Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: UNIPROT:P51532 (transcriptional activator)
 6,546 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

We have identified a Drosophila transcription factor that binds to fat body-specific enhancers of alcohol dehydrogenase (Adh) and yolk protein genes. DNA sequence analysis of cDNA clones encoding this protein, box B-binding factor-2 (BBF-2), indicates that it is a member of the CREB/ATF family of transcriptional regulatory proteins. A number of observations suggest that BBF-2 is involved in fat body-specific expression: Mutations that disrupt BBF-2 binding to two different Adh fat body enhancers in vitro decrease the activity of these enhancers in transgenic flies. BBF-2 mRNA is present in all cell types examined, and the protein is present in cells that express ADH. Finally, BBF-2 is a transcriptional activator in Drosophila tissue culture cells. Remarkably, BBF-2 also binds specifically to regulatory elements required for liver-specific expression of the human Adh and rat tyrosine aminotransferase genes. Thus, BBF-2 and the DNA sequence to which it binds may be important components of a tissue-specific regulatory mechanism conserved between Drosophila and man.
 ...
PMID:A Drosophila CREB/ATF transcriptional activator binds to both fat body- and liver-specific regulatory elements. 153 59

The ALCR protein is the transcriptional activator of the ethanol utilization pathway in the filamentous fungus Aspergillus nidulans. This activator belongs to a family of fungal proteins having a conserved DNA-binding domain containing six cysteines (C6 class) with some striking features. At variance with other motifs of this class, the binding domain of ALCR is strongly asymmetrical in relation to the central cysteines and moreover was predicted to adopt a helix-turn-helix structure. This domain of ALCR was synthesized in Escherichia coli and purified as a glutathione-S-transferase fusion protein. Our results show that the transcriptional activator ALCR is a DNA-binding protein. The DNA-binding motif contains zinc that is necessary for the specific DNA binding. The ALCR peptide binds upstream of the coding region of alcR to two specific targets with different affinities that are characterized by a conserved 5-nucleotide core, 5'-CCGCA-3' (or its reverse). One site, the lower-affinity binding site, is a direct repeat, and the other, the higher-affinity binding site, is a palindromic sequence with dyad symmetry. Therefore, the ALCR binding protein is able to recognize one DNA sequence in two different configurations. An alcR mutant obtained by deletion of the two specific targets in the cis-acting region of the alcR gene is unable to grow on ethanol and does not express any alcohol dehydrogenase activity. These results demonstrate that the binding sites are in vivo functional targets (UASalc) for the ALCR protein in A. nidulans. They corroborate prior evidence that alcR is autoregulated.
 ...
PMID:Identification of the promoter region involved in the autoregulation of the transcriptional activator ALCR in Aspergillus nidulans. 156 30

The substrate specificity of the cAMP-dependent protein kinase (cAPK) from Saccharomyces cerevisiae has been investigated using synthetic peptides corresponding to the local phosphorylation site sequence around Ser-230 in the yeast transcriptional activator ADR1. ADR1 is required for the expression of the glucose-repressible alcohol dehydrogenase. Yeast cAPK (encoded by the TPK1 gene) phosphorylated Ser-230 in the synthetic peptide ADR1-217-234, VRKRYLKKLTRRASFSAQ-NH2, with a Km of 5.3 microM compared with 46 microM for LRRASLG (Kemptide). Porcine heart cAPK phosphorylated the ADR1 peptide and Kemptide with the considerable lower Km values of 0.23 and 1.6 microM, respectively. These results indicate that the ADR1 peptide is an excellent substrate for cAPK. Both the yeast and mammalian protein kinases qualitatively shared a number of substrate specificity determinants in common involving residues on the proximal NH2-terminal side and up to the +4 position of the COOH-terminal side of the phosphoacceptor. The mammalian enzyme, however, had a much higher affinity for its substrates than did the yeast enzyme. In addition, the yeast and mammalian enzymes displayed several quantitative differences in their preferences for particular peptide substrates. In particular, the mammalian enzyme strongly preferred substrates with NH2-terminal extensions beyond the -4 position relative to the phosphoacceptor. These results suggest that all eukaryotic cAPKs recognize similar but not identical substrate specificity determinants. They also suggest that the different affinities for substrates that inhere to the individual enzymes could influence their physiological roles.
 ...
PMID:Substrate specificities for yeast and mammalian cAMP-dependent protein kinases are similar but not identical. 191 32

