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)

The GCN2 protein of Saccharomyces cerevisiae stimulates the expression of amino acid biosynthetic genes under conditions of amino acid starvation by derepressing GCN4, a transcriptional activator of these genes. GCN2 contains sequences homologous to the catalytic domain of protein kinases. We show here that substitution of a highly conserved lysine in the presumed ATP-binding site of this domain impairs the derepression of histidine biosynthetic genes under GCN4 control. This result supports the idea that protein kinase activity is required for GCN2 positive regulatory function. Determination of the nucleotide sequence of the entire GCN2 complementation unit, and measurement of the molecular weight of GCN2 protein expressed in vivo, indicate that GCN2 is a Mr approximately 180,000 protein and contains a Mr approximately 60,000 segment homologous to histidyl-tRNA synthetases (HisRSs) juxtaposed to the protein kinase domain. Several two-codon insertion mutations in the HisRS-related coding sequences inactivate GCN2 regulatory function. Based on these results, we propose that the GCN2 HisRS domain responds to the presence of uncharged tRNA by activating the adjacent protein kinase moiety, thus providing a means of coupling GCN2-mediated derepression of GCN4 expression to the availability of amino acids.
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PMID:Juxtaposition of domains homologous to protein kinases and histidyl-tRNA synthetases in GCN2 protein suggests a mechanism for coupling GCN4 expression to amino acid availability. 266 Jan 41

The transcriptional activator ADR1 from Saccharomyces cerevisiae is a postulated DNA-binding protein that controls the expression of the glucose-repressible alcohol dehydrogenase (ADH2). Carboxy-terminal deletions of the ADR1 protein (1,323 amino acids in length) were used to localize its functional regions. The transcriptional activation region was localized to the N-terminal 220 amino acids of ADR1 containing two DNA-binding zinc finger motifs. In addition to the N terminus, a large part of the ADR1 sequence was shown to be essential for complete activation of ADH2. Deletion of the putative phosphorylation region, defined by ADR1c mutations that overcome glucose repression, did not render ADH2 expression insensitive to glucose repression. Instead, this region (amino acids 220 through 253) was found to be required by ADR1 to bypass glucose repression. These results suggest that ADR1c mutations enhance ADR1 function, rather than block an interaction of the putative phosphorylation region with a repressor molecule. Furthermore, the protein kinase CCR1 was shown to affect ADH2 expression when the putative phosphorylation region was removed, indicating that CCR1 does not act solely through this region. A functional ADR1 gene was also found to be necessary for growth on glycerol-containing medium. The N-terminal 506 amino acids of ADR1 were required for this newly identified function, indicating that ADH2 activation and glycerol growth are controlled by separate regions of ADR1.
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PMID:Identification of functional regions in the yeast transcriptional activator ADR1. 329 Jun 50

The initiation of transcription from the nitrogen-regulated promoter glnAp2 requires RNA polymerase containing sigma 54, the transcriptional activator NRI, and the protein kinase NRII, responsible for the conversion of NRI to the active NRI-phosphate. NRI-phosphate does not increase the ability of sigma 54-containing RNA polymerase to bind to the promoter, but rather stimulates the conversion of an initial promoter:polymerase complex to the transcriptionally active open complex. The presence on the DNA template of high-affinity binding sites for NRI/NRI-phosphate, normally located 130 and 100 bp upstream of the site of transcription initiation, results in a 4- to 5-fold lowering of the concentration of NRI required for the formation of the open complex. These high-affinity NRI binding sites facilitate open complex formation when they are moved to positions 700 bp further upstream or 950 bp downstream of glnAp2 on linear DNA templates.
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PMID:Initiation of transcription at the bacterial glnAp2 promoter by purified E. coli components is facilitated by enhancers. 330 60

The protein kinase MO15/CDK7 has recently been shown to be associated with the general transcription factor TFIIH and to be capable of phosphorylating the RNA polymerase II carboxy-terminal domain. Here, we show that a monoclonal MO15/CDK7 antibody coimmunoprecipitates, from a rat liver nuclear extract, all components of the RNA polymerase II transcription apparatus required for initiation at the albumin and adenovirus major late promoters. The immunoprecipitate includes RNA polymerase II, TFIID, TFIIB, TFIIH, TFIIF, and TFIIE, but is devoid of transcriptional activator proteins, such as HNF1, HNF4, and C/EBP alpha. The finding of an autonomously initiating RNA polymerase II holoenzyme in mammalian cells suggests conceptual similarities between transcription initiation in prokaryotes and eukaryotes.
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PMID:A mammalian RNA polymerase II holoenzyme containing all components required for promoter-specific transcription initiation. 755 66

