", "type": "Protein", "text": [ "B7" ], "offsets": [ [ 1590, 1592 ] ], "normalized": [] }, { "id": "PMID-7543515_T31", "type": "Protein", "text": [ "LFA-3" ], "offsets": [ [ 1597, 1602 ] ], "normalized": [] }, { "id": "PMID-7543515_T32", "type": "Protein", "text": [ "B7" ], "offsets": [ [ 1714, 1716 ] ], "normalized": [] }, { "id": "PMID-7543515_T33", "type": "Protein", "text": [ "LFA-3" ], "offsets": [ [ 1721, 1726 ] ], "normalized": [] }, { "id": "PMID-7543515_T34", "type": "Protein", "text": [ "IL-2" ], "offsets": [ [ 1744, 1748 ] ], "normalized": [] } ]

[ { "id": "PMID-7543515_E1", "type": "Gene_expression", "trigger": { "text": [ "coexpressing" ], "offsets": [ [ 253, 265 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "PMID-7543515_T6" } ] }, { "id": "PMID-7543515_E2", "type": "Gene_expression", "trigger": { "text": [ "coexpressing" ], "offsets": [ [ 253, 265 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "PMID-7543515_T5" } ] }, { "id": "PMID-7543515_E3", "type": "Positive_regulation", "trigger": { "text": [ "costimulated" ], "offsets": [ [ 377, 389 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "PMID-7543515_E7" }, { "role": "Cause", "ref_id": "PMID-7543515_T7" } ] }, { "id": "PMID-7543515_E4", "type": "Positive_regulation", "trigger": { "text": [ "costimulated" ], "offsets": [ [ 377, 389 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "PMID-7543515_E8" }, { "role": "Cause", "ref_id": "PMID-7543515_T7" } ] }, { "id": "PMID-7543515_E5", "type": "Positive_regulation", "trigger": { "text": [ "costimulated" ], "offsets": [ [ 377, 389 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "PMID-7543515_E8" }, { "role": "Cause", "ref_id": "PMID-7543515_T8" } ] }, { "id": "PMID-7543515_E6", "type": "Positive_regulation", "trigger": { "text": [ "costimulated" ], "offsets": [ [ 377, 389 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "PMID-7543515_E7" }, { "role": "Cause", "ref_id": "PMID-7543515_T8" } ] }, { "id": "PMID-7543515_E7", "type": "Transcription", "trigger": { "text": [ "transcription" ], "offsets": [ [ 395, 408 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "PMID-7543515_T9" } ] }, { "id": "PMID-7543515_E8", "type": "Transcription", "trigger": { "text": [ "mRNA expression" ], "offsets": [ [ 413, 428 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "PMID-7543515_T9" } ] }, { "id": "PMID-7543515_E9", "type": "Positive_regulation", "trigger": { "text": [ "increase" ], "offsets": [ [ 454, 462 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "PMID-7543515_E10" } ] }, { "id": "PMID-7543515_E10", "type": "Transcription", "trigger": { "text": [ "transcription" ], "offsets": [ [ 471, 484 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "PMID-7543515_T11" } ] }, { "id": "PMID-7543515_E11", "type": "Regulation", "trigger": { "text": [ "effect" ], "offsets": [ [ 545, 551 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "PMID-7543515_E10" }, { "role": "Cause", "ref_id": "PMID-7543515_T14" } ] }, { "id": "PMID-7543515_E12", "type": "Regulation", "trigger": { "text": [ "effect" ], "offsets": [ [ 545, 551 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "PMID-7543515_E10" }, { "role": "Cause", "ref_id": "PMID-7543515_T15" } ] }, { "id": "PMID-7543515_E13", "type": "Regulation", "trigger": { "text": [ "effects" ], "offsets": [ [ 1703, 1710 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "PMID-7543515_E14" } ] }, { "id": "PMID-7543515_E14", "type": "Gene_expression", "trigger": { "text": [ "expression" ], "offsets": [ [ 1749, 1759 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "PMID-7543515_T34" } ] } ]

[]

[]

[ { "id": "PMID-7545467__text", "type": "abstract", "text": [ "Regulation of granulocyte-macrophage colony-stimulating factor and E-selectin expression in endothelial cells by cyclosporin A and the T-cell transcription factor NFAT. \nNuclear factor of activated T cells (NFAT) was originally described as a T-cell-specific transcription factor athat supported the activation of cytokine gene expression and mediated the immunoregulatory effects of cyclosporin A (CsA). As we observed that activated endothelial cells also expressed NFAT, we tested the antiinflammatory properties of CsA in endothelial cells. Significantly, CsA completely suppressed the induction of NFAT in endothelial cells and inhibited the activity of granulocyte-macrophage colony-stimulating factor (GM-CSF) gene regulatory elements that use NFAT by 60%. CsA similarly mediated a reduction of up to 65% in GM-CSF mRNA and protein expression in activated endothelial cells. CsA also suppressed E-selectin, but not vascular cell adhesion molecule-1 (VCAM-1) expression in endothelial cells, even though the E-selectin promoter is activated by NF-kappa B rather than NFAT. Hence, induction of cell surface expression of this leukocyte adhesion molecule by tumor necrosis factor (TNF)-alpha was reduced by 40% in the presence of CsA, and this was reflected by a 29% decrease in neutrophil adhesion. The effects of CsA on endothelial cells were also detected at the chromatin structure level, as DNasel hypersensitive sites within both the GM-CSF enhancer and the E-selectin promoter were suppressed by CsA. This represents the first report of NFAT in endothelial cells and suggests mechanisms by which CsA could function as an antiinflammatory agent. " ], "offsets": [ [ 0, 1656 ] ] } ]

[ { "id": "PMID-7545467_T1", "type": "Protein", "text": [ "granulocyte-macrophage colony-stimulating factor" ], "offsets": [ [ 14, 62 ] ], "normalized": [] }, { "id": "PMID-7545467_T2", "type": "Protein", "text": [ "E-selectin" ], "offsets": [ [ 67, 77 ] ], "normalized": [] }, { "id": "PMID-7545467_T3", "type": "Protein", "text": [ "granulocyte-macrophage colony-stimulating factor" ], "offsets": [ [ 659, 707 ] ], "normalized": [] }, { "id": "PMID-7545467_T4", "type": "Protein", "text": [ "GM-CSF" ], "offsets": [ [ 709, 715 ] ], "normalized": [] }, { "id": "PMID-7545467_T5", "type": "Protein", "text": [ "GM-CSF" ], "offsets": [ [ 815, 821 ] ], "normalized": [] }, { "id": "PMID-7545467_T6", "type": "Protein", "text": [ "E-selectin" ], "offsets": [ [ 902, 912 ] ], "normalized": [] }, { "id": "PMID-7545467_T7", "type": "Protein", "text": [ "vascular cell adhesion molecule-1" ], "offsets": [ [ 922, 955 ] ], "normalized": [] }, { "id": "PMID-7545467_T8", "type": "Protein", "text": [ "VCAM-1" ], "offsets": [ [ 957, 963 ] ], "normalized": [] }, { "id": "PMID-7545467_T9", "type": "Protein", "text": [ "E-selectin" ], "offsets": [ [ 1014, 1024 ] ], "normalized": [] }, { "id": "PMID-7545467_T10", "type": "Protein", "text": [ "tumor necrosis factor (TNF)-alpha" ], "offsets": [ [ 1162, 1195 ] ], "normalized": [] }, { "id": "PMID-7545467_T11", "type": "Protein", "text": [ "DNasel" ], "offsets": [ [ 1400, 1406 ] ], "normalized": [] }, { "id": "PMID-7545467_T12", "type": "Protein", "text": [ "GM-CSF" ], "offsets": [ [ 1444, 1450 ] ], "normalized": [] }, { "id": "PMID-7545467_T13", "type": "Protein", "text": [ "E-selectin" ], "offsets": [ [ 1468, 1478 ] ], "normalized": [] }, { "id": "PMID-7545467_T21", "type": "Entity", "text": [ "promoter" ], "offsets": [ [ 1025, 1033 ] ], "normalized": [] } ]

[ { "id": "PMID-7545467_E1", "type": "Regulation", "trigger": { "text": [ "Regulation" ], "offsets": [ [ 0, 10 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "PMID-7545467_E4" } ] }, { "id": "PMID-7545467_E2", "type": "Regulation", "trigger": { "text": [ "Regulation" ], "offsets": [ [ 0, 10 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "PMID-7545467_E3" } ] }, { "id": "PMID-7545467_E3", "type": "Gene_expression", "trigger": { "text": [ "expression" ], "offsets": [ [ 78, 88 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "PMID-7545467_T2" } ] }, { "id": "PMID-7545467_E4", "type": "Gene_expression", "trigger": { "text": [ "expression" ], "offsets": [ [ 78, 88 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "PMID-7545467_T1" } ] }, { "id": "PMID-7545467_E5", "type": "Negative_regulation", "trigger": { "text": [ "mediated a reduction" ], "offsets": [ [ 778, 798 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "PMID-7545467_E8" } ] }, { "id": "PMID-7545467_E6", "type": "Negative_regulation", "trigger": { "text": [ "mediated a reduction" ], "offsets": [ [ 778, 798 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "PMID-7545467_E7" } ] }, { "id": "PMID-7545467_E7", "type": "Transcription", "trigger": { "text": [ "expression" ], "offsets": [ [ 839, 849 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "PMID-7545467_T5" } ] }, { "id": "PMID-7545467_E8", "type": "Gene_expression", "trigger": { "text": [ "expression" ], "offsets": [ [ 839, 849 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "PMID-7545467_T5" } ] }, { "id": "PMID-7545467_E9", "type": "Negative_regulation", "trigger": { "text": [ "suppressed" ], "offsets": [ [ 891, 901 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "PMID-7545467_E12" } ] }, { "id": "PMID-7545467_E10", "type": "Negative_regulation", "trigger": { "text": [ "suppressed" ], "offsets": [ [ 891, 901 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "PMID-7545467_E11" } ] }, { "id": "PMID-7545467_E11", "type": "Gene_expression", "trigger": { "text": [ "expression" ], "offsets": [ [ 965, 975 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "PMID-7545467_T6" } ] }, { "id": "PMID-7545467_E12", "type": "Gene_expression", "trigger": { "text": [ "expression" ], "offsets": [ [ 965, 975 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "PMID-7545467_T8" } ] }, { "id": "PMID-7545467_E13", "type": "Positive_regulation", "trigger": { "text": [ "activated" ], "offsets": [ [ 1037, 1046 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "PMID-7545467_T9" }, { "role": "Site", "ref_id": "PMID-7545467_T21" } ] }, { "id": "PMID-7545467_E14", "type": "Positive_regulation", "trigger": { "text": [ "induction" ], "offsets": [ [ 1086, 1095 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "PMID-7545467_E15" }, { "role": "Cause", "ref_id": "PMID-7545467_T10" } ] }, { "id": "PMID-7545467_E15", "type": "Gene_expression", "trigger": { "text": [ "expression" ], "offsets": [ [ 1112, 1122 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "PMID-7545467_T9" } ] }, { "id": "PMID-7545467_E16", "type": "Negative_regulation", "trigger": { "text": [ "reduced" ], "offsets": [ [ 1200, 1207 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "PMID-7545467_E14" } ] } ]

[ { "id": "PMID-7545467_1", "entity_ids": [ "PMID-7545467_T3", "PMID-7545467_T4" ] }, { "id": "PMID-7545467_2", "entity_ids": [ "PMID-7545467_T8", "PMID-7545467_T7" ] } ]

[]

[ { "id": "PMID-7554389__text", "type": "abstract", "text": [ "Signalling via CD28 of human naive neonatal T lymphocytes. \nAccessory molecules play a crucial role in the development of the T cell response to antigenic challenge. We have examined the role of CD28 in modulating the 'naive' neonatal T cell response to anti-CD2-mediated activation. To compare the role of CD28, neonatal and adult T cells were stimulated with a pair of mitogenic anti-CD2 antibodies in the presence or absence of anti-CD28 MoAb. With anti-CD2 alone, neonatal T cells proliferated slightly but produced no detectable IL-2, whereas adult T cells proliferated vigorously, with significant IL-2 production. Costimulation with anti-CD28 MoAb greatly enhanced the proliferative response of neonatal T cells to levels equivalent to those of adult T cells, whereas adult T cells showed only slight increases. Although IL-2 secretion was increased in the presence of anti-CD28 MoAb, neonatal T cell IL-2 production remained lower than in adults. In contrast, enhancement of IL-2 mRNA expression in neonates was similar to adult levels. Anti-CD28 MoAb costimulation increased NF kappa B levels in neonates, albeit to levels lower than that of adults. The cellular mechanism governing the diminished proliferative response of neonatal T lymphocytes to anti-CD2 may therefore be due to decreased NF kappa B induction, reduced IL-2 mRNA expression and deficient IL-2 production. Although anti-CD28 MoAb costimulation enhances all of the above signals, NF kappa B and IL-2 levels remain lower than in adults, suggesting the need for further activation requirements in the neonate. " ], "offsets": [ [ 0, 1585 ] ] } ]

[ { "id": "PMID-7554389_T1", "type": "Protein", "text": [ "CD28" ], "offsets": [ [ 15, 19 ] ], "normalized": [] }, { "id": "PMID-7554389_T2", "type": "Protein", "text": [ "CD28" ], "offsets": [ [ 195, 199 ] ], "normalized": [] }, { "id": "PMID-7554389_T3", "type": "Protein", "text": [ "CD28" ], "offsets": [ [ 307, 311 ] ], "normalized": [] }, { "id": "PMID-7554389_T4", "type": "Protein", "text": [ "CD28" ], "offsets": [ [ 436, 440 ] ], "normalized": [] }, { "id": "PMID-7554389_T5", "type": "Protein", "text": [ "IL-2" ], "offsets": [ [ 534, 538 ] ], "normalized": [] }, { "id": "PMID-7554389_T6", "type": "Protein", "text": [ "IL-2" ], "offsets": [ [ 604, 608 ] ], "normalized": [] }, { "id": "PMID-7554389_T7", "type": "Protein", "text": [ "CD28" ], "offsets": [ [ 645, 649 ] ], "normalized": [] }, { "id": "PMID-7554389_T8", "type": "Protein", "text": [ "IL-2" ], "offsets": [ [ 828, 832 ] ], "normalized": [] }, { "id": "PMID-7554389_T9", "type": "Protein", "text": [ "CD28" ], "offsets": [ [ 881, 885 ] ], "normalized": [] }, { "id": "PMID-7554389_T10", "type": "Protein", "text": [ "IL-2" ], "offsets": [ [ 908, 912 ] ], "normalized": [] }, { "id": "PMID-7554389_T11", "type": "Protein", "text": [ "IL-2" ], "offsets": [ [ 983, 987 ] ], "normalized": [] }, { "id": "PMID-7554389_T12", "type": "Protein", "text": [ "CD28" ], "offsets": [ [ 1050, 1054 ] ], "normalized": [] }, { "id": "PMID-7554389_T13", "type": "Protein", "text": [ "IL-2" ], "offsets": [ [ 1332, 1336 ] ], "normalized": [] }, { "id": "PMID-7554389_T14", "type": "Protein", "text": [ "IL-2" ], "offsets": [ [ 1367, 1371 ] ], "normalized": [] }, { "id": "PMID-7554389_T15", "type": "Protein", "text": [ "CD28" ], "offsets": [ [ 1398, 1402 ] ], "normalized": [] }, { "id": "PMID-7554389_T16", "type": "Protein", "text": [ "IL-2" ], "offsets": [ [ 1472, 1476 ] ], "normalized": [] } ]

[ { "id": "PMID-7554389_E1", "type": "Positive_regulation", "trigger": { "text": [ "With" ], "offsets": [ [ 447, 451 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "PMID-7554389_E4" } ] }, { "id": "PMID-7554389_E2", "type": "Positive_regulation", "trigger": { "text": [ "With" ], "offsets": [ [ 447, 451 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "PMID-7554389_E3" } ] }, { "id": "PMID-7554389_E3", "type": "Gene_expression", "trigger": { "text": [ "produced" ], "offsets": [ [ 511, 519 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "PMID-7554389_T5" } ] }, { "id": "PMID-7554389_E4", "type": "Gene_expression", "trigger": { "text": [ "production" ], "offsets": [ [ 609, 619 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "PMID-7554389_T6" } ] }, { "id": "PMID-7554389_E5", "type": "Localization", "trigger": { "text": [ "secretion" ], "offsets": [ [ 833, 842 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "PMID-7554389_T8" } ] }, { "id": "PMID-7554389_E6", "type": "Positive_regulation", "trigger": { "text": [ "increased" ], "offsets": [ [ 847, 856 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "PMID-7554389_E5" } ] }, { "id": "PMID-7554389_E7", "type": "Gene_expression", "trigger": { "text": [ "production" ], "offsets": [ [ 913, 923 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "PMID-7554389_T10" } ] }, { "id": "PMID-7554389_E8", "type": "Positive_regulation", "trigger": { "text": [ "enhancement" ], "offsets": [ [ 968, 979 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "PMID-7554389_E9" } ] }, { "id": "PMID-7554389_E9", "type": "Transcription", "trigger": { "text": [ "expression" ], "offsets": [ [ 993, 1003 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "PMID-7554389_T11" } ] }, { "id": "PMID-7554389_E10", "type": "Negative_regulation", "trigger": { "text": [ "reduced" ], "offsets": [ [ 1324, 1331 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "PMID-7554389_E11" } ] }, { "id": "PMID-7554389_E11", "type": "Transcription", "trigger": { "text": [ "expression" ], "offsets": [ [ 1342, 1352 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "PMID-7554389_T13" } ] }, { "id": "PMID-7554389_E12", "type": "Negative_regulation", "trigger": { "text": [ "deficient" ], "offsets": [ [ 1357, 1366 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "PMID-7554389_E13" } ] }, { "id": "PMID-7554389_E13", "type": "Gene_expression", "trigger": { "text": [ "production" ], "offsets": [ [ 1372, 1382 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "PMID-7554389_T14" } ] }, { "id": "PMID-7554389_E14", "type": "Positive_regulation", "trigger": { "text": [ "enhances" ], "offsets": [ [ 1422, 1430 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "PMID-7554389_T14" } ] } ]

[]

[]

[ { "id": "PMID-7565683__text", "type": "abstract", "text": [ "N- and C-terminal sequences control degradation of MAD3/I kappa B alpha in response to inducers of NF-kappa B activity. \nThe proteolytic degradation of the inhibitory protein MAD3/I kappa B alpha in response to extracellular stimulation is a prerequisite step in the activation of the transcription factor NF-kappa B. Analysis of the expression of human I kappa B alpha protein in stable transfectants of mouse 70Z/3 cells shows that, as for the endogenous murine protein, exogenous I kappa B alpha is degraded in response to inducers of NF-kappa B activity, such as phorbol myristate acetate or lipopolysaccharide. In addition, pretreatment of the cells with the proteasome inhibitor N-Ac-Leu-Leu-norleucinal inhibits this ligand-induced degradation and, in agreement with previous studies, stabilizes a hyperphosphorylated form of the human I kappa B alpha protein. By expressing mutant forms of the human protein in this cell line, we have been able to delineate the sequences responsible for both the ligand-induced phosphorylation and the degradation of I kappa B alpha. Our results show that deletion of the C terminus of the I kappa B alpha molecule up to amino acid 279 abolishes constitutive but not ligand-inducible phosphorylation and inhibits ligand-inducible degradation. Further analysis reveals that the inducible phosphorylation of I kappa B alpha maps to two serines in the N terminus of the protein (residues 32 and 36) and that the mutation of either residue is sufficient to abolish ligand-induced degradation, whereas both residues must be mutated to abolish inducible phosphorylation of the protein. (ABSTRACT TRUNCATED AT 250 WORDS) " ], "offsets": [ [ 0, 1656 ] ] } ]

[ { "id": "PMID-7565683_T1", "type": "Protein", "text": [ "MAD3" ], "offsets": [ [ 51, 55 ] ], "normalized": [] }, { "id": "PMID-7565683_T2", "type": "Protein", "text": [ "I kappa B alpha" ], "offsets": [ [ 56, 71 ] ], "normalized": [] }, { "id": "PMID-7565683_T3", "type": "Protein", "text": [ "MAD3" ], "offsets": [ [ 175, 179 ] ], "normalized": [] }, { "id": "PMID-7565683_T4", "type": "Protein", "text": [ "I kappa B alpha" ], "offsets": [ [ 180, 195 ] ], "normalized": [] }, { "id": "PMID-7565683_T5", "type": "Protein", "text": [ "I kappa B alpha" ], "offsets": [ [ 354, 369 ] ], "normalized": [] }, { "id": "PMID-7565683_T6", "type": "Protein", "text": [ "I kappa B alpha" ], "offsets": [ [ 483, 498 ] ], "normalized": [] }, { "id": "PMID-7565683_T7", "type": "Protein", "text": [ "I kappa B alpha" ], "offsets": [ [ 843, 858 ] ], "normalized": [] }, { "id": "PMID-7565683_T8", "type": "Protein", "text": [ "I kappa B alpha" ], "offsets": [ [ 1059, 1074 ] ], "normalized": [] }, { "id": "PMID-7565683_T9", "type": "Protein", "text": [ "I kappa B alpha" ], "offsets": [ [ 1132, 1147 ] ], "normalized": [] }, { "id": "PMID-7565683_T10", "type": "Protein", "text": [ "I kappa B alpha" ], "offsets": [ [ 1348, 1363 ] ], "normalized": [] } ]

