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)

IME1 encodes a transcriptional activator required for the transcription of meiosis-specific genes and initiation of meiosis in Saccharomyces cerevisiae. The transcription of IME1 is repressed in the presence of glucose, and a low basal level of IME1 RNA is observed in vegetative cultures with acetate as the sole carbon source. Upon nitrogen depletion a transient induction in the transcription of IME1 is observed in MATa/MATalpha diploids but not in MAT-insufficient strains. In this study we demonstrate that the transcription of IME1 is controlled by an extremely unusual large 5' region, over 2,100 bp long. This area is divided into four different upstream controlling sequences (UCS). UCS2 promotes the transcription of IME1 in the presence of a nonfermentable carbon source. UCS2 is flanked by three negative regions: UCS1, which exhibits URS activity in the presence of nitrogen, and UCS3 and UCS4, which repress the activity of UCS2 in MAT-insufficient cells. UCS2 consists of alternate positive and negative elements: three distinct constitutive URS elements that prevent the function of any upstream activating sequence (UAS) under all growth conditions, a constitutive UAS element that promotes expression under all growth conditions, a UAS element that is active only in vegetative media, and two discrete elements that function as UASs in the presence of acetate. Sequence analysis of IME1 revealed the presence of two almost identical 30- to 32-bp repeats. Surprisingly, one repeat, IREd, exhibits constitutive URS activity, whereas the other repeat, IREu, serves as a carbon-source-regulated UAS element. The RAS-cyclic AMP-dependent protein kinase cAPK pathway prevents the UAS activity of IREu in the presence of glucose as the sole carbon source, while the transcriptional activators Msn2p and Msn4p promote the UAS activity of this repeat in the presence of acetate. We suggest that the use of multiple negative and positive elements is essential to restrict transcription to the appropriate conditions and that the combinatorial effect of the entire region leads to the regulated transcription of IME1.
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PMID:Multiple and distinct activation and repression sequences mediate the regulated transcription of IME1, a transcriptional activator of meiosis-specific genes in Saccharomyces cerevisiae. 952 70

Glucose-regulated transcription of the L-type pyruvate kinase (L-PK) gene is mediated through its glucose response element (GlRE/L4 box) composed of two degenerated E-boxes. Upstream stimulatory factor (USF) is a component of the transcriptional glucose response complex built up on the GlRE. Cooperation of the GlRE with the contiguous binding site (L3 box) for the orphan nuclear receptor hepatocyte nuclear factor 4 (HNF4) has also been suggested. We compared by transient transfection assays the effects of USF2a and other basic helix-loop-helix leucine zipper (bHLH-LZ) factors (TFE3, c-Myc, SREBP/ADD1) on the activity and glucose responsiveness of a minimal L-PK promoter directed by oligomerized glucose response units (L4L3 boxes). We found that: (i) although USF2a is intrinsically a moderate transcriptional activator, it has a strong stimulatory effect on the activity of the L4L3-based reporter construct in hepatocyte-derived cells and interferes with the glucose responsiveness; (ii) despite its potent ability as a transactivator, TFE3 alone is barely active on the GlRE in hepatocyte-derived cells; (iii) TFE3 as USF2a acts synergistically with HNF4 and abolishes glucose responsiveness of the promoter when overexpressed; (iv) in contrast, overexpression of HNF4 alone stimulates activity of the promoter without interfering with glucose responsiveness; (v) SREBP/ADD1 has a very weak activity on the L4L3 elements, only detectable in the presence of HNF4, and c-Myc does not interact with the GIRE of the L-PK promoter. Our studies indicate that different bHLH-LZ transcription factors known to recognize CACGTG-type E-boxes are not equivalent in acting through the L-PK glucose response element, with USF proteins being especially efficient in hepatocyte-derived cells.
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PMID:Effect of different basic helix-loop-helix leucine zipper factors on the glucose response unit of the L-type pyruvate kinase gene. 969 82