T-cell activation requires two different signals. The T-cell receptor's recognition of a specific antigen on antigen-presenting cells provides one, and the second signal comes from costimulatory molecules such as CD28. In contrast, T cells that are stimulated with antigen in the absence of the CD28 costimulatory signal can become anergic (nonresponsive). The CD28 response element (CD28RE) has been identified as the DNA element mediating interleukin 2 (IL-2) gene activation by CD28 costimulation. Our previous work demonstrates that the Rel/NF-kappa B family proteins c-Rel, RelA (p65), and NFKB1 (p50) are involved in the complex that binds to the CD28RE. We also showed that c-Rel, but not NFKB1 (p50), can bind to the CD28RE and activate CD28RE-driven transcription in cotransfection assays. However, the role of RelA (p65) in CD28 signaling has not yet been addressed. We provide evidence that RelA (p65) itself bound directly to the CD28RE of the IL-2 promoter and other lymphokine promoters. In addition, RelA (p65) was a potent transcriptional activator of the CD28RE in vivo. We show that a RelA (p65)-c-Rel heterodimer bound to the CD28RE and synergistically activated the CD28RE enhancer activity. We also demonstrate that activated Raf-1 kinase synergized with RelA (p65) in activating the CD28RE enhancer activity. Interestingly, a soluble anti-CD28 monoclonal antibody alone, in the absence of other stimuli, also synergized with RelA (p65) in activating the CD28RE. Furthermore, we show that RelA (p65) activated expression of the wild-type IL-2 promoter but not the CD28RE-mutated IL-2 promoter. A combination of RelA (p65) and NFKB1 (p50) also activated the IL-2 promoter through the CD28RE site. These results demonstrate the functional regulation of the CD28RE, within the IL-2 promoter, by Rel/NF-kappa B transcription factors.
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PMID:RelA is a potent transcriptional activator of the CD28 response element within the interleukin 2 promoter. 762 20

The transcript for the high-affinity Ca2+/calmodulin-binding protein calspermin is generated from the gene encoding Ca2+/calmodulin-dependent protein kinase IV only in postmeiotic germ cells during spermatogenesis. We demonstrate that this testis-specific calspermin transcript can be produced in heterologous cells by utilization of a promoter located in an intron of the calmodulin (CaM) kinase IV gene. Critical motifs within this promoter are two cyclic AMP response element (CRE)-like sequences located about -70 and -50 bp upstream of the transcriptional initiation site. Both CRE motifs are footprinted by the authentic testis-specific transcriptional activator CREM tau or by CREM tau present in adult testis nuclear extract. Whereas a 2.1-kb DNA fragment containing the calspermin promoter is inactive when transfected into NIH 3T3 cells, activity can be restored by cotransfection of CREM tau and protein kinase A or CaM kinase IV but not CaM kinase II alpha. Restoration of activity is greatly reduced by mutation of the two CRE motifs. Since CRE-like motifs have been identified in many genes uniquely expressed in postmeiotic germ cells, which contain abundant CREM tau protein, we suggest that CREM tau may function as one transcription factor responsible for the expression of postmeiotic germ cell-specific genes.
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PMID:Calspermin gene transcription is regulated by two cyclic AMP response elements contained in an alternative promoter in the calmodulin kinase IV gene. 779 65