[ { "id": "PMID-7565683_E1", "type": "Regulation", "trigger": { "text": [ "control" ], "offsets": [ [ 28, 35 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "PMID-7565683_E2" } ] }, { "id": "PMID-7565683_E2", "type": "Protein_catabolism", "trigger": { "text": [ "degradation" ], "offsets": [ [ 36, 47 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "PMID-7565683_T1" } ] }, { "id": "PMID-7565683_E3", "type": "Positive_regulation", "trigger": { "text": [ "in response to" ], "offsets": [ [ 72, 86 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "PMID-7565683_E2" } ] }, { "id": "PMID-7565683_E4", "type": "Protein_catabolism", "trigger": { "text": [ "proteolytic degradation" ], "offsets": [ [ 125, 148 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "PMID-7565683_T3" } ] }, { "id": "PMID-7565683_E5", "type": "Positive_regulation", "trigger": { "text": [ "in response to" ], "offsets": [ [ 196, 210 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "PMID-7565683_E4" } ] }, { "id": "PMID-7565683_E6", "type": "Gene_expression", "trigger": { "text": [ "expression" ], "offsets": [ [ 334, 344 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "PMID-7565683_T5" } ] }, { "id": "PMID-7565683_E7", "type": "Protein_catabolism", "trigger": { "text": [ "degraded" ], "offsets": [ [ 502, 510 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "PMID-7565683_T6" } ] }, { "id": "PMID-7565683_E8", "type": "Positive_regulation", "trigger": { "text": [ "in response to" ], "offsets": [ [ 511, 525 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "PMID-7565683_E7" } ] }, { "id": "PMID-7565683_E9", "type": "Positive_regulation", "trigger": { "text": [ "stabilizes" ], "offsets": [ [ 792, 802 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "PMID-7565683_T7" } ] }, { "id": "PMID-7565683_E10", "type": "Phosphorylation", "trigger": { "text": [ "hyperphosphorylated" ], "offsets": [ [ 805, 824 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "PMID-7565683_T7" } ] }, { "id": "PMID-7565683_E11", "type": "Positive_regulation", "trigger": { "text": [ "induced" ], "offsets": [ [ 1012, 1019 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "PMID-7565683_E13" } ] }, { "id": "PMID-7565683_E12", "type": "Positive_regulation", "trigger": { "text": [ "induced" ], "offsets": [ [ 1012, 1019 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "PMID-7565683_E14" } ] }, { "id": "PMID-7565683_E13", "type": "Phosphorylation", "trigger": { "text": [ "phosphorylation" ], "offsets": [ [ 1020, 1035 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "PMID-7565683_T8" } ] }, { "id": "PMID-7565683_E14", "type": "Protein_catabolism", "trigger": { "text": [ "degradation" ], "offsets": [ [ 1044, 1055 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "PMID-7565683_T8" } ] }, { "id": "PMID-7565683_E15", "type": "Positive_regulation", "trigger": { "text": [ "inducible" ], "offsets": [ [ 1319, 1328 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "PMID-7565683_E16" } ] }, { "id": "PMID-7565683_E16", "type": "Phosphorylation", "trigger": { "text": [ "phosphorylation" ], "offsets": [ [ 1329, 1344 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "PMID-7565683_T10" } ] }, { "id": "PMID-7565683_E17", "type": "Negative_regulation", "trigger": { "text": [ "abolish" ], "offsets": [ [ 1495, 1502 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "PMID-7565683_E19" } ] }, { "id": "PMID-7565683_E18", "type": "Positive_regulation", "trigger": { "text": [ "induced" ], "offsets": [ [ 1510, 1517 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "PMID-7565683_E19" } ] }, { "id": "PMID-7565683_E19", "type": "Protein_catabolism", "trigger": { "text": [ "degradation" ], "offsets": [ [ 1518, 1529 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "PMID-7565683_T10" } ] }, { "id": "PMID-7565683_E20", "type": "Negative_regulation", "trigger": { "text": [ "abolish" ], "offsets": [ [ 1572, 1579 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "PMID-7565683_E23" } ] }, { "id": "PMID-7565683_E21", "type": "Negative_regulation", "trigger": { "text": [ "abolish" ], "offsets": [ [ 1572, 1579 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "PMID-7565683_E22" } ] }, { "id": "PMID-7565683_E22", "type": "Positive_regulation", "trigger": { "text": [ "inducible" ], "offsets": [ [ 1580, 1589 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "PMID-7565683_E23" } ] }, { "id": "PMID-7565683_E23", "type": "Phosphorylation", "trigger": { "text": [ "phosphorylation" ], "offsets": [ [ 1590, 1605 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "PMID-7565683_T10" } ] } ]

[ { "id": "PMID-7565683_1", "entity_ids": [ "PMID-7565683_T1", "PMID-7565683_T2" ] }, { "id": "PMID-7565683_2", "entity_ids": [ "PMID-7565683_T3", "PMID-7565683_T4" ] } ]

[]

[ { "id": "PMID-7565732__text", "type": "abstract", "text": [ "Transcriptional repression of the interleukin-2 gene by vitamin D3: direct inhibition of NFATp/AP-1 complex formation by a nuclear hormone receptor. \nT-lymphocyte proliferation is suppressed by 1,25-dihydroxyvitamin D3 [1,25(OH)2D3], the active metabolite of vitamin D3, and is associated with a decrease in interleukin 2 (IL-2), gamma interferon, and granulocyte-macrophage colony-stimulating factor mRNA levels. We report here that 1,25(OH)2D3-mediated repression in Jurkat cells is cycloheximide resistant, suggesting that it is a direct transcriptional repressive effect on IL-2 expression by the vitamin D3 receptor (VDR). We therefore examined vitamin D3-mediated repression of activated IL-2 expression by cotransfecting Jurkat cells with IL-2 promoter/reporter constructs and a VDR overexpression vector and by DNA binding. We delineated an element conferring both DNA binding by the receptor in vitro and 1,25(OH)2D3-mediated repression in vivo to a short 40-bp region encompassing an important positive regulatory element, NF-AT-1, which is bound by a T-cell-specific transcription factor, NFATp, as well as by AP-1. VDR DNA-binding mutants were unable to either bind to this element in vitro or repress in vivo; the VDR DNA-binding domain alone, however, bound the element but also could not repress IL-2 expression. These results indicate that DNA binding by VDR is necessary but not sufficient to mediate IL-2 repression. By combining partially purified proteins in vitro, we observed the loss of the bound NFATp/AP-1-DNA complex upon inclusion of VDR or VDR-retinoid X receptor. Order of addition and off-rate experiments indicate that the VDR-retinoid X receptor heterodimer blocks NFATp/AP-1 complex formation and then stably associates with the NF-AT-1 element. This direct inhibition by a nuclear hormone receptor of transcriptional activators of the IL-2 gene may provide a mechanistic explanation of how vitamin derivatives can act as potent immunosuppressive agents. " ], "offsets": [ [ 0, 1988 ] ] } ]

[ { "id": "PMID-7565732_T1", "type": "Protein", "text": [ "interleukin-2" ], "offsets": [ [ 34, 47 ] ], "normalized": [] }, { "id": "PMID-7565732_T2", "type": "Protein", "text": [ "NFATp" ], "offsets": [ [ 89, 94 ] ], "normalized": [] }, { "id": "PMID-7565732_T3", "type": "Protein", "text": [ "interleukin 2" ], "offsets": [ [ 308, 321 ] ], "normalized": [] }, { "id": "PMID-7565732_T4", "type": "Protein", "text": [ "IL-2" ], "offsets": [ [ 323, 327 ] ], "normalized": [] }, { "id": "PMID-7565732_T5", "type": "Protein", "text": [ "IL-2" ], "offsets": [ [ 578, 582 ] ], "normalized": [] }, { "id": "PMID-7565732_T6", "type": "Protein", "text": [ "vitamin D3 receptor" ], "offsets": [ [ 601, 620 ] ], "normalized": [] }, { "id": "PMID-7565732_T7", "type": "Protein", "text": [ "VDR" ], "offsets": [ [ 622, 625 ] ], "normalized": [] }, { "id": "PMID-7565732_T8", "type": "Protein", "text": [ "IL-2" ], "offsets": [ [ 694, 698 ] ], "normalized": [] }, { "id": "PMID-7565732_T9", "type": "Protein", "text": [ "IL-2" ], "offsets": [ [ 746, 750 ] ], "normalized": [] }, { "id": "PMID-7565732_T10", "type": "Protein", "text": [ "VDR" ], "offsets": [ [ 786, 789 ] ], "normalized": [] }, { "id": "PMID-7565732_T11", "type": "Protein", "text": [ "NF-AT-1" ], "offsets": [ [ 1033, 1040 ] ], "normalized": [] }, { "id": "PMID-7565732_T12", "type": "Protein", "text": [ "NFATp" ], "offsets": [ [ 1100, 1105 ] ], "normalized": [] }, { "id": "PMID-7565732_T13", "type": "Protein", "text": [ "VDR" ], "offsets": [ [ 1127, 1130 ] ], "normalized": [] }, { "id": "PMID-7565732_T14", "type": "Protein", "text": [ "VDR" ], "offsets": [ [ 1227, 1230 ] ], "normalized": [] }, { "id": "PMID-7565732_T15", "type": "Protein", "text": [ "IL-2" ], "offsets": [ [ 1311, 1315 ] ], "normalized": [] }, { "id": "PMID-7565732_T16", "type": "Protein", "text": [ "VDR" ], "offsets": [ [ 1371, 1374 ] ], "normalized": [] }, { "id": "PMID-7565732_T17", "type": "Protein", "text": [ "IL-2" ], "offsets": [ [ 1418, 1422 ] ], "normalized": [] }, { "id": "PMID-7565732_T18", "type": "Protein", "text": [ "NFATp" ], "offsets": [ [ 1520, 1525 ] ], "normalized": [] }, { "id": "PMID-7565732_T19", "type": "Protein", "text": [ "VDR" ], "offsets": [ [ 1561, 1564 ] ], "normalized": [] }, { "id": "PMID-7565732_T20", "type": "Protein", "text": [ "VDR" ], "offsets": [ [ 1568, 1571 ] ], "normalized": [] }, { "id": "PMID-7565732_T21", "type": "Protein", "text": [ "VDR" ], "offsets": [ [ 1654, 1657 ] ], "normalized": [] }, { "id": "PMID-7565732_T22", "type": "Protein", "text": [ "NFATp" ], "offsets": [ [ 1697, 1702 ] ], "normalized": [] }, { "id": "PMID-7565732_T23", "type": "Protein", "text": [ "NF-AT-1" ], "offsets": [ [ 1762, 1769 ] ], "normalized": [] }, { "id": "PMID-7565732_T24", "type": "Protein", "text": [ "IL-2" ], "offsets": [ [ 1869, 1873 ] ], "normalized": [] } ]

[ { "id": "PMID-7565732_E1", "type": "Negative_regulation", "trigger": { "text": [ "Transcriptional repression" ], "offsets": [ [ 0, 26 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "PMID-7565732_T1" } ] }, { "id": "PMID-7565732_E2", "type": "Negative_regulation", "trigger": { "text": [ "inhibition" ], "offsets": [ [ 75, 85 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "PMID-7565732_E3" } ] }, { "id": "PMID-7565732_E3", "type": "Binding", "trigger": { "text": [ "complex formation" ], "offsets": [ [ 100, 117 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "PMID-7565732_T2" } ] }, { "id": "PMID-7565732_E4", "type": "Negative_regulation", "trigger": { "text": [ "decrease" ], "offsets": [ [ 296, 304 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "PMID-7565732_T4" } ] }, { "id": "PMID-7565732_E5", "type": "Negative_regulation", "trigger": { "text": [ "repressive effect" ], "offsets": [ [ 557, 574 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "PMID-7565732_E6" }, { "role": "Cause", "ref_id": "PMID-7565732_T7" } ] }, { "id": "PMID-7565732_E6", "type": "Transcription", "trigger": { "text": [ "expression" ], "offsets": [ [ 583, 593 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "PMID-7565732_T5" } ] }, { "id": "PMID-7565732_E7", "type": "Negative_regulation", "trigger": { "text": [ "repression" ], "offsets": [ [ 670, 680 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "PMID-7565732_E10" }, { "role": "Cause", "ref_id": "PMID-7565732_E12" } ] }, { "id": "PMID-7565732_E8", "type": "Negative_regulation", "trigger": { "text": [ "repression" ], "offsets": [ [ 670, 680 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "PMID-7565732_E10" }, { "role": "Cause", "ref_id": "PMID-7565732_E11" } ] }, { "id": "PMID-7565732_E9", "type": "Positive_regulation", "trigger": { "text": [ "activated" ], "offsets": [ [ 684, 693 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "PMID-7565732_T8" } ] }, { "id": "PMID-7565732_E10", "type": "Gene_expression", "trigger": { "text": [ "expression" ], "offsets": [ [ 699, 709 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "PMID-7565732_T8" } ] }, { "id": "PMID-7565732_E11", "type": "Gene_expression", "trigger": { "text": [ "cotransfecting" ], "offsets": [ [ 713, 727 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "PMID-7565732_T10" } ] }, { "id": "PMID-7565732_E12", "type": "Gene_expression", "trigger": { "text": [ "cotransfecting" ], "offsets": [ [ 713, 727 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "PMID-7565732_T9" } ] }, { "id": "PMID-7565732_E13", "type": "Regulation", "trigger": { "text": [ "conferring" ], "offsets": [ [ 857, 867 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "PMID-7565732_E14" } ] }, { "id": "PMID-7565732_E14", "type": "Binding", "trigger": { "text": [ "binding" ], "offsets": [ [ 877, 884 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "PMID-7565732_T10" } ] }, { "id": "PMID-7565732_E15", "type": "Binding", "trigger": { "text": [ "bound" ], "offsets": [ [ 1051, 1056 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "PMID-7565732_T11" }, { "role": "Theme", "ref_id": "PMID-7565732_T12" } ] }, { "id": "PMID-7565732_E16", "type": "Binding", "trigger": { "text": [ "bound" ], "offsets": [ [ 1051, 1056 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "PMID-7565732_T11" } ] }, { "id": "PMID-7565732_E17", "type": "Binding", "trigger": { "text": [ "binding mutants" ], "offsets": [ [ 1135, 1150 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "PMID-7565732_T13" } ] }, { "id": "PMID-7565732_E18", "type": "Negative_regulation", "trigger": { "text": [ "repress" ], "offsets": [ [ 1206, 1213 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "PMID-7565732_E20" }, { "role": "Cause", "ref_id": "PMID-7565732_E17" } ] }, { "id": "PMID-7565732_E19", "type": "Negative_regulation", "trigger": { "text": [ "repress" ], "offsets": [ [ 1303, 1310 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "PMID-7565732_E20" } ] }, { "id": "PMID-7565732_E20", "type": "Gene_expression", "trigger": { "text": [ "expression" ], "offsets": [ [ 1316, 1326 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "PMID-7565732_T15" } ] }, { "id": "PMID-7565732_E21", "type": "Binding", "trigger": { "text": [ "binding" ], "offsets": [ [ 1360, 1367 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "PMID-7565732_T16" } ] }, { "id": "PMID-7565732_E22", "type": "Positive_regulation", "trigger": { "text": [ "necessary but not sufficient to mediate" ], "offsets": [ [ 1378, 1417 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "PMID-7565732_E23" }, { "role": "Cause", "ref_id": "PMID-7565732_E21" } ] }, { "id": "PMID-7565732_E23", "type": "Negative_regulation", "trigger": { "text": [ "repression" ], "offsets": [ [ 1423, 1433 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "PMID-7565732_T17" } ] }, { "id": "PMID-7565732_E24", "type": "Negative_regulation", "trigger": { "text": [ "loss" ], "offsets": [ [ 1502, 1506 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "PMID-7565732_E26" }, { "role": "Cause", "ref_id": "PMID-7565732_T20" } ] }, { "id": "PMID-7565732_E25", "type": "Negative_regulation", "trigger": { "text": [ "loss" ], "offsets": [ [ 1502, 1506 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "PMID-7565732_E26" }, { "role": "Cause", "ref_id": "PMID-7565732_T19" } ] }, { "id": "PMID-7565732_E26", "type": "Binding", "trigger": { "text": [ "bound" ], "offsets": [ [ 1514, 1519 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "PMID-7565732_T18" } ] }, { "id": "PMID-7565732_E27", "type": "Negative_regulation", "trigger": { "text": [ "blocks" ], "offsets": [ [ 1690, 1696 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "PMID-7565732_E28" }, { "role": "Cause", "ref_id": "PMID-7565732_T21" } ] }, { "id": "PMID-7565732_E28", "type": "Binding", "trigger": { "text": [ "complex formation" ], "offsets": [ [ 1708, 1725 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "PMID-7565732_T22" } ] }, { "id": "PMID-7565732_E29", "type": "Binding", "trigger": { "text": [ "associates" ], "offsets": [ [ 1742, 1752 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "PMID-7565732_T21" }, { "role": "Theme", "ref_id": "PMID-7565732_T23" } ] }, { "id": "PMID-7565732_E30", "type": "Positive_regulation", "trigger": { "text": [ "transcriptional activators" ], "offsets": [ [ 1835, 1861 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "PMID-7565732_T24" } ] } ]

[ { "id": "PMID-7565732_1", "entity_ids": [ "PMID-7565732_T4", "PMID-7565732_T3" ] }, { "id": "PMID-7565732_2", "entity_ids": [ "PMID-7565732_T7", "PMID-7565732_T6" ] } ]

[]

[ { "id": "PMID-7565811__text", "type": "abstract", "text": [ "An interferon-gamma activation sequence mediates the transcriptional regulation of the IgG Fc receptor type IC gene by interferon-gamma. \nExpression of the IgG Fc receptor type I (Fc gamma RI) on myeloid cells is dramatically increased by treatment with interferon-gamma (IFN-gamma). We observed that Fc gamma RI transcript levels in monoblast-like U937 cells were elevated within 3 hr and peaked 12 hr after exposure to IFN-gamma. Treatment of U937 with IFN-gamma for 9 hr in the presence of cycloheximide led to super-induction of Fc gamma RI expression. Nuclear run-on analysis revealed that the rate of Fc gamma RI transcription was increased by IFN-gamma. Genomic sequence upstream of the Fc gamma RIC gene was cloned and subjected to primer extension analysis, which demonstrated a single transcription initiation site without a TATA box. Transient transfections of CAT reporter gene constructs containing various Fc gamma RIC promoter sequences into U937 cells revealed that a 20-bp region surrounding the transcription start site (-7 to +13) was capable of mediating transcription initiation and that an IFN-gamma responsive element (GIRE) was present within 74 bp upstream of the transcription initiation site. A 17-bp sequence between positions -51 and -35 conferred IFN-gamma responsiveness on a heterologous promoter. Double-stranded GIRE sequence, but not a scrambled sequence, was specifically bound by nuclear proteins from IFN-gamma treated U937 cells. Gel shift experiments further showed that the STAT1 alpha protein bound to the Fc gamma RIC GIRE in response to IFN-gamma treatment of U937 cells. The Fc gamma RIC GIRE is homologous to the IFN-gamma activation sequence (GAS) of the guanylate binding protein and to X box elements of class II MHC genes. Our results demonstrate that transcriptional regulation of the Fc gamma RIC gene by IFN-gamma involves the binding of STAT1 alpha to a 17-bp GAS homology in the proximal promoter. " ], "offsets": [ [ 0, 1953 ] ] } ]

