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Query: UNIPROT:P51532 (transcriptional activator)
 6,546 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

In the transcriptional response of Saccharomyces cerevisiae to stress, both activators and repressors are implicated. Here we demonstrate that the ion homeostasis determinant, HAL1, is regulated by two antagonistically operating bZIP transcription factors, the Sko1p repressor and the Gcn4p activator. A single CRE-like sequence (CRE(HAL1)) at position -222 to -215 with the palindromic core sequence TTACGTAA is essential for stress-induced expression of HAL1. Down-regulation of HAL1 under normal growth conditions requires specific binding of Sko1p to CRE(HAL1) and the corepressor gene SSN6. Release from this repression depends on the function of the high-osmolarity glycerol pathway. The Gcn4p transcriptional activator binds in vitro to the same CRE(HAL1) and is necessary for up-regulated HAL1 expression in vivo, indicating a dual control mechanism by a repressor-activator pair occupying the same promoter target sequence. gcn4 mutants display a strong sensitivity to elevated K(+) or Na(+) concentrations in the growth medium. In addition to reduced HAL1 expression, this sensitivity is explained by the fact that amino acid uptake is drastically impaired by high Na(+) and K(+) concentrations in wild-type yeast cells. The reduced amino acid biosynthesis of gcn4 mutants would result in amino acid deprivation. Together with the induction of HAL1 by amino acid starvation, these results suggest that salt stress and amino acid availability are physiologically interconnected.
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PMID:The Sko1p repressor and Gcn4p activator antagonistically modulate stress-regulated transcription in Saccharomyces cerevisiae. 1111 77

The Schizosaccharomyces pombe fbp1 gene, which encodes fructose-1,6-bis-phosphatase, is transcriptionally repressed by glucose through the activation of the cAMP-dependent protein kinase A (PKA) and transcriptionally activated by glucose starvation through the activation of a mitogen-activated protein kinase (MAPK). To identify transcriptional regulators acting downstream from or in parallel to PKA, we screened an adh-driven cDNA plasmid library for genes that increase fbp1 transcription in a strain with elevated PKA activity. Two such clones express amino-terminally truncated forms of the S. pombe tup12 protein that resembles the Saccharomyces cerevisiae Tup1p global corepressor. These clones appear to act as dominant negative alleles. Deletion of both tup12 and the closely related tup11 gene causes a 100-fold increase in fbp1-lacZ expression, indicating that tup11 and tup12 are redundant negative regulators of fbp1 transcription. In strains lacking tup11 and tup12, the atf1-pcr1 transcriptional activator continues to play a central role in fbp1-lacZ expression; however, spc1 MAPK phosphorylation of atf1 is no longer essential for its activation. We discuss possible models for the role of tup11- and tup12-mediated repression with respect to signaling from the MAPK and PKA pathways. A third clone identified in our screen expresses the php5 protein subunit of the CCAAT-binding factor (CBF). Deletion of php5 reduces fbp1 expression under both repressed and derepressed conditions. The CBF appears to act in parallel to atf1-pcr1, although it is unclear whether or not CBF activity is regulated by PKA.
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PMID:Transcriptional regulators of the Schizosaccharomyces pombe fbp1 gene include two redundant Tup1p-like corepressors and the CCAAT binding factor activation complex. 1123 5

The AarP protein in Providencia stuartii encodes a small transcriptional activator which activates the chromosomal aminoglycoside acetyltransferase aac(2')-Ia gene. In addition, AarP activates genes involved in a multiple antibiotic resistance (Mar) phenotype. Expression of an aarP-lacZ fusion increased in a density-dependent manner and reached peak levels at stationary phase. The expression of an aarP-lacZ fusion could be prematurely activated in cells at early to mid-exponential phase by the addition of spent culture supernatants from stationary phase cultures or by ethyl acetate extracts of these supernatants. Nutrient starvation had a negligible effect on aarP expression. In a search for mutations that block aarP activation at stationary phase, a mini-Tn5Cm insertion has been identified within a gene whose product was 77% identical to SspA, a regulatory protein involved in stationary phase gene expression and virulence. An unmarked sspA null allele (sspA2) was created by allelic replacement to further examine the role of sspA in P. stuartii. The sspA2 allele resulted in substantial decrease in aarP mRNA accumulation at various phases of growth. Furthermore, in an sspA mutant background, the aarP-lacZ fusion was no longer activated by an extracellular signal.
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PMID:Role of SspA in the density-dependent expression of the transcriptional activator AarP in Providencia stuartii. 1125 43

