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 ada gene of Escherichia coli encodes a 39-kDa protein which serves both as a transcriptional activator of the adaptive response to alkylating agents and as a DNA repair enzyme demethylating O6-methyl-guanine and phosphotriester residues. Here, the isolated Ada protein was found to be readily cleaved into two fragments of similar size by treatment with trypsin, chymotrypsin, subtilisin, or V8 protease. The fragments retained their respective methyltransferase activities. The Ada protein is, therefore, comprised of two stable active domains united by a central hinge region of about 10 amino acids. Post-translational modification of the Ada protein by methylation of a specific cysteine residue in the NH2-terminal domain is known to convert it to an efficient transcriptional activator. This residue has now been identified as Cys-69.
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PMID:Functional domains and methyl acceptor sites of the Escherichia coli ada protein. 316 36

The TyrR protein of Escherichia coli is the chief transcriptional regulator of several genes essential for aromatic amino acid biosynthesis and transport. It was established in previous studies that this protein binds ATP, that the TyrR.ATP complex has enhanced affinity for tyrosine, and that the susceptibility of the TyrR protein to hydrolysis by trypsin is altered by ATP. Here we show that the TyrR protein has ATPase activity, which is stimulated by tyrosine. In this respect the TyrR protein resembles the transcriptional activator NtrC. The NtrC protein contains an internal polypeptide segment, 220 amino acid residues in length, with a high degree of identity to the TyrR protein, that contains the presumptive ATPase catalytic center.
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PMID:ATPase activity of TyrR, a transcriptional regulatory protein for sigma 70 RNA polymerase. 851 43

BkdR is the positive transcriptional activator of the inducible bkd operon of Pseudomonas putida. Evidence is accumulating that L-branched-chain amino acids are the inducers of the operon, and the data obtained in this study show that they induce a conformational change in BkdR. Addition of L-branched-chain amino acids increased the susceptibility of BkdR to trypsin with the cleavage between Arg-51 and Gln-52 on the C-terminal side of the DNA-binding domain. L-Valine also caused an increased fluorescence emission intensity and produced significant changes in the circular dichroism spectrum of BkdR. Analytical ultracentrifugation confirmed earlier data obtained from gel filtration that BkdR was a tetramer with a Stokes radius of 32 +/- 3 A and an axial ratio of 2:1.
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PMID:Binding of L-branched-chain amino acids causes a conformational change in BkdR. 898 9

Azotobacter vinelandii NIFL is a nitrogen fixation-specific regulatory flavoprotein that modulates the activity of the transcriptional activator NIFA in response to oxygen and fixed nitrogen in vivo. NIFL is also responsive to ADP in vitro. Limited proteolysis of NIFL indicates that it comprises a relatively stable N-terminal domain and a C-terminal domain that is protected from trypsin digestion in the presence of adenosine nucleotides. ATP protects the protein from cleavage in the vicinity of potential nucleotide-binding sites in the C-terminus, whereas ADP protects the entire C-terminal domain. NIFL has an apparent Kd of 130 microM for ATP and 16 microM for ADP. The purified N-terminal domain has an identical UV/visible absorption spectrum to the wild-type protein and is reduced by sodium dithionite, demonstrating that it is a flavin-binding domain. The isolated N-terminal domain does not inhibit NIFA activity. A subdomain fragment containing 160 residues of the C-terminal region, including the nucleotide-binding sites, is also not competent to inhibit NIFA. Removal of the first 146 residues of NIFL, which includes a conserved S-motif (PAS-like domain), found in a large family of sensory proteins from eubacteria, archea and eukarya eliminates the redox response. However, this truncated protein remains competent to inhibit NIFA activity in response to ADP in vitro and to the level of fixed nitrogen in vivo. The redox and nitrogen-sensing functions of A. vinelandii NIFL are therefore separable and are discrete functions of the protein.
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PMID:The redox- and fixed nitrogen-responsive regulatory protein NIFL from Azotobacter vinelandii comprises discrete flavin and nucleotide-binding domains. 959 6