[ { "id": "PMID-7565811_T1", "type": "Protein", "text": [ "interferon-gamma" ], "offsets": [ [ 3, 19 ] ], "normalized": [] }, { "id": "PMID-7565811_T2", "type": "Protein", "text": [ "IgG Fc receptor type IC" ], "offsets": [ [ 87, 110 ] ], "normalized": [] }, { "id": "PMID-7565811_T3", "type": "Protein", "text": [ "interferon-gamma" ], "offsets": [ [ 119, 135 ] ], "normalized": [] }, { "id": "PMID-7565811_T4", "type": "Protein", "text": [ "IgG Fc receptor type I" ], "offsets": [ [ 156, 178 ] ], "normalized": [] }, { "id": "PMID-7565811_T5", "type": "Protein", "text": [ "Fc gamma RI" ], "offsets": [ [ 180, 191 ] ], "normalized": [] }, { "id": "PMID-7565811_T6", "type": "Protein", "text": [ "interferon-gamma" ], "offsets": [ [ 254, 270 ] ], "normalized": [] }, { "id": "PMID-7565811_T7", "type": "Protein", "text": [ "IFN-gamma" ], "offsets": [ [ 272, 281 ] ], "normalized": [] }, { "id": "PMID-7565811_T8", "type": "Protein", "text": [ "Fc gamma RI" ], "offsets": [ [ 301, 312 ] ], "normalized": [] }, { "id": "PMID-7565811_T9", "type": "Protein", "text": [ "IFN-gamma" ], "offsets": [ [ 421, 430 ] ], "normalized": [] }, { "id": "PMID-7565811_T10", "type": "Protein", "text": [ "IFN-gamma" ], "offsets": [ [ 455, 464 ] ], "normalized": [] }, { "id": "PMID-7565811_T11", "type": "Protein", "text": [ "Fc gamma RI" ], "offsets": [ [ 533, 544 ] ], "normalized": [] }, { "id": "PMID-7565811_T12", "type": "Protein", "text": [ "Fc gamma RI" ], "offsets": [ [ 607, 618 ] ], "normalized": [] }, { "id": "PMID-7565811_T13", "type": "Protein", "text": [ "IFN-gamma" ], "offsets": [ [ 650, 659 ] ], "normalized": [] }, { "id": "PMID-7565811_T14", "type": "Protein", "text": [ "Fc gamma RIC" ], "offsets": [ [ 694, 706 ] ], "normalized": [] }, { "id": "PMID-7565811_T15", "type": "Protein", "text": [ "CAT" ], "offsets": [ [ 872, 875 ] ], "normalized": [] }, { "id": "PMID-7565811_T16", "type": "Protein", "text": [ "Fc gamma RIC" ], "offsets": [ [ 920, 932 ] ], "normalized": [] }, { "id": "PMID-7565811_T17", "type": "Protein", "text": [ "IFN-gamma" ], "offsets": [ [ 1112, 1121 ] ], "normalized": [] }, { "id": "PMID-7565811_T18", "type": "Protein", "text": [ "IFN-gamma" ], "offsets": [ [ 1277, 1286 ] ], "normalized": [] }, { "id": "PMID-7565811_T19", "type": "Protein", "text": [ "IFN-gamma" ], "offsets": [ [ 1439, 1448 ] ], "normalized": [] }, { "id": "PMID-7565811_T20", "type": "Protein", "text": [ "STAT1 alpha" ], "offsets": [ [ 1515, 1526 ] ], "normalized": [] }, { "id": "PMID-7565811_T21", "type": "Protein", "text": [ "Fc gamma RIC" ], "offsets": [ [ 1548, 1560 ] ], "normalized": [] }, { "id": "PMID-7565811_T22", "type": "Protein", "text": [ "IFN-gamma" ], "offsets": [ [ 1581, 1590 ] ], "normalized": [] }, { "id": "PMID-7565811_T23", "type": "Protein", "text": [ "Fc gamma RIC" ], "offsets": [ [ 1620, 1632 ] ], "normalized": [] }, { "id": "PMID-7565811_T24", "type": "Protein", "text": [ "IFN-gamma" ], "offsets": [ [ 1659, 1668 ] ], "normalized": [] }, { "id": "PMID-7565811_T25", "type": "Protein", "text": [ "Fc gamma RIC" ], "offsets": [ [ 1836, 1848 ] ], "normalized": [] }, { "id": "PMID-7565811_T26", "type": "Protein", "text": [ "IFN-gamma" ], "offsets": [ [ 1857, 1866 ] ], "normalized": [] }, { "id": "PMID-7565811_T27", "type": "Protein", "text": [ "STAT1 alpha" ], "offsets": [ [ 1891, 1902 ] ], "normalized": [] } ]

[ { "id": "PMID-7565811_E1", "type": "Positive_regulation", "trigger": { "text": [ "mediates" ], "offsets": [ [ 40, 48 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "PMID-7565811_E2" } ] }, { "id": "PMID-7565811_E2", "type": "Regulation", "trigger": { "text": [ "transcriptional regulation" ], "offsets": [ [ 53, 79 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "PMID-7565811_T2" }, { "role": "Cause", "ref_id": "PMID-7565811_T3" } ] }, { "id": "PMID-7565811_E3", "type": "Gene_expression", "trigger": { "text": [ "Expression" ], "offsets": [ [ 138, 148 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "PMID-7565811_T5" } ] }, { "id": "PMID-7565811_E4", "type": "Positive_regulation", "trigger": { "text": [ "increased" ], "offsets": [ [ 226, 235 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "PMID-7565811_E3" } ] }, { "id": "PMID-7565811_E5", "type": "Positive_regulation", "trigger": { "text": [ "elevated" ], "offsets": [ [ 365, 373 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "PMID-7565811_T8" } ] }, { "id": "PMID-7565811_E6", "type": "Positive_regulation", "trigger": { "text": [ "led" ], "offsets": [ [ 507, 510 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "PMID-7565811_E7" } ] }, { "id": "PMID-7565811_E7", "type": "Positive_regulation", "trigger": { "text": [ "super" ], "offsets": [ [ 514, 519 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "PMID-7565811_E8" } ] }, { "id": "PMID-7565811_E8", "type": "Positive_regulation", "trigger": { "text": [ "induction" ], "offsets": [ [ 520, 529 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "PMID-7565811_E9" } ] }, { "id": "PMID-7565811_E9", "type": "Gene_expression", "trigger": { "text": [ "expression" ], "offsets": [ [ 545, 555 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "PMID-7565811_T11" } ] }, { "id": "PMID-7565811_E10", "type": "Transcription", "trigger": { "text": [ "transcription" ], "offsets": [ [ 619, 632 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "PMID-7565811_T12" } ] }, { "id": "PMID-7565811_E11", "type": "Positive_regulation", "trigger": { "text": [ "increased" ], "offsets": [ [ 637, 646 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "PMID-7565811_E10" }, { "role": "Cause", "ref_id": "PMID-7565811_T13" } ] }, { "id": "PMID-7565811_E12", "type": "Binding", "trigger": { "text": [ "bound" ], "offsets": [ [ 1535, 1540 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "PMID-7565811_T20" } ] }, { "id": "PMID-7565811_E13", "type": "Positive_regulation", "trigger": { "text": [ "in response to" ], "offsets": [ [ 1566, 1580 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "PMID-7565811_E12" } ] }, { "id": "PMID-7565811_E14", "type": "Regulation", "trigger": { "text": [ "transcriptional regulation" ], "offsets": [ [ 1802, 1828 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "PMID-7565811_T25" }, { "role": "Cause", "ref_id": "PMID-7565811_T26" } ] }, { "id": "PMID-7565811_E15", "type": "Regulation", "trigger": { "text": [ "involves" ], "offsets": [ [ 1867, 1875 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "PMID-7565811_E14" }, { "role": "Cause", "ref_id": "PMID-7565811_E16" } ] }, { "id": "PMID-7565811_E16", "type": "Binding", "trigger": { "text": [ "binding" ], "offsets": [ [ 1880, 1887 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "PMID-7565811_T27" } ] } ]

[ { "id": "PMID-7565811_1", "entity_ids": [ "PMID-7565811_T5", "PMID-7565811_T4" ] }, { "id": "PMID-7565811_2", "entity_ids": [ "PMID-7565811_T6", "PMID-7565811_T7" ] } ]

[]

[ { "id": "PMID-7569976__text", "type": "abstract", "text": [ "Immunosuppression by glucocorticoids: inhibition of NF-kappa B activity through induction of I kappa B synthesis [see comments] \nGlucocorticoids are among the most potent anti-inflammatory and immunosuppressive agents. They inhibit synthesis of almost all known cytokines and of several cell surface molecules required for immune function, but the mechanism underlying this activity has been unclear. Here it is shown that glucocorticoids are potent inhibitors of nuclear factor kappa B (NF-kappa B) activation in mice and cultured cells. This inhibition is mediated by induction of the I kappa B alpha inhibitory protein, which traps activated NF-kappa B in inactive cytoplasmic complexes. Because NF-kappa B activates many immunoregulatory genes in response to pro-inflammatory stimuli, the inhibition of its activity can be a major component of the anti-inflammatory activity of glucocorticoids. " ], "offsets": [ [ 0, 899 ] ] } ]

[ { "id": "PMID-7569976_T1", "type": "Protein", "text": [ "I kappa B alpha" ], "offsets": [ [ 587, 602 ] ], "normalized": [] } ]

[]

[]

[]

[ { "id": "PMID-7578980__text", "type": "abstract", "text": [ "IFN-gamma priming of monocytes enhances LPS-induced TNF production by augmenting both transcription and MRNA stability. \nThe induction of cytokine expression in monocytes/macrophages by bacterial endotoxin or lipopolysaccharide is a critical, highly regulated host defence response. The augmentation of LPS responses by interferon gamma (IFN-gamma), referred to as priming, is well established. However, the mechanism(s) by which priming occurs is poorly defined. Using tumour necrosis factor (TNF) induction as a model, experiments were designed to analyse in detail the priming effect on the LPS response in human monocytes. Priming by IFN-gamma was primarily manifested at the level of TNF mRNA accumulation. IFN-gamma pre-treatment affected the magnitude rather than the sensitivity of the LPS response. Priming occurred after several hours of treatment, and the primed state was induced by either IFN-gamma or GM-CSF, but not M-CSF. Primed monocytes transcribed TNF mRNA at a higher rate than freshly isolated monocytes upon activation with LPS. The increased transcriptional rate correlated with a marked increase in nuclear factor-kappa B activity in these cells as determined by electrophoretic mobility shift assay using a consensus NF-kappa B oligonucleotide. An additional significant finding was than TNF mRNA induced in primed cells was much more stable than in unprimed cells (T1/2 increased 6-8-fold). Consistent with the increased mRNA stability, the duration of mRNA accumulation was longer following LPS stimulation in primed monocytes, in addition to being of greater magnitude. Finally, primed and unprimed cells possessed a differential sensitivity to the kinase inhibitor H-89. H-89 substantially suppressed LPS-induced TNF mRNA accumulation in unprimed cells, but had no effect on primed monocytes following LPS stimulation. (ABSTRACT TRUNCATED AT 250 WORDS) " ], "offsets": [ [ 0, 1882 ] ] } ]

[ { "id": "PMID-7578980_T1", "type": "Protein", "text": [ "IFN-gamma" ], "offsets": [ [ 0, 9 ] ], "normalized": [] }, { "id": "PMID-7578980_T2", "type": "Protein", "text": [ "interferon gamma" ], "offsets": [ [ 320, 336 ] ], "normalized": [] }, { "id": "PMID-7578980_T3", "type": "Protein", "text": [ "IFN-gamma" ], "offsets": [ [ 338, 347 ] ], "normalized": [] }, { "id": "PMID-7578980_T4", "type": "Protein", "text": [ "IFN-gamma" ], "offsets": [ [ 638, 647 ] ], "normalized": [] }, { "id": "PMID-7578980_T5", "type": "Protein", "text": [ "IFN-gamma" ], "offsets": [ [ 712, 721 ] ], "normalized": [] }, { "id": "PMID-7578980_T6", "type": "Protein", "text": [ "IFN-gamma" ], "offsets": [ [ 902, 911 ] ], "normalized": [] }, { "id": "PMID-7578980_T7", "type": "Protein", "text": [ "GM-CSF" ], "offsets": [ [ 915, 921 ] ], "normalized": [] }, { "id": "PMID-7578980_T8", "type": "Protein", "text": [ "M-CSF" ], "offsets": [ [ 931, 936 ] ], "normalized": [] } ]

[]

[ { "id": "PMID-7578980_1", "entity_ids": [ "PMID-7578980_T2", "PMID-7578980_T3" ] } ]

[]

[ { "id": "PMID-7579328__text", "type": "abstract", "text": [ "The myeloid zinc finger gene, MZF-1, regulates the CD34 promoter in vitro. \nMZF-1 is a C2H2 zinc finger gene encoding a putative transcriptional regulator of myeloid differentiation. The MZF-1 protein contains 13 C2H2 zinc fingers arranged in bipartite DNA binding domains containing zinc fingers through 4 and, in the carboxy-terminus, 5 through 13. We previously identified the DNA consensus binding site recognized by the two DNA binding domains. To assess the transcription regulatory function of MZF-1, the full-length MZF-1 coding region was fused to the DNA binding domain of the yeast transactivator GAL4. The expression vector was cotransfected with the chloramphenicol acetyl transferase (CAT) reporter gene regulated by the thymidine kinase promoter containing GAL4 DNA binding sites into NIH 3T3, 293, K562, and Jurkat cell lines. MZF-1 represses CAT reporter gene expression via GAL4 binding sites in the nonhematopoietic cell lines NIH 3T3 and 293. In contrast, MZF-1 activates CAT reporter gene expression in the hematopoietic cell lines K562 and Jurkat. The MZF-1 binding sites are present in the promoters of several genes expressed during myeloid differentiation, including the CD34 promoter. MZF-1 transcriptional regulation of this physiologically relevant promoter was assessed in both hematopoietic and nonhematopoietic cell lines. Recombinant MZF-1 protein specifically binds to the consensus binding sites in the CD34 promoter in mobility shift assays. MZF-1 expression vectors were cotransfected with the luciferase reporter plasmids regulated by the CD34 promoter into both nonhematopoietic and hematopoietic cell lines. As with the heterologous DNA binding domain, MZF-1 represses reporter gene expression in nonhematopoietic cell lines and activates expression in hematopoietic cell lines. Activation of CD34 expression in hematopoietic cell lines is dependent on the presence of intact MZF-1 binding sites. The cell type-specific regulation of the CD34 promoter by MZF-1 suggests the presence of tissue-specific regulators/adapters or differential MZF-1 modifications that determine MZF-1 transcriptional regulatory function. " ], "offsets": [ [ 0, 2155 ] ] } ]

[ { "id": "PMID-7579328_T1", "type": "Protein", "text": [ "MZF-1" ], "offsets": [ [ 30, 35 ] ], "normalized": [] }, { "id": "PMID-7579328_T2", "type": "Protein", "text": [ "CD34" ], "offsets": [ [ 51, 55 ] ], "normalized": [] }, { "id": "PMID-7579328_T3", "type": "Protein", "text": [ "MZF-1" ], "offsets": [ [ 76, 81 ] ], "normalized": [] }, { "id": "PMID-7579328_T4", "type": "Protein", "text": [ "MZF-1" ], "offsets": [ [ 187, 192 ] ], "normalized": [] }, { "id": "PMID-7579328_T5", "type": "Protein", "text": [ "MZF-1" ], "offsets": [ [ 501, 506 ] ], "normalized": [] }, { "id": "PMID-7579328_T6", "type": "Protein", "text": [ "MZF-1" ], "offsets": [ [ 524, 529 ] ], "normalized": [] }, { "id": "PMID-7579328_T7", "type": "Protein", "text": [ "GAL4" ], "offsets": [ [ 608, 612 ] ], "normalized": [] }, { "id": "PMID-7579328_T8", "type": "Protein", "text": [ "chloramphenicol acetyl transferase" ], "offsets": [ [ 663, 697 ] ], "normalized": [] }, { "id": "PMID-7579328_T9", "type": "Protein", "text": [ "CAT" ], "offsets": [ [ 699, 702 ] ], "normalized": [] }, { "id": "PMID-7579328_T10", "type": "Protein", "text": [ "thymidine kinase" ], "offsets": [ [ 735, 751 ] ], "normalized": [] }, { "id": "PMID-7579328_T11", "type": "Protein", "text": [ "GAL4" ], "offsets": [ [ 772, 776 ] ], "normalized": [] }, { "id": "PMID-7579328_T12", "type": "Protein", "text": [ "MZF-1" ], "offsets": [ [ 843, 848 ] ], "normalized": [] }, { "id": "PMID-7579328_T13", "type": "Protein", "text": [ "CAT" ], "offsets": [ [ 859, 862 ] ], "normalized": [] }, { "id": "PMID-7579328_T14", "type": "Protein", "text": [ "GAL4" ], "offsets": [ [ 892, 896 ] ], "normalized": [] }, { "id": "PMID-7579328_T15", "type": "Protein", "text": [ "MZF-1" ], "offsets": [ [ 976, 981 ] ], "normalized": [] }, { "id": "PMID-7579328_T16", "type": "Protein", "text": [ "CAT" ], "offsets": [ [ 992, 995 ] ], "normalized": [] }, { "id": "PMID-7579328_T17", "type": "Protein", "text": [ "MZF-1" ], "offsets": [ [ 1074, 1079 ] ], "normalized": [] }, { "id": "PMID-7579328_T18", "type": "Protein", "text": [ "CD34" ], "offsets": [ [ 1196, 1200 ] ], "normalized": [] }, { "id": "PMID-7579328_T19", "type": "Protein", "text": [ "MZF-1" ], "offsets": [ [ 1211, 1216 ] ], "normalized": [] }, { "id": "PMID-7579328_T20", "type": "Protein", "text": [ "MZF-1" ], "offsets": [ [ 1366, 1371 ] ], "normalized": [] }, { "id": "PMID-7579328_T21", "type": "Protein", "text": [ "CD34" ], "offsets": [ [ 1437, 1441 ] ], "normalized": [] }, { "id": "PMID-7579328_T22", "type": "Protein", "text": [ "MZF-1" ], "offsets": [ [ 1477, 1482 ] ], "normalized": [] }, { "id": "PMID-7579328_T23", "type": "Protein", "text": [ "CD34" ], "offsets": [ [ 1576, 1580 ] ], "normalized": [] }, { "id": "PMID-7579328_T24", "type": "Protein", "text": [ "MZF-1" ], "offsets": [ [ 1692, 1697 ] ], "normalized": [] }, { "id": "PMID-7579328_T25", "type": "Protein", "text": [ "CD34" ], "offsets": [ [ 1832, 1836 ] ], "normalized": [] }, { "id": "PMID-7579328_T26", "type": "Protein", "text": [ "MZF-1" ], "offsets": [ [ 1915, 1920 ] ], "normalized": [] }, { "id": "PMID-7579328_T27", "type": "Protein", "text": [ "CD34" ], "offsets": [ [ 1977, 1981 ] ], "normalized": [] }, { "id": "PMID-7579328_T28", "type": "Protein", "text": [ "MZF-1" ], "offsets": [ [ 1994, 1999 ] ], "normalized": [] }, { "id": "PMID-7579328_T29", "type": "Protein", "text": [ "MZF-1" ], "offsets": [ [ 2077, 2082 ] ], "normalized": [] }, { "id": "PMID-7579328_T30", "type": "Protein", "text": [ "MZF-1" ], "offsets": [ [ 2112, 2117 ] ], "normalized": [] }, { "id": "PMID-7579328_T32", "type": "Entity", "text": [ "promoter" ], "offsets": [ [ 56, 64 ] ], "normalized": [] }, { "id": "PMID-7579328_T36", "type": "Entity", "text": [ "promoter" ], "offsets": [ [ 752, 760 ] ], "normalized": [] }, { "id": "PMID-7579328_T43", "type": "Entity", "text": [ "promoter" ], "offsets": [ [ 1201, 1209 ] ], "normalized": [] }, { "id": "PMID-7579328_T46", "type": "Entity", "text": [ "consensus binding sites" ], "offsets": [ [ 1406, 1429 ] ], "normalized": [] }, { "id": "PMID-7579328_T51", "type": "Entity", "text": [ "promoter" ], "offsets": [ [ 1982, 1990 ] ], "normalized": [] } ]

[ { "id": "PMID-7579328_E1", "type": "Regulation", "trigger": { "text": [ "regulates" ], "offsets": [ [ 37, 46 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "PMID-7579328_T2" }, { "role": "Cause", "ref_id": "PMID-7579328_T1" }, { "role": "Site", "ref_id": "PMID-7579328_T32" } ] }, { "id": "PMID-7579328_E2", "type": "Gene_expression", "trigger": { "text": [ "cotransfected" ], "offsets": [ [ 640, 653 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "PMID-7579328_T6" } ] }, { "id": "PMID-7579328_E3", "type": "Positive_regulation", "trigger": { "text": [ "cotransfected" ], "offsets": [ [ 640, 653 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "PMID-7579328_E2" } ] }, { "id": "PMID-7579328_E4", "type": "Regulation", "trigger": { "text": [ "regulated" ], "offsets": [ [ 718, 727 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "PMID-7579328_T9" }, { "role": "Cause", "ref_id": "PMID-7579328_T10" }, { "role": "CSite", "ref_id": "PMID-7579328_T36" } ] }, { "id": "PMID-7579328_E5", "type": "Negative_regulation", "trigger": { "text": [ "represses" ], "offsets": [ [ 849, 858 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "PMID-7579328_E6" }, { "role": "Cause", "ref_id": "PMID-7579328_T12" } ] }, { "id": "PMID-7579328_E6", "type": "Gene_expression", "trigger": { "text": [ "expression" ], "offsets": [ [ 877, 887 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "PMID-7579328_T13" } ] }, { "id": "PMID-7579328_E7", "type": "Positive_regulation", "trigger": { "text": [ "via" ], "offsets": [ [ 888, 891 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "PMID-7579328_E5" }, { "role": "Cause", "ref_id": "PMID-7579328_T14" } ] }, { "id": "PMID-7579328_E8", "type": "Positive_regulation", "trigger": { "text": [ "activates" ], "offsets": [ [ 982, 991 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "PMID-7579328_E9" }, { "role": "Cause", "ref_id": "PMID-7579328_T15" } ] }, { "id": "PMID-7579328_E9", "type": "Gene_expression", "trigger": { "text": [ "expression" ], "offsets": [ [ 1010, 1020 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "PMID-7579328_T16" } ] }, { "id": "PMID-7579328_E10", "type": "Gene_expression", "trigger": { "text": [ "expressed" ], "offsets": [ [ 1140, 1149 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "PMID-7579328_T18" } ] }, { "id": "PMID-7579328_E11", "type": "Regulation", "trigger": { "text": [ "transcriptional regulation" ], "offsets": [ [ 1217, 1243 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "PMID-7579328_T18" }, { "role": "Cause", "ref_id": "PMID-7579328_T19" }, { "role": "Site", "ref_id": "PMID-7579328_T43" } ] }, { "id": "PMID-7579328_E12", "type": "Binding", "trigger": { "text": [ "binds" ], "offsets": [ [ 1393, 1398 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "PMID-7579328_T20" }, { "role": "Theme", "ref_id": "PMID-7579328_T21" }, { "role": "Site", "ref_id": "PMID-7579328_T46" } ] }, { "id": "PMID-7579328_E13", "type": "Positive_regulation", "trigger": { "text": [ "Activation" ], "offsets": [ [ 1818, 1828 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "PMID-7579328_E14" } ] }, { "id": "PMID-7579328_E14", "type": "Gene_expression", "trigger": { "text": [ "expression" ], "offsets": [ [ 1837, 1847 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "PMID-7579328_T25" } ] }, { "id": "PMID-7579328_E15", "type": "Positive_regulation", "trigger": { "text": [ "dependent" ], "offsets": [ [ 1879, 1888 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "PMID-7579328_E13" } ] }, { "id": "PMID-7579328_E16", "type": "Regulation", "trigger": { "text": [ "regulation" ], "offsets": [ [ 1959, 1969 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "PMID-7579328_T27" }, { "role": "Cause", "ref_id": "PMID-7579328_T28" }, { "role": "Site", "ref_id": "PMID-7579328_T51" } ] }, { "id": "PMID-7579328_E17", "type": "Regulation", "trigger": { "text": [ "determine" ], "offsets": [ [ 2102, 2111 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "PMID-7579328_E16" } ] } ]