The yeast transcriptional activator Adr1p controls expression of the glucose-repressible alcohol dehydrogenase gene (ADH2), genes involved in glycerol metabolism, and genes required for peroxisome biogenesis and function. Previous data suggested that promoter-specific activation domains might contribute to expression of the different types of ADR1-dependent genes. By using gene fusions encoding the Gal4p DNA binding domain and portions of Adr1p, we identified a single, strong acidic activation domain spanning amino acids 420-462 of Adr1p. Both acidic and hydrophobic amino acids within this activation domain were important for its function. The critical hydrophobic residues are in a motif previously identified in p53 and related acidic activators. A mini-Adr1 protein consisting of the DNA binding domain of Adr1p fused to this 42-residue activation domain carried out all of the known functions of wild-type ADR1. It conferred stringent glucose repression on the ADH2 locus and on UAS1-containing reporter genes. The putative inhibitory region of Adr1p encompassing the protein kinase A phosphorylation site at Ser-230 is thus not essential for glucose repression mediated by ADR1. Mini-ADR1 allowed efficient derepression of gene expression. In addition it complemented an ADR1-null allele for growth on glycerol and oleate media, indicating efficient activation of genes required for glycerol metabolism and peroxisome biogenesis. Thus, a single activation domain can activate all ADR1-dependent promoters.
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PMID:Characterization of a p53-related activation domain in Adr1p that is sufficient for ADR1-dependent gene expression. 982 83

The product of the ACR1 gene is essential for growth of Saccharomyces cerevisiae on ethanol or acetate as sole carbon source, and its expression is subject to glucose repression. It was previously shown that Acr1p is a membrane protein which specifically transports succinate and fumarate. Its suggested function is to shuttle cytosolic succinate from the glyoxylate cycle into the mitochondria in exchange for fumarate, an activity that is essential during gluconeogenic growth on C2 compounds. In this study we show that ACR1 is coregulated with the genes coding for the key enzymes of the glyoxylate cycle and gluconeogenesis: ICL1, MLS1 and PCK1, FBP1 respectively. We demonstrate that derepression of ACR1 is strictly dependent on the Zn2Cys6-type transcriptional activator Cat8p. A detailed deletion analysis of the ACR1 promoter revealed that 69% of the derepression of ACR1 is mediated by three cis-acting elements, located between positions -679 and -569 relative to the translational start, which show a high degree of similarity to the UAS/CSRE elements of PCK1, FBP1, ICL1 and MLS1. Our results, in conjunction with previous biochemical data, clearly identify Acr1p as an element which is directly involved in gluconeogenesis, functioning as the mitochondrial carrier which links the anaplerotic reactions of the glyoxylate cycle to the TCA cycle.
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PMID:The succinate/fumarate transporter Acr1p of Saccharomyces cerevisiae is part of the gluconeogenic pathway and its expression is regulated by Cat8p. 989 15

A gene encoding a third alpha-galactosidase (AglB) from Aspergillus niger has been cloned and sequenced. The gene consists of an open reading frame of 1,750 bp containing six introns. The gene encodes a protein of 443 amino acids which contains a eukaryotic signal sequence of 16 amino acids and seven putative N-glycosylation sites. The mature protein has a calculated molecular mass of 48,835 Da and a predicted pI of 4.6. An alignment of the AglB amino acid sequence with those of other alpha-galactosidases revealed that it belongs to a subfamily of alpha-galactosidases that also includes A. niger AglA. A. niger AglC belongs to a different subfamily that consists mainly of prokaryotic alpha-galactosidases. The expression of aglA, aglB, aglC, and lacA, the latter of which encodes an A. niger beta-galactosidase, has been studied by using a number of monomeric, oligomeric, and polymeric compounds as growth substrates. Expression of aglA is only detected on galactose and galactose-containing oligomers and polymers. The aglB gene is expressed on all of the carbon sources tested, including glucose. Elevated expression was observed on xylan, which could be assigned to regulation via XlnR, the xylanolytic transcriptional activator. Expression of aglC was only observed on glucose, fructose, and combinations of glucose with xylose and galactose. High expression of lacA was detected on arabinose, xylose, xylan, and pectin. Similar to aglB, the expression on xylose and xylan can be assigned to regulation via XlnR. All four genes have distinct expression patterns which seem to mirror the natural substrates of the encoded proteins.
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PMID:Differential expression of three alpha-galactosidase genes and a single beta-galactosidase gene from Aspergillus niger. 1034 26