In mammalian cells transcription factors of the AP-1 family are activated by either stress signals such as UV radiation, or mitogenic signals such as growth factors. Here we show that a similar situation exists in the yeast Saccharomyces cerevisiae. The AP-1 transcriptional activator Gcn4, known to be activated by stress signals such as UV radiation and amino acids starvation, is also induced by growth stimulation such as glucose. We show that glucose-dependent Gcn4 activation is mediated through the Ras/cAMP pathway. This pathway is also responsible for UV-dependent Gcn4 activation but is not involved in Gcn4 activation by amino acid starvation. Thus, the unusual phenomenon of activation of mitogenic pathways and AP-1 factors by contradictory stimuli through Ras is conserved from yeast to mammals. We also show that activation of Gcn4 by glucose and UV requires Gcn2 activity. However, in contrast to its role in amino acid starvation, Gcn2 does not increase eIF2alpha phosphorylation or translation of GCN4 mRNA in response to glucose or UV. These findings suggest a novel mechanism of action for Gcn2. The finding that Gcn4 is activated in response to glucose via the Ras/cAMP pathway suggests that this cascade coordinates glucose metabolism with amino acids and purine biosynthesis and thereby ensures availability of both energy and essential building blocks for continuation of the cell cycle.
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PMID:Gcn2 mediates Gcn4 activation in response to glucose stimulation or UV radiation not via GCN4 translation. 1135 Sep 78

Starvation for amino acids induces Gcn4p, a transcriptional activator of amino acid biosynthetic genes in Saccharomyces cerevisiae. In an effort to identify all genes regulated by Gcn4p during amino acid starvation, we performed cDNA microarray analysis. Data from 21 pairs of hybridization experiments using two different strains derived from S288c revealed that more than 1,000 genes were induced, and a similar number were repressed, by a factor of 2 or more in response to histidine starvation imposed by 3-aminotriazole (3AT). Profiling of a gcn4Delta strain and a constitutively induced mutant showed that Gcn4p is required for the full induction by 3AT of at least 539 genes, termed Gcn4p targets. Genes in every amino acid biosynthetic pathway except cysteine and genes encoding amino acid precursors, vitamin biosynthetic enzymes, peroxisomal components, mitochondrial carrier proteins, and autophagy proteins were all identified as Gcn4p targets. Unexpectedly, genes involved in amino acid biosynthesis represent only a quarter of the Gcn4p target genes. Gcn4p also activates genes involved in glycogen homeostasis, and mutant analysis showed that Gcn4p suppresses glycogen levels in amino acid-starved cells. Numerous genes encoding protein kinases and transcription factors were identified as targets, suggesting that Gcn4p is a master regulator of gene expression. Interestingly, expression profiles for 3AT and the alkylating agent methyl methanesulfonate (MMS) overlapped extensively, and MMS induced GCN4 translation. Thus, the broad transcriptional response evoked by Gcn4p is produced by diverse stress conditions. Finally, profiling of a gcn4Delta mutant uncovered an alternative induction pathway operating at many Gcn4p target genes in histidine-starved cells.
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PMID:Transcriptional profiling shows that Gcn4p is a master regulator of gene expression during amino acid starvation in yeast. 1139 Jun 63

The CPCA protein of the filamentous fungus Aspergillus nidulans is a member of the c-Jun-like transcriptional activator family. It acts as central transcription factor of the cross-pathway regulatory network of amino acid biosynthesis and is functionally exchangeable for the general control transcriptional activator Gcn4p of Saccharomyces cerevisiae. In contrast to GCN4, expression of cpcA is strongly regulated by two equally important mechanisms with additive effects that lead to a fivefold increased CPCA protein amount under amino acid starvation conditions. One component of cpcA regulation involves a transcriptional autoregulatory mechanism via a CPCA recognition element (CPRE) in the cpcA promoter that causes a sevenfold increased cpcA mRNA level when cells are starved for amino acids. Point mutations in the CPRE cause a constitutively low mRNA level of cpcA and a halved protein level when amino acids are limited. Moreover, two upstream open reading frames (uORFs) in the 5' region of the cpcA mRNA are important for a translational regulatory mechanism. Destruction of both short uORFs results in a sixfold increased CPCA protein level under nonstarvation conditions and a 10-fold increase under starvation conditions. Mutations in both the CPRE and uORF regulatory elements lead to an intermediate effect, with a low cpcA mRNA level but a threefold increased CPCA protein level independent of amino acid availability. These data argue for a combined regulation of cpcA that includes a translational regulation like that of yeast GCN4 as well as a transcriptional regulation like that of the mammalian jun and fos genes.
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PMID:Transcriptional autoregulation and inhibition of mRNA translation of amino acid regulator gene cpcA of filamentous fungus Aspergillus nidulans. 1155 22