[ { "id": "PMID-7579328_1", "entity_ids": [ "PMID-7579328_T9", "PMID-7579328_T8" ] } ]

[]

[ { "id": "PMID-7585505__text", "type": "abstract", "text": [ "The normal cell cycle activation program is exploited during the infection of quiescent B lymphocytes by Epstein-Barr virus. \nB lymphocytes in the peripheral circulation are maintained in a non-proliferative state. Antigen recognition stimulates limited proliferation, whereas infection with Epstein-Barr virus (EBV) results in continual proliferation and the outgrowth of immortal cell lines. Because it is not clear at which point in cell cycle the peripheral B lymphocytes are arrested, we characterized the expression of several cell cycle-associated genes in quiescent and stimulated cells. We show that the expression of four cell genes, cdc-2, cyclin E, CD23, and cyclin D2, are up-regulated approximately 100-fold as a result of EBV-mediated immortalization. Because these genes play a positive role in cell proliferation, we suggest that this regulatory switch contributes to controlling entry into the cell cycle. Transient stimulation of quiescent B lymphocytes with either a cocktail of anti-CD40, anti-IgM, and IL4, or EBV results in the rapid expression of the same four genes, suggesting that, after infection, EBV exploits the normal program of B-lymphocyte cell cycle activation. " ], "offsets": [ [ 0, 1197 ] ] } ]

[ { "id": "PMID-7585505_T1", "type": "Protein", "text": [ "cdc-2" ], "offsets": [ [ 644, 649 ] ], "normalized": [] }, { "id": "PMID-7585505_T2", "type": "Protein", "text": [ "cyclin E" ], "offsets": [ [ 651, 659 ] ], "normalized": [] }, { "id": "PMID-7585505_T3", "type": "Protein", "text": [ "CD23" ], "offsets": [ [ 661, 665 ] ], "normalized": [] }, { "id": "PMID-7585505_T4", "type": "Protein", "text": [ "cyclin D2" ], "offsets": [ [ 671, 680 ] ], "normalized": [] }, { "id": "PMID-7585505_T5", "type": "Protein", "text": [ "CD40" ], "offsets": [ [ 1004, 1008 ] ], "normalized": [] }, { "id": "PMID-7585505_T6", "type": "Protein", "text": [ "IL4" ], "offsets": [ [ 1024, 1027 ] ], "normalized": [] } ]

[ { "id": "PMID-7585505_E1", "type": "Gene_expression", "trigger": { "text": [ "expression" ], "offsets": [ [ 613, 623 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "PMID-7585505_T2" } ] }, { "id": "PMID-7585505_E2", "type": "Gene_expression", "trigger": { "text": [ "expression" ], "offsets": [ [ 613, 623 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "PMID-7585505_T3" } ] }, { "id": "PMID-7585505_E3", "type": "Gene_expression", "trigger": { "text": [ "expression" ], "offsets": [ [ 613, 623 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "PMID-7585505_T1" } ] }, { "id": "PMID-7585505_E4", "type": "Gene_expression", "trigger": { "text": [ "expression" ], "offsets": [ [ 613, 623 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "PMID-7585505_T4" } ] }, { "id": "PMID-7585505_E5", "type": "Positive_regulation", "trigger": { "text": [ "up-regulated" ], "offsets": [ [ 686, 698 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "PMID-7585505_E1" } ] }, { "id": "PMID-7585505_E6", "type": "Positive_regulation", "trigger": { "text": [ "up-regulated" ], "offsets": [ [ 686, 698 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "PMID-7585505_E3" } ] }, { "id": "PMID-7585505_E7", "type": "Positive_regulation", "trigger": { "text": [ "up-regulated" ], "offsets": [ [ 686, 698 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "PMID-7585505_E4" } ] }, { "id": "PMID-7585505_E8", "type": "Positive_regulation", "trigger": { "text": [ "up-regulated" ], "offsets": [ [ 686, 698 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "PMID-7585505_E2" } ] }, { "id": "PMID-7585505_E9", "type": "Positive_regulation", "trigger": { "text": [ "results" ], "offsets": [ [ 1036, 1043 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "PMID-7585505_E16" } ] }, { "id": "PMID-7585505_E10", "type": "Positive_regulation", "trigger": { "text": [ "results" ], "offsets": [ [ 1036, 1043 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "PMID-7585505_E15" } ] }, { "id": "PMID-7585505_E11", "type": "Positive_regulation", "trigger": { "text": [ "results" ], "offsets": [ [ 1036, 1043 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "PMID-7585505_E13" } ] }, { "id": "PMID-7585505_E12", "type": "Positive_regulation", "trigger": { "text": [ "results" ], "offsets": [ [ 1036, 1043 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "PMID-7585505_E14" } ] }, { "id": "PMID-7585505_E13", "type": "Gene_expression", "trigger": { "text": [ "expression" ], "offsets": [ [ 1057, 1067 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "PMID-7585505_T4" } ] }, { "id": "PMID-7585505_E14", "type": "Gene_expression", "trigger": { "text": [ "expression" ], "offsets": [ [ 1057, 1067 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "PMID-7585505_T1" } ] }, { "id": "PMID-7585505_E15", "type": "Gene_expression", "trigger": { "text": [ "expression" ], "offsets": [ [ 1057, 1067 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "PMID-7585505_T2" } ] }, { "id": "PMID-7585505_E16", "type": "Gene_expression", "trigger": { "text": [ "expression" ], "offsets": [ [ 1057, 1067 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "PMID-7585505_T3" } ] } ]

[]

[]

[ { "id": "PMID-7589085__text", "type": "abstract", "text": [ "CD30 ligation induces nuclear factor-kappa B activation in human T cell lines. \nCD30 is a recently described member of the tumor necrosis factor/nerve growth factor receptor superfamily. In this report, we show that following incubation of L540 cells (Hodgkin's disease-derived, T cell-like, CD30+ cells) with the agonistic anti-CD30 monoclonal antibodies (mAb) M44 and M67, two nuclear factor (NF)-kappa B DNA binding activities were induced in nuclear extracts, as determined in gel retardation assays. The effect of the mAb towards NF-kappa B activation was rapid, as it occurred within 20 min, and was sustained for up to 6 h. By comparison, an isotype-matched antibody had no effect on NF-kappa B activation. Moreover, in human T helper (Th) clones functionally characterized as being of the type 0, type 1 and type 2 (28%, < 1% und 93% CD30+, respectively), the extent of CD30-mediated NF-kappa B activation correlated with the proportion of CD30+ cells. In all cell lines investigated, the NF-kappa B complexes induced following CD30 engagement were shown to contain p50 NF-kappa B1, p65 RelA, and possibly other transcription factors. Collectively, our results demonstrate that nuclear translocation and activation of NF-kappa B rank among the short-term cellular responses elicited following CD30 ligation. " ], "offsets": [ [ 0, 1316 ] ] } ]

[ { "id": "PMID-7589085_T1", "type": "Protein", "text": [ "CD30" ], "offsets": [ [ 0, 4 ] ], "normalized": [] }, { "id": "PMID-7589085_T2", "type": "Protein", "text": [ "CD30" ], "offsets": [ [ 80, 84 ] ], "normalized": [] }, { "id": "PMID-7589085_T3", "type": "Protein", "text": [ "CD30" ], "offsets": [ [ 292, 296 ] ], "normalized": [] }, { "id": "PMID-7589085_T4", "type": "Protein", "text": [ "CD30" ], "offsets": [ [ 329, 333 ] ], "normalized": [] }, { "id": "PMID-7589085_T5", "type": "Protein", "text": [ "CD30" ], "offsets": [ [ 878, 882 ] ], "normalized": [] }, { "id": "PMID-7589085_T6", "type": "Protein", "text": [ "CD30" ], "offsets": [ [ 948, 952 ] ], "normalized": [] }, { "id": "PMID-7589085_T7", "type": "Protein", "text": [ "CD30" ], "offsets": [ [ 1036, 1040 ] ], "normalized": [] }, { "id": "PMID-7589085_T8", "type": "Protein", "text": [ "p50 NF-kappa B1" ], "offsets": [ [ 1074, 1089 ] ], "normalized": [] }, { "id": "PMID-7589085_T9", "type": "Protein", "text": [ "p65 RelA" ], "offsets": [ [ 1091, 1099 ] ], "normalized": [] }, { "id": "PMID-7589085_T10", "type": "Protein", "text": [ "CD30" ], "offsets": [ [ 1301, 1305 ] ], "normalized": [] } ]

[ { "id": "PMID-7589085_E1", "type": "Binding", "trigger": { "text": [ "ligation" ], "offsets": [ [ 5, 13 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "PMID-7589085_T1" } ] }, { "id": "PMID-7589085_E2", "type": "Binding", "trigger": { "text": [ "engagement" ], "offsets": [ [ 1041, 1051 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "PMID-7589085_T7" } ] }, { "id": "PMID-7589085_E3", "type": "Binding", "trigger": { "text": [ "ligation" ], "offsets": [ [ 1306, 1314 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "PMID-7589085_T10" } ] } ]

[]

[]

[ { "id": "PMID-7590249__text", "type": "abstract", "text": [ "Constitutive NF-kappa B activation, enhanced granulopoiesis, and neonatal lethality in I kappa B alpha-deficient mice. \nTranscription factors belonging to the NF-kappa B family are controlled by inhibitory I kappa B proteins, mainly I kappa B alpha and I kappa B beta. Apparently normal at birth, I kappa B alpha-/- mice exhibit severe runting, skin defects, and extensive granulopoiesis postnatally, typically dying by 8 days. Hematopoietic tissues from these mice display elevated levels of both nuclear NF-kappa B and mRNAs of some, but not all, genes thought to be regulated by NF-kappa B. NF-kappa B elevation results in these phenotypic abnormalities because mice lacking both I kappa B alpha and the p50 subunit of NF-kappa B show a dramatically delayed onset of abnormalities. In contrast to hematopoietic cells, I kappa B alpha-/- embryonic fibroblasts show minimal constitutive NF-kappa B, as well as normal signal-dependent NF-kappa B activation that is concomitant with I kappa B beta degradation. Our results indicate that I kappa b beta, but not I kappa B alpha, is required for the signal-dependent activation of NF-kappa B in fibroblasts. However, I kappa B alpha is required for the postinduction repression of NF-kappa B in fibroblasts. These results define distinct roles for the two forms of I kappa B and demonstrate the necessity for stringent control of NF-kappa B. " ], "offsets": [ [ 0, 1389 ] ] } ]

[ { "id": "PMID-7590249_T1", "type": "Protein", "text": [ "I kappa B alpha" ], "offsets": [ [ 87, 102 ] ], "normalized": [] }, { "id": "PMID-7590249_T2", "type": "Protein", "text": [ "I kappa B alpha" ], "offsets": [ [ 233, 248 ] ], "normalized": [] }, { "id": "PMID-7590249_T3", "type": "Protein", "text": [ "I kappa B beta" ], "offsets": [ [ 253, 267 ] ], "normalized": [] }, { "id": "PMID-7590249_T4", "type": "Protein", "text": [ "I kappa B alpha" ], "offsets": [ [ 297, 312 ] ], "normalized": [] }, { "id": "PMID-7590249_T5", "type": "Protein", "text": [ "I kappa B alpha" ], "offsets": [ [ 683, 698 ] ], "normalized": [] }, { "id": "PMID-7590249_T6", "type": "Protein", "text": [ "p50" ], "offsets": [ [ 707, 710 ] ], "normalized": [] }, { "id": "PMID-7590249_T7", "type": "Protein", "text": [ "I kappa B alpha" ], "offsets": [ [ 821, 836 ] ], "normalized": [] }, { "id": "PMID-7590249_T8", "type": "Protein", "text": [ "I kappa B beta" ], "offsets": [ [ 982, 996 ] ], "normalized": [] }, { "id": "PMID-7590249_T9", "type": "Protein", "text": [ "I kappa b beta" ], "offsets": [ [ 1036, 1050 ] ], "normalized": [] }, { "id": "PMID-7590249_T10", "type": "Protein", "text": [ "I kappa B alpha" ], "offsets": [ [ 1060, 1075 ] ], "normalized": [] }, { "id": "PMID-7590249_T11", "type": "Protein", "text": [ "I kappa B alpha" ], "offsets": [ [ 1164, 1179 ] ], "normalized": [] } ]

[ { "id": "PMID-7590249_E1", "type": "Gene_expression", "trigger": { "text": [ "deficient" ], "offsets": [ [ 103, 112 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "PMID-7590249_T1" } ] }, { "id": "PMID-7590249_E2", "type": "Negative_regulation", "trigger": { "text": [ "lacking" ], "offsets": [ [ 670, 677 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "PMID-7590249_T5" } ] }, { "id": "PMID-7590249_E3", "type": "Negative_regulation", "trigger": { "text": [ "lacking" ], "offsets": [ [ 670, 677 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "PMID-7590249_T6" } ] }, { "id": "PMID-7590249_E4", "type": "Protein_catabolism", "trigger": { "text": [ "degradation" ], "offsets": [ [ 997, 1008 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "PMID-7590249_T8" } ] } ]

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[ { "id": "PMID-7590666__text", "type": "abstract", "text": [ "Vitamin E therapy of acute CCl4-induced hepatic injury in mice is associated with inhibition of nuclear factor kappa B binding. \nOxidative stress, with reactive oxygen intermediate formation, may represent a common mechanism by which liver injury is induced by diverse etiologies. Oxidative stress enhances nuclear factor kappa B (NF-kappa B) activity, and NF-kappa B activity has been shown to enhance the expression of cytotoxic cytokines. Acute hepatic injury caused by reactive oxygen intermediate production was induced by an intraperitoneal injection of CCl4 in mice. This injury was significantly inhibited by intravenous pretreatment of the mice with a water-soluble emulsion of alpha-tocopherol. Alpha-tocopherol treatment of the mice given the CCl4 also reduced the NF-kappa B binding to levels approaching those found in normal mice. In vitro treatment of a monocyte/macrophage cell line with CCl4 led to enhanced NF-kappa B binding and an increase in tumor necrosis factor-alpha (TNF-alpha) messenger RNA levels. Liver specimens taken from patients with acute fulminant hepatitis had markedly increased NF-kappa B binding activity in comparison with the binding of normal livers. These data demonstrate that abolishing acute hepatic injury with alpha-tocopherol, a free radical scavenger, also eliminated increased NF-kappa B binding. It is tempting to speculate that enhanced NF-kappa B expression caused by free radical production/oxidative stress may modulate liver injury, perhaps through an effect on cytotoxic cytokine synthesis. " ], "offsets": [ [ 0, 1548 ] ] } ]

[ { "id": "PMID-7590666_T1", "type": "Protein", "text": [ "tumor necrosis factor-alpha" ], "offsets": [ [ 963, 990 ] ], "normalized": [] }, { "id": "PMID-7590666_T2", "type": "Protein", "text": [ "TNF-alpha" ], "offsets": [ [ 992, 1001 ] ], "normalized": [] } ]

[ { "id": "PMID-7590666_E1", "type": "Positive_regulation", "trigger": { "text": [ "increase" ], "offsets": [ [ 951, 959 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "PMID-7590666_T1" } ] } ]

[ { "id": "PMID-7590666_1", "entity_ids": [ "PMID-7590666_T1", "PMID-7590666_T2" ] } ]

[]

[ { "id": "PMID-7594456__text", "type": "abstract", "text": [ "Activation of the signal transducer and transcription (STAT) signaling pathway in a primary T cell response. Critical role for IL-6. \nThe T cell activation is initiated by interaction of specific Ags with TCR, followed by activation of intracellular biochemical events leading to activation of several genes. The activation of signal transducer and activator of transcription (STAT) proteins in a primary TCR-mediated activation of T cells have been explored. In purified human peripheral blood T cells, nuclear STAT proteins were activated approximately 3 h after activation by cross-linked anti-CD3 Abs. These STAT proteins were detected by using the IFN-gamma-activated sequence (GAS) and related oligonucleotides as probes in electrophoretic mobility shift assay. Analysis of the nuclear extracts with anti-STAT Abs indicated that they contained STAT-3 and additional proteins crossreactive with the STAT family. The induction of STAT activity was inhibited completely by pretreatment with either cycloheximide or cyclosporin A, thus indicating that the induction was due to a secondary factor produced by the activated T cells. As neutralizing anti-IL-6 Abs effectively down-regulated the early induction of STAT proteins and as exogenously added IL-6 rapidly activated DNA binding similar to TCR-mediated bindings, it can be concluded that IL-6 is the factor responsible for the activation of STAT proteins in a primary T cell response. " ], "offsets": [ [ 0, 1443 ] ] } ]

[ { "id": "PMID-7594456_T1", "type": "Protein", "text": [ "IL-6" ], "offsets": [ [ 127, 131 ] ], "normalized": [] }, { "id": "PMID-7594456_T2", "type": "Protein", "text": [ "Ags" ], "offsets": [ [ 196, 199 ] ], "normalized": [] }, { "id": "PMID-7594456_T3", "type": "Protein", "text": [ "CD3" ], "offsets": [ [ 597, 600 ] ], "normalized": [] }, { "id": "PMID-7594456_T4", "type": "Protein", "text": [ "STAT-3" ], "offsets": [ [ 850, 856 ] ], "normalized": [] }, { "id": "PMID-7594456_T5", "type": "Protein", "text": [ "IL-6" ], "offsets": [ [ 1154, 1158 ] ], "normalized": [] }, { "id": "PMID-7594456_T6", "type": "Protein", "text": [ "IL-6" ], "offsets": [ [ 1252, 1256 ] ], "normalized": [] }, { "id": "PMID-7594456_T7", "type": "Protein", "text": [ "IL-6" ], "offsets": [ [ 1346, 1350 ] ], "normalized": [] } ]

[ { "id": "PMID-7594456_E1", "type": "Binding", "trigger": { "text": [ "interaction" ], "offsets": [ [ 172, 183 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "PMID-7594456_T2" } ] }, { "id": "PMID-7594456_E2", "type": "Regulation", "trigger": { "text": [ "followed" ], "offsets": [ [ 210, 218 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "PMID-7594456_E1" } ] }, { "id": "PMID-7594456_E3", "type": "Positive_regulation", "trigger": { "text": [ "activated" ], "offsets": [ [ 1265, 1274 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "PMID-7594456_T6" } ] } ]

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[ { "id": "PMID-7594468__text", "type": "abstract", "text": [ "Regulation of IkB alpha phosphorylation by PKC- and Ca(2+)-dependent signal transduction pathways. \nThe Ca(2+)-dependent phosphatase calcineurin, a target of FK506 and CsA, synergizes with PKC-induced activation of nuclear factor (NF)-kappa B in T cell lines. We have investigated whether this synergy is present in other cell types and the mechanism(s) by which these two pathways lead to NF-kappa B activation. While this synergy is present in other cell types, in the monocytic cell line U937 calcineurin is also sufficient to activate NF-kappa B. Having previously shown that Ca(2+)- and PKC-dependent pathways synergize by accelerating the degradation of IkB alpha, we focused on the regulation of IkB alpha phosphorylation. While PKC-dependent pathways sequentially result in the phosphorylation and in an incomplete degradation of IkB alpha in T cell lines, co-activation of Ca(2+)-dependent pathways accelerates the rate of IkB alpha phosphorylation and results in its complete degradation. Activation of Ca(2+)-dependent pathways alone do not result in the phosphorylation and/or degradation of IkB alpha in Jurkat T or in U937 cells. Treatment of T cells with the selective PKC inhibitor GF109203X abrogates the PMA-induced IkB alpha phosphorylation/degradation irrespective of activation of Ca(2+)-dependent pathways, but not the phosphorylation and degradation of IkB alpha induced by TNF-alpha, a PKC-independent stimulus. Contrary to the interaction with PKC, Ca(2+)-dependent pathways synergize with TNF-alpha not at the level of IkB alpha phosphorylation, but at the level of its degradation. These results indicate that Ca(2+)-dependent pathways, including the phosphatase calcineurin, participate in the regulation of NF-kappa B in a cell specific fashion and synergize with PKC-dependent and -independent pathways at the level of IkB alpha phosphorylation and degradation. " ], "offsets": [ [ 0, 1892 ] ] } ]