It was previously observed that increased dosages of the ADR1 gene, which encodes a yeast transcriptional activator required for alcohol dehydrogenase II (ADH II) expression, cause a decreased rate of growth in medium containing ethanol as the carbon source. Here we show that observed reduction in growth rate is mediated by the ADR1 protein which, when overexpressed, increases the frequency of cytoplasmic petites. Unlike previously characterized mutations known to potentiate petite formation, the ADR1 effect is dominant, with the petite frequency rising concomitantly with increasing ADR1 dosage. The ability of ADR1 to increase the frequency of mitochondrial mutation is correlated with its ability to activate ADH II transcription but is independent of the level of ADH II being expressed. Based on restoration tests using characterized mit- strains, ADR1 appears to cause non-specific deletions within the mitochondrial genome to produce rho- petites. Pedigree analysis of ADR1-overproducing strains indicates that only daughter cells become petite. This pattern is analogous to that observed for petite induction by growth at elevated temperature and by treatment with the acridine dye euflavine. One strain resistant to ADR1-induced petite formation displayed cross-resistance to petite mutation by growth at elevated temperature and euflavine treatment, yet was susceptible to petite induction by ethidium bromide. These results suggest that ADR1 overexpression disrupts the fidelity of mitochondrial DNA replication or repair.
 ...
PMID:Overexpression of the yeast transcriptional activator ADR1 induces mutation of the mitochondrial genome. 267 4

The transcriptional activator ADR1 from Saccharomyces cerevisiae is a postulated DNA-binding protein that controls the expression of the glucose-repressible alcohol dehydrogenase (ADH2). Carboxy-terminal deletions of the ADR1 protein (1,323 amino acids in length) were used to localize its functional regions. The transcriptional activation region was localized to the N-terminal 220 amino acids of ADR1 containing two DNA-binding zinc finger motifs. In addition to the N terminus, a large part of the ADR1 sequence was shown to be essential for complete activation of ADH2. Deletion of the putative phosphorylation region, defined by ADR1c mutations that overcome glucose repression, did not render ADH2 expression insensitive to glucose repression. Instead, this region (amino acids 220 through 253) was found to be required by ADR1 to bypass glucose repression. These results suggest that ADR1c mutations enhance ADR1 function, rather than block an interaction of the putative phosphorylation region with a repressor molecule. Furthermore, the protein kinase CCR1 was shown to affect ADH2 expression when the putative phosphorylation region was removed, indicating that CCR1 does not act solely through this region. A functional ADR1 gene was also found to be necessary for growth on glycerol-containing medium. The N-terminal 506 amino acids of ADR1 were required for this newly identified function, indicating that ADH2 activation and glycerol growth are controlled by separate regions of ADR1.
 ...
PMID:Identification of functional regions in the yeast transcriptional activator ADR1. 329 Jun 50

The dosage of the transcriptional activator ADR1 was varied in order to study the regulation of the glucose-repressible alcohol dehydrogenase (ADH II) from Saccharomyces cerevisiae. ADH II activity during glucose growth conditions was shown to increase linearly with increasing ADR1 gene dosage. In contrast, under derepressed growth conditions a 100-fold increase in ADR1 copy number resulted in only a 4-fold increase in ADH II expression. Saturation of ADH II gene expression by ADR1 under derepressed conditions was shown not to result from decreased ADR1 transcription. Increases in ADH2 gene dosage in conjunction with high ADR1 gene dosages resulted in increased ADH II activity, indicating that ADH2 was the limiting factor during derepression. Under glucose-repressed conditions the activator CCR1 was not required for ADR1 activity. During derepression increasing ADR1 dosage could partially compensate for a CCR1 defect. Increasing CCR1 gene dosage, however, had no effect on ADH2 expression regardless of the ADR1 allele present. These results suggest that CCR1 acts through ADR1 in controlling ADH2 expression. It was also observed that high numbers of ADR1, or a few copies of ADR1-5c, substantially increased the cell doubling time under ethanol growth conditions, indicating that increased ADR1 activity is toxic.
 ...
PMID:The effects of ADR1 and CCR1 gene dosage on the regulation of the glucose-repressible alcohol dehydrogenase from Saccharomyces cerevisiae. 330 3

