Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UNIPROT:P51532 (transcriptional activator)
 6,546 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Human T-cell leukemia virus type 1 (HTLV-1) encodes a transcriptional activator, Tax, whose activity is believed to contribute significantly to cellular transformation. Tax stimulates transcription from the proviral promoter as well as from promoters for a variety of cellular genes. The mechanism through which Tax communicates to the general transcription factors and RNA polymerase II has not been completely determined. We investigated whether Tax could function directly through the general transcription factors and RNA polymerase II or if other intermediary factors or coactivators were required. Our results show that a system consisting of purified recombinant TFIIA, TFIIB, TFIIE, TFIIF, CREB, and Tax, along with highly purified RNA polymerase II, affinity-purified epitope-tagged TFIID, and semipurified TFIIH, supports basal transcription of the HTLV-1 promoter but is not responsive to Tax. Two additional activities were required for Tax to stimulate transcription. We demonstrate that one of these activities is poly(ADP-ribose) polymerase (PARP), a molecule that has been previously identified to be the transcriptional coactivator PC1. PARP functions as a coactivator in our assays at molar concentrations approximately equal to those of the DNA and equal to or less than those of the transcription factors in the assay. We further demonstrate that PARP stimulates Tax-activated transcription in vivo, demonstrating that this biochemical approach has functionally identified a novel target for the retroviral transcriptional activator Tax.
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PMID:Identification of poly(ADP-ribose) polymerase as a transcriptional coactivator of the human T-cell leukemia virus type 1 Tax protein. 1066 46

The major histocompatibility complex (MHC) class I genes are induced synergistically by interferons (IFN) and tumor necrosis factor (TNF), a response thought to involve the cooperative action of Rel/NF-kB and interferon regulatory factor (IRF) transcription factors. The IFN-gamma-inducible class II transcriptional activator (CIITA) has recently been shown to transactivate MHC class I as well as class II genes, and this investigation shows that CIITA synergizes strongly with RelA to stimulate HLA class I expression. The functional interaction of CIITA and RelA requires both promoter elements and the upstream Rel binding site and is not seen with a class II reporter. The promoter elements necessary for CIITA action are also required for induction by IFN-alpha. HLA-A and HLA-B loci respond differentially to IFNs, and we identify locus-specific differences in critical promoter elements in addition to known polymorphisms in the Rel and IRF binding sites. The HLA-A promoter is transactivated relatively poorly by CIITA and does not interact detectably with CREB proteins implicated in CIITA recruitment, but the synergism with RelA can compensate for this weakness. The present findings illustrate that multiple transcription factors cooperate to regulate class I expression and that their relative importance differs according to the locus and cell type examined. (Blood. 2000;95:3804-3808)
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PMID:Synergistic induction of HLA class I expression by RelA and CIITA. 1124 41

CREB-2 (also called ATF4, TAXREB67, or C/ATF) is an evolutionarily conserved member of the CREB/ATF family of basic-leucine zipper transcription factors. CREB-2 is expressed ubiquitously in the adult mouse and can function as both a transcriptional activator and a repressor. However, little was understood about the normal function of CREB-2 in mammalian development or organ physiology. In this report we have used gene targeting to produce CREB-2-deficient (CREB-2-/-) mice. Adult CREB-2-/- mice displayed microphthalmia due to the complete absence of a lens. Early embryonic lens development including formation of the optic vesicle, primary lens fibers, and proliferating anterior epithelial cells occurred normally in these mice. However, beginning at ED 14.5 the CREB-2-deficient anterior epithelial lens cells underwent massive and synchronous apoptosis. This was followed by the complete resorption of the developing lens. Consistent with this defect in anterior epithelial cell survival, in situ hybridization studies showed that CREB-2 is expressed at high levels in wild-type anterior epithelial lens cells at ED 14.5. The defect in lens formation seen in the CREB-2-/- mice was not associated with qualitative defects in the expression of Pax-6, alphaA-crystallin, c-maf, or PDGF-R alpha. However, apoptosis of the anterior epithelial cells was mediated by a p53-dependent cell death pathway because ablation of the p53 gene rescued anterior epithelial cell death and allowed the formation of a lens in the absence of CREB-2. Taken together, these results identify CREB-2 as an important regulator of mammalian lens development.
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PMID:Microphthalmia due to p53-mediated apoptosis of anterior lens epithelial cells in mice lacking the CREB-2 transcription factor. 1088 50

