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

The early growth response gene 1 (Egr-1) is a member of the family of immediate early response genes. Egr-1 encodes a nuclear phosphoprotein that binds a specific nonameric DNA sequence through three zinc-finger domains and functions as a transcriptional activator. We tested whether the vasoactive agents platelet-derived growth factor (PDGF), arginine vasopressin (AVP), serotonin (5-HT), and angiotensin II (ANG II) induced Egr-1 mRNA in cultured rat mesangial cells (MCs) and investigated the role of protein kinase C (PKC) in mediating the induction process. PDGF, AVP, and 5-HT induced Egr-1 mRNA within 15 min, reaching peak levels at 45-60 min. After PDGF and 5-HT stimulation, Egr-1 mRNA levels returned to baseline within 4 h, whereas AVP induced a sustained increase for up to 8 h. There was a very close correlation between doses required for Egr-1 induction and induction of MC proliferation. ANG II was a very weak MC mitogen and induced only a small increase in Egr-1 mRNA. Comparison of control cells with cells depleted of PKC by 48 h of PMA treatment revealed that induction of Egr-1 by PDGF and 5-HT is independent of PKC. In contrast, however, the Egr-1 response to AVP was diminished in PKC-depleted cells. AVP induced Egr-1 mRNA 10.9-fold in control cells, compared with 7.8-fold in PKC-depleted cells. Egr-1 mRNA after AVP stimulation remained elevated in control cells for up to 8 h but returned to baseline after 120 min in PKC-depleted cells. Similar results were obtained using the PKC-inhibitor H-7. Using immunocytochemistry, PDGF and AVP were found to induce Egr-1 protein within 30 min localized to the nucleus. We conclude that there is a strong correlation between induction of Egr-1 after stimulation with PDGF, AVP, 5-HT, and ANG II and the proliferative response elicited by these agents in MCs. AVP induces Egr-1 by both PKC-dependent and PKC-independent pathways, whereas the effects of PDGF and 5-HT are independent of PKC.
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PMID:Effect of vasoactive agents on induction of Egr-1 in rat mesangial cells: correlation with mitogenicity. 141 34

In both Salmonella typhimurium and Escherichia coli, CysB is a LysR family transcriptional activator, which regulates genes of the cysteine regulon. Transcription activation of cys genes also requires an inducer, N-acetyl-L-serine, and cysB mutants that do not require inducer are termed constitutive, i.e. cysBc. After finding that two independently isolated cysBc mutants are substituted at amino acid residue threonine-149 (T149), we isolated the other 17 single-amino-acid substitutions by site-directed mutagenesis. Of the 19 mutant alleles, 11 supported normal growth on sulphate, and nine of these were cysBc. Four other mutants were 'leaky' cysB+, and four were cysB-. Insertions of up to 14 amino acids were also tolerated at T149, and two of three such mutants were cysBc. An allele containing a TAG translation terminator at codon 149 had no detectable function in a delta cysB strain, but gave a constitutive phenotype when introduced into either wild-type S. typhimurium or the E. coli strain NK1, which contains a cysB- mutation in a predicted helix-turn-helix region that interferes with specific binding of CysB to DNA and with autoregulation of cysB. The peptide encoded by the T149ter allele is proposed to interact with the wild-type CysB peptide or with the NK1 mutant peptide to form hetero-oligomers that do not require N-acetyl-L-serine for cys gene activation.
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PMID:Residue threonine-149 of the Salmonella typhimurium CysB transcription activator: mutations causing constitutive expression of positively regulated genes of the cysteine regulon. 781 39

Molecular, biochemical and epidemiological evidence implicate HTLV-I as an etiologic agent of adult T cell leukemia (ATL). The Tax protein of HTLV-I, a positive transcriptional activator of HTLV-I gene expression, is a viral oncogene that also increases transcription of cellular genes including GM-CSF, IL-2R alpha and IL-2. One of the cellular targets of the trans-activating effects of Tax is the NF-kappa B/Rel family of transcription factors, pleiotropic regulators of immunoregulatory, cytokine and viral gene expression. In this report, we demonstrate that NFKB2 (lyt-10) and c-Rel are overexpressed in HTLV-I infected and Tax-expressing cells and, together, account for the majority of the constitutive NF-kappa B binding activity in these cells before and after PMA stimulation. Most importantly, we show a Tax-dependent correlation between expression of NFKB2(p100) and processing to the DNA binding NFKB2(p52) form, induction of c-Rel, and trans-activation of NF-kappa B-mediated gene expression. Furthermore, the NFKB2 precursor is physically associated with c-Rel and with Tax in HTLV-I infected cells. We propose that NFKB2 synthesis and processing allows continuous nuclear expression of an otherwise cytoplasmic protein and, in conjunction with overexpression of c-Rel, NFKB2 alters the NF-kappa B signalling pathway and contributes to leukemic transformation of T cells by HTLV-I.
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PMID:Overproduction of NFKB2 (lyt-10) and c-Rel: a mechanism for HTLV-I Tax-mediated trans-activation via the NF-kappa B signalling pathway. 810 27

