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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 activation of eukaryotic heat shock genes, the acquisition of a binding ability to specific DNA sequence by a transcriptional activator, heat shock factor (HSF), is believed to be a crucial step. The induction of this new DNA binding activity of HSF is also obtained in a cell-free system (in vitro activation) by hyperthermia or at physiological temperature by calcium ions, low pH, urea, or non-ionic detergent. We report here the in vitro activation of HSF by treating at 0 degrees C a HeLa cell-free system with the aldehyde 4-hydroxynonenal (HNE), a highly cytotoxic product of lipid peroxidation. The in vitro activation of HSF by HNE occurred only if some components of the cell-free system were not sedimented at 100,000 x g. The reason for this is unclear but the release of active HSF from nuclei of unshocked cells and the involvement of Ca2+ contained in the mitochondria and ER have been excluded. Although HNE is known to be a sulfhydryl blocking agent, the results obtained with N-ethylmaleimide suggest that different mechanisms might be involved in the in vitro activation of HSF by HNE.
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PMID:In vitro activation of heat shock transcription factor by 4-hydroxynonenal. 139 24

The toxR gene of Vibrio cholerae encodes a transcriptional activator required for the expression of the cholera toxin genes (ctxAB) and more than 15 other genes encoding secreted or membrane proteins. The latter group includes virulence genes involved in the biogenesis of the TCP pilus, the accessory colonization factor, and such ToxR-activated genes as tagA, mutations in which cause no detectable virulence defect in the suckling mouse model. To analyze the regulation of expression and the structure of tagA, we have cloned and sequenced about 2 kb of DNA upstream from a tagA::TnphoA fusion. While the portion of the tagA gene product examined presented no extensive similarity to any known protein, the amino acid sequence deduced from an open reading frame (designated aldA) located upstream from and in opposite orientation to tagA was highly similar to the sequences of eukaryotic aldehyde dehydrogenases. An assay of aldehyde dehydrogenase activity in extracts of a wild-type V. cholerae strainand an aldA mutant confirmed that aldA encodes an aldehyde dehydrogenase. Expression of the aldA gene was studied together with that of tagA in both V. cholerae and Escherichia coli. The expression of both tagA and aldA was environmentally regulated and dependent on a functional toxR gene in V. cholerae, but neither promoter was activated by ToxR in E. coli, suggesting that expression of tagA and aldA requires an additional transcriptional activator besides ToxR. The aldA gene is the first example of a gene encoding a cytoplasmic protein that is under the control of ToxR, and this suggests that metabolic enzymes may constitute novel members of virulence regulons in bacteria.
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PMID:Expression of the Vibrio cholerae gene encoding aldehyde dehydrogenase is under control of ToxR, the cholera toxin transcriptional activator. 190 10

Studies on the quinic acid utilisation gene (qut) cluster in Aspergillus nidulans showed that the genes encoding transcriptional activator and repressor proteins evolved by co-opting duplicated copies of genes encoding metabolic enzymes. In order to test the hypothesis that this was a general route for the genesis of regulatory proteins, the origins of the major control protein mediating nitrogen metabolite repression (an example of inter-pathway regulation) and ethanol utilisation (an example of intra-pathway regulation) in filamentous fungi were sought. The regulatory proteins mediating nitrogen metabolite repression were deduced to have originated in a duplication of genes encoding the anthranilate synthase complex which is active in the shikimate pathway. The major protein regulating ethanol utilisation was deduced to have its origin in the fusion of duplicated genes encoding the aldehyde and alcohol dehydrogenases (ALDA and ALCA). These data strongly support the view that transcriptional regulatory proteins evolve by the recruitment of functional domains provided by metabolic enzymes.
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PMID:Evolution of transcription-regulating proteins by enzyme recruitment: molecular models for nitrogen metabolite repression and ethanol utilisation in eukaryotes. 928 Jul 33

The recent discovery that the fish pathogen Vibrio salmonicida is closely related to the luminous bacteria Vibrio fischeri and Vibrio logei suggested that V. salmonicida might also be capable of bioluminescence. Interestingly, cells of V. salmonicida were found to produce light in culture, but only when exposed to either an aliphatic aldehyde and/or the major V. fischeri autoinducer N-(3-oxo-hexanoyl)-L-homoserine lactone, a transcriptional activator of the luminescence (lux) genes. An extract of spent medium of V. salmonicida that should contain any V. salmonicida acyl-homoserine lactone autoinducer, when added to V. fischeri cells, led to an induction of their luminescence. These results show that V. salmonicida is a newly recognized luminous bacterial species that apparently both produces an autoinducer activity and responds to exogenous V. fischeri autoinducer.
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PMID:Cryptic luminescence in the cold-water fish pathogen Vibrio salmonicida. 1020 Oct 98