The authors previously reported that one of the cAMP-response elements (CREs) of the human beta3-AR gene, beta3CRE2, interacts with a nuclear factor which is distinct from CREB/ATF family. We named this factor WATSF-1 (white adipose tissue specific factor-1) since it is preferentially expressed in WAT. In this work, we have shown the absence of DNA binding or transcriptional activity of this factor in several non-adipose cells tested. By computer analysis, beta3CRE2 was found to constitute an octameric element that is highly homologous to the binding site for some members of the nuclear hormone receptor superfamily. Using the response elements of other adipocyte-specific nuclear receptors as competitors, a 'cross-talk' between WATSF-1 and these response elements has been demonstrated. However, the affinity of WATSF-1 for these response elements differs from that for beta3CRE2 (self), implying that WATSF-1 is distinct from these adipocyte-specific nuclear receptors. Furthermore the DNA-binding activity of WATSF-1 was shown to be enhanced by phosphatase treatment, suggesting that phosphorylation may play an important role in the functional modulation of this factor. In an effort to prove that it is indeed an adipocyte-specific factor, we used 3T3-L1 cells, a cellular model of WAT, that can undergo differentiation into adipocytes. The DNA binding and transcriptional activity of this factor appeared during differentiation of the cells. Taken together, these results demonstrate that WATSF-1 is a putative white adipocyte-specific nuclear orphan receptor induced during adipogenesis and is a transcriptional activator through one of the CREs of the human beta3-AR gene. Targeting this factor may be a novel therapeutic approach to stimulation of the beta3-AR signal transduction pathway in adipose tissues.
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PMID:A putative white adipose tissue specific nuclear orphan receptor that interacts with the cAMP-response element of the human beta3-adrenergic receptor gene. 1094 Apr 87

Human T-cell leukemia virus type I (HTLV-I) is the etiological agent for adult T-cell leukemia (ATL), as well as for tropical spastic paraparesis (TSP) and HTLV-I associate myelopathy (HAM). A biological understanding of the involvement of HTLV-I and in ATL has focused significantly on the workings of the virally-encoded 40 kDa phospho-oncoprotein, Tax. Tax is a transcriptional activator. Its ability to modulate the expression and function of many cellular genes has been reasoned to be a major contributory mechanism explaining HTLV-I-mediated transformation of cells. In activating cellular gene expression, Tax impinges upon several cellular signal-transduction pathways, including those for CREB/ATF and NF-kappa B. In this paper, we review aspects of Tax's transcriptional potential with particular focus on recent evidence linking Tax to IKK (I kappa B-kinase)-complex and MAP3Ks (mitogen-activated protein kinase kinase kinases).
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PMID:Functional activities of the human T-cell leukemia virus type I Tax oncoprotein: cellular signaling through NF-kappa B. 1132 3

The expression of liver-specific genes is regulated by unequivocally allocated transcription factors via proper responsible elements within their promoters. We identified a novel transcription factor, CREB-H, and found that its expression was restricted in the liver among 16 human tissues tested. A region of CREB-H exhibited significant homology to the basic leucine zipper (b-Zip) domain of members of the CREB/ATF family: mammalian LZIP and Drosophila BBF-2 that binds to box-B, a Drosophila enhancer modulating the fat-body-specific gene expression. CREB-H contained a hydrophobic region representing a putative transmembrane domain, like LZIP. Constructing a variety of CREB-H fusion proteins with the GAL4 DNA-binding domain disclosed that CREB-H functioned as a transcriptional activator and its N-terminal 149 amino acids accounted for the activation ability. Gel mobility sift assays revealed that CREB-H did not bind to the C/EBP, AP-1 and NF-kappaB elements but specifically bound to CRE and the box-B element. Luciferase reporter assays demonstrated that like BBF-2, CREB-H activated transcription via the box-B element and that a deletion of the putative transmembrane domain increased the activation of reporter expression significantly. Furthermore, a fusion protein of GFP and full-length CREB-H was localized in reticular structures surrounding the nucleus, whereas a fusion protein of GFP and a deletion mutant lacking the putative transmembrane domain was mainly in the nucleus. These findings suggest that CREB-H plays an important role in transcriptional regulation of genes specifically expressed in the liver, and that the putative transmembrane domain may be associated with modulation of its function as the transcriptional activator.
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PMID:CREB-H: a novel mammalian transcription factor belonging to the CREB/ATF family and functioning via the box-B element with a liver-specific expression. 1135 85

We review the involvement of the cyclic AMP responsive DNA element (CRE) and the ATF/CREB (activating transcription factor/CRE binding protein) family of transcription factors in the regulation and pathology of clinically important viruses that infect humans, including the herpesviridae, adenoviridae, parvoviridae, hepadnaviridae, and retroviridae families. CRE sequences found in specific regulatory elements of human viruses are listed, and the functional evidence for CRE activity, in the form of DNA binding assays, mutational studies, transfection and transcriptional activation experiments, or in vitro transcription assays, is summarized. Manipulation of cellular processes is required for virus replication in human cells following infection. A primary target of many viruses is the cellular transcription machinery, and several human viruses contain transcriptional activator and repressor proteins that affect cellular transcription. Through their effect on cellular transcription, viral genes alter the pattern of cellular gene expression, and thereby affect the differentiation state and cell cycle progression of the infected cell. We summarize evidence demonstrating that the CRE and its binding proteins are involved in the activity of the viruses, implicating their function in the pathogenesis of human diseases. The targeting of specific transcription factor pathways as a potential therapeutic approach is discussed. Copyright 1996 S. Karger AG, Basel
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PMID:Evidence for the Role of Cyclic AMP-Responsive Elements in Human Virus Replication and Disease. 1172 11