We observed that the transcription of Saccharomyces cerevisiae cytoplasmic thiol peroxidase type II (cTPx II) (YDR453C) is regulated in response to various stresses (e.g. oxidative stress, carbon starvation, and heat-shock). It has been suggested that both transcription-activating proteins, Yap1p and Skn7p, regulate the transcription of cTPx II upon exposure to oxidative stress. However, a dramatic loss of transcriptional response to various stresses in yeast mutant strains lacking both Msn2p and Msn4p suggests that the transcription factors act as a principal transcriptional activator. In addition to two Yap1p response elements (YREs), TTACTAA and TTAGTAA, the presence of two stress response elements (STREs) (CCCCT) in the upstream sequence of cTPx II also suggests that Msn2p/Msn4p could control stress-induced expression of cTPx II. Analysis of the transcriptional activity of site-directed mutagenesis of the putative STREs (STRE1 and STRE2) and YREs (TRE1 and YRE2) in terms of the activity of a lacZ reporter gene under control of the cTPx II promoter indicates that STRE2 acts as a principal binding element essential for transactivation of the cTPx II promoter. The transcriptional activity of the cTPx II promoter was exponentially increased after postdiauxic growth. The transcriptional activity of the cTPx II promoter is greatly increased by rapamycin. Deletion of Tor1, Tor2, Ras1, and Ras2 resulted in a considerable induction when compared with their parent strains, suggesting that the transcription of cTPx II is under negative control of the Ras/cAMP and target of rapamycin signaling pathways. Taken together, these results suggest that cTPx II is a target of Msn2p/Msn4p transcription factors under negative control of the Ras-protein kinase A and target of rapamycin signaling pathways. Furthermore, the accumulation of cTPx II upon exposure to oxidative stress and during the postdiauxic shift suggests an important antioxidant role in stationary phase yeast cells.
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PMID:Msn2p/Msn4p act as a key transcriptional activator of yeast cytoplasmic thiol peroxidase II. 1182 10

Protein kinase GCN2 regulates translation initiation by phosphorylating eukaryotic initiation factor 2alpha (eIF2alpha), impeding general protein synthesis but specifically inducing translation of GCN4, a transcriptional activator of amino acid biosynthetic genes in Saccharomyces cerevisiae. GCN2 activity is stimulated in amino acid-deprived cells through binding of uncharged tRNA to a domain related to histidyl tRNA synthetase. We show that GCN2 is phosphorylated by another kinase on serine 577, located N-terminal to the kinase domain. Mutation of Ser-577 to alanine produced partial activation of GCN2 in nonstarved cells, increasing the level of phosphorylated eIF2alpha, derepressing GCN4 expression, and elevating the cellular levels of tryptophan and histidine. The Ala-577 mutation also increased the tRNA binding affinity of purified GCN2, which can account for the elevated kinase activity of GCN2-S577A in nonstarved cells where uncharged tRNA levels are low. Whereas Ser-577 remains phosphorylated in amino acid-starved cells, its dephosphorylation could mediate GCN2 activation in other stress or starvation conditions by lowering the threshold of uncharged tRNA required to activate the protein.
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PMID:Serine 577 is phosphorylated and negatively affects the tRNA binding and eIF2alpha kinase activities of GCN2. 1207 Jan 58

The subcellular localization of Msn2, a transcriptional activator of STRE (stress response element)-regulated genes, is modulated by carbon source availability. In cells growing in glucose, Msn2 is located mainly in the cytosol, whereas in carbon source-starved cells, Msn2 is located largely inside the nucleus. However, in cells lacking Reg1 (the regulatory subunit of the Reg1/Glc7 protein phosphatase complex), the regulation of subcellular distribution is absent, Msn2 being constitutively present in the cytosol. The localization defect in these mutants is specific for carbon starvation stress, and it is because of the presence of an abnormally active Snf1 protein kinase that inhibits the nuclear localization of Msn2 upon carbon starvation. Active Snf1 kinase is also able to avoid the effects of rapamycin, a drug that by inhibiting the TOR kinase pathway leads to a nuclear localization of Msn2 in wild type cells. Therefore, active Snf1 and the TOR kinase pathway may affect similar cytosolic steps in the regulation of the subcellular localization of Msn2.
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PMID:Convergence of the target of rapamycin and the Snf1 protein kinase pathways in the regulation of the subcellular localization of Msn2, a transcriptional activator of STRE (Stress Response Element)-regulated genes. 1209 9

Regulated intracellular localization of Gln3, the transcriptional activator responsible for nitrogen catabolite repression (NCR)-sensitive transcription, permits Saccharomyces cerevisiae to utilize good nitrogen sources (e.g. glutamine and ammonia) in preference to poor ones (e.g. proline). During nitrogen starvation or growth in medium containing a poor nitrogen source, Gln3 is nuclear and NCR-sensitive transcription is high. However, when cells are grown in excess nitrogen, Gln3 is localized to the cytoplasm with a concomitant decrease in gene expression. Treating cells with the Tor protein inhibitor, rapamycin, mimics nitrogen starvation. Recently, carbon starvation has been reported to cause nuclear localization of Gln3 and increased NCR-sensitive transcription. Here we show that nuclear localization of Gln3 during carbon starvation derives from its indirect effects on nitrogen metabolism, i.e. Gln3 does not move into the nucleus of carbon-starved cells if glutamine rather than ammonia is provided as the nitrogen source. In addition, these studies have clearly shown Gln3 is not uniformly distributed in the cytoplasm, but rather localizes to punctate or tubular structures. Analysis of these images by deconvolution microscopy suggests that Gln3 is concentrated in or associated with a highly structured system in the cytosol, one that is possibly vesicular in nature. This finding may impact significantly on how we view (i) the mechanism by which Tor regulates the intracellular localization of Gln3 and (ii) how proteins move into and out of the nucleus.
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PMID:Cytoplasmic compartmentation of Gln3 during nitrogen catabolite repression and the mechanism of its nuclear localization during carbon starvation in Saccharomyces cerevisiae. 1214 Feb 87


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