SJL mouse lymphomas (reticulum cell sarcomas, or RCSs) of germinal center B cell origin express an endogenous mouse mammary tumor virus (mtv-29) superantigen (vSAg) that stimulates Vbeta16+ T cells to produce cytokines essential for RCS growth. Normal or LPS-activated SJL/J B cells contain two to three larger mRNAs for mouse mammary tumor virus-long terminal repeat (LTR) but not the 1.8-kb mRNA, which is prominent in RCS cells and encodes the vSAg-29. mRNAs from RCS and normal lymphoid cells were characterized by Northern hybridization using DNA probes from various regions of mtv-29, as well as by reverse transcription PCR, RNase protection, and primer extension. The larger mtv-29 transcripts, coding for envelope protein, are initiated in the 5' LTR, as expected. Surprisingly, the 1.8-kb mRNA, encoding the open reading frame of the LTR, is initiated in the middle of the env region and spliced in the 3' env. This is the first report of an mtv-vSAg transcript that is not controlled by promoter(s) located in the 5' LTR. The env initiation site appears identical to that of the mouse mammary tumor virus env transcriptional activator-directed PMA-induced defective LTR transcript in the C57BL6 T cell lymphoma, EL-4. The stimulus independence, B lymphoma specificity, and absence of deletions within either the 5' or 3' LTR regions of mtv-29 in RCS distinguish the situation in RCS cells from that in EL-4. These findings suggest that the novel mtv-29-vSAg transcript reflects an RCS-cell-specific regulation of transcription.
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PMID:Control of endogenous mouse mammary tumor virus superantigen expression in SJL lymphomas by a promoter within the env region. 887 50

The complex network of cytokines that are involved in inflammatory and immunoregulatory responses plays a critical role in the pathogenesis of HIV infection. RANTES (regulated upon activation, normal T cell expressed and secreted) is a cytokine that belongs to the beta-chemokine family; it is chemoattractant for CD4+/CD45RO T cells, it is produced by various cell types including CD8+ and CD4+ T cells as well as monocytes/macrophages, and has recently been shown to suppress replication of macrophage-tropic strains of HIV in CD4+ T cells. To investigate the molecular mechanisms of RANTES expression, the RANTES promoter region was analyzed by transient expression and gel-mobility shift assays. We demonstrate that: 1) RANTES promoter activity is up-regulated by PMA plus ionomycin, coexpression of the p65 subunit of nuclear factor (NF)-kappa B, the proinflammatory cytokines TNF-alpha and IL-1 beta, and the CD28 costimulatory pathway; 2) the RANTES promoter region contains four NF-kappa B binding sites at positions -30, -44, -213, and -579 relative to the transcription start site; 3) one site (-213) is an NF-AT (nuclear factor of activated T cells) binding site that also has weak affinity to NF-kappa B, and the most distal site (-579) also serves as a CD28-responsive element; and 4) mutation on any of those NF-kappa B sites or coexpression of I kappa B alpha (cytoplasmic inhibitor of NF-kappa B) markedly reduced the promoter activity. Thus, NF-kappa B, a potent transcriptional activator of HIV expression, is also involved in the expression of RANTES, a chemokine that blocks infection by macrophage-tropic strains of HIV.
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PMID:Nuclear factor-kappa B potently up-regulates the promoter activity of RANTES, a chemokine that blocks HIV infection. 912 Mar 10

In Herbaspirillum seropedicae, an endophytic diazotroph, nif gene expression is under the control of the transcriptional activator NifA. We have over-expressed and purified a protein containing the central and C-terminal domains of the H. seropedicae NifA protein, N-truncated NifA, fused to a His-Tag sequence. This fusion protein was found to be partially soluble and was purified by affinity chromatography. Band shift and footprinting assays showed that the N-truncated NifA protein was able to bind specifically to the H. seropedicae nifB promoter region. In vivo analysis showed that this protein activated the nifH promoter of Klebsiella pneumoniae in Escherichia coli only in the absence of oxygen and this activation was not negatively controlled by ammonium ions.
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PMID:Expression and functional analysis of an N-truncated NifA protein of Herbaspirillum seropedicae. 1021 62

