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)

Immunosuppressive states with accompanying alterations in cytokine profiles have been postulated to play a vital role in the reactivation of viruses from latency. Cytokines regulate gene expression by activating transcription factors via well-characterized signal transduction pathways. In this study, we report the identification of a novel inducible protein, GBP-i, that binds to a double-stranded GGA/C-rich region of the transcriptional control region of the human papovavirus JC virus (JCV), specifically within the origin of viral DNA replication. GBP-i is distinct from previously characterized GC-box-binding proteins with respect to both its sequence specificity and its electrophoretic mobility on native and denaturing gels. GBP-i responds within 90 min to phorbol myristate acetate stimulation; however, unlike typical phorbol myristate acetate-inducible factors, this rapid induction is regulated primarily at the transcriptional level. Further, the induction of GBP-i appears to be widespread and mediated by many inflammatory cytokines, including interleukin-1 beta, tumor necrosis factor alpha, gamma interferon, and transforming growth factor beta. Interestingly, the induced protein acts as a transcriptional repressor in its native context in the JCVL promoter. However, when its binding sequence is transposed to a heterologous promoter, GBP-i appears to function as a transcriptional activator. The data presented here suggest a role for GBP-i in cytokine-mediated induction of viral and cellular genes.
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PMID:Identification and characterization of a novel GGA/C-binding protein, GBP-i, that is rapidly inducible by cytokines. 796 18

Apoptosis is an important regulatory process during normal development and maturation. We find that the proliferation-arresting and differentiation-inducing compound sodium n-butyrate (NaB) triggers a marked host chromatin degradation. This apoptotic process is independent of, but commensurate with, a rapid increase in viral mRNA synthesis and subsequent release of HIV-1 virus in transformed human cell lines harboring tat- (HLM1) or tat+ (U1, ACH-2) dormant HIV-1 proviruses. This compound stimulates a reversible accumulation of the characteristic viral mRNAs at a much faster rate than two other DNA degradation inducers such as tumor necrosis factor-alpha and phorbol 12-myristate 13-acetate. The transcriptional activator butyrate analogue, alpha-amino-n-butyrate, failed to cause similar phenotypic changes. These results suggest that common regulatory signals may be involved in activation of apoptosis genes and latent provirus by NaB.
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PMID:Induction of developmentally programmed cell death and activation of HIV by sodium butyrate. 800 66

HeLa cells contain a DNA-binding activity which associates with a kappa B-like DNA element, termed Rel-related protein-binding element (RRBE), localized upstream of the human urokinase promoter. We have purified this activity from the HeLa cell cytosol and have shown that it represents a performed heteromeric complex between p65 (RelA) and c-Rel. Coexpression of c-Rel and p65 (RelA) by in vitro translation formed a DNA-binding complex indistinguishable from purified cellular c-Rel-p65 (RelA) in mobility shift assays. The c-Rel-p65 (RelA) complex was also formed in COS7 cells upon coexpression of c-Rel and p65 (RelA) cDNAs. Cotransfection experiments with COS7 cells, using expression plasmids encoding p50, p65 (RelA), or c-Rel and reporter constructs containing a trimerized RRBE, revealed that c-Rel-p65 (RelA) is a potent activator of the RRBE, giving rise to transcriptional activity higher than that observed with NF-kappa B (p50-p65). In the cytosol, the c-Rel-p65 (RelA) complex existed in a latent, non-DNA-binding form but could be activated by detergent treatment, suggesting that it was associated with an I kappa B protein. Recombinant I kappa B-alpha inhibited the DNA-binding activity of c-Rel-p65 (RelA) via association with either c-Rel or p65 (RelA). Finally, NF-kappa B and c-Rel-p65 (RelA) complexes were found to be differentially expressed and regulated in different cells. The two complexes were present in equimolar amounts in HeLa cells and K562 cells. Stimulation with tetradecanoyl phorbol acetate (TPA) resulted in the nuclear translocation of both NF-kappa B and c-Rel-p65 (RelA) in HeLa cells and of NF-kappa B in HepG2 cells but had no effect on either complex in K562 cells. In addition, TPA stimulation of HepG2 cells induced the expression of a cytosolic latent c-Rel-p65 (RelA) complex which, however, was not translocated to the nucleus. In conclusion, our findings show that c-Rel-p65 (RelA) is an inducible and very potent transcriptional activator which is differentially activated in a cell-type-specific manner.
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PMID:Purification, reconstitution, and I kappa B association of the c-Rel-p65 (RelA) complex, a strong activator of transcription. 813 61