We have identified a Drosophila transcription factor that binds a sequence element found in the larval promoters of all known alcohol dehydrogenase (Adh) genes. DNA sequence analysis of cDNA clones encoding this protein, box A-binding factor (ABF), reveals that it is a member of the GATA family of transcriptional regulatory factors. ABF-binding sites within the D. mulleri and D. melanogaster larval Adh promoters function as positive regulatory elements and in cotransfection experiments, ABF functions as a transcriptional activator. In further support of a role for ABF in the regulation of Adh expression, ABF mRNA is expressed in the embryonic fat body, a tissue that contains high levels of Adh mRNA. Our studies demonstrate that the fat body develops from segmentally repeated clusters of mesodermal cells, which later expand and coalesce to form the mature fat body. These observations establish ABF as the earliest known fat body precursor marker in the Drosophila embryo. Together with the established role of GATA factors during mammalian development, these results suggest that ABF may play a key role in the organogenesis of the fat body.
 ...
PMID:A Drosophila GATA family member that binds to Adh regulatory sequences is expressed in the developing fat body. 818 33

The yeast transcriptional activator ADR1 is required for expression of the glucose-repressible alcohol dehydrogenase gene (ADH2), as well as genes involved in glycerol metabolism. The N-terminal half of the ADR1 protein was shown to contain three separate transactivation domains, including one (TADI) that encompasses the zinc finger DNA-binding domain. While TADII and TADIII were shown to be functionally redundant in activating ADH2 expression, deletion of only TADIII impaired ADR1 control of glycerol metabolism genes. None of these activation domains appeared to be carbon source regulated when separated from the ADH2 promoter context. Interspersed among these activation domains were two regions which, when removed, increased ADR1 activity; one was localized to the site of ADR1c mutations (residues 227 to 239) that allow glucose-insensitive ADH2 expression. The 227-to-239 region blocked ADR1 activity independently of the TAD present on ADR1, ADR1 DNA binding, and specific ADH2 promoter sequences. In addition, this region inhibited the function of a heterologous transcriptional activator. These results are consistent with the existence of an extragenic factor that binds the ADR1c region and represses ADR1 activity and suggest that other factors are responsible for aiding ADR1 in the carbon source regulation of ADH2.
 ...
PMID:Dissection of the ADR1 protein reveals multiple, functionally redundant activation domains interspersed with inhibitory regions: evidence for a repressor binding to the ADR1c region. 826 31

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.
 ...
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

Previously, we demonstrated that ABP-1 (arylphorin gene-specific binding protein-1), which is suggested to be the transcriptional activator of the arylphorin gene of Sarcophaga peregrina, is present in NIH-Sape-4 cells, which do not express arylphorin. As well as ABP-1, these cells were found to contain another protein (ABP-2) that probably binds to the same sequence as that to which ABP-1 binds [Adachi, N., Kubo, T., and Natori, S. (1993) J. Biochem. 114, 55-60]. We purified ABP-2 from a nuclear extract of NIH-Sape-4 cells and compared its DNA-binding activity with that of ABP-1. Both ABP-1 and ABP-2 were found to bind to the same sequence in the arylphorin gene with the same affinity and stability, but an ABP-2-specific hypersensitive site was detected by DNase I footprinting analysis. Analyses of proteolytic fragments suggested that both ABP-1 and ABP-2 have Zn fingers showing high similarity with that of AEF-1, a transcriptional repressor of the Drosophila melanogaster alcohol dehydrogenase gene that binds to a sequence very similar to that binding ABP-1 and ABP-2. We isolated a candidate cDNA for ABP-2, and the protein it encoded contained nine Zn fingers and regions rich in alanine, glutamine, serine/threonine, glycine, histidine, and asparagine.
 ...
PMID:Purification, characterization, and cDNA cloning of ABP-2 (arylphorin gene-specific binding protein-2) that specifically binds to the ABP-1-binding sequence in the arylphorin gene of Sarcophaga peregrina. 901 Jul 76


1 2 Next >>