[ { "id": "PMID-7594468_T1", "type": "Protein", "text": [ "IkB alpha" ], "offsets": [ [ 14, 23 ] ], "normalized": [] }, { "id": "PMID-7594468_T2", "type": "Protein", "text": [ "IkB alpha" ], "offsets": [ [ 660, 669 ] ], "normalized": [] }, { "id": "PMID-7594468_T3", "type": "Protein", "text": [ "IkB alpha" ], "offsets": [ [ 703, 712 ] ], "normalized": [] }, { "id": "PMID-7594468_T4", "type": "Protein", "text": [ "IkB alpha" ], "offsets": [ [ 838, 847 ] ], "normalized": [] }, { "id": "PMID-7594468_T5", "type": "Protein", "text": [ "IkB alpha" ], "offsets": [ [ 932, 941 ] ], "normalized": [] }, { "id": "PMID-7594468_T6", "type": "Protein", "text": [ "IkB alpha" ], "offsets": [ [ 1104, 1113 ] ], "normalized": [] }, { "id": "PMID-7594468_T7", "type": "Protein", "text": [ "IkB alpha" ], "offsets": [ [ 1234, 1243 ] ], "normalized": [] }, { "id": "PMID-7594468_T8", "type": "Protein", "text": [ "IkB alpha" ], "offsets": [ [ 1376, 1385 ] ], "normalized": [] }, { "id": "PMID-7594468_T9", "type": "Protein", "text": [ "TNF-alpha" ], "offsets": [ [ 1397, 1406 ] ], "normalized": [] }, { "id": "PMID-7594468_T10", "type": "Protein", "text": [ "TNF-alpha" ], "offsets": [ [ 1515, 1524 ] ], "normalized": [] }, { "id": "PMID-7594468_T11", "type": "Protein", "text": [ "IkB alpha" ], "offsets": [ [ 1545, 1554 ] ], "normalized": [] }, { "id": "PMID-7594468_T12", "type": "Protein", "text": [ "IkB alpha" ], "offsets": [ [ 1849, 1858 ] ], "normalized": [] } ]

[ { "id": "PMID-7594468_E1", "type": "Regulation", "trigger": { "text": [ "Regulation" ], "offsets": [ [ 0, 10 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "PMID-7594468_E2" } ] }, { "id": "PMID-7594468_E2", "type": "Phosphorylation", "trigger": { "text": [ "phosphorylation" ], "offsets": [ [ 24, 39 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "PMID-7594468_T1" } ] }, { "id": "PMID-7594468_E3", "type": "Positive_regulation", "trigger": { "text": [ "pathways synergize" ], "offsets": [ [ 606, 624 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "PMID-7594468_E4" } ] }, { "id": "PMID-7594468_E4", "type": "Positive_regulation", "trigger": { "text": [ "accelerating" ], "offsets": [ [ 628, 640 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "PMID-7594468_E5" } ] }, { "id": "PMID-7594468_E5", "type": "Protein_catabolism", "trigger": { "text": [ "degradation" ], "offsets": [ [ 645, 656 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "PMID-7594468_T2" } ] }, { "id": "PMID-7594468_E6", "type": "Regulation", "trigger": { "text": [ "regulation" ], "offsets": [ [ 689, 699 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "PMID-7594468_E7" } ] }, { "id": "PMID-7594468_E7", "type": "Phosphorylation", "trigger": { "text": [ "phosphorylation" ], "offsets": [ [ 713, 728 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "PMID-7594468_T3" } ] }, { "id": "PMID-7594468_E8", "type": "Positive_regulation", "trigger": { "text": [ "result" ], "offsets": [ [ 772, 778 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "PMID-7594468_E11" } ] }, { "id": "PMID-7594468_E9", "type": "Positive_regulation", "trigger": { "text": [ "result" ], "offsets": [ [ 772, 778 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "PMID-7594468_E10" } ] }, { "id": "PMID-7594468_E10", "type": "Phosphorylation", "trigger": { "text": [ "phosphorylation" ], "offsets": [ [ 786, 801 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "PMID-7594468_T4" } ] }, { "id": "PMID-7594468_E11", "type": "Protein_catabolism", "trigger": { "text": [ "degradation" ], "offsets": [ [ 823, 834 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "PMID-7594468_T4" } ] }, { "id": "PMID-7594468_E12", "type": "Positive_regulation", "trigger": { "text": [ "accelerates" ], "offsets": [ [ 908, 919 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "PMID-7594468_E13" } ] }, { "id": "PMID-7594468_E13", "type": "Phosphorylation", "trigger": { "text": [ "phosphorylation" ], "offsets": [ [ 942, 957 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "PMID-7594468_T5" } ] }, { "id": "PMID-7594468_E14", "type": "Negative_regulation", "trigger": { "text": [ "results" ], "offsets": [ [ 962, 969 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "PMID-7594468_E15" } ] }, { "id": "PMID-7594468_E15", "type": "Protein_catabolism", "trigger": { "text": [ "complete degradation" ], "offsets": [ [ 977, 997 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "PMID-7594468_T5" } ] }, { "id": "PMID-7594468_E16", "type": "Positive_regulation", "trigger": { "text": [ "result" ], "offsets": [ [ 1052, 1058 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "PMID-7594468_E19" } ] }, { "id": "PMID-7594468_E17", "type": "Positive_regulation", "trigger": { "text": [ "result" ], "offsets": [ [ 1052, 1058 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "PMID-7594468_E18" } ] }, { "id": "PMID-7594468_E18", "type": "Phosphorylation", "trigger": { "text": [ "phosphorylation" ], "offsets": [ [ 1066, 1081 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "PMID-7594468_T6" } ] }, { "id": "PMID-7594468_E19", "type": "Protein_catabolism", "trigger": { "text": [ "degradation" ], "offsets": [ [ 1089, 1100 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "PMID-7594468_T6" } ] }, { "id": "PMID-7594468_E20", "type": "Negative_regulation", "trigger": { "text": [ "abrogates" ], "offsets": [ [ 1208, 1217 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "PMID-7594468_E30" } ] }, { "id": "PMID-7594468_E21", "type": "Negative_regulation", "trigger": { "text": [ "abrogates" ], "offsets": [ [ 1208, 1217 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "PMID-7594468_E31" } ] }, { "id": "PMID-7594468_E22", "type": "Negative_regulation", "trigger": { "text": [ "abrogates" ], "offsets": [ [ 1208, 1217 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "PMID-7594468_E24" } ] }, { "id": "PMID-7594468_E23", "type": "Negative_regulation", "trigger": { "text": [ "abrogates" ], "offsets": [ [ 1208, 1217 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "PMID-7594468_E25" } ] }, { "id": "PMID-7594468_E24", "type": "Positive_regulation", "trigger": { "text": [ "induced" ], "offsets": [ [ 1226, 1233 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "PMID-7594468_E27" } ] }, { "id": "PMID-7594468_E25", "type": "Positive_regulation", "trigger": { "text": [ "induced" ], "offsets": [ [ 1226, 1233 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "PMID-7594468_E26" } ] }, { "id": "PMID-7594468_E26", "type": "Phosphorylation", "trigger": { "text": [ "phosphorylation" ], "offsets": [ [ 1244, 1259 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "PMID-7594468_T7" } ] }, { "id": "PMID-7594468_E27", "type": "Protein_catabolism", "trigger": { "text": [ "degradation" ], "offsets": [ [ 1260, 1271 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "PMID-7594468_T7" } ] }, { "id": "PMID-7594468_E28", "type": "Phosphorylation", "trigger": { "text": [ "phosphorylation" ], "offsets": [ [ 1341, 1356 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "PMID-7594468_T8" } ] }, { "id": "PMID-7594468_E29", "type": "Protein_catabolism", "trigger": { "text": [ "degradation" ], "offsets": [ [ 1361, 1372 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "PMID-7594468_T8" } ] }, { "id": "PMID-7594468_E30", "type": "Positive_regulation", "trigger": { "text": [ "induced" ], "offsets": [ [ 1386, 1393 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "PMID-7594468_E28" }, { "role": "Cause", "ref_id": "PMID-7594468_T9" } ] }, { "id": "PMID-7594468_E31", "type": "Positive_regulation", "trigger": { "text": [ "induced" ], "offsets": [ [ 1386, 1393 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "PMID-7594468_E29" }, { "role": "Cause", "ref_id": "PMID-7594468_T9" } ] }, { "id": "PMID-7594468_E32", "type": "Positive_regulation", "trigger": { "text": [ "synergize" ], "offsets": [ [ 1500, 1509 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "PMID-7594468_E34" }, { "role": "Cause", "ref_id": "PMID-7594468_T10" } ] }, { "id": "PMID-7594468_E33", "type": "Positive_regulation", "trigger": { "text": [ "synergize" ], "offsets": [ [ 1500, 1509 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "PMID-7594468_E35" }, { "role": "Cause", "ref_id": "PMID-7594468_T10" } ] }, { "id": "PMID-7594468_E34", "type": "Phosphorylation", "trigger": { "text": [ "phosphorylation" ], "offsets": [ [ 1555, 1570 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "PMID-7594468_T11" } ] }, { "id": "PMID-7594468_E35", "type": "Protein_catabolism", "trigger": { "text": [ "degradation" ], "offsets": [ [ 1596, 1607 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "PMID-7594468_T11" } ] }, { "id": "PMID-7594468_E36", "type": "Positive_regulation", "trigger": { "text": [ "synergize" ], "offsets": [ [ 1778, 1787 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "PMID-7594468_E38" } ] }, { "id": "PMID-7594468_E37", "type": "Positive_regulation", "trigger": { "text": [ "synergize" ], "offsets": [ [ 1778, 1787 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "PMID-7594468_E39" } ] }, { "id": "PMID-7594468_E38", "type": "Phosphorylation", "trigger": { "text": [ "phosphorylation" ], "offsets": [ [ 1859, 1874 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "PMID-7594468_T12" } ] }, { "id": "PMID-7594468_E39", "type": "Protein_catabolism", "trigger": { "text": [ "degradation" ], "offsets": [ [ 1879, 1890 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "PMID-7594468_T12" } ] } ]

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[]

[ { "id": "PMID-7594489__text", "type": "abstract", "text": [ "Triggering of complement receptors CR1 (CD35) and CR3 (CD11b/CD18) induces nuclear translocation of NF-kappa B (p50/p65) in human monocytes and enhances viral replication in HIV-infected monocytic cells. \nMonocyte/macrophages may harbor HIV in a nonproductive fashion for prolonged periods of time. Viral gene expression may be reactivated by stimulation of the cells with LPS or cytokines such as TNF-alpha in vitro. The effect of LPS and TNF-alpha is mediated by their ability to induce nuclear translocation of the DNA-binding heterodimer NF-kappa B (p50/p65), which binds to a specific sequence in the HIV-long terminal repeat. The present study demonstrates that triggering of complement receptors CR1 (CD35) and CR3 (CD11b/CD18) enhances viral replication in HIV-infected human monocytic cells. Monocytic cell lines and normal peripheral blood monocytes were infected with HIV-1 in vitro and cultured in the presence or absence of F(ab')2 fragments of monoclonal anti-CR1 or anti-CR3 Abs or with C3 fragments. Stimulation of CR1 or CR3 induces a two- to fourfold increase in the amount of cell-associated and released p24 Ag in cell cultures that was equivalent to that observed in control cultures triggered with LPS. We further observed that stimulation of CR1 or CR3 induces the nuclear translocation of NF-kappa B p50/p65 in infected cells. Translocation of NF-kappa B p50/p65 was also observed following stimulation of CR1 or CR3 of uninfected peripheral blood monocytes from HIV-seronegative donors. The amount of protein translocated was similar to that observed when cells were stimulated with rhTNF-alpha. TNF-alpha did not mediate the translocation of NF-kappa B p50/p65 induced by triggering of complement receptors. Taken together, these observations suggest that HIV gene expression may be activated in infected monocytes through interaction of the cells with complement-opsonized particles and that enhanced viral replication is associated with C3 receptor-mediated nuclear translocation of the NF-kappa B complex. " ], "offsets": [ [ 0, 2035 ] ] } ]

[ { "id": "PMID-7594489_T1", "type": "Protein", "text": [ "CR1" ], "offsets": [ [ 35, 38 ] ], "normalized": [] }, { "id": "PMID-7594489_T2", "type": "Protein", "text": [ "CD35" ], "offsets": [ [ 40, 44 ] ], "normalized": [] }, { "id": "PMID-7594489_T3", "type": "Protein", "text": [ "CD11b" ], "offsets": [ [ 55, 60 ] ], "normalized": [] }, { "id": "PMID-7594489_T4", "type": "Protein", "text": [ "CD18" ], "offsets": [ [ 61, 65 ] ], "normalized": [] }, { "id": "PMID-7594489_T5", "type": "Protein", "text": [ "p50" ], "offsets": [ [ 112, 115 ] ], "normalized": [] }, { "id": "PMID-7594489_T6", "type": "Protein", "text": [ "p65" ], "offsets": [ [ 116, 119 ] ], "normalized": [] }, { "id": "PMID-7594489_T7", "type": "Protein", "text": [ "TNF-alpha" ], "offsets": [ [ 398, 407 ] ], "normalized": [] }, { "id": "PMID-7594489_T8", "type": "Protein", "text": [ "TNF-alpha" ], "offsets": [ [ 440, 449 ] ], "normalized": [] }, { "id": "PMID-7594489_T9", "type": "Protein", "text": [ "p50" ], "offsets": [ [ 554, 557 ] ], "normalized": [] }, { "id": "PMID-7594489_T10", "type": "Protein", "text": [ "p65" ], "offsets": [ [ 558, 561 ] ], "normalized": [] }, { "id": "PMID-7594489_T11", "type": "Protein", "text": [ "CR1" ], "offsets": [ [ 703, 706 ] ], "normalized": [] }, { "id": "PMID-7594489_T12", "type": "Protein", "text": [ "CD35" ], "offsets": [ [ 708, 712 ] ], "normalized": [] }, { "id": "PMID-7594489_T13", "type": "Protein", "text": [ "CD11b" ], "offsets": [ [ 723, 728 ] ], "normalized": [] }, { "id": "PMID-7594489_T14", "type": "Protein", "text": [ "CD18" ], "offsets": [ [ 729, 733 ] ], "normalized": [] }, { "id": "PMID-7594489_T15", "type": "Protein", "text": [ "CR1" ], "offsets": [ [ 974, 977 ] ], "normalized": [] }, { "id": "PMID-7594489_T16", "type": "Protein", "text": [ "CR1" ], "offsets": [ [ 1031, 1034 ] ], "normalized": [] }, { "id": "PMID-7594489_T17", "type": "Protein", "text": [ "p24" ], "offsets": [ [ 1124, 1127 ] ], "normalized": [] }, { "id": "PMID-7594489_T18", "type": "Protein", "text": [ "CR1" ], "offsets": [ [ 1265, 1268 ] ], "normalized": [] }, { "id": "PMID-7594489_T19", "type": "Protein", "text": [ "p50" ], "offsets": [ [ 1324, 1327 ] ], "normalized": [] }, { "id": "PMID-7594489_T20", "type": "Protein", "text": [ "p65" ], "offsets": [ [ 1328, 1331 ] ], "normalized": [] }, { "id": "PMID-7594489_T21", "type": "Protein", "text": [ "p50" ], "offsets": [ [ 1379, 1382 ] ], "normalized": [] }, { "id": "PMID-7594489_T22", "type": "Protein", "text": [ "p65" ], "offsets": [ [ 1383, 1386 ] ], "normalized": [] }, { "id": "PMID-7594489_T23", "type": "Protein", "text": [ "CR1" ], "offsets": [ [ 1430, 1433 ] ], "normalized": [] }, { "id": "PMID-7594489_T24", "type": "Protein", "text": [ "TNF-alpha" ], "offsets": [ [ 1621, 1630 ] ], "normalized": [] }, { "id": "PMID-7594489_T25", "type": "Protein", "text": [ "p50" ], "offsets": [ [ 1679, 1682 ] ], "normalized": [] }, { "id": "PMID-7594489_T26", "type": "Protein", "text": [ "p65" ], "offsets": [ [ 1683, 1686 ] ], "normalized": [] }, { "id": "PMID-7594489_T29", "type": "Entity", "text": [ "nuclear" ], "offsets": [ [ 75, 82 ] ], "normalized": [] }, { "id": "PMID-7594489_T32", "type": "Entity", "text": [ "nuclear" ], "offsets": [ [ 489, 496 ] ], "normalized": [] }, { "id": "PMID-7594489_T40", "type": "Entity", "text": [ "nuclear" ], "offsets": [ [ 1288, 1295 ] ], "normalized": [] } ]