Infection of HeLa cells with poliovirus leads to rapid shut-off of host cell transcription by RNA polymerase II. Previous results have suggested that both the basal transcription factor TBP (TATA-binding protein) and transcription activator proteins such as CREB (cyclic AMP-responsive element-binding protein) and Oct-1 (the octamer-binding factor) are cleaved by the viral-encoded protease, 3C(Pro). Here we demonstrate that the transcriptional activator (and tumor suppressor) p53 is degraded by the viral protease 3C both in vivo and in vitro. Unlike other transcription factors that are directly cleaved by 3C(pro), degradation of p53 requires a HeLa cell activity in addition to 3C(Pro). The degradation of p53 by 3C(Pro) does not appear to involve the ubiquitin pathway of protein degradation. Vaccinia virus infection of HeLa cells leads to inactivation of the cellular activity required for 3C(Pro)-mediated degradation of p53. The vaccinia-encoded protein (CrmA) is known to inhibit caspase I (ICE protease) that converts inactive IL-1beta to an active secreted form. Incubation of HeLa cells with caspase I inhibitor Z-VAD-fmk does not interfere with 3C(Pro)-mediated degradation of p53. The cellular activity present in extracts of HeLa cells can be fractionated through phosphocellulose. A partially purified fraction that elutes at 0.6 M KCl from phosphocellulose contains the activity that degrades p53 in a 3C(Pro)-dependent manner. These results suggest that both poliovirus-encoded protease 3C(Pro) and a cellular activity are required for the degradation of p53 observed in cells infected with poliovirus.
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PMID:Poliovirus 3C protease-mediated degradation of transcriptional activator p53 requires a cellular activity. 1187 95

Expression of human T-cell leukemia virus type 1 (HTLV-1) is regulated by the viral transcriptional activator Tax. Tax activates viral transcription through interaction with the cellular transcription factor CREB and the coactivators CBP/p300. One key property of the coactivators is the presence of histone acetyltransferase (HAT) activity, which enables p300/CBP to modify nucleosome structure. The data presented in this manuscript demonstrate that full-length p300 and CBP facilitate transcription of a reconstituted chromatin template in the presence of Tax and CREB. The ability of p300 and CBP to activate transcription from the chromatin template is dependent upon the HAT activity. Moreover, the coactivator HAT activity must be tethered to the template by Tax and CREB, since a p300 mutant that fails to interact with Tax did not facilitate transcription or acetylate histones. p300 acetylates histones H3 and H4 within nucleosomes located in the promoter and 5' proximal regions of the template. Nucleosome acetylation is accompanied by an increase in the level of binding of RNA polymerase II transcription factor TFIID and RNA polymerase II to the promoter. Interestingly, we found distinct transcriptional activities between CBP and p300. CBP, but not p300, possesses an N-terminal activation domain which directly activates Tax-mediated HTLV-1 transcription from a naked DNA template. Finally, using the chromatin immunoprecipitation assay, we provide the first direct experimental evidence that p300 and CBP are associated with the HTLV-1 long terminal repeat in vivo.
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PMID:Acetylation of nucleosomal histones by p300 facilitates transcription from tax-responsive human T-cell leukemia virus type 1 chromatin template. 1205 56

The yeast ATF/CREB repressor Sko1(Acr1) regulates genes that are induced upon hyperosmotic stress by recruiting the Cyc8(Ssn6)-Tup1 corepressor complex to target promoters. During hyperosmotic stress, Hog1 MAP kinase associates with target promoters, phosphorylates Sko1, and converts Sko1 into a transcriptional activator. Unexpectedly, Tup1 remains bound to target promoters during osmotic stress. Sko1, Hog1, and Tup1 are all important for recruitment of SAGA histone acetylase and SWI/SNF nucleosome-remodeling complexes to osmotic-inducible promoters, and both complexes are important for activation upon osmotic stress. Thus, osmotic induction involves a switch of Sko1-Cyc8-Tup1 from a repressing to an activating state in a process that is triggered by Hog1 phosphorylation. Cyc8-Tup1 is not simply a corepressor but is also involved in recruiting SWI/SNF and SAGA during the transcriptional induction process.
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PMID:Hog1 kinase converts the Sko1-Cyc8-Tup1 repressor complex into an activator that recruits SAGA and SWI/SNF in response to osmotic stress. 1208 27


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