To utilise maltose as a carbon source Saccharomyces cerevisiae needs one or more functional MAL loci that contain the MALx1 gene encoding maltose permease, MALx2 encoding maltase, and MALx3 encoding a transcriptional activator. Maltose causes a rapid MALx3-dependent induction of MAL gene transcription, and glucose represses this activation via Mig1p. A MALx3 gene conveying high MAL gene expression in the absence of maltose in a malx3 laboratory mutant strain has been isolated from baker's yeast. The construction of hybrid genes between the isolated gene and a highly regulated MALx3 gene showed that constitutivity was the result of multiple amino-acid alterations throughout the structural gene. The combined effect of these amino-acid alterations was shown to be stronger than the sum of their individual effects on constitutivity. Analysis in glucose-repressed conditions confirmed that increased MALx3 transcript levels increased the glucose insensitivity of MAL gene expression but did not affect constitutivity. Analysis of four mutations between aa 343 and 375, lying within a proposed negative regulatory domain, showed that the single mutation of Leu343Phe increased the glucose insensitivity of MAL gene expression by 30-fold. These results demonstrate that not only Mig1p modulation of MALx3 expression, but also the MALx3 protein structure, is involved in the glucose-insensitive expression of the MAL genes.
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PMID:Leu343Phe substitution in the Malx3 protein of Saccharomyces cerevisiae increases the constitutivity and glucose insensitivity of MAL gene expression. 1036 55

Expression of the catalase-peroxidase of Caulobacter crescentus, a gram-negative member of the alpha subdivision of the Proteobacteria, is 50-fold higher in stationary-phase cultures than in exponential cultures. To identify regulators of the starvation response, Tn5 insertion mutants were isolated with reduced expression of a katG::lacZ fusion on glucose starvation. One insertion interrupted an open reading frame encoding a protein with significant amino acid sequence identity to TipA, a helix-turn-helix transcriptional activator in the response of Streptomyces lividans to the peptide antibiotic thiostrepton, and lesser sequence similarity to other helix-turn-helix regulators in the MerR family. The C. crescentus orthologue of tipA was named skgA (stationary-phase regulation of katG). Stationary-phase expression of katG was reduced by 70% in the skgA::Tn5 mutant, and stationary-phase resistance to hydrogen peroxide decreased by a factor of 10. Like the wild type, the skgA mutant exhibited starvation-induced cross-resistance to heat and acid shock, entered into the helical morphology that occurs after 9 to 12 days in stationary phase, and during exponential growth induced katG in response to hydrogen peroxide challenge. Expression of skgA increased 5- to 10-fold in late exponential phase. skgA is the first regulator of a starvation-induced stress response identified in C. crescentus. SkgA is not a global regulator of the stationary-phase stress response; its action encompasses the oxidative stress-hydrogen peroxide response but not acid or heat responses. Moreover, SkgA is not an alternative sigma factor, like RpoS, which controls multiple aspects of starvation-induced cross-resistance to stress in enteric bacteria. These observations raise the possibility that regulation of stationary-phase gene expression in this member of the alpha subdivision of the Proteobacteria is different from that in Escherichia coli and other members of the gamma subdivision.
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PMID:Identification of a regulator that controls stationary-phase expression of catalase-peroxidase in Caulobacter crescentus. 1049 30