Expression of the structural genes for alcohol and aldehyde dehydrogenase, alcA and aldA, respectively, enables the fungus Aspergillus nidulans to grow on ethanol. The pathway-specific transcriptional activator AlcR mediates the induction of ethanol catabolism in the presence of a coinducing compound. Ethanol catabolism is further subject to negative control mediated by the general carbon catabolite repressor CreA. Here we show that, in contrast to alcA and alcR, the aldA gene is not directly subject to CreA repression. A single cis-acting element mediates AlcR activation of aldA. Furthermore, we show that the induction of the alc gene system is linked to in situ aldehyde dehydrogenase activity. In aldA loss-of-function mutants, the alc genes are induced under normally noninducing conditions. This pseudo-constitutive expression correlates with the nature of the mutations, suggesting that this feature is caused by an intracellular accumulation of a coinducing compound. Conversely, constitutive overexpression of aldA results in suppression of induction in the presence of ethanol. This shows unambiguously that acetaldehyde is the sole physiological inducer of ethanol catabolism. We hypothesize that the intracellular acetaldehyde concentration is the critical factor governing the induction of the alc gene system.
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PMID:Regulation of the aldehyde dehydrogenase gene (aldA) and its role in the control of the coinducer level necessary for induction of the ethanol utilization pathway in Aspergillus nidulans. 1110 39

Previous experiments in mice and zebrafish led to the hypothesis that an asymmetric distribution of the transcriptional activator retinoic acid (RA) causes ventral-dorsal polarity in the vertebrate eye anlage. A high concentration of RA in the ventral retinal neuroepithelium has been suggested to induce developmental events that finally establish topographic order in the retinotectal projection along the vertical eye axis. In the present study we have investigated potential sources and sinks of RA during embryonic development of the chick retina. At embryonic day (E)1 to E2, when the spatial determination of the eye primordia takes place, no RA synthesis by aldehyde dehydrogenases was detectable, and neither immunoreactivity for retinaldehyde dehydrogenase RALDH-2 nor for cellular retinoic acid binding protein CRABP-I was observed. These components of RA signal transduction appeared in the eye between E3 and E5. At later stages, RA-measurements with a reporter cell line showed highest synthesis in the retinal pigment epithelium (RPE) and at the ventral and dorsal poles of the retina. RA degradation occurred mostly in a horizontal region in the middle of the retina with only small differences along the nasal-temporal axis. CRABP-I immunoreactivity appeared first in differentiating retinal ganglion cells with no indication of a spatial gradient across the ventral-dorsal eye axis. RA-production depended on three NAD+-dependent enzyme activities, which could be competitively inhibited by citral. One enzyme, located in the dorsal retina (corresponding to mouse RALDH-1), and one enzyme in the RPE (RALDH-2) were aldehyde dehydrogenases of the same molecular weight (monomers about 55 kDa) but with different isoelectric points (6.5-6.9; 4.9-5.4). The third RA-synthesizing activity (pI 6.0-6.3) was limited to the ventral retina, and likely corresponded to mouse RALDH-3. The restricted localization of retinoid-metabolizing activities along the dorsal-ventral axis of the embryonic chick retina does support the idea that RA is involved in dorsal-ventral eye patterning. However, the late time of appearance of aldehyde dehydrogenase activities and CRABP-I points to functions in cellular differentiation that are distinct from the initiation of the dorsal-ventral polarity.
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PMID:Sources and sink of retinoic acid in the embryonic chick retina: distribution of aldehyde dehydrogenase activities, CRABP-I, and sites of retinoic acid inactivation. 1133

This article reviews our knowledge of the ethanol utilization pathway (alc system) in the hyphal fungus Aspergillus nidulans. We discuss the progress made over the past decade in elucidating the two regulatory circuits controlling ethanol catabolism at the level of transcription, specific induction, and carbon catabolite repression, and show how their interplay modulates the utilization of nutrient carbon sources. The mechanisms featuring in this regulation are presented and their modes of action are discussed: First, AlcR, the transcriptional activator, which demonstrates quite remarkable structural features and an original mode of action; second, the physiological inducer acetaldehyde, whose intracellular accumulation induces the alc genes and thereby a catabolic flux while avoiding intoxification; third, CreA, the transcriptional repressor mediating carbon catabolite repression in A. nidulans, which acts in different ways on the various alc genes; Fourth, the promoters of the structural genes for alcohol dehydrogenase (alcA) and aldehyde dehydrogenase (aldA) and the regulatory alcR gene, which exhibit exceptional strength compared to other genes of the respective classes. alc gene expression depends on the number and localization of regulatory cis-acting elements and on the particular interaction between the two regulator proteins, AlcR and CreA, binding to them. All these characteristics make the ethanol regulon a suitable system for induced expression of heterologous protein in filamentous fungi.
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PMID:Ethanol catabolism in Aspergillus nidulans: a model system for studying gene regulation. 1155 Jul 94