HvGAMYB, a MYB transcription factor previously shown to be expressed in barley aleurone cells in response to gibberellin during germination, also has an important role in gene regulation during endosperm development. The mRNA was detected early (10 DAF) in the seeds where it accumulates, not only in the aleurone layer, starchy endosperm, nucellar projection and vascular tissue, but also in the immature embryo as shown by in situ hybridization analysis. The HvGAMYB protein, expressed in bacteria, binds to oligonucleotides containing the 5'-TAACAAC-3' or 5'-CAACTAAC-3' sequences, derived from the promoter regions of the endosperm-specific genes Hor2 and Itr1, encoding a B-hordein and trypsin-inhibitor BTI-CMe, respectively. Binding is prevented when these motifs are mutated to 5'-TgACAAg-3' and 5'-CgACTgAC-3'. Transient expression experiments in co-bombarded developing endosperms demonstrate that HvGAMYB trans-activates transcription from native Hor2 and Itr1 promoters through binding to the intact motifs described above. Trans-activation of the Hor2 promoter also requires an intact prolamine box (PB). This suggests that HvGAMYB interacts in developing barley endosperms with the PB-binding factor BPBF, an endosperm-specific DOF transcriptional activator of the Hor2 gene. The in vivo interaction experiment between HvGAMYB and BPBF was done in the yeast two-hybrid system, where HvGAMYB potentiates the BPBF trans-activation capacity through interaction with its C-terminal domain.
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PMID:The GAMYB protein from barley interacts with the DOF transcription factor BPBF and activates endosperm-specific genes during seed development. 1184 78

The expression of genes required for the synthesis of molybdenum nitrogenase in Azotobacter vinelandii is controlled by the NifL-NifA transcriptional regulatory complex in response to nitrogen, carbon, and redox status. Activation of nif gene expression by the transcriptional activator NifA is inhibited by direct protein-protein interaction with NifL under conditions unfavorable for nitrogen fixation. We have recently shown that the NifL-NifA system responds directly to physiological concentrations of 2-oxoglutarate, resulting in relief of NifA activity from inhibition by NifL under conditions when fixed nitrogen is limiting. The inhibitory activity of NifL is restored under conditions of excess combined nitrogen through the binding of the signal transduction protein Av GlnK to the carboxyl-terminal domain of NifL. The amino-terminal domain of NifA comprises a GAF domain implicated in the regulatory response to NifL. A truncated form of NifA lacking this domain is not responsive to 2-oxoglutarate in the presence of NifL, suggesting that the GAF domain is required for the response to this ligand. Using isothermal titration calorimetry, we demonstrate stoichiometric binding of 2-oxoglutarate to both the isolated GAF domain and the full-length A. vinelandii NifA protein with a dissociation constant of approximately 60 microm. Limited proteolysis experiments indicate that the binding of 2-oxoglutarate increases the susceptibility of the GAF domain to trypsin digestion and also prevents NifL from protecting these cleavage sites. However, protection by NifL is restored when the non-modified (non-uridylylated) form of Av GlnK is also present. Our results suggest that the binding of 2-oxoglutarate to the GAF domain of NifA may induce a conformational change that prevents inhibition by NifL under conditions when fixed nitrogen is limiting.
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PMID:The amino-terminal GAF domain of Azotobacter vinelandii NifA binds 2-oxoglutarate to resist inhibition by NifL under nitrogen-limiting conditions. 1275 52

The estrogen receptor-related receptor gamma (ERR gamma/ERR3/NR3B3) is the newest member of the ERR subfamily that also includes ERR alpha and ERR beta. All three isoforms share a high degree of amino acid identity especially in the DNA binding domain. ERR gamma is a constitutively active transcriptional activator that regulates reporter elements driven by steroidogenic factor 1 response element (SF-1RE) and estrogen response element. However, it has the highest potency on a derivative of SF-1RE present in the small heterodimer partner gene promoter called sft4 and unlike ERR alpha and -beta, it fails to activate a palindromic thyroid hormone response element. To investigate the mechanism behind this response element-specific differential transcriptional activity of ERR gamma, the interactions of ERR gamma and the aforementioned response elements was monitored. EMSA and chromatin immunoprecipitation assays demonstrated that ERR gamma binds to sft4, SF-1RE, and palindromic thyroid hormone response element albeit with different degrees of affinity, but causes hyperacetylation of sft4 and SF-1RE templates only. Limited proteolysis assays showed that ERR gamma, bound to different elements, shows differential trypsin sensitivity. A search for novel coregulators of ERR gamma led to the identification of receptor interacting protein 140 as a potent corepressor and peroxisome proliferator-activated receptor gamma coactivator 1 as a potent coactivator of ERR gamma. DNA-dependent pull-down and transient transfection assays demonstrated that, on different DNA elements, ERR gamma exhibits differential cofactor interactions, which in turn dictate its transcriptional activity. Because ERR gamma shows a similar tissue distribution as peroxisome proliferator-activated receptor gamma coactivator 1 and receptor interacting protein 140, these two coregulators may act as key components of ERR gamma-mediated transcription.
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PMID:Deoxyribonucleic acid response element-dependent regulation of transcription by orphan nuclear receptor estrogen receptor-related receptor gamma. 1464 97