[ { "id": "PMID-7594489_E1", "type": "Positive_regulation", "trigger": { "text": [ "Triggering" ], "offsets": [ [ 0, 10 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "PMID-7594489_T2" } ] }, { "id": "PMID-7594489_E2", "type": "Positive_regulation", "trigger": { "text": [ "Triggering" ], "offsets": [ [ 0, 10 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "PMID-7594489_T3" } ] }, { "id": "PMID-7594489_E3", "type": "Positive_regulation", "trigger": { "text": [ "Triggering" ], "offsets": [ [ 0, 10 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "PMID-7594489_T4" } ] }, { "id": "PMID-7594489_E4", "type": "Positive_regulation", "trigger": { "text": [ "induces" ], "offsets": [ [ 67, 74 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "PMID-7594489_E10" }, { "role": "Cause", "ref_id": "PMID-7594489_E2" } ] }, { "id": "PMID-7594489_E5", "type": "Positive_regulation", "trigger": { "text": [ "induces" ], "offsets": [ [ 67, 74 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "PMID-7594489_E10" }, { "role": "Cause", "ref_id": "PMID-7594489_E3" } ] }, { "id": "PMID-7594489_E6", "type": "Positive_regulation", "trigger": { "text": [ "induces" ], "offsets": [ [ 67, 74 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "PMID-7594489_E11" }, { "role": "Cause", "ref_id": "PMID-7594489_E1" } ] }, { "id": "PMID-7594489_E7", "type": "Positive_regulation", "trigger": { "text": [ "induces" ], "offsets": [ [ 67, 74 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "PMID-7594489_E10" }, { "role": "Cause", "ref_id": "PMID-7594489_E1" } ] }, { "id": "PMID-7594489_E8", "type": "Positive_regulation", "trigger": { "text": [ "induces" ], "offsets": [ [ 67, 74 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "PMID-7594489_E11" }, { "role": "Cause", "ref_id": "PMID-7594489_E3" } ] }, { "id": "PMID-7594489_E9", "type": "Positive_regulation", "trigger": { "text": [ "induces" ], "offsets": [ [ 67, 74 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "PMID-7594489_E11" }, { "role": "Cause", "ref_id": "PMID-7594489_E2" } ] }, { "id": "PMID-7594489_E10", "type": "Localization", "trigger": { "text": [ "translocation" ], "offsets": [ [ 83, 96 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "PMID-7594489_T6" }, { "role": "ToLoc", "ref_id": "PMID-7594489_T29" } ] }, { "id": "PMID-7594489_E11", "type": "Localization", "trigger": { "text": [ "translocation" ], "offsets": [ [ 83, 96 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "PMID-7594489_T5" }, { "role": "ToLoc", "ref_id": "PMID-7594489_T29" } ] }, { "id": "PMID-7594489_E12", "type": "Positive_regulation", "trigger": { "text": [ "induce" ], "offsets": [ [ 482, 488 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "PMID-7594489_E16" } ] }, { "id": "PMID-7594489_E13", "type": "Positive_regulation", "trigger": { "text": [ "induce" ], "offsets": [ [ 482, 488 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "PMID-7594489_E17" } ] }, { "id": "PMID-7594489_E14", "type": "Positive_regulation", "trigger": { "text": [ "induce" ], "offsets": [ [ 482, 488 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "PMID-7594489_E17" }, { "role": "Cause", "ref_id": "PMID-7594489_T8" } ] }, { "id": "PMID-7594489_E15", "type": "Positive_regulation", "trigger": { "text": [ "induce" ], "offsets": [ [ 482, 488 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "PMID-7594489_E16" }, { "role": "Cause", "ref_id": "PMID-7594489_T8" } ] }, { "id": "PMID-7594489_E16", "type": "Localization", "trigger": { "text": [ "translocation" ], "offsets": [ [ 497, 510 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "PMID-7594489_T9" }, { "role": "ToLoc", "ref_id": "PMID-7594489_T32" } ] }, { "id": "PMID-7594489_E17", "type": "Localization", "trigger": { "text": [ "translocation" ], "offsets": [ [ 497, 510 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "PMID-7594489_T10" }, { "role": "ToLoc", "ref_id": "PMID-7594489_T32" } ] }, { "id": "PMID-7594489_E18", "type": "Binding", "trigger": { "text": [ "binds" ], "offsets": [ [ 570, 575 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "PMID-7594489_T10" } ] }, { "id": "PMID-7594489_E19", "type": "Binding", "trigger": { "text": [ "binds" ], "offsets": [ [ 570, 575 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "PMID-7594489_T9" } ] }, { "id": "PMID-7594489_E20", "type": "Positive_regulation", "trigger": { "text": [ "triggering" ], "offsets": [ [ 668, 678 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "PMID-7594489_T12" } ] }, { "id": "PMID-7594489_E21", "type": "Positive_regulation", "trigger": { "text": [ "triggering" ], "offsets": [ [ 668, 678 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "PMID-7594489_T13" } ] }, { "id": "PMID-7594489_E22", "type": "Positive_regulation", "trigger": { "text": [ "triggering" ], "offsets": [ [ 668, 678 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "PMID-7594489_T14" } ] }, { "id": "PMID-7594489_E23", "type": "Positive_regulation", "trigger": { "text": [ "Stimulation" ], "offsets": [ [ 1016, 1027 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "PMID-7594489_T16" } ] }, { "id": "PMID-7594489_E24", "type": "Positive_regulation", "trigger": { "text": [ "increase" ], "offsets": [ [ 1069, 1077 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "PMID-7594489_T17" } ] }, { "id": "PMID-7594489_E25", "type": "Positive_regulation", "trigger": { "text": [ "increase" ], "offsets": [ [ 1069, 1077 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "PMID-7594489_T17" }, { "role": "Cause", "ref_id": "PMID-7594489_E23" } ] }, { "id": "PMID-7594489_E26", "type": "Positive_regulation", "trigger": { "text": [ "stimulation" ], "offsets": [ [ 1250, 1261 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "PMID-7594489_T18" } ] }, { "id": "PMID-7594489_E27", "type": "Positive_regulation", "trigger": { "text": [ "induces" ], "offsets": [ [ 1276, 1283 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "PMID-7594489_E32" } ] }, { "id": "PMID-7594489_E28", "type": "Positive_regulation", "trigger": { "text": [ "induces" ], "offsets": [ [ 1276, 1283 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "PMID-7594489_E31" }, { "role": "Cause", "ref_id": "PMID-7594489_E26" } ] }, { "id": "PMID-7594489_E29", "type": "Positive_regulation", "trigger": { "text": [ "induces" ], "offsets": [ [ 1276, 1283 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "PMID-7594489_E31" } ] }, { "id": "PMID-7594489_E30", "type": "Positive_regulation", "trigger": { "text": [ "induces" ], "offsets": [ [ 1276, 1283 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "PMID-7594489_E32" }, { "role": "Cause", "ref_id": "PMID-7594489_E26" } ] }, { "id": "PMID-7594489_E31", "type": "Localization", "trigger": { "text": [ "translocation" ], "offsets": [ [ 1296, 1309 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "PMID-7594489_T20" }, { "role": "ToLoc", "ref_id": "PMID-7594489_T40" } ] }, { "id": "PMID-7594489_E32", "type": "Localization", "trigger": { "text": [ "translocation" ], "offsets": [ [ 1296, 1309 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "PMID-7594489_T19" }, { "role": "ToLoc", "ref_id": "PMID-7594489_T40" } ] }, { "id": "PMID-7594489_E33", "type": "Localization", "trigger": { "text": [ "Translocation" ], "offsets": [ [ 1351, 1364 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "PMID-7594489_T21" } ] }, { "id": "PMID-7594489_E34", "type": "Localization", "trigger": { "text": [ "Translocation" ], "offsets": [ [ 1351, 1364 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "PMID-7594489_T22" } ] }, { "id": "PMID-7594489_E35", "type": "Positive_regulation", "trigger": { "text": [ "observed" ], "offsets": [ [ 1396, 1404 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "PMID-7594489_E34" }, { "role": "Cause", "ref_id": "PMID-7594489_E39" } ] }, { "id": "PMID-7594489_E36", "type": "Positive_regulation", "trigger": { "text": [ "observed" ], "offsets": [ [ 1396, 1404 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "PMID-7594489_E33" }, { "role": "Cause", "ref_id": "PMID-7594489_E39" } ] }, { "id": "PMID-7594489_E37", "type": "Positive_regulation", "trigger": { "text": [ "observed" ], "offsets": [ [ 1396, 1404 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "PMID-7594489_E33" } ] }, { "id": "PMID-7594489_E38", "type": "Positive_regulation", "trigger": { "text": [ "observed" ], "offsets": [ [ 1396, 1404 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "PMID-7594489_E34" } ] }, { "id": "PMID-7594489_E39", "type": "Positive_regulation", "trigger": { "text": [ "stimulation" ], "offsets": [ [ 1415, 1426 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "PMID-7594489_T23" } ] }, { "id": "PMID-7594489_E40", "type": "Localization", "trigger": { "text": [ "translocated" ], "offsets": [ [ 1534, 1546 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "PMID-7594489_T21" } ] }, { "id": "PMID-7594489_E41", "type": "Localization", "trigger": { "text": [ "translocated" ], "offsets": [ [ 1534, 1546 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "PMID-7594489_T22" } ] }, { "id": "PMID-7594489_E42", "type": "Positive_regulation", "trigger": { "text": [ "observed" ], "offsets": [ [ 1567, 1575 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "PMID-7594489_E40" } ] }, { "id": "PMID-7594489_E43", "type": "Positive_regulation", "trigger": { "text": [ "observed" ], "offsets": [ [ 1567, 1575 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "PMID-7594489_E41" } ] }, { "id": "PMID-7594489_E44", "type": "Positive_regulation", "trigger": { "text": [ "mediate" ], "offsets": [ [ 1639, 1646 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "PMID-7594489_E49" }, { "role": "Cause", "ref_id": "PMID-7594489_T24" } ] }, { "id": "PMID-7594489_E45", "type": "Positive_regulation", "trigger": { "text": [ "mediate" ], "offsets": [ [ 1639, 1646 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "PMID-7594489_E48" }, { "role": "Cause", "ref_id": "PMID-7594489_T24" } ] }, { "id": "PMID-7594489_E46", "type": "Localization", "trigger": { "text": [ "translocation" ], "offsets": [ [ 1651, 1664 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "PMID-7594489_T25" } ] }, { "id": "PMID-7594489_E47", "type": "Localization", "trigger": { "text": [ "translocation" ], "offsets": [ [ 1651, 1664 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "PMID-7594489_T26" } ] }, { "id": "PMID-7594489_E48", "type": "Positive_regulation", "trigger": { "text": [ "induced" ], "offsets": [ [ 1687, 1694 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "PMID-7594489_T25" } ] }, { "id": "PMID-7594489_E49", "type": "Positive_regulation", "trigger": { "text": [ "induced" ], "offsets": [ [ 1687, 1694 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "PMID-7594489_T26" } ] } ]

[ { "id": "PMID-7594489_1", "entity_ids": [ "PMID-7594489_T2", "PMID-7594489_T1" ] }, { "id": "PMID-7594489_2", "entity_ids": [ "PMID-7594489_T12", "PMID-7594489_T11" ] } ]

[]

[ { "id": "PMID-7594540__text", "type": "abstract", "text": [ "Nuclear factor-IL6 activates the human IL-4 promoter in T cells. \nPositive regulatory element I (PRE-I) is a strong enhancer element essential for expression of the human IL-4 gene. To identify transcription factors binding to PRE-I, we screened a cDNA expression library from Jurkat T cells and isolated a cDNA encoding nuclear factor (NF)-IL6 (also known as C/EBP beta). NF-IL6 mRNA was found in human Jurkat T cells and in the mouse Th2 clone D10, but not in Th1 clone 29. rNF-IL6 expressed in bacteria was shown to specifically bind to PRE-I. PRE-I forms multiple DNA-protein complexes with nuclear extracts from Jurkat cells. Some of these complexes were demonstrated to contain NF-IL6 by using anti-C/EBP beta Abs. Overexpression of NF-IL6 enhanced expression of the chloramphenicol acetyl transferase reporter gene linked to the PRE-I-thymidine kinase or the human IL-4 promoter more than 10-fold in Jurkat cells. Promoter deletion studies revealed two additional NF-IL6 binding sites located at positions -44 to -36 (C/EBP proximal) and -87 to -79 (C/EBP medial), respectively. Our results demonstrate that NF-IL6 is involved in transcriptional activation of the human IL-4 promoter in T cells. " ], "offsets": [ [ 0, 1203 ] ] } ]

[ { "id": "PMID-7594540_T1", "type": "Protein", "text": [ "Nuclear factor-IL6" ], "offsets": [ [ 0, 18 ] ], "normalized": [] }, { "id": "PMID-7594540_T2", "type": "Protein", "text": [ "IL-4" ], "offsets": [ [ 39, 43 ] ], "normalized": [] }, { "id": "PMID-7594540_T3", "type": "Protein", "text": [ "IL-4" ], "offsets": [ [ 171, 175 ] ], "normalized": [] }, { "id": "PMID-7594540_T4", "type": "Protein", "text": [ "(NF)-IL6" ], "offsets": [ [ 336, 344 ] ], "normalized": [] }, { "id": "PMID-7594540_T5", "type": "Protein", "text": [ "C/EBP beta" ], "offsets": [ [ 360, 370 ] ], "normalized": [] }, { "id": "PMID-7594540_T6", "type": "Protein", "text": [ "NF-IL6" ], "offsets": [ [ 373, 379 ] ], "normalized": [] }, { "id": "PMID-7594540_T7", "type": "Protein", "text": [ "rNF-IL6" ], "offsets": [ [ 476, 483 ] ], "normalized": [] }, { "id": "PMID-7594540_T8", "type": "Protein", "text": [ "NF-IL6" ], "offsets": [ [ 684, 690 ] ], "normalized": [] }, { "id": "PMID-7594540_T9", "type": "Protein", "text": [ "C/EBP beta" ], "offsets": [ [ 705, 715 ] ], "normalized": [] }, { "id": "PMID-7594540_T10", "type": "Protein", "text": [ "NF-IL6" ], "offsets": [ [ 739, 745 ] ], "normalized": [] }, { "id": "PMID-7594540_T11", "type": "Protein", "text": [ "chloramphenicol acetyl transferase" ], "offsets": [ [ 773, 807 ] ], "normalized": [] }, { "id": "PMID-7594540_T12", "type": "Protein", "text": [ "IL-4" ], "offsets": [ [ 872, 876 ] ], "normalized": [] }, { "id": "PMID-7594540_T13", "type": "Protein", "text": [ "NF-IL6" ], "offsets": [ [ 971, 977 ] ], "normalized": [] }, { "id": "PMID-7594540_T14", "type": "Protein", "text": [ "NF-IL6" ], "offsets": [ [ 1115, 1121 ] ], "normalized": [] }, { "id": "PMID-7594540_T15", "type": "Protein", "text": [ "IL-4" ], "offsets": [ [ 1177, 1181 ] ], "normalized": [] }, { "id": "PMID-7594540_T17", "type": "Entity", "text": [ "promoter" ], "offsets": [ [ 44, 52 ] ], "normalized": [] }, { "id": "PMID-7594540_T30", "type": "Entity", "text": [ "promoter" ], "offsets": [ [ 1182, 1190 ] ], "normalized": [] } ]

[ { "id": "PMID-7594540_E1", "type": "Positive_regulation", "trigger": { "text": [ "activates" ], "offsets": [ [ 19, 28 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "PMID-7594540_T2" }, { "role": "Cause", "ref_id": "PMID-7594540_T1" }, { "role": "Site", "ref_id": "PMID-7594540_T17" } ] }, { "id": "PMID-7594540_E2", "type": "Positive_regulation", "trigger": { "text": [ "essential" ], "offsets": [ [ 133, 142 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "PMID-7594540_E3" } ] }, { "id": "PMID-7594540_E3", "type": "Gene_expression", "trigger": { "text": [ "expression" ], "offsets": [ [ 147, 157 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "PMID-7594540_T3" } ] }, { "id": "PMID-7594540_E4", "type": "Transcription", "trigger": { "text": [ "found" ], "offsets": [ [ 389, 394 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "PMID-7594540_T6" } ] }, { "id": "PMID-7594540_E5", "type": "Gene_expression", "trigger": { "text": [ "expressed" ], "offsets": [ [ 484, 493 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "PMID-7594540_T7" } ] }, { "id": "PMID-7594540_E6", "type": "Binding", "trigger": { "text": [ "bind" ], "offsets": [ [ 532, 536 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "PMID-7594540_T7" } ] }, { "id": "PMID-7594540_E7", "type": "Binding", "trigger": { "text": [ "complexes" ], "offsets": [ [ 645, 654 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "PMID-7594540_T8" } ] }, { "id": "PMID-7594540_E8", "type": "Gene_expression", "trigger": { "text": [ "Overexpression" ], "offsets": [ [ 721, 735 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "PMID-7594540_T10" } ] }, { "id": "PMID-7594540_E9", "type": "Positive_regulation", "trigger": { "text": [ "Overexpression" ], "offsets": [ [ 721, 735 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "PMID-7594540_E8" } ] }, { "id": "PMID-7594540_E10", "type": "Positive_regulation", "trigger": { "text": [ "enhanced" ], "offsets": [ [ 746, 754 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "PMID-7594540_E11" }, { "role": "Cause", "ref_id": "PMID-7594540_E9" } ] }, { "id": "PMID-7594540_E11", "type": "Gene_expression", "trigger": { "text": [ "expression" ], "offsets": [ [ 755, 765 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "PMID-7594540_T11" } ] }, { "id": "PMID-7594540_E12", "type": "Regulation", "trigger": { "text": [ "involved" ], "offsets": [ [ 1125, 1133 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "PMID-7594540_E13" }, { "role": "Cause", "ref_id": "PMID-7594540_T14" } ] }, { "id": "PMID-7594540_E13", "type": "Positive_regulation", "trigger": { "text": [ "transcriptional activation" ], "offsets": [ [ 1137, 1163 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "PMID-7594540_T15" }, { "role": "Site", "ref_id": "PMID-7594540_T30" } ] } ]

[ { "id": "PMID-7594540_1", "entity_ids": [ "PMID-7594540_T4", "PMID-7594540_T5" ] } ]

[]

[ { "id": "PMID-7609053__text", "type": "abstract", "text": [ "The peri-kappa B site mediates human immunodeficiency virus type 2 enhancer activation in monocytes but not in T cells. \nHuman immunodeficiency virus type 2 (HIV-2), like HIV-1, causes AIDS and is associated with AIDS cases primarily in West Africa. HIV-1 and HIV-2 display significant differences in nucleic acid sequence and in the natural history of clinical disease. Consistent with these differences, we have previously demonstrated that the enhancer/promoter region of HIV-2 functions quite differently from that of HIV-1. Whereas activation of the HIV-1 enhancer following T-cell stimulation is mediated largely through binding of the transcription factor NF-kappa B to two adjacent kappa B sites in the HIV-1 long terminal repeat, activation of the HIV-2 enhancer in monocytes and T cells is dependent on four cis-acting elements: a single kappa B site, two purine-rich binding sites, PuB1 and PuB2, and a pets site. We have now identified a novel cis-acting element within the HIV-2 enhancer, immediately upstream of the kappa B site, designated peri-kappa B. This site is conserved among isolates of HIV-2 and the closely related simian immunodeficiency virus, and transfection assays show this site to mediate HIV-2 enhancer activation following stimulation of monocytic but not T-cell lines. This is the first description of an HIV-2 enhancer element which displays such monocyte specificity, and no comparable enhancer element has been clearly defined for HIV-1. While a nuclear factor(s) from both peripheral blood monocytes and T cells binds the peri-kappa B site, electrophoretic mobility shift assays suggest that either a different protein binds to this site in monocytes versus T cells or that the protein recognizing this enhancer element undergoes differential modification in monocytes and T cells, thus supporting the transfection data. Further, while specific constitutive binding to the peri-kappa B site is seen in monocytes, stimulation with phorbol esters induces additional, specific binding. Understanding the monocyte-specific function of the peri-kappa B factor may ultimately provide insight into the different role monocytes and T cells play in HIV pathogenesis. " ], "offsets": [ [ 0, 2197 ] ] } ]

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[ { "id": "PMID-7622191__text", "type": "abstract", "text": [ "Thapsigargin induces IL-2 receptor alpha-chain in human peripheral and Jurkat T cells via a protein kinase C-independent mechanism. \nThapsigargin (TG), an inhibitor of Ca(2+)-ATPase, depletes intracellular Ca2+ stores and induces a sustained Ca2+ influx without altering phosphatidyl inositol levels. TG plus phorbol myristate acetate (PMA) but not TG alone induced IL-2 in Jurkat T cells, suggesting that TG had no effect on protein kinase C (PKC). However, TG induced increases in IL-2R alpha protein as well as IL-2R alpha mRNA in Jurkat T cells in a dose-dependent manner. A similar increase in IL-2R alpha by TG was also observed in human peripheral T cells. Further, like PMA, TG markedly induced NF kappa B in Jurkat T cells. However, TG and PMA exhibited a synergistic action on IL-2R alpha expression, suggesting that TG and PMA induce IL-2R alpha through distinct pathways. PMA- but not TG-induced IL-2R alpha is inhibited by the PKC inhibitor H7, whereas TG- but not PMA-induced IL-2R alpha was inhibited by cholera toxin, forskolin and 1,9-dideoxy forskolin. In toto, these results suggest that TG induces IL-2R alpha in human T cells through a PKC-independent pathway. " ], "offsets": [ [ 0, 1182 ] ] } ]

[ { "id": "PMID-7622191_T1", "type": "Protein", "text": [ "IL-2 receptor alpha-chain" ], "offsets": [ [ 21, 46 ] ], "normalized": [] }, { "id": "PMID-7622191_T2", "type": "Protein", "text": [ "IL-2" ], "offsets": [ [ 366, 370 ] ], "normalized": [] }, { "id": "PMID-7622191_T3", "type": "Protein", "text": [ "IL-2R alpha" ], "offsets": [ [ 483, 494 ] ], "normalized": [] }, { "id": "PMID-7622191_T4", "type": "Protein", "text": [ "IL-2R alpha" ], "offsets": [ [ 514, 525 ] ], "normalized": [] }, { "id": "PMID-7622191_T5", "type": "Protein", "text": [ "IL-2R alpha" ], "offsets": [ [ 599, 610 ] ], "normalized": [] }, { "id": "PMID-7622191_T6", "type": "Protein", "text": [ "IL-2R alpha" ], "offsets": [ [ 787, 798 ] ], "normalized": [] }, { "id": "PMID-7622191_T7", "type": "Protein", "text": [ "IL-2R alpha" ], "offsets": [ [ 845, 856 ] ], "normalized": [] }, { "id": "PMID-7622191_T8", "type": "Protein", "text": [ "IL-2R alpha" ], "offsets": [ [ 908, 919 ] ], "normalized": [] }, { "id": "PMID-7622191_T9", "type": "Protein", "text": [ "IL-2R alpha" ], "offsets": [ [ 990, 1001 ] ], "normalized": [] }, { "id": "PMID-7622191_T10", "type": "Protein", "text": [ "IL-2R alpha" ], "offsets": [ [ 1118, 1129 ] ], "normalized": [] }, { "id": "PMID-7622191_T12", "type": "Entity", "text": [ "protein kinase C-independent mechanism" ], "offsets": [ [ 92, 130 ] ], "normalized": [] } ]

[ { "id": "PMID-7622191_E1", "type": "Positive_regulation", "trigger": { "text": [ "induces" ], "offsets": [ [ 13, 20 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "PMID-7622191_T1" }, { "role": "Cause", "ref_id": "PMID-7622191_E2" } ] }, { "id": "PMID-7622191_E2", "type": "Positive_regulation", "trigger": { "text": [ "induces" ], "offsets": [ [ 13, 20 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "PMID-7622191_T1" }, { "role": "Site", "ref_id": "PMID-7622191_T12" } ] }, { "id": "PMID-7622191_E3", "type": "Positive_regulation", "trigger": { "text": [ "induced" ], "offsets": [ [ 358, 365 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "PMID-7622191_T2" } ] }, { "id": "PMID-7622191_E4", "type": "Positive_regulation", "trigger": { "text": [ "increases" ], "offsets": [ [ 470, 479 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "PMID-7622191_T3" } ] }, { "id": "PMID-7622191_E5", "type": "Positive_regulation", "trigger": { "text": [ "increases" ], "offsets": [ [ 470, 479 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "PMID-7622191_T4" } ] }, { "id": "PMID-7622191_E6", "type": "Positive_regulation", "trigger": { "text": [ "increase" ], "offsets": [ [ 587, 595 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "PMID-7622191_T5" } ] }, { "id": "PMID-7622191_E7", "type": "Regulation", "trigger": { "text": [ "synergistic action" ], "offsets": [ [ 765, 783 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "PMID-7622191_E8" } ] }, { "id": "PMID-7622191_E8", "type": "Gene_expression", "trigger": { "text": [ "expression" ], "offsets": [ [ 799, 809 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "PMID-7622191_T6" } ] }, { "id": "PMID-7622191_E9", "type": "Positive_regulation", "trigger": { "text": [ "induce" ], "offsets": [ [ 838, 844 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "PMID-7622191_T7" } ] }, { "id": "PMID-7622191_E10", "type": "Positive_regulation", "trigger": { "text": [ "induced" ], "offsets": [ [ 900, 907 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "PMID-7622191_T8" } ] }, { "id": "PMID-7622191_E11", "type": "Negative_regulation", "trigger": { "text": [ "inhibited" ], "offsets": [ [ 923, 932 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "PMID-7622191_E10" } ] }, { "id": "PMID-7622191_E12", "type": "Positive_regulation", "trigger": { "text": [ "induced" ], "offsets": [ [ 982, 989 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "PMID-7622191_T9" } ] }, { "id": "PMID-7622191_E13", "type": "Negative_regulation", "trigger": { "text": [ "inhibited" ], "offsets": [ [ 1006, 1015 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "PMID-7622191_E12" } ] }, { "id": "PMID-7622191_E14", "type": "Positive_regulation", "trigger": { "text": [ "induces" ], "offsets": [ [ 1110, 1117 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "PMID-7622191_T10" } ] } ]

