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 FixL/FixJ two-component system is a global regulator of nitrogen-fixation genes in Rhizobium meliloti. The transcriptional activator FixJ contains two modules: its N-terminal module is homologous with other two-component regulators; its C-terminal module shows homology with various transcriptional activators, and with the C-terminal region of sigma factors, which is involved in the discrimination of the -35 region of bacterial promoters. We show that the C-terminal module of FixJ contains the entire transcription activation function, and that the N-terminal module regulates this activity negatively. Oligonucleotide-directed mutagenesis of the transcriptional activator module demonstrated the importance of a potential helix-turn-helix structure.
Mol Microbiol 1991 Apr
PMID:Modular structure of FixJ: homology of the transcriptional activator domain with the -35 binding domain of sigma factors. 185 13

The fission yeast Schizosaccharomyces pombe is immensely diverged from budding yeast (Saccharomyces cerevisiae) on an evolutionary time scale. We have used a fission yeast library to clone a homolog of S. cerevisiae HAP2, which along with HAP3 and HAP4 forms a transcriptional activation complex that binds to the CCAAT box. The S. pombe homolog php2 (S. pombe HAP2) was obtained by functional complementation in an S. cerevisiae hap2 mutant and retains the ability to associate with HAP3 and HAP4. We have previously demonstrated that the HAP2 subunit of the CCAAT-binding transcriptional activation complex from S. cerevisiae contains a 65-amino-acid "essential core" structure that is divisible into subunit association and DNA recognition domains. Here we show that Php2 contains a 60-amino-acid block that is 82% identical to this core. The remainder of the 334-amino-acid protein is completely without homology to HAP2. The function of php2 in S. pombe was investigated by disrupting the gene. Strikingly, like HAP2 in S. cerevisiae, the S. pombe gene is specifically involved in mitochondrial function. This contrasts to the situation in mammals, in which the homologous CCAAT-binding complex is a global transcriptional activator.
Mol Cell Biol 1991 Feb
PMID:The Schizosaccharomyces pombe homolog of Saccharomyces cerevisiae HAP2 reveals selective and stringent conservation of the small essential core protein domain. 189 84

Carbonyl reductase (NADPH: secondary-alcohol oxidoreductase; EC 1.1.1.184), a widely distributed NADPH-dependent enzyme considered as both an aldo-keto reductase and a quinone reductase, was cloned from a human liver genomic library and transiently expressed in COS7 cells. The gene contains 3142 bases comprising three exons and two introns. The absence of a CAAT and TATA box and the presence of a GC-rich island are characteristic of many "housekeeping" genes. Transient expression of the genomic gene in COS7 cells using an expression vector containing an SV40 origin of replication resulted in a greater than 50-fold increase in both menadione reductase activity and daunorubicin reductase activity, suggesting that both activities are derived from the same enzyme. Carbonyl reductase mRNA levels reflected enzyme activity levels in the transfected cells. Other parameters, such as pH profile, cofactor requirements, substrates, and inhibitors, were similar to those of carbonyl reductase purified by other investigators. Potential regulatory elements with consensus sequences for two GC boxes and the transcriptional activator protein AP-2 were present upstream of the transcriptional start site. Although the precise role of carbonyl reductase is unknown, the enzyme is involved in drug metabolism and in the reduction of activated carbonyl compounds. Its ability to act as a quinone reductase also implies a potential to modulate oxygen free radicals.
Mol Pharmacol 1991 Oct
PMID:Genomic sequence and expression of a cloned human carbonyl reductase gene with daunorubicin reductase activity. 192 84

The rate of ribosome formation in yeast is precisely adjusted to the physiological demands of the cell. During all growth conditions a balance is maintained in the production of all ribosomal constituents. Coordinate expression of the ribosomal protein (rp) genes is primarily accomplished at the transcriptional level. Transcription activation of the majority of the rp-genes is mediated through common upstream activating sequences, so-called RPG boxes, which occur usually in a tandem at a distance of 200-500 bp from the start codon. These RPG-boxes represent binding sites for a transcriptional activator, called TUF or RAP. The concentration of TUF parallels the cellular growth rate and evidence exists that the response of rp-genes upon nutritional changes is mediated by this factor. Recent findings indicate that TUF/RAP also activates other gene families involved in cellular growth rate. Furthermore, this multifunctional protein also binds to the mating-type silencer and telomeres in yeast. Some other rp-genes (e.g. those encoding S33 and L45) do not contain an RPG-box. They appear to be activated by another multifunctional protein, called ABF1 or SUF, by binding to another nucleotide motif. This multifunctional protein also activates other gene families, and in addition binds to the mating type silencer and ARS-elements.
Mol Cell Biochem
PMID:Coordinate expression of ribosomal protein genes in yeast as a function of cellular growth rate. 192 98