AdpA is the key transcriptional activator for a number of genes of various functions in the A-factor regulatory cascade in Streptomyces griseus, forming an AdpA regulon. Trypsin-like activity was detected at a late stage of growth in the wild-type strain but not in an A-factor-deficient mutant. Consistent with these observations, two trypsin genes, sprT and sprU, in S. griseus were found to be members of the AdpA regulon; AdpA activated the transcription of both genes by binding to the operators located at about -50 nucleotide positions with respect to the transcriptional start point. The transcription of sprT and sprU, induced by AdpA, was most active at the onset of sporulation. Most trypsin activity exerted by S. griseus was attributed to SprT, because trypsin activity in an sprT-disrupted mutant was greatly reduced but that in an sprU-disrupted mutant was only slightly reduced. This was consistent with the observation that the amount of the sprT mRNA was much greater than that of the sprU transcript. Disruption of both sprT and sprU (mutant DeltasprTU) reduced trypsin activity to almost zero, indicating that no trypsin genes other than these two were present in S. griseus. Even the double mutant DeltasprTU grew normally and developed aerial hyphae and spores over the same time course as the wild-type strain.
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PMID:Transcriptional control by A-factor of two trypsin genes in Streptomyces griseus. 1560 13

The DOF protein, SAD, previously shown to be a transcriptional activator in barley aleurone cells upon seed germination, also has an important role in gene regulation during endosperm development. mRNA was detected in early (10 days after flowering) developing barley seeds where it accumulated in the starchy endosperm, aleurone cells, nucellar projection, vascular tissues and the immature embryo, as shown by RT-PCR and in situ hybridization analyses. The SAD protein, expressed in bacteria, binds to oligonucleotides containing the prolamine box, 5'-A/TAAAG-3'sequence, derived from the promoter regions of the endosperm-specific genes Hor2 and Itr1, encoding a B-hordein and trypsin-inhibitor BTI-CMe, respectively. SAD competed for the same binding sites with another endosperm-expressed DOF protein, BPBF. Transient expression experiments in co-bombarded developing endosperms demonstrated that SAD trans-activated transcription from Hor2 and Itr1 promoters through binding to the intact DOF motifs. When the two DOF factors are co-bombarded together an additive effect was observed upon the expression of the Itr1 gene. In-frame fusion of the Sad ORF to the reporter green fluorescent protein gene directs the fluorescence expression to the nucleus in transiently transformed onion epidermal layers. The visualization of fluorescence in the nucleus of onion cells, using the bimolecular fluorescent complex (BiFC) approach, has shown the in vivo interaction between SAD and the R2R3MYB protein GAMYB. The interaction in plant cells has also been documented for the DOF protein BPBF and GAMYB, but nuclear interaction could not be detected between BPBF and SAD by this procedure.
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PMID:The DOF protein, SAD, interacts with GAMYB in plant nuclei and activates transcription of endosperm-specific genes during barley seed development. 1591 80

The sgtR1 and sgtR2 genes encoding putative regulators similar to the Aha1 and ArsR families, respectively, were identified downstream from the sprT gene. To investigate their function, expression vectors containing various combinations of sprT, sgtR1, and sgtR2 were transformed into Streptomyces lividans and Streptomyces griseus. The trypsin activity levels produced by S. lividans harboring pWHM3-TR2 (sprT and sgtR2) or pWHM3-TR1R2 (sprT, sgtR2, and sgtR2) were, respectively, 6.6 or 8.9 times that of S. lividans transformed with pWHM3-T (sprT). In the pWHM3-TR1R2 transformant, the transcription of sprT consistently occurred during the earlier stages of growth and was maintained at a higher level throughout the 6 days of cultivation. Streptomyces griseus IFO13350 harboring pWHM3-TR1R2 also produced trypsin activity 2.1 times that of the pWHM3-T transformant. However, all S. griseus Delta adpA transformants produced lower SGT activity than the wild-type strain, and none could overcome the deficiency in AdpA transcriptional activator, suggesting that AdpA is an absolute prerequisite for sprT expression. The sprT transcript was detected at a high level only in the wild-type strain, but the sgtR1 and sgtR2 transcript levels were very similar between the S. griseus IFO13350 and Delta adpA strains. This clearly demonstrates that the transcription of the sgtR1 and sgtR2 genes is not dependent on AdpA and that they are therefore not members of the AdpA regulon.
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PMID:Characterization of the sgtR1 and sgtR2 genes and their role in regulating expression of the sprT gene encoding Streptomyces griseus trypsin. 1782 68


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