Feruloyl esterases can remove aromatic residues (e.g., ferulic acid) from plant cell wall polysaccharides (xylan, pectin) and are essential for complete degradation of these polysaccharides. Expression of the feruloyl esterase-encoding gene (faeA) from Aspergillus niger depends on D-xylose (expression is mediated by XlnR, the xylanolytic transcriptional activator) and on a second system that responds to aromatic compounds with a defined ring structure, such as ferulic acid and vanillic acid. Several compounds were tested, and all of the inducing compounds contained a benzene ring which had a methoxy group at C-3 and a hydroxy group at C-4 but was not substituted at C-5. Various aliphatic groups occurred at C-1. faeA expression in the presence of xylose or ferulic acid was repressed by glucose. faeA expression in the presence of ferulic acid and xylose was greater than faeA expression in the presence of either compound alone. The various inducing systems allow A. niger to produce feruloyl esterase not only during growth on xylan but also during growth on other ferulic acid-containing cell wall polysaccharides, such as pectin.
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PMID:Regulation of the feruloyl esterase (faeA) gene from Aspergillus niger. 1058 9

Crh of Bacillus subtilis exhibits 45% sequence identity when compared to histidine-containing protein (HPr), a phosphocarrier protein of the phosphoenolpyruvate (PEP):sugar phosphotransferase system (PTS). Crh can be phosphorylated by ATP at the regulatory Ser-46 and similar to P-Ser-HPr, P-Ser-Crh plays a role in carbon-catabolite repression. The sequence around the phosphorylatable Ser-46 in Crh exhibits strong similarity to the corresponding sequence of HPr of Gram-positive and a few Gram-negative bacteria. In contrast, the catalytic His-15, the site of PEP-dependent phosphorylation in HPr, is replaced with a glutamine in Crh. When Gln-15 was exchanged for a histidyl residue, in vitro PEP-dependent enzyme I-catalysed phosphorylation of the mutant Crh was observed. However, expression of the crhQ15H mutant allele did not restore growth of a ptsH deletion strain on the PTS sugars glucose, fructose or mannitol or on the non-PTS sugar glycerol. In contrast, Q15H mutant Crh could phosphorylate the transcriptional activator LevR as well as LevD, the enzyme IIA of the fructose-specific lev-PTS, which together with enzyme I, HPr and LevE forms the phosphorylation cascade regulating induction of the lev operon via LevR. As a consequence, the constitutive expression from the lev promoter observed in a (delta)ptsH strain became inducible with fructose when the crhQ15H allele was expressed in this strain.
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PMID:The Q15H mutation enables Crh, a Bacillus subtilis HPr-like protein, to carry out some regulatory HPr functions, but does not make it an effective phosphocarrier for sugar transport. 1058 28

ADR1 encodes a transcriptional activator that regulates genes involved in carbon source utilization in Saccharomyces cerevisiae. ADR1 is itself repressed by glucose, but the significance of this repression for regulating target genes is not known. To test if the reduction in Adr1 levels contributes to glucose repression of ADH2 expression, we generated yeast strains in which the level of Adr1 produced during growth in glucose-containing medium is similar to that present in wild-type cells grown in the absence of glucose. In these Adr1-overproducing strains, ADH2 expression remained tightly repressed, and UAS1, the element in the ADH2 promoter that binds Adr1, was sufficient to maintain glucose repression. Post-translational modification of Adr1 activity is implicated in repression, since ADH2 derepression occurred in the absence of de novo protein synthesis. The N-terminal 172 amino acids of Adr1, containing the DNA binding and nuclear localization domains, fused to the Herpesvirus VP16-encoded transcription activation domain, conferred regulated expression at UAS1. Nuclear localization of an Adr1-GFP fusion protein was not glucose-regulated, suggesting that the DNA binding domain of Adr1 is sufficient to confer regulated expression on target genes. A Gal4-Adr1 fusion protein was unable to confer glucose repression at GAL4-dependent promoters, suggesting that regulation mediated by ADR1 is specific to UAS1.
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PMID:Post-translational regulation of Adr1 activity is mediated by its DNA binding domain. 1060 11


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