The recently cloned fli-1 gene is a member of the ets oncogene family that is preferentially expressed in hematopoietic cells. It is a target of dysregulation by Friend leukemia virus insertion and translocation in Ewing's sarcoma and neuroepithelioma. In this report, we have studied the function and regulation of both murine and human fli-1. Analysis of the human and mouse fli-1 proteins showed that fli-1 binds to specific DNA sequences highly related to m-ets-2 binding sites. Methylation protection experiments showed that fli-1 and m-ets-2 contacted the same nucleotides in two different binding sites. The fli-1 protein was shown to be a transcriptional activator in co-transfection studies. Stimulation of murine bone marrow macrophages by mediators of inflammation, such as lipopolysaccharide, phorbol 12-myristate 13-acetate, interleukin-1, and interferon-gamma resulted in the reduced expression of fli-1 mRNA. fli-1 was only expressed in a defined subset of human erythroleukemia cell lines.
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PMID:Characterization of the ets oncogene family member, fli-1. 844 42

The transactivator HTLV-I Tax activates the promoter of the gene coding for the interleukin 2 alpha-chain receptor (IL-2R alpha) via a kappa B site that can bind several protein species of the rel family. Tax1 strongly activates the enhancer activity of this motif, in both epithelial HeLa and lymphoid Jurkat cells. This activation was not observed in undifferentiated embryocarcinoma F9 cells. Overexpression of the p50, p65 and Rel proteins in these cells showed that significant activation of the IL-2R alpha kappa B site was observed only with Rel and Rel plus p65. Moreover, whereas both Tax and phorbol 12-myristate 13-acetate (PMA) are able to efficiently induce the binding of NF-kappa B to the IL-2R alpha kappa B site, PMA is functionally inactive. Using the DNA affinity precipitation assay, we observed that Tax1 is able to efficiently induce the binding of Rel, whereas PMA is not. This established a clear difference between both stimuli, indicating that Rel is the functionally active factor. We conclude from these results that the functional activity of members of the rel family is regulated by their interaction with DNA and that Rel can be a potent transcriptional activator on specific kappa B sites.
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PMID:The transcriptionally active factors mediating the effect of the HTLV-I Tax transactivator on the IL-2R alpha kappa B enhancer include the product of the c-rel proto-oncogene. 845 41

The 72 kDa 1E1 protein of human cytomegalovirus (HCMV) is one of a few viral regulatory proteins expressed immediately after infection of a host cell. Although it is now well-established that 1E1 is a potent transcriptional activator of the human immunodeficiency virus (HIV) long terminal repeat (LTR), the identity of the nucleotide sequence responsive to 1E1 remains elusive and the molecular mechanism of this interaction is not well-understood. We have constructed various LTR mutants and tested them for their ability to be activated by 1E1 using transient transfection assays. Mutations in the NF-kappa B sites, of either a few changes in the nucleotide sequence or a deletion of the entire region, abrogated 1E1-driven transactivation. Deletion of the Tat-responsive element (TAR) had no significant effect on reporter expression. Mutations in the Sp1 sites or the TATA box significantly lowered LTR activity, but this is probably due to an effect on the general transcription system, as these elements are also required for the transactivation of the LTR by many stimulators including Tat, tumour necrosis factor alpha (TNF-alpha). E1A/E1B and phorbol myristate acetate (PMA). In addition, gel retardation analysis demonstrated that NF- kappa B activity was significantly increased in human T lymphoid H9 and monocytic U937 cell lines constitutively expressing 1E1. Taken together, these data suggest that NF- kappa B plays a central role in the 1E1 transactivation of the HIV LTR.
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PMID:Essential role of NF-kappa B in transactivation of the human immunodeficiency virus long terminal repeat by the human cytomegalovirus 1E1 protein. 855 31

NGFI-B is an immediate early gene and orphan member of the nuclear receptor superfamily. It is induced in several tissues, including brain, and in cultured cerebellar granule cells in response to different stimuli. Since both the induction of its mRNA as well as the level and function of its gene product are under the control of the inducing stimulus, we wanted to study the final outcome of the stimulus, i.e., transcriptional activity, by means of a specific, artificial reporter gene in cultured CNS cells. Cultured cerebellar granule cells and astrocytes were transfected with an NGFI-B responsive reporter gene to study the role of NGFI-B as a transcriptional activator after stimulation of the protein kinase A and C pathways. In both cell types, stimulation of either protein kinase A or C with forskolin (10 microM) or phorbol 12-myristate 13-acetate (0.1 microM), respectively, gave up to fivefold induction of the reporter gene. In the granule cells a combined treatment gave a strong synergistic induction of the reporter gene. The astrocytes showed only weak synergy, indicating cell-specific regulation of the target gene by the two kinases.
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PMID:Activation of a reporter gene responsive to NGFI-B in cultured neurons and astrocytes. 874 51