We have studied transcriptional control of the murine terminal deoxynucleotidyltransferase (TdT) gene, which is activated specifically in immature B and T lymphocytes. This analysis has led to the identification and purification of a 50-kDa sequence-specific DNA-binding protein, LyF-1, that interacts with the approximate consensus sequence PyPyTGGGAGPu and is enriched in cells at most stages of B- and T-cell differentiation. LyF-1 binds tightly to an element in the TdT promoter that we show is required for transcription in lymphocytes. LyF-1 also interacts with an element in the immunoglobulin mu enhancer, called microB, that was recently shown to be important for lymphocyte-specific enhancer activity. Moreover, LyF-1 binds to the promoters for the lymphocyte-specific genes lambda 5, VpreB, and lck, all of which we speculate have additional features in common with the TdT promoter. Thus, LyF-1 may be a general transcriptional activator for genes whose expression is restricted to the B- and/or T-lymphocyte lineages.
Mol Cell Biol 1991 Oct
PMID:LyF-1, a transcriptional regulator that interacts with a novel class of promoters for lymphocyte-specific genes. 192 43

The nucleotide sequence of nirA, mediating nitrate induction in Aspergillus nidulans, has been determined. Alignment of the cDNA and the genomic DNA sequence indicates that the gene contains four introns and encodes a protein of 892 amino acids. The deduced NIRA protein displays all characteristics of a transcriptional activator. A putative double-stranded DNA-binding domain in the amino-terminal part comprises six cysteine residues, characteristic for the GAL4 family of zinc finger proteins. An amino-terminal highly acidic region and two proline-rich regions are also present. The nucleotide sequences of two mutations were determined after they were mapped by transformation with overlapping DNA fragments, amplified by the polymerase chain reaction. nirA87, a mutation conferring noninducibility by nitrate and nitrite, has a -1 frameshift at triplet 340, which eliminates 549 C-terminal amino acids from the polypeptide. Under the assumption that the truncated polypeptide is stable, it comprises the zinc finger domain and the acidic region, which seem not sufficient for transcriptional activation. nirAd-106, an allele conferring nitrogen metabolite derepression of nitrate and nitrite reductase activity, includes two transitions, changing a glutamic acid to a lysine and a valine to an alanine, situated between a basic and a proline-rich region of the protein. Northern (RNA) analysis of the wild type and of constitutive (nirAc) and derepressed (nirAd) mutants show that the nirA transcript does not vary between these strains, being in all cases constitutively expressed. On the other hand, transcript levels of structural genes (niaD and niiA) do vary, being highly inducible in the wild type but constitutively expressed in the nirAc mutant. The nirAd mutant appears phenotypically derepressed, because the niaD and niiA transcript levels are overinduced in the presence of nitrate but are still partially repressed in the presence of ammonium.
Mol Cell Biol 1991 Nov
PMID:nirA, the pathway-specific regulatory gene of nitrate assimilation in Aspergillus nidulans, encodes a putative GAL4-type zinc finger protein and contains four introns in highly conserved regions. 192 75

Mouse lymphoma cell line W7M320b, a mutant WEH17 line, requires higher than normal concentrations of glucocorticoid to elicit the hormone responses that are characteristic of this lineage. Complementary DNA clones representing the glucocorticoid receptor (GR) mRNA were derived from the mutant cells, and the sequences coding for the hormone-binding domain were substituted for the analogous wild-type sequences in a GR cDNA expression vector. The function of the resulting GR proteins was tested by transient expression in COS-7 cells along with a glucocorticoid-inducible reporter gene in the presence of varying concentrations of glucocorticoid. From these assays and DNA sequence analyses, two independent functionally significant point mutations in the GR hormone-binding domain were identified. A mutant GR protein containing the single amino acid substitution, Pro547 to Ala, was still functional as a transcriptional activator, but only at hormone concentrations 100 times higher than those required by the wild-type receptor. A second mutant GR protein with a Cys742 to Gly substitution was unstable and almost completely nonfunctional.
Mol Endocrinol 1991 Jun
PMID:Two point mutations in the hormone-binding domain of the mouse glucocorticoid receptor that dramatically reduce its function. 192 94

