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 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

Ethanol-utilization in Aspergillus nidulans is mediated by alcohol dehydrogenase I and aldehyde dehydrogenase encoded by alcA and aldA, respectively. Both genes are under the transcriptional control of the specific activator AlcR and the general carbon catabolite repressor CreA. The alcR and alcA genes are closely linked in chromosome VII; aldA is located in chromosome VIII. We have identified five other transcripts that are expressed from the same genomic region as alcA and alcR. They are inducible by the gratuitous inducer ethyl methyl ketone (EMK), and are carbon catabolite repressed. The corresponding genes, designated alcM, alcS, alcO, alcP, and alcU, are differentially regulated by the specific transcriptional activator AlcR, and they are not all under the direct control by the CreA repressor. Some of the inducible transcripts are very abundant in the cell, whereas others are poorly expressed. Two sets of genes, alcM/alcS and alcR/alcO, are divergently transcribed and probably share a common cis-acting region, whereas alcP and alcU are individually transcribed from the same strand as alcA and alcR, and have their own promoters. The significance of the alc gene clustering is discussed. At least four of the five novel alc genes in the cluster are not essential for ethanol metabolism.
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PMID:A newly identified gene cluster in Aspergillus nidulans comprises five novel genes localized in the alc region that are controlled both by the specific transactivator AlcR and the general carbon-catabolite repressor CreA. 873 27

The aryl hydrocarbon receptor (AHR) is a transcriptional activator of genes encoding a group of drug-metabolizing enzymes, including cytochrome P450 1A1 (CYP1A1), glutathione S-transferase, tumor-associated aldehyde dehydrogenase and quinone reductase. Both the constitutive and inducible expression of these genes in the liver is zonated, i.e., dominant in hepatocytes of the centrilobular region, a poorly understood position-dependent phenomenon. By comparing cell lysates obtained from opposite acinar regions we observed that immunoreactive AHR protein was almost exclusively confined to centrilobular cells. The AHR mRNA, as analyzed from cell lysates by reverse transcriptase polymerase chain reaction, exhibited a similar, although somewhat less pronounced zonation. By contrast, only slight zonation of the AHR nuclear translocator mRNA was observed. Treatment of rats with omeprazole, an atypical nonligand activator of the AHR, caused a zone-specific induction of CYP1A1 in the centrilobular region similar to that seen after pretreatment with the AHR ligand 3-methylcholanthrene. Our results suggest that the zone-restricted expression of AHR protein will allow the constitutive and inducible expression of AHR-regulated genes in the centrilobular region, but will limit their expression in the periportal region.
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PMID:Selective centrilobular expression of the aryl hydrocarbon receptor in rat liver. 899 35

After traumatic injury to the central nervous system (CNS), various cytokines orchestrate the physiological responses of injured neurons and glial cells. The control of these intercellular signals is of major interest from a medical point of view. Since the transcriptional activator retinoic acid (RA) is known to regulate gene expression of cytokines in various cell culture systems we investigated the role of RA signaling in glial cells. The transcriptional activity of RA-induced genes is largely determined by the distribution of RA, which in turn depends on the local oxidation of retinaldehyde (RAL). This is synthesized from retinol or internalized as a component of vitamin A. Using high-pressure liquid chromatography and an RA-sensitive reporter cell line, we showed that OLN-93 cells, which serve as a model system for CNS oligodendrocytes, convert all-trans-RAL to the biologically active form all-trans-RA, but neither oxidize 9-cis-RAL nor isomerize RA enzymatically. The oligodendrocyte cell line expresses a cytosolic aldehyde dehydrogenase with an apparent molecular weight of 54-57 kDa and pI of 5.3-5.7. As indicated by a zymography bioassay, this enzyme is responsible for RA synthesis. The reaction requires NAD+ as cosubstrate and can be inhibited by disulfiram and citral. No other RA-producing enzyme activities were detected. These findings are in accordance with a putative role for retinoid signaling in neuroglial interactions in the CNS.
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PMID:OLN-93 oligodendrocytes synthesize all-trans-retinoic acid in vitro. 1107 15

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

The Bacillus subtilis ycnG (gabT) and ycnH (gabD) genes were shown to encode gamma-aminobutyrate (GABA) aminotransferase and succinic semi-aldehyde dehydrogenase, respectively, and to form a GABA-inducible operon. Null mutations in gabT, gabD or the divergently transcribed ycnF (gabR) gene blocked the utilization of GABA as sole nitrogen source. GabR proved to be a transcriptional activator of the gabTD operon and a negative autoregulator. The target of GabR action was localized to an 87 bp region that includes both gabR and gabT promoters. GabR is a member of a novel but widespread family of chimeric bacterial proteins that have apparent DNA-binding and aminotransferase domains. Mutations in conserved residues of the putative aminotransferase domain abolished GabR function as a transcriptional activator, but did not affect its activity as a negative autoregulator.
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PMID:GabR, a member of a novel protein family, regulates the utilization of gamma-aminobutyrate in Bacillus subtilis. 1212 65

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


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