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[ { "id": "PMID-7623828__text", "type": "abstract", "text": [ "A functional T-cell receptor signaling pathway is required for p95vav activity. \nStimulation of the T-cell antigen receptor (TCR) induces activation of multiple tyrosine kinases, resulting in phosphorylation of numerous intracellular substrates. One substrate is p95vav, which is expressed exclusively in hematopoietic and trophoblast cells. It contains a number of structural motifs, including Src homology 2, Src homology 3, and pleckstrin homology domains and a putative guanine nucleotide exchange domain. The role of p95vav in TCR-mediated signaling processes is unclear. Here, we show that overexpression of p95vav alone in Jurkat T cells leads to activation of the nuclear factors, including NFAT, involved in interleukin-2 expression. Furthermore, p95vav synergizes with TCR stimulation in inducing NFAT- and interleukin-2-dependent transcription. In contrast, NFAT activation by a G-protein-coupled receptor is not modulated by p95vav overexpression, suggesting that the effect is specific to the TCR signaling pathways. Although removal of the first 67 amino acids of p95vav activates its transforming potential in NIH 3T3 cells, this region appears to be required for its function in T cells. We further demonstrate that the p95vav-induced NFAT activation is not mimicked by Ras activation, though its function is dependent upon Ras and Raf. Furthermore, the activating function of p95vav is blocked by FK506, suggesting that its activity also depends on calcineurin. To further dissect p95vav involvement in TCR signaling, we analyzed various Jurkat mutants deficient in TCR signaling function or TCR expression and showed that an intact TCR signaling pathway is required for p95vav to function. However, overexpression of p95vav does not appear to influence TCR-induced protein tyrosine phosphorylation or increases in cytoplasmic free calcium. Taken together, our data suggest that p95vav plays an important role at an yet unidentified proximal position in the TCR signaling cascade. " ], "offsets": [ [ 0, 1998 ] ] } ]

[ { "id": "PMID-7623828_T1", "type": "Protein", "text": [ "p95vav" ], "offsets": [ [ 63, 69 ] ], "normalized": [] }, { "id": "PMID-7623828_T2", "type": "Protein", "text": [ "p95vav" ], "offsets": [ [ 263, 269 ] ], "normalized": [] }, { "id": "PMID-7623828_T3", "type": "Protein", "text": [ "p95vav" ], "offsets": [ [ 522, 528 ] ], "normalized": [] }, { "id": "PMID-7623828_T4", "type": "Protein", "text": [ "p95vav" ], "offsets": [ [ 614, 620 ] ], "normalized": [] }, { "id": "PMID-7623828_T5", "type": "Protein", "text": [ "interleukin-2" ], "offsets": [ [ 717, 730 ] ], "normalized": [] }, { "id": "PMID-7623828_T6", "type": "Protein", "text": [ "p95vav" ], "offsets": [ [ 756, 762 ] ], "normalized": [] }, { "id": "PMID-7623828_T7", "type": "Protein", "text": [ "interleukin-2" ], "offsets": [ [ 817, 830 ] ], "normalized": [] }, { "id": "PMID-7623828_T8", "type": "Protein", "text": [ "p95vav" ], "offsets": [ [ 937, 943 ] ], "normalized": [] }, { "id": "PMID-7623828_T9", "type": "Protein", "text": [ "p95vav" ], "offsets": [ [ 1078, 1084 ] ], "normalized": [] }, { "id": "PMID-7623828_T10", "type": "Protein", "text": [ "p95vav" ], "offsets": [ [ 1236, 1242 ] ], "normalized": [] }, { "id": "PMID-7623828_T11", "type": "Protein", "text": [ "p95vav" ], "offsets": [ [ 1393, 1399 ] ], "normalized": [] }, { "id": "PMID-7623828_T12", "type": "Protein", "text": [ "calcineurin" ], "offsets": [ [ 1466, 1477 ] ], "normalized": [] }, { "id": "PMID-7623828_T13", "type": "Protein", "text": [ "p95vav" ], "offsets": [ [ 1498, 1504 ] ], "normalized": [] }, { "id": "PMID-7623828_T14", "type": "Protein", "text": [ "p95vav" ], "offsets": [ [ 1688, 1694 ] ], "normalized": [] }, { "id": "PMID-7623828_T15", "type": "Protein", "text": [ "p95vav" ], "offsets": [ [ 1735, 1741 ] ], "normalized": [] }, { "id": "PMID-7623828_T16", "type": "Protein", "text": [ "p95vav" ], "offsets": [ [ 1896, 1902 ] ], "normalized": [] } ]

[ { "id": "PMID-7623828_E1", "type": "Positive_regulation", "trigger": { "text": [ "required" ], "offsets": [ [ 50, 58 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "PMID-7623828_T1" } ] }, { "id": "PMID-7623828_E2", "type": "Gene_expression", "trigger": { "text": [ "expressed" ], "offsets": [ [ 280, 289 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "PMID-7623828_T2" } ] }, { "id": "PMID-7623828_E3", "type": "Positive_regulation", "trigger": { "text": [ "overexpression" ], "offsets": [ [ 596, 610 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "PMID-7623828_E4" } ] }, { "id": "PMID-7623828_E4", "type": "Gene_expression", "trigger": { "text": [ "overexpression" ], "offsets": [ [ 596, 610 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "PMID-7623828_T4" } ] }, { "id": "PMID-7623828_E5", "type": "Regulation", "trigger": { "text": [ "involved" ], "offsets": [ [ 705, 713 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "PMID-7623828_E6" } ] }, { "id": "PMID-7623828_E6", "type": "Gene_expression", "trigger": { "text": [ "expression" ], "offsets": [ [ 731, 741 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "PMID-7623828_T5" } ] }, { "id": "PMID-7623828_E7", "type": "Positive_regulation", "trigger": { "text": [ "overexpression" ], "offsets": [ [ 944, 958 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "PMID-7623828_E8" } ] }, { "id": "PMID-7623828_E8", "type": "Gene_expression", "trigger": { "text": [ "overexpression" ], "offsets": [ [ 944, 958 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "PMID-7623828_T8" } ] }, { "id": "PMID-7623828_E9", "type": "Positive_regulation", "trigger": { "text": [ "overexpression" ], "offsets": [ [ 1717, 1731 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "PMID-7623828_T15" } ] }, { "id": "PMID-7623828_E10", "type": "Gene_expression", "trigger": { "text": [ "overexpression" ], "offsets": [ [ 1717, 1731 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "PMID-7623828_T15" } ] } ]

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[]

[ { "id": "PMID-7629157__text", "type": "abstract", "text": [ "Activation of NF-kappa B by phosphatase inhibitors involves the phosphorylation of I kappa B alpha at phosphatase 2A-sensitive sites. \nActivation of NF-kappa B by various cellular stimuli involves the phosphorylation and subsequent degradation of its inhibitor, I kappa B alpha, although the underlying mechanism remains unclear. In the present study, the role of serine/threonine phosphatases in the regulation of I kappa B alpha phosphorylation was investigated. Our studies demonstrate that incubation of human T cells with low concentrations (approximately 1-5 nM) of calyculin A or okadaic acid, potent inhibitors of protein phosphatase type 1 (PP-1) and type 2A (PP-2A), induces the phosphorylation of I kappa B alpha even in the absence of any cellular stimulus. This action of the phosphatase inhibitors, which is associated with the activation of the RelA.p50 NF-kappa B heterodimer, is not affected by agents that block the induction of I kappa B alpha phosphorylation by tumor necrosis factor alpha (TNF-alpha). Furthermore, the phosphorylated I kappa B alpha from calyculin A-treated cells, but not that from TNF-alpha-stimulated cells, is sensitive to PP-2A in vitro, suggesting the existence of fundamental differences in the phosphorylation of I kappa B alpha induced by the two different NF-kappa B inducers. However, induction of I kappa B alpha phosphorylation by both TNF-alpha and the phosphatase inhibitors is associated with the subsequent degradation of I kappa B alpha. We further demonstrate that TNF-alpha- and calyculin A-induced I kappa B alpha degradation exhibits similar but not identical sensitivities to a proteasome inhibitor. Together, these results suggest that phosphorylation of I kappa B alpha, mediated through both the TNF-alpha-inducible and the PP-2A-opposing kinases, may serve to target I kappa B alpha for proteasome-mediated degradation. " ], "offsets": [ [ 0, 1885 ] ] } ]

[ { "id": "PMID-7629157_T1", "type": "Protein", "text": [ "I kappa B alpha" ], "offsets": [ [ 83, 98 ] ], "normalized": [] }, { "id": "PMID-7629157_T2", "type": "Protein", "text": [ "I kappa B alpha" ], "offsets": [ [ 262, 277 ] ], "normalized": [] }, { "id": "PMID-7629157_T3", "type": "Protein", "text": [ "I kappa B alpha" ], "offsets": [ [ 415, 430 ] ], "normalized": [] }, { "id": "PMID-7629157_T4", "type": "Protein", "text": [ "I kappa B alpha" ], "offsets": [ [ 708, 723 ] ], "normalized": [] }, { "id": "PMID-7629157_T5", "type": "Protein", "text": [ "RelA" ], "offsets": [ [ 860, 864 ] ], "normalized": [] }, { "id": "PMID-7629157_T6", "type": "Protein", "text": [ "p50" ], "offsets": [ [ 865, 868 ] ], "normalized": [] }, { "id": "PMID-7629157_T7", "type": "Protein", "text": [ "I kappa B alpha" ], "offsets": [ [ 947, 962 ] ], "normalized": [] }, { "id": "PMID-7629157_T8", "type": "Protein", "text": [ "tumor necrosis factor alpha" ], "offsets": [ [ 982, 1009 ] ], "normalized": [] }, { "id": "PMID-7629157_T9", "type": "Protein", "text": [ "TNF-alpha" ], "offsets": [ [ 1011, 1020 ] ], "normalized": [] }, { "id": "PMID-7629157_T10", "type": "Protein", "text": [ "I kappa B alpha" ], "offsets": [ [ 1055, 1070 ] ], "normalized": [] }, { "id": "PMID-7629157_T11", "type": "Protein", "text": [ "TNF-alpha" ], "offsets": [ [ 1121, 1130 ] ], "normalized": [] }, { "id": "PMID-7629157_T12", "type": "Protein", "text": [ "I kappa B alpha" ], "offsets": [ [ 1259, 1274 ] ], "normalized": [] }, { "id": "PMID-7629157_T13", "type": "Protein", "text": [ "I kappa B alpha" ], "offsets": [ [ 1347, 1362 ] ], "normalized": [] }, { "id": "PMID-7629157_T14", "type": "Protein", "text": [ "TNF-alpha" ], "offsets": [ [ 1387, 1396 ] ], "normalized": [] }, { "id": "PMID-7629157_T15", "type": "Protein", "text": [ "I kappa B alpha" ], "offsets": [ [ 1477, 1492 ] ], "normalized": [] }, { "id": "PMID-7629157_T16", "type": "Protein", "text": [ "TNF-alpha" ], "offsets": [ [ 1522, 1531 ] ], "normalized": [] }, { "id": "PMID-7629157_T17", "type": "Protein", "text": [ "I kappa B alpha" ], "offsets": [ [ 1557, 1572 ] ], "normalized": [] }, { "id": "PMID-7629157_T18", "type": "Protein", "text": [ "I kappa B alpha" ], "offsets": [ [ 1717, 1732 ] ], "normalized": [] }, { "id": "PMID-7629157_T19", "type": "Protein", "text": [ "TNF-alpha" ], "offsets": [ [ 1760, 1769 ] ], "normalized": [] }, { "id": "PMID-7629157_T20", "type": "Protein", "text": [ "I kappa B alpha" ], "offsets": [ [ 1832, 1847 ] ], "normalized": [] } ]

[ { "id": "PMID-7629157_E1", "type": "Phosphorylation", "trigger": { "text": [ "phosphorylation" ], "offsets": [ [ 64, 79 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "PMID-7629157_T1" } ] }, { "id": "PMID-7629157_E2", "type": "Phosphorylation", "trigger": { "text": [ "phosphorylation" ], "offsets": [ [ 201, 216 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "PMID-7629157_T2" } ] }, { "id": "PMID-7629157_E3", "type": "Protein_catabolism", "trigger": { "text": [ "degradation" ], "offsets": [ [ 232, 243 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "PMID-7629157_T2" } ] }, { "id": "PMID-7629157_E4", "type": "Regulation", "trigger": { "text": [ "regulation" ], "offsets": [ [ 401, 411 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "PMID-7629157_E5" } ] }, { "id": "PMID-7629157_E5", "type": "Phosphorylation", "trigger": { "text": [ "phosphorylation" ], "offsets": [ [ 431, 446 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "PMID-7629157_T3" } ] }, { "id": "PMID-7629157_E6", "type": "Positive_regulation", "trigger": { "text": [ "induces" ], "offsets": [ [ 677, 684 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "PMID-7629157_E7" } ] }, { "id": "PMID-7629157_E7", "type": "Phosphorylation", "trigger": { "text": [ "phosphorylation" ], "offsets": [ [ 689, 704 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "PMID-7629157_T4" } ] }, { "id": "PMID-7629157_E8", "type": "Regulation", "trigger": { "text": [ "absence" ], "offsets": [ [ 736, 743 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "PMID-7629157_E6" } ] }, { "id": "PMID-7629157_E9", "type": "Positive_regulation", "trigger": { "text": [ "activation" ], "offsets": [ [ 842, 852 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "PMID-7629157_T6" } ] }, { "id": "PMID-7629157_E10", "type": "Positive_regulation", "trigger": { "text": [ "activation" ], "offsets": [ [ 842, 852 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "PMID-7629157_T5" } ] }, { "id": "PMID-7629157_E11", "type": "Regulation", "trigger": { "text": [ "affected" ], "offsets": [ [ 900, 908 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "PMID-7629157_E6" } ] }, { "id": "PMID-7629157_E12", "type": "Negative_regulation", "trigger": { "text": [ "block" ], "offsets": [ [ 924, 929 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "PMID-7629157_E13" } ] }, { "id": "PMID-7629157_E13", "type": "Positive_regulation", "trigger": { "text": [ "induction" ], "offsets": [ [ 934, 943 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "PMID-7629157_E14" }, { "role": "Cause", "ref_id": "PMID-7629157_T9" } ] }, { "id": "PMID-7629157_E14", "type": "Phosphorylation", "trigger": { "text": [ "phosphorylation" ], "offsets": [ [ 963, 978 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "PMID-7629157_T7" } ] }, { "id": "PMID-7629157_E15", "type": "Phosphorylation", "trigger": { "text": [ "phosphorylated" ], "offsets": [ [ 1040, 1054 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "PMID-7629157_T10" } ] }, { "id": "PMID-7629157_E16", "type": "Phosphorylation", "trigger": { "text": [ "phosphorylation" ], "offsets": [ [ 1240, 1255 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "PMID-7629157_T12" } ] }, { "id": "PMID-7629157_E17", "type": "Positive_regulation", "trigger": { "text": [ "induced" ], "offsets": [ [ 1275, 1282 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "PMID-7629157_E16" } ] }, { "id": "PMID-7629157_E18", "type": "Positive_regulation", "trigger": { "text": [ "induced" ], "offsets": [ [ 1275, 1282 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "PMID-7629157_E16" }, { "role": "Cause", "ref_id": "PMID-7629157_T11" } ] }, { "id": "PMID-7629157_E19", "type": "Positive_regulation", "trigger": { "text": [ "induction" ], "offsets": [ [ 1334, 1343 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "PMID-7629157_E21" } ] }, { "id": "PMID-7629157_E20", "type": "Positive_regulation", "trigger": { "text": [ "induction" ], "offsets": [ [ 1334, 1343 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "PMID-7629157_E21" }, { "role": "Cause", "ref_id": "PMID-7629157_T14" } ] }, { "id": "PMID-7629157_E21", "type": "Phosphorylation", "trigger": { "text": [ "phosphorylation" ], "offsets": [ [ 1363, 1378 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "PMID-7629157_T13" } ] }, { "id": "PMID-7629157_E22", "type": "Protein_catabolism", "trigger": { "text": [ "degradation" ], "offsets": [ [ 1462, 1473 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "PMID-7629157_T15" } ] }, { "id": "PMID-7629157_E23", "type": "Positive_regulation", "trigger": { "text": [ "induced" ], "offsets": [ [ 1549, 1556 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "PMID-7629157_E25" } ] }, { "id": "PMID-7629157_E24", "type": "Positive_regulation", "trigger": { "text": [ "induced" ], "offsets": [ [ 1549, 1556 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "PMID-7629157_E25" }, { "role": "Cause", "ref_id": "PMID-7629157_T16" } ] }, { "id": "PMID-7629157_E25", "type": "Protein_catabolism", "trigger": { "text": [ "degradation" ], "offsets": [ [ 1573, 1584 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "PMID-7629157_T17" } ] }, { "id": "PMID-7629157_E26", "type": "Phosphorylation", "trigger": { "text": [ "phosphorylation" ], "offsets": [ [ 1698, 1713 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "PMID-7629157_T18" } ] }, { "id": "PMID-7629157_E27", "type": "Positive_regulation", "trigger": { "text": [ "mediated" ], "offsets": [ [ 1734, 1742 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "PMID-7629157_E26" } ] }, { "id": "PMID-7629157_E28", "type": "Regulation", "trigger": { "text": [ "serve to target" ], "offsets": [ [ 1816, 1831 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "PMID-7629157_E30" } ] }, { "id": "PMID-7629157_E29", "type": "Regulation", "trigger": { "text": [ "serve to target" ], "offsets": [ [ 1816, 1831 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "PMID-7629157_E30" }, { "role": "Cause", "ref_id": "PMID-7629157_E27" } ] }, { "id": "PMID-7629157_E30", "type": "Positive_regulation", "trigger": { "text": [ "mediated" ], "offsets": [ [ 1863, 1871 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "PMID-7629157_E31" } ] }, { "id": "PMID-7629157_E31", "type": "Protein_catabolism", "trigger": { "text": [ "degradation" ], "offsets": [ [ 1872, 1883 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "PMID-7629157_T20" } ] } ]

[ { "id": "PMID-7629157_1", "entity_ids": [ "PMID-7629157_T9", "PMID-7629157_T8" ] } ]

[]

[ { "id": "PMID-7629508__text", "type": "abstract", "text": [ "Functional roles of the transcription factor Oct-2A and the high mobility group protein I/Y in HLA-DRA gene expression. \nThe class II major histocompatibility complex gene HLA-DRA is expressed in B cells, activated T lymphocytes, and in antigen-presenting cells. In addition, HLA-DRA gene expression is inducible in a variety of cell types by interferon-gamma (IFN-gamma). Here we show that the lymphoid-specific transcription factor Oct-2A plays a critical role in HLA-DRA gene expression in class II-positive B cell lines, and that the high mobility group protein (HMG) I/Y binds to multiple sites within the DRA promoter, including the Oct-2A binding site. Coexpression of HMG I/Y and Oct-2 in cell lines lacking Oct-2 results in high levels of HLA-DRA gene expression, and in vitro DNA-binding studies reveal that HMG I/Y stimulates Oct-2A binding to the HLA-DRA promoter. Thus, Oct-2A and HMG I/Y may synergize to activate HLA-DRA expression in B cells. By contrast, Oct-2A is not involved in the IFN-gamma induction of the HLA-DRA gene in HeLa cells, but antisense HMG I/Y dramatically decreases the level of induction. We conclude that distinct sets of transcription factors are involved in the two modes of HLA-DRA expression, and that HMG I/Y may be important for B cell-specific expression, and is essential for IFN-gamma induction. " ], "offsets": [ [ 0, 1343 ] ] } ]

[ { "id": "PMID-7629508_T1", "type": "Protein", "text": [ "Oct-2A" ], "offsets": [ [ 45, 51 ] ], "normalized": [] }, { "id": "PMID-7629508_T2", "type": "Protein", "text": [ "I/Y" ], "offsets": [ [ 88, 91 ] ], "normalized": [] }, { "id": "PMID-7629508_T3", "type": "Protein", "text": [ "interferon-gamma" ], "offsets": [ [ 343, 359 ] ], "normalized": [] }, { "id": "PMID-7629508_T4", "type": "Protein", "text": [ "IFN-gamma" ], "offsets": [ [ 361, 370 ] ], "normalized": [] }, { "id": "PMID-7629508_T5", "type": "Protein", "text": [ "Oct-2A" ], "offsets": [ [ 434, 440 ] ], "normalized": [] }, { "id": "PMID-7629508_T6", "type": "Protein", "text": [ "I/Y" ], "offsets": [ [ 572, 575 ] ], "normalized": [] }, { "id": "PMID-7629508_T7", "type": "Protein", "text": [ "Oct-2A" ], "offsets": [ [ 639, 645 ] ], "normalized": [] }, { "id": "PMID-7629508_T8", "type": "Protein", "text": [ "I/Y" ], "offsets": [ [ 680, 683 ] ], "normalized": [] }, { "id": "PMID-7629508_T9", "type": "Protein", "text": [ "Oct-2" ], "offsets": [ [ 688, 693 ] ], "normalized": [] }, { "id": "PMID-7629508_T10", "type": "Protein", "text": [ "Oct-2" ], "offsets": [ [ 716, 721 ] ], "normalized": [] }, { "id": "PMID-7629508_T11", "type": "Protein", "text": [ "I/Y" ], "offsets": [ [ 822, 825 ] ], "normalized": [] }, { "id": "PMID-7629508_T12", "type": "Protein", "text": [ "Oct-2A" ], "offsets": [ [ 837, 843 ] ], "normalized": [] }, { "id": "PMID-7629508_T13", "type": "Protein", "text": [ "Oct-2A" ], "offsets": [ [ 883, 889 ] ], "normalized": [] }, { "id": "PMID-7629508_T14", "type": "Protein", "text": [ "I/Y" ], "offsets": [ [ 898, 901 ] ], "normalized": [] }, { "id": "PMID-7629508_T15", "type": "Protein", "text": [ "Oct-2A" ], "offsets": [ [ 972, 978 ] ], "normalized": [] }, { "id": "PMID-7629508_T16", "type": "Protein", "text": [ "IFN-gamma" ], "offsets": [ [ 1002, 1011 ] ], "normalized": [] }, { "id": "PMID-7629508_T17", "type": "Protein", "text": [ "I/Y" ], "offsets": [ [ 1075, 1078 ] ], "normalized": [] }, { "id": "PMID-7629508_T18", "type": "Protein", "text": [ "I/Y" ], "offsets": [ [ 1248, 1251 ] ], "normalized": [] }, { "id": "PMID-7629508_T19", "type": "Protein", "text": [ "IFN-gamma" ], "offsets": [ [ 1322, 1331 ] ], "normalized": [] } ]