AP1 is a heterodimeric complex containing products of the Jun and Fos oncogene families. The c-fos and c-jun protooncogenes act as transcriptional activator for numerous cellular genes, and the overexpression of these genes may cause malignant transformation. In this study, to show evidence of a possible inhibition of AP1 transcriptional activity in molecular mechanisms of foodborne molecules, known to be negative modulators of carcinogenesis, we established two rat liver epithelial (REL) cell lines overexpressing either c-fos (43C line) or c-jun (RELcJ1 line) oncoproteins. Contrary to the 43C line, which was spontaneously transformed, the c-jun-transfected REL cells were only transformed in vitro after 12-O-tetra-decanoylphorbol 13-acetate (TPA) exposure. All trans-retinoic acid (RA) abolished the transformation of the 43C line and TPA-treated RELcJ1 cells, suggesting that RA could decrease AP1 activity in these cells despite c-fos or c-jun overexpression. Furthermore, we show for the first time that a flavonoid, quercetin, which is a natural component of vegetables, inhibited only the transformation of the 43C line. The spontaneous transformation of the c-fos-transfected REL cells was associated with the appearance of c-fos/AP1 complexes binding TRE, suggesting that c-fos/AP1 complexes are involved in the antitransforming mechanism of quercetin.
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PMID:Suppression of oncogene-induced transformation by quercetin and retinoic acid in rat liver epithelial cells. 877 34

Carboxy-terminally truncated hepatitis B virus (HBV) middle surface proteins (MHBst) show a transcriptional activator function. Two different subtypes of MHBst activators can be distinguished: an ER-localized type, represented here by MHBst76 (truncated at amino acid 76), and a cytosol-localized type, represented here by MHBst63. To characterize the MHBst activator on the protein level and to analyze posttranslational modifications, we established recombinant baculoviruses encoding for fusion proteins of MHBst76 or MHBst63 and of an amino terminal hexa-his tag. Both proteins could be obtained in high purity by affinity chromatography using Ni-nitrilo-tri-acetate agarose. In addition, 6H-MHBst76 was also isolated from transiently transfected HepG2 cells. Both the Spodoptera frugiperda (Sf9) cell-derived and the HepG2 cell-derived MHBst proteins were found to be unglycosylated. A detailed analysis of Sf9 cell-derived 6H-MHFBst76 by electrospray-ionization mass spectrometry showed that a fraction of this protein is N-terminally acetylated and phosphorylated or sulfated. Electric-field-mediated transfer of the highly purified proteins into reporter cells demonstrated that the isolated proteins are functional transcriptional activators. These experiments further showed that Sf9 cell-derived and HepG2 cell-derived 6H-MHBst do not differ in their functionality. This system allowed production and purification of functional 6H-MHBst in amounts sufficient enough to allow a further detailed analysis of MHBst activators on the protein level.
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PMID:Isolation of highly purified, functional carboxy-terminally truncated hepatitis B virus middle surface protein activators from eucaryotic expression systems. 878 14

The product of the Escherichia coli aidB gene is homologous to human isovaleryl-coenzyme A dehydrogenase (IVD), an enzyme involved in the breakdown of the amino acid leucine. The aidB gene is not expressed constitutively, but its transcription is induced via distinct mechanisms in response to: (i) exposure to alkylating agents; (ii) acetate at a slightly acidic pH; and (iii) anoxia. Induction by alkylating agents is mediated by the transcriptional activator Ada, in its methylated form (meAda); the other forms of induction are Ada independent and require sigma s, the alternative sigma factor mainly expressed during the stationary phase of bacterial growth. In this report we show that, in the absence of any transcriptional factor, aidB is efficiently transcribed in vitro by the sigma s, but not by the sigma 70, form of RNA polymerase holoenzyme. In the presence of meAda, levels of transcription by both forms of RNA polymerase are significantly increased. However, sigma s-dependent transcription of aidB is inhibited both in vitro and in vivo by binding of the transcriptional regulator Lrp (leucine responsive protein) to the aidB promoter region (PaidB). Lrp acts as a specific repressor for sigma s-dependent transcription of aidB. Leucine counteracts Lrp binding to P aidB, as does binding to P aidB of me Ada, which causes Lrp to dissociate from the promoter. The physiological significance of aidB transcription regulation is discussed.
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PMID:The leucine-responsive regulatory protein (Lrp) acts as a specific repressor for sigma s-dependent transcription of the Escherichia coli aidB gene. 880 48


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