Aldehyde oxidoreductase of Eubacterium acidaminophilum was purified to homogeneity under strict anaerobic conditions using a four-step procedure. The purified enzyme was present as a monomer with an apparent molecular mass of 67 kDa and contained 6.0 +/- 0.1 iron, 1.1 +/- 0.2 tungsten, about 0.6 mol pterin cofactor and zinc, but no molybdenum. The enzyme activity was induced if a molar excess of electron donors, such as serine and/or formate, were supplied in the growth medium compared to readily available electron acceptors such as glycine betaine. Many aldehydes served as good substrates, thus enzyme activity obtained with acetaldehyde, propionaldehyde, butyraldehyde, isovaleraldehyde and benzaldehyde differed by a factor of less than two. Kinetic parameters were determined for all substrates tested. Oligonucleotides deduced from the N-terminal amino acid sequence were used to isolate the encoding aorA gene and adjacent DNA regions. The deduced amino acid sequence of the aldehyde oxidoreductase exhibited high similarities to other tungsten-containing aldehyde oxidoreductases from archaea. Transcription of the aorA gene was monocistronic and started from a sigma 54-dependent promoter. Upstream of aorA, the gene aorR is localized whose product is similar to sigma 54-dependent transcriptional activator proteins and, thus, AorR is probably involved in the regulation of aorA expression.
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PMID:Tungsten-containing aldehyde oxidoreductase of Eubacterium acidaminophilum. 1468 34

The ethanol utilization pathway (alc system) of Aspergillus nidulans requires two structural genes, alcA and aldA, which encode the two enzymes (alcohol dehydrogenase and aldehyde dehydrogenase, respectively) allowing conversion of ethanol into acetate via acetyldehyde, and a regulatory gene, alcR, encoding the pathway-specific autoregulated transcriptional activator. The alcR and alcA genes are clustered with three other genes that are also positively regulated by alcR, although they are dispensable for growth on ethanol. In this study, we characterized alcS, the most abundantly transcribed of these three genes. alcS is strictly co-regulated with alcA, and encodes a 262-amino acid protein. Sequence comparison with protein databases detected a putative conserved domain that is characteristic of the novel GPR1/FUN34/YaaH membrane protein family. It was shown that the AlcS protein is located in the plasma membrane. Deletion or overexpression of alcS did not result in any obvious phenotype. In particular, AlcS does not appear to be essential for the transport of ethanol, acetaldehyde or acetate. Basic Local Alignment Search Tool analysis against the A. nidulans genome led to the identification of two novel ethanol- and ethylacetate-induced genes encoding other members of the GPR1/FUN34/YaaH family, AN5226 and AN8390.
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PMID:Functional analysis of alcS, a gene of the alc cluster in Aspergillus nidulans. 1653 Oct 87

Saccharomyces cerevisiae was exposed to inhibitory concentrations of the three phenolic phenylpropanoids: coniferyl aldehyde, ferulic acid, and isoeugenol. Deoxyribonucleic acid microarray analysis was employed as one approach to generate a set of candidate genes for deletion mutant analysis to determine the potential contribution of the corresponding gene products to the resistance against toxic concentrations of phenolic fermentation inhibitors. Three S. cerevisiae deletion mutants with increased sensitivity to coniferyl aldehyde were identified: yap1Delta, atr1Delta, and flr1Delta. The rate of reduction of coniferyl aldehyde to coniferyl alcohol decreased sixfold when the gene encoding the transcriptional activator Yap1p was deleted, and threefold when the Yap1p-controlled genes encoding Atr1p and Flr1p were deleted. Growth, glucose consumption, and ethanol formation progressed after a lag phase during which coniferyl aldehyde reduction and coniferyl alcohol formation occurred. The results link ATR1, FLR1, and YAP1 by their ability to confer resistance to coniferyl aldehyde and show that deletion of any of these three genes impairs the ability of S. cerevisiae to withstand coniferyl aldehyde and detoxify it by reduction. Furthermore, the results suggest that overexpression of ATR1, FLR1, and YAP1 is of interest for the construction of novel yeast strains with improved resistance against inhibitors in lignocellulose hydrolysates.
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PMID:Identification of Saccharomyces cerevisiae genes involved in the resistance to phenolic fermentation inhibitors. 1984 83


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