[ { "id": "PMID-7629508_E1", "type": "Binding", "trigger": { "text": [ "binds" ], "offsets": [ [ 576, 581 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "PMID-7629508_T6" } ] }, { "id": "PMID-7629508_E2", "type": "Gene_expression", "trigger": { "text": [ "Coexpression" ], "offsets": [ [ 660, 672 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "PMID-7629508_T8" } ] }, { "id": "PMID-7629508_E3", "type": "Gene_expression", "trigger": { "text": [ "Coexpression" ], "offsets": [ [ 660, 672 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "PMID-7629508_T9" } ] }, { "id": "PMID-7629508_E4", "type": "Positive_regulation", "trigger": { "text": [ "stimulates" ], "offsets": [ [ 826, 836 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "PMID-7629508_E5" }, { "role": "Cause", "ref_id": "PMID-7629508_T11" } ] }, { "id": "PMID-7629508_E5", "type": "Binding", "trigger": { "text": [ "binding" ], "offsets": [ [ 844, 851 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "PMID-7629508_T12" } ] } ]

[ { "id": "PMID-7629508_1", "entity_ids": [ "PMID-7629508_T3", "PMID-7629508_T4" ] } ]

[]

[ { "id": "PMID-7635985__text", "type": "abstract", "text": [ "Interleukin 4 activates a signal transducer and activator of transcription (Stat) protein which interacts with an interferon-gamma activation site-like sequence upstream of the I epsilon exon in a human B cell line. Evidence for the involvement of Janus kinase 3 and interleukin-4 Stat. \nGerm line C transcripts can be induced by IL-4 in the human B cell line, BL-2. Utilizing a IFN-gamma activation site-like DNA sequence element located upstream of the I epsilon exon, we demonstrated by gel mobility shift assays that IL-4 induced a binding activity in the cytosol and nucleus of BL-2 cells. This factor was designated IL-4 NAF (IL-4-induced nuclear-activating factors) and was identified as a tyrosine phosphoprotein, which translocates from the cytosol to the nucleus upon IL-4 treatment. Because these are the characteristics of a signal transducer and activator of transcription (Stat) protein, we determined whether antibodies to Stat proteins will interfere with gel mobility shift and found that antibodies to IL-4 Stat, also known as Stat6, but not antibodies to other Stat proteins, interfere with the formation of the IL-4 NAF complex. Congruous with the involvement of a Stat protein, IL-4 induced robust Janus kinase 3 (JAK3) activity in BL-2 cells. Cotransfection of JAK3 with IL-4 Stat into COS-7 cells produced an intracellular activity which bound the same IFN-gamma activation site-like sequence and comigrated with IL-4 NAF in electrophoretic mobility shift assay. These results show that IL-4 NAF is IL-4 Stat, which is activated by JAK3 in response to IL-4 receptor engagement. " ], "offsets": [ [ 0, 1601 ] ] } ]

[ { "id": "PMID-7635985_T1", "type": "Protein", "text": [ "Interleukin 4" ], "offsets": [ [ 0, 13 ] ], "normalized": [] }, { "id": "PMID-7635985_T2", "type": "Protein", "text": [ "interferon-gamma" ], "offsets": [ [ 114, 130 ] ], "normalized": [] }, { "id": "PMID-7635985_T3", "type": "Protein", "text": [ "Janus kinase 3" ], "offsets": [ [ 248, 262 ] ], "normalized": [] }, { "id": "PMID-7635985_T4", "type": "Protein", "text": [ "interleukin-4" ], "offsets": [ [ 267, 280 ] ], "normalized": [] }, { "id": "PMID-7635985_T5", "type": "Protein", "text": [ "IL-4" ], "offsets": [ [ 330, 334 ] ], "normalized": [] }, { "id": "PMID-7635985_T6", "type": "Protein", "text": [ "IFN-gamma" ], "offsets": [ [ 379, 388 ] ], "normalized": [] }, { "id": "PMID-7635985_T7", "type": "Protein", "text": [ "IL-4" ], "offsets": [ [ 521, 525 ] ], "normalized": [] }, { "id": "PMID-7635985_T8", "type": "Protein", "text": [ "IL-4" ], "offsets": [ [ 622, 626 ] ], "normalized": [] }, { "id": "PMID-7635985_T9", "type": "Protein", "text": [ "IL-4" ], "offsets": [ [ 632, 636 ] ], "normalized": [] }, { "id": "PMID-7635985_T10", "type": "Protein", "text": [ "IL-4" ], "offsets": [ [ 778, 782 ] ], "normalized": [] }, { "id": "PMID-7635985_T11", "type": "Protein", "text": [ "IL-4 Stat" ], "offsets": [ [ 1020, 1029 ] ], "normalized": [] }, { "id": "PMID-7635985_T12", "type": "Protein", "text": [ "Stat6" ], "offsets": [ [ 1045, 1050 ] ], "normalized": [] }, { "id": "PMID-7635985_T13", "type": "Protein", "text": [ "IL-4" ], "offsets": [ [ 1131, 1135 ] ], "normalized": [] }, { "id": "PMID-7635985_T14", "type": "Protein", "text": [ "IL-4" ], "offsets": [ [ 1199, 1203 ] ], "normalized": [] }, { "id": "PMID-7635985_T15", "type": "Protein", "text": [ "Janus kinase 3" ], "offsets": [ [ 1219, 1233 ] ], "normalized": [] }, { "id": "PMID-7635985_T16", "type": "Protein", "text": [ "JAK3" ], "offsets": [ [ 1235, 1239 ] ], "normalized": [] }, { "id": "PMID-7635985_T17", "type": "Protein", "text": [ "JAK3" ], "offsets": [ [ 1283, 1287 ] ], "normalized": [] }, { "id": "PMID-7635985_T18", "type": "Protein", "text": [ "IL-4" ], "offsets": [ [ 1293, 1297 ] ], "normalized": [] }, { "id": "PMID-7635985_T19", "type": "Protein", "text": [ "IFN-gamma" ], "offsets": [ [ 1376, 1385 ] ], "normalized": [] }, { "id": "PMID-7635985_T20", "type": "Protein", "text": [ "IL-4" ], "offsets": [ [ 1436, 1440 ] ], "normalized": [] }, { "id": "PMID-7635985_T21", "type": "Protein", "text": [ "IL-4" ], "offsets": [ [ 1510, 1514 ] ], "normalized": [] }, { "id": "PMID-7635985_T22", "type": "Protein", "text": [ "IL-4" ], "offsets": [ [ 1522, 1526 ] ], "normalized": [] }, { "id": "PMID-7635985_T23", "type": "Protein", "text": [ "JAK3" ], "offsets": [ [ 1555, 1559 ] ], "normalized": [] }, { "id": "PMID-7635985_T24", "type": "Protein", "text": [ "IL-4" ], "offsets": [ [ 1575, 1579 ] ], "normalized": [] } ]

[ { "id": "PMID-7635985_E1", "type": "Positive_regulation", "trigger": { "text": [ "induced" ], "offsets": [ [ 1204, 1211 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "PMID-7635985_T16" }, { "role": "Cause", "ref_id": "PMID-7635985_T14" } ] }, { "id": "PMID-7635985_E2", "type": "Positive_regulation", "trigger": { "text": [ "Cotransfection" ], "offsets": [ [ 1265, 1279 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "PMID-7635985_E5" } ] }, { "id": "PMID-7635985_E3", "type": "Positive_regulation", "trigger": { "text": [ "Cotransfection" ], "offsets": [ [ 1265, 1279 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "PMID-7635985_E4" } ] }, { "id": "PMID-7635985_E4", "type": "Gene_expression", "trigger": { "text": [ "Cotransfection" ], "offsets": [ [ 1265, 1279 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "PMID-7635985_T18" } ] }, { "id": "PMID-7635985_E5", "type": "Gene_expression", "trigger": { "text": [ "Cotransfection" ], "offsets": [ [ 1265, 1279 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "PMID-7635985_T17" } ] }, { "id": "PMID-7635985_E6", "type": "Binding", "trigger": { "text": [ "comigrated" ], "offsets": [ [ 1420, 1430 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "PMID-7635985_T20" } ] }, { "id": "PMID-7635985_E7", "type": "Positive_regulation", "trigger": { "text": [ "activated" ], "offsets": [ [ 1542, 1551 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "PMID-7635985_T21" }, { "role": "Cause", "ref_id": "PMID-7635985_T23" } ] }, { "id": "PMID-7635985_E8", "type": "Positive_regulation", "trigger": { "text": [ "in response to" ], "offsets": [ [ 1560, 1574 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "PMID-7635985_E7" } ] } ]

[ { "id": "PMID-7635985_1", "entity_ids": [ "PMID-7635985_T11", "PMID-7635985_T12" ] }, { "id": "PMID-7635985_2", "entity_ids": [ "PMID-7635985_T16", "PMID-7635985_T15" ] } ]

[]

[ { "id": "PMID-7637809__text", "type": "abstract", "text": [ "An IRF-1-dependent pathway of DNA damage-induced apoptosis in mitogen-activated T lymphocytes. \nLymphocytes are particularly susceptible to DNA damage-induced apoptosis, a response which may serve as a form of 'altruistic suicide' to counter their intrinsic high potential for mutation and clonal expansion. The tumour suppressor p53 has been shown to regulate this type of apoptosis in thymocytes, but an as yet unknown, p53-independent pathway(s) appears to mediate the same event in mitogen-activated mature T lymphocytes. Here we show DNA damage-induced apoptosis in these T lymphocytes is dependent on the antioncogenic transcription factor interferon regulatory factor (IRF)-1. Thus two different anti-onco-genic transcription factors, p53 and IRF-1, are required for distinct apoptotic pathways in T lymphocytes. We also show that mitogen induction of the interleukin-1 beta converting enzyme (ICE) gene, a mammalian homologue of the Caenorhabditis elegans cell death gene ced-3, is IRF-1-dependent. Ectopic overexpression of IRF-1 results in the activation of the endogenous gene for ICE and enhances the sensitivity of cells to radiation-induced apoptosis. " ], "offsets": [ [ 0, 1166 ] ] } ]

[ { "id": "PMID-7637809_T1", "type": "Protein", "text": [ "IRF-1" ], "offsets": [ [ 3, 8 ] ], "normalized": [] }, { "id": "PMID-7637809_T2", "type": "Protein", "text": [ "p53" ], "offsets": [ [ 330, 333 ] ], "normalized": [] }, { "id": "PMID-7637809_T3", "type": "Protein", "text": [ "p53" ], "offsets": [ [ 422, 425 ] ], "normalized": [] }, { "id": "PMID-7637809_T4", "type": "Protein", "text": [ "interferon regulatory factor (IRF)-1" ], "offsets": [ [ 646, 682 ] ], "normalized": [] }, { "id": "PMID-7637809_T5", "type": "Protein", "text": [ "p53" ], "offsets": [ [ 742, 745 ] ], "normalized": [] }, { "id": "PMID-7637809_T6", "type": "Protein", "text": [ "IRF-1" ], "offsets": [ [ 750, 755 ] ], "normalized": [] }, { "id": "PMID-7637809_T7", "type": "Protein", "text": [ "interleukin-1 beta converting enzyme" ], "offsets": [ [ 863, 899 ] ], "normalized": [] }, { "id": "PMID-7637809_T8", "type": "Protein", "text": [ "ICE" ], "offsets": [ [ 901, 904 ] ], "normalized": [] }, { "id": "PMID-7637809_T9", "type": "Protein", "text": [ "ced-3" ], "offsets": [ [ 980, 985 ] ], "normalized": [] }, { "id": "PMID-7637809_T10", "type": "Protein", "text": [ "IRF-1" ], "offsets": [ [ 990, 995 ] ], "normalized": [] }, { "id": "PMID-7637809_T11", "type": "Protein", "text": [ "IRF-1" ], "offsets": [ [ 1033, 1038 ] ], "normalized": [] }, { "id": "PMID-7637809_T12", "type": "Protein", "text": [ "ICE" ], "offsets": [ [ 1092, 1095 ] ], "normalized": [] } ]

[ { "id": "PMID-7637809_E1", "type": "Positive_regulation", "trigger": { "text": [ "induction" ], "offsets": [ [ 846, 855 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "PMID-7637809_T8" } ] }, { "id": "PMID-7637809_E2", "type": "Regulation", "trigger": { "text": [ "dependent" ], "offsets": [ [ 996, 1005 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "PMID-7637809_E1" }, { "role": "Cause", "ref_id": "PMID-7637809_T10" } ] }, { "id": "PMID-7637809_E3", "type": "Gene_expression", "trigger": { "text": [ "overexpression" ], "offsets": [ [ 1015, 1029 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "PMID-7637809_T11" } ] }, { "id": "PMID-7637809_E4", "type": "Positive_regulation", "trigger": { "text": [ "overexpression" ], "offsets": [ [ 1015, 1029 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "PMID-7637809_E3" } ] }, { "id": "PMID-7637809_E5", "type": "Positive_regulation", "trigger": { "text": [ "results" ], "offsets": [ [ 1039, 1046 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "PMID-7637809_E6" }, { "role": "Cause", "ref_id": "PMID-7637809_E4" } ] }, { "id": "PMID-7637809_E6", "type": "Positive_regulation", "trigger": { "text": [ "activation" ], "offsets": [ [ 1054, 1064 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "PMID-7637809_T12" } ] } ]

[ { "id": "PMID-7637809_1", "entity_ids": [ "PMID-7637809_T8", "PMID-7637809_T7" ] } ]

[]

[ { "id": "PMID-7640302__text", "type": "abstract", "text": [ "Regulation of c-jun mRNA expression by hydroxyurea in human K562 cells during erythroid differentiation [published erratum appears in Biochim Biophys Acta 1995 Dec 27;1264(3):409] \nHydroxyurea (HU) is an antitumor agent which also induces hemoglobinization during erythroid differentiation. In addition, HU stimulates the synthesis of fetal hemoglobin in sickle cell anemia patients. To further understand its mechanism of action, we investigated the effects of HU on regulation of c-jun expression prior to the onset of erythroid differentiation of K562 cells. HU induced a dose-dependent stimulation of c-jun synthesis. The levels of c-jun mRNA was elevated 4 to 7.5-fold by HU within 2 h. This was followed by a gradual decline to the basal level by 24 h. Both nuclear run-on and actinomycin D pulse experiments strongly indicate that HU regulates c-jun mRNA expression by increasing the rate of synthesis as well as stabilizing the c-jun mRNA. In addition, the level of jun protein was elevated by 2 to 5-fold within 4 h in HU treated cells. Furthermore, concentrations of HU below 250 microM slightly increased the 5X AP-1/CAT activity. These results strongly suggest that HU induces both transcriptional and post-transcription regulation of c-jun during erythroid differentiation. " ], "offsets": [ [ 0, 1287 ] ] } ]

[ { "id": "PMID-7640302_T1", "type": "Protein", "text": [ "c-jun" ], "offsets": [ [ 14, 19 ] ], "normalized": [] }, { "id": "PMID-7640302_T2", "type": "Protein", "text": [ "c-jun" ], "offsets": [ [ 482, 487 ] ], "normalized": [] }, { "id": "PMID-7640302_T3", "type": "Protein", "text": [ "c-jun" ], "offsets": [ [ 605, 610 ] ], "normalized": [] }, { "id": "PMID-7640302_T4", "type": "Protein", "text": [ "c-jun" ], "offsets": [ [ 636, 641 ] ], "normalized": [] }, { "id": "PMID-7640302_T5", "type": "Protein", "text": [ "c-jun" ], "offsets": [ [ 851, 856 ] ], "normalized": [] }, { "id": "PMID-7640302_T6", "type": "Protein", "text": [ "c-jun" ], "offsets": [ [ 936, 941 ] ], "normalized": [] }, { "id": "PMID-7640302_T7", "type": "Protein", "text": [ "c-jun" ], "offsets": [ [ 1247, 1252 ] ], "normalized": [] } ]

[ { "id": "PMID-7640302_E1", "type": "Regulation", "trigger": { "text": [ "Regulation" ], "offsets": [ [ 0, 10 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "PMID-7640302_E2" } ] }, { "id": "PMID-7640302_E2", "type": "Transcription", "trigger": { "text": [ "expression" ], "offsets": [ [ 25, 35 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "PMID-7640302_T1" } ] }, { "id": "PMID-7640302_E3", "type": "Regulation", "trigger": { "text": [ "effects" ], "offsets": [ [ 451, 458 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "PMID-7640302_E4" } ] }, { "id": "PMID-7640302_E4", "type": "Regulation", "trigger": { "text": [ "regulation" ], "offsets": [ [ 468, 478 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "PMID-7640302_E5" } ] }, { "id": "PMID-7640302_E5", "type": "Gene_expression", "trigger": { "text": [ "expression" ], "offsets": [ [ 488, 498 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "PMID-7640302_T2" } ] }, { "id": "PMID-7640302_E6", "type": "Positive_regulation", "trigger": { "text": [ "induced" ], "offsets": [ [ 565, 572 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "PMID-7640302_E7" } ] }, { "id": "PMID-7640302_E7", "type": "Positive_regulation", "trigger": { "text": [ "stimulation" ], "offsets": [ [ 590, 601 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "PMID-7640302_E8" } ] }, { "id": "PMID-7640302_E8", "type": "Gene_expression", "trigger": { "text": [ "synthesis" ], "offsets": [ [ 611, 620 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "PMID-7640302_T3" } ] }, { "id": "PMID-7640302_E9", "type": "Positive_regulation", "trigger": { "text": [ "elevated" ], "offsets": [ [ 651, 659 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "PMID-7640302_T4" } ] }, { "id": "PMID-7640302_E10", "type": "Negative_regulation", "trigger": { "text": [ "decline" ], "offsets": [ [ 723, 730 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "PMID-7640302_E9" } ] }, { "id": "PMID-7640302_E11", "type": "Regulation", "trigger": { "text": [ "regulates" ], "offsets": [ [ 841, 850 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "PMID-7640302_E12" }, { "role": "Cause", "ref_id": "PMID-7640302_E13" } ] }, { "id": "PMID-7640302_E12", "type": "Transcription", "trigger": { "text": [ "expression" ], "offsets": [ [ 862, 872 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "PMID-7640302_T5" } ] }, { "id": "PMID-7640302_E13", "type": "Positive_regulation", "trigger": { "text": [ "increasing" ], "offsets": [ [ 876, 886 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "PMID-7640302_E14" } ] }, { "id": "PMID-7640302_E14", "type": "Transcription", "trigger": { "text": [ "synthesis" ], "offsets": [ [ 899, 908 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "PMID-7640302_T6" } ] }, { "id": "PMID-7640302_E15", "type": "Positive_regulation", "trigger": { "text": [ "stabilizing" ], "offsets": [ [ 920, 931 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "PMID-7640302_T6" } ] }, { "id": "PMID-7640302_E16", "type": "Positive_regulation", "trigger": { "text": [ "induces" ], "offsets": [ [ 1181, 1188 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "PMID-7640302_E21" } ] }, { "id": "PMID-7640302_E17", "type": "Positive_regulation", "trigger": { "text": [ "induces" ], "offsets": [ [ 1181, 1188 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "PMID-7640302_E20" } ] }, { "id": "PMID-7640302_E18", "type": "Transcription", "trigger": { "text": [ "transcriptional" ], "offsets": [ [ 1194, 1209 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "PMID-7640302_T7" } ] }, { "id": "PMID-7640302_E19", "type": "Gene_expression", "trigger": { "text": [ "post-transcription" ], "offsets": [ [ 1214, 1232 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "PMID-7640302_T7" } ] }, { "id": "PMID-7640302_E20", "type": "Regulation", "trigger": { "text": [ "regulation" ], "offsets": [ [ 1233, 1243 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "PMID-7640302_E19" } ] }, { "id": "PMID-7640302_E21", "type": "Regulation", "trigger": { "text": [ "regulation" ], "offsets": [ [ 1233, 1243 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "PMID-7640302_E18" } ] } ]

[]

[]