Treatment of hamster cells in culture with the DNA alkylating agent N-methyl-N'-nitro-N-nitrosoguanidine (MNNG) induces DNA polymerase beta (beta-pol) gene expression and cellular levels of the enzyme. Transcriptional activity of a cloned beta-pol promoter in transient expression assays is also stimulated. Among the requirements for these responses are methylation damage to genomic DNA, cellular cAMP-dependent protein kinase, and the ATF/CREB site of the cloned beta-pol promoter. In the present study, HeLa cell nuclear extract from MNNG-treated cells was much more active in an in vitro transcription assay than nuclear extract from normal cells. By using an oligonucleotide affinity column to deplete the nuclear extract of ATF/CREB, we showed that the difference was due to ATF/CREB activator. Purified ATF/CREB activator from MNNG-treated cells was approximately 10-fold more active than ATF/CREB purified from normal cells as a transcriptional activator for the depleted nuclear extract. ATF/CREB in the extract from normal cells is known to activate in vitro transcription by increasing the rate of promoter clearance [Narayan, S., Widen, S. G., Beard, W. A., & Wilson, S. H. (1994) J. Biol. Chem. 269, 12755-12763]. With ATF/CREB from MNNG-treated cells, the amount of preinitiation complex formed was much greater than with ATF/CREB from normal cells, and the kinetics of both the closed to open preinitiation complex isomerization and promoter clearance were altered. These results indicate that the mechanism of transcriptional activation secondary to DNA alkylation damage is recruitment of more preinitiation complex and alteration of the kinetic scheme of transcription initiation.
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PMID:DNA damage-induced transcriptional activation of a human DNA polymerase beta chimeric promoter: recruitment of preinitiation complex in vitro by ATF/CREB. 781 26

Agrobacterium tumefaciens contains about 25 vir genes localized on a 200-kb tumour-inducing (Ti) plasmid that direct a conjugation-like transfer of tumorigenic DNA from the bacterium to the nuclei of infected plant cells. These genes are strongly and coordinately induced during infection in response to three different classes of stimuli which are thought to be key chemical features of a typical wound site. These stimuli are (i) guaiacol and syringol derivatives such as acetosyringone, (ii) sugars such as glucose and glucuronic acid, and (iii) acidic pH. The sensing of these compounds is carried out by the VirA, VirG and ChvE proteins. VirA is a four-domain histidine protein kinase, while VirG is a transcriptional activator which is activated by VirA-mediated phosphorylation. ChvE is a chromosomally encoded periplasmic sugar binding protein which is required for sensing sugars but dispensable for sensing the other two stimuli. Here we will review the nature of these chemical stimuli, the structure and function of the three regulatory proteins, their similarity to sensors found in human and animal pathogens, the factors influencing their pool size, and their role in the host range of different strains of A. tumefaciens.
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PMID:Host recognition by the VirA, VirG two-component regulatory proteins of agrobacterium tumefaciens. 785 33

The mammalian transcriptional activator CREB binds as a dimer to a broad spectrum of inducible promoters. CREB activity is modulated by several signalling agents (protein kinase A [PKA], Ca2+, and transforming growth factor beta) and via functional interactions with cell-specific transcription factors. In addition, CREB can activate transcription constitutively and repress the activity of several other transcriptional activators. The mechanisms that allow CREB to act in such a malleable manner and the role that CREB dimerization might play in this are poorly understood. To probe the latter issue, we have created monomeric forms of CREB by fusing CREB to the DNA-binding domain of a protein (B-cell specific activator protein [BSAP]) that binds to DNA as a monomer. Remarkably, monomeric CREB acts as a potent, constitutive activator under conditions in which native CREB is inducible by PKA. Thus, CREB contains constitutive activation regions that are unable to function in native CREB. Two glutamine-rich domains that are important for native, PKA-inducible CREB activity are required for the constitutive activity of monomeric CREB. In contrast, two elements within the kinase-inducible domain of CREB are dispensable for constitutive activity. We discuss our results in relation to inducible and constitutive CREB activity and the potential modes of action of other activators that directly interact with CREB.
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PMID:A monomeric derivative of the cellular transcription factor CREB functions as a constitutive activator. 793 35

Overexpression of the YAP1 transcriptional activator renders yeast cells resistant to multiple metabolic inhibitors. In an effort to identify other gene products required for this phenotype we have isolated genomic mutations which neutralize this effect. One such mutation was further characterized and the affected gene was shown to be identical to TPS2 which encodes trehalose phosphate phosphatase, an enzyme catalysing the second step in trehalose biosynthesis. We have analysed the transcriptional regulation of the TPS2 gene and have shown that its transcription is induced by a variety of stressful conditions caused by metabolic inhibitors, osmotic shock and heat shock. This transcriptional activation is mediated by multiple stress promoter elements (C4T) and requires the function of Yap1p as well as reduced activity of the cAMP-regulated protein kinase. Using an appropriate reporter gene we have shown that Yap1p is generally required for transcriptional regulation through the C4T stress element. These results show that the YAP1 protein has a pivotal role in the metabolic stress response and the acquisition of stress tolerance.
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PMID:Yap1p, a yeast transcriptional activator that mediates multidrug resistance, regulates the metabolic stress response. 807 99


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