AmpR, the transcriptional regulator for the Citrobacter freundii ampC beta-lactamase gene, was purified. The purified AmpR had DNA-binding activity, the same molecular mass (32 kDa) on sodium dodecyl sulphate/polyacrylamide gel electrophoresis as previously described, and N-terminal sequencing of the first 15 amino acids was in agreement with that predicted from the nucleotide sequence. Two mutants were isolated that abolish DNA-binding and beta-lactamase induction and which map in the amino- and carboxyl-terminal ends of AmpR, respectively. The mutation in the amino terminus (S35F) was located in a helix-turn-helix region showing high homology to other members of the LysR regulator family. Therefore this mutation may directly abolish the contact between AmpR and its operator sequence. It is suggested that the C-terminal mutation (Y264N) affects subunit interactions in AmpR. One constitutive mutant was isolated which mapped in the centre of the ampR gene. This G102E mutant leads to constitutive beta-lactamase expression in the absence of both beta-lactam inducer and ampG, a gene essential for induction in wild-type enterobacteria. Another mutant protein, D135Y, showed wild-type properties in an ampG+ and an ampG::kan background, but could, unlike wild-type AmpR, activate the ampC gene in an ampG1 mutant background. It is thought that ampG1 is a missense mutant. These two types of ampR mutants suggest that activation of ampC transcription is dependent on the conversion of AmpR into a transcriptional activator and that this activation may normally involve interactions with AmpG.
Mol Microbiol 1991 Jul
PMID:Purification and mutant analysis of Citrobacter freundii AmpR, the regulator for chromosomal AmpC beta-lactamase. 194 5

cAMP-dependent protein kinase (cAPK) is implicated in the inactivation of the yeast transcriptional activator ADR1, which regulates glucose-repressible ADH2 gene expression. The interdependence of cAPK, SCH9 (a protein kinase that when overexpressed can functionally substitute for cAPK), and the CCR1 (SNF1) protein kinase that is required for ADH2 expression was studied. SCH9 was found to be required for ADH2 expression in contrast to the inhibitory role played by cAPK. CCR1 and SCH9 were observed to affect ADH2 expression independently of both ADR1 and cAPK. In contrast, cAPK was shown to exert its effects on ADH2 solely through ADR1. These results indicate that the SCH9 and CCR1 protein kinases are components of regulatory pathways separate from that utilized by cAPK to control ADR1 activity and ADH2 expression.
Mol Gen Genet 1991 Oct
PMID:The CCR1 (SNF1) and SCH9 protein kinases act independently of cAMP-dependent protein kinase and the transcriptional activator ADR1 in controlling yeast ADH2 expression. 194 27

We have cloned the negative regulatory gene (DAL80) of the allantoin catabolic pathway, characterized its structure, and determined the physiological conditions that control DAL80 expression and its influence on the expression of nitrogen catabolic genes. Disruption of the DAL80 gene demonstrated that it regulates multiple nitrogen catabolic pathways. Inducer-independent expression was observed for the allantoin pathway genes DAL7 and DUR1,2, as well as the UGA1 gene required for gamma-aminobutyrate catabolism in the disruption mutant. DAL80 transcription was itself highly sensitive to nitrogen catabolite repression (NCR), and its promoter contained 12 sequences homologous to the NCR-sensitive UASNTR. The deduced DAL80 protein structure contains zinc finger and coiled-coil motifs. The DAL80 zinc finger motif possessed high homology to the transcriptional activator proteins required for expression of NCR-sensitive genes in fungi and the yeast GLN3 gene product required for functioning of the NCR-sensitive DAL UASNTR. It was also homologous to the three GATAA-binding proteins reported to be transcriptional activators in avian and mammalian tissues. The latter correlations raise the possibility that both positive and negative regulators of allantoin pathway transcription may bind to similar sequences.
Mol Cell Biol 1991 Dec
PMID:Expression of the DAL80 gene, whose product is homologous to the GATA factors and is a negative regulator of multiple nitrogen catabolic genes in Saccharomyces cerevisiae, is sensitive to nitrogen catabolite repression. 156 60


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