Interleukin-5 (IL-5) controls the development of eosinophilia and contributes to a number of disease states including asthma. Expression of IL-5 is inducible under tight transcriptional regulation. This requires the contribution of several promoter elements; however, the conserved lymphokine element 0 (CLE0) in particular, is essential for expression of IL-5. In this study, we report the nuclear factors which regulate human IL-5 CLE0 activity in the human cell line PER-117. Using specific antibodies, we identified the transcriptional factors Oct-1 and Oct-2 binding to the 5' region of the CLE0 element. The involvement of Oct factors with CLE0 has not been reported previously in any of the lymphokines. In addition, the CLE0 element also appeared to complex with the transcriptional activator AP-1, consisting of the family members Jun D and Fra-2. We observed the binding of Oct-1 to be constitutive in comparison to Oct-2 and AP-1, both of which were induced in response to cell activation by PMA/A23187. Although the interaction of all three factors with CLE0 was closely linked and overlapping, residues critical to their binding were identified. We demonstrate, using site-directed mutagenesis and cotransfection experiments, that the CLE0 element is indispensable for IL-5 promoter activity and that Octamer factors contribute to the positive regulation of the hIL-5 gene.
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PMID:The activity of the human interleukin-5 conserved lymphokine element 0 is regulated by octamer factors in human cells. 1049 Nov 86

The NtrX protein has been identified as a transcriptional activator of genes involved in the metabolic control of alternative nitrogen sources, acting as a member of a two-component regulatory system. The in silico analysis of the NtrX amino acid sequence shows that this protein contains an N-terminal receiver domain, a central AAA+ superfamily domain and a C-terminal DNA binding domain. To over-express and purify this protein, the ntrX gene of Azospirillum brasilense lacking the first eight codons was cloned into the vector pET29a+. The NtrX protein was over-expressed as an S.Tag fusion protein induced by l-arabinose in the Escherichia coli strain BL21AI and purified by ion exchange and affinity chromatography. The ATPase activity of NtrX was measured by coupling the ATP conversion to ADP with NADH oxidation. The ATPase activity of NtrX was stimulated in the presence of A. brasilense sigma(54)/NtrC-dependent promoter of the glnBA gene. Phosphorylation by carbamyl-phosphate also stimulated ATPase, in a manner similar to the NtrC protein. Together our results suggest that NtrX is active in the phosphorylated form and that there may be a cross-talk between the NtrYX and NtrBC regulatory systems in A. brasilense.
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PMID:Purification and characterisation of Azospirillum brasilense N-truncated NtrX protein. 1730 59

HIV-1 transcription is tightly regulated: silent in long-term latency and highly active in acutely-infected cells. Transcription is activated by the viral protein Tat, which recruits the elongation factor P-TEFb by binding the TAR sequence present in nascent HIV-1 RNAs. In this study, we analyzed the dynamic of the TAR:Tat:P-TEFb complex in living cells, by performing FRAP experiments at HIV-1 transcription sites. Our results indicate that a large fraction of Tat present at these sites is recruited by Cyclin T1. We found that in the presence of Tat, Cdk9 remained bound to nascent HIV-1 RNAs for 71s. In contrast, when transcription was activated by PMA/ionomycin, in the absence of Tat, Cdk9 turned-over rapidly and resided on the HIV-1 promoter for only 11s. Thus, the mechanism of trans-activation determines the residency time of P-TEFb at the HIV-1 gene, possibly explaining why Tat is such a potent transcriptional activator. In addition, we observed that Tat occupied HIV-1 transcription sites for 55s, suggesting that the TAR:Tat:P-TEFb complex dissociates from the polymerase following transcription initiation, and undergoes subsequent cycles of association/dissociation.
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PMID:A real-time view of the TAR:Tat:P-TEFb complex at HIV-1 transcription sites. 1753 37

ZFPs (Zinc Finger Proteins) play important roles in various cellular functions, including transcriptional activation, transcriptional repression, cell proliferation, and development. C(2)H(2) (Cys-Cys-His-His motif) ZFPs are the most abundant proteins among the founding members of the ZFP super family in eukaryotes. In this study, we isolate a novel C(2)H(2) ZNF (Zinc Finger) gene ZNFD. It contains an ORF (Open Reading Frame) with a length of 990 bp, encoding 329 amino acids. The predicted protein contains a C(2)H(2) zinc finger. RT-PCR analysis in 18 human adult tissues indicated that it was expressed in five human adult tissues. Green fluorescence protein localization analysis showed that human ZNFD was located in the nucleus of Hela cells. Overexpression of ZNFD in the COS7 cells activates the transcriptional activities of AP1(PMA) (Activator of protein 1, that responds specifically to phorbol ester). Together the data indicate that ZNFD is probably a new type of C(2)H(2) ZFP and the ZNFD protein may act as a transcriptional activator in PKC (protein kinase C) signal pathway to mediate cellular functions.
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PMID:Isolation and characterization of a novel zinc finger gene, ZNFD, activating AP1(PMA) transcriptional activities. 2016 41


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