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)

PhoB protein is the transcriptional activator for genes in the phosphate regulon of Escherichia coli, such as phoA and pstS, that are induced by phosphate deprivation. PhoR protein activates PhoB when phosphate is limiting and inactivates it when phosphate is in excess. We constructed a plasmid with a mutant phoR gene (phoR1084), which encoded a PhoR protein (PhoR1084) lacking the amino-terminal hydrophobic region of the intact protein. The cells carrying the plasmid overproduced PhoR1084, which was recovered in the soluble fraction of the cell lysate. We purified the Phor1084 protein and showed that it was autophosphorylated in the presence of ATP, and the phosphate group on the protein was rapidly transferred to PhoB. The phosphorylation of PhoB protein occurred concurrently with the acquisition of the ability to activate transcription from the pstS promoter. On the basis of these findings, we propose that phosphorylated PhoB protein activates transcription from the promoters of the phosphate regulon, and that the role of PhoR is to catalyze the formation and breakdown of phosphorylated PhoB in response to phosphate concentrations in the medium.
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PMID:Signal transduction in the phosphate regulon of Escherichia coli involves phosphotransfer between PhoR and PhoB proteins. 269 38

The initiation of transcription from the nitrogen-regulated promoter glnAp2 requires RNA polymerase containing sigma 54, the transcriptional activator NRI, and the protein kinase NRII, responsible for the conversion of NRI to the active NRI-phosphate. NRI-phosphate does not increase the ability of sigma 54-containing RNA polymerase to bind to the promoter, but rather stimulates the conversion of an initial promoter:polymerase complex to the transcriptionally active open complex. The presence on the DNA template of high-affinity binding sites for NRI/NRI-phosphate, normally located 130 and 100 bp upstream of the site of transcription initiation, results in a 4- to 5-fold lowering of the concentration of NRI required for the formation of the open complex. These high-affinity NRI binding sites facilitate open complex formation when they are moved to positions 700 bp further upstream or 950 bp downstream of glnAp2 on linear DNA templates.
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PMID:Initiation of transcription at the bacterial glnAp2 promoter by purified E. coli components is facilitated by enhancers. 330 60

Although oxidative stress is involved in many human diseases, little is known of its molecular basis in eukaryotes. In a genetic approach, S. cerevisiae was used to identify elements involved in oxidative stress. By using hydrogen peroxide as an agent for oxidative stress, 34 mutants were identified. All mutants were recessive and fell into 16 complementation groups (pos1 to pos16 for peroxide sensitivity). They corresponded to single mutations as shown by a 2:2 segregation pattern. Enzymes reportedly involved in oxidative stress, such as glucose-6-phosphate dehydrogenase, glutathione reductase, superoxide dismutase, as well as glutathione concentrations, were investigated in wild-type and mutant-cells. One complementation group lacked glucose-6-phosphate dehydrogenase and was shown to be allelic to the glucose-6-phosphate dehydrogenase structural gene ZWF1/MET19. In other mutants all enzymes supposedly involved in oxidative-stress resistance were still present. However, several mutants showed strongly elevated levels of glutathione reductase, gluconate-6-phosphate dehydrogenase and glucose-6-phosphate dehydrogenase. One complementation group, pos9, was highly sensitive to oxidative stress and revealed the same growth phenotype as the previously described yap1/par1 mutant coding for the yeast homologue of mammalian transcriptional activator protein, c-Jun, of the proto-oncogenic AP-1 complex. However, unlike par1 mutants, which showed diminished activities of oxidative-stress enzymes and glutathion level, the pos9 mutants did not reveal any such changes. In contrast to other recombinants between pos mutations and par1, the sensitivity did not further increase in par1 pos9 recombinants, which may indicate that both mutations belong to the same regulating circuit.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Mutants of Saccharomyces cerevisiae sensitive to oxidative and osmotic stress. 758 28

The PhoB protein, the transcriptional activator for the genes belonging to the phosphate regulon in Escherichia coli, was autophosphorylated in the presence of acetyl phosphate (acP) in vitro. The properties of phospho-PhoB, such as stability upon acid or alkali treatment and activating pstS transcription by RNA polymerase holoenzyme, were the same as those of phospho-PhoB produced from phospho-PhoR or phospho-PhoM. These results indicate that PhoB is an enzyme that catalyzes its own phosphorylation using acP, a low-molecular-weight metabolic intermediate.
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PMID:Autophosphorylation and activation of transcriptional activator PhoB of Escherichia coli by acetyl phosphate in vitro. 764 40

The soil bacterium Rhizobium meliloti fixes dinitrogen when associated with root nodules formed on its plant host, Medicago sativa (alfalfa). The expression of most of the known genes required for nitrogen fixation (nif and fix genes), including the structural genes for nitrogenase, is induced in response to a decrease in oxygen concentration. Induction of nif and fix gene expression by low oxygen is physiologically relevant because a low-oxygen environment is maintained in root nodules to prevent inactivation of the highly oxygen-sensitive nitrogenase enzyme. The genes responsible for sensing and transducing the low oxygen signal, fixL and fixJ, encode proteins (FixL and FixJ, respectively) that are homologous to a large family of bacterial proteins involved in signal transduction, the two component regulatory system proteins. The two components consist of a sensor protein, to which FixL is homologous, and a response regulator protein, to which FixJ is homologous. The sensor protein respond to an activating signal by autophosphorylating and then transferring the phosphate to its cognate response regulator protein. The phosphorylated response regulator, which is often a transcriptional activator, is then able to activate its target. A cascade model of nif and fix gene regulation in R. meliloti has been proposed, whereby FixL acts as an oxygen sensor as the initial event in the cascade and transmits this information to FixJ. FixJ, which possesses a putative helix-turn-helix DNA-binding motif, then activates transcription of the nifA and fixK genes. The nifA and fixK gene products, are transcriptional activators of at least 14 other nif and fix genes.
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PMID:Genetic regulation of nitrogen fixation in Rhizobium meliloti. 777 92

The phoE promoter region in Escherichia coli contains a -10 region, typical of sigma 70-dependent promoters and, instead of a normal -35 region, a so-called pho box, to which the transcriptional activator phospho-PhoB binds under low phosphate conditions. A second pho box is present upstream of the first one and is required for full expression of phoE during phosphate starvation. To determine whether the lack of expression under high phosphate conditions is due solely to the absence of a genuine -35 box, the -10 region was further optimized towards the consensus -10 sequence and promoter activity was measured using alkaline phosphatase as a reporter. The mutations resulted in a drastic increment in the basal level of expression under high phosphate conditions, indicating that the deviations from consensus in the -10 region also play a role in determining the poor expression of the wild-type promoter under these conditions. The expression under high phosphate conditions was partly dependent on the presence of the phoB gene, showing that a small amount of active PhoB must be present under these circumstances. During phosphate starvation, the activity of the mutant promoters was further induced. The upstream pho box was not required for full expression from the mutant promoters under these conditions. Apparently, the wild-type phoE promoter is carefully balanced by deviations from the optimal Pribnow box sequence that reduce expression under high phosphate conditions and by the presence of several copies of the pho box, which enhance expression under phosphate starvation.
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PMID:Effect of mutations in the -10 region of the phoE promoter in Escherichia coli on regulation of gene expression. 781 30

The initiation of transcription at the sigma 54-dependent promoter glnAp2 of Escherichia coli is activated by the protein NR1(NTRC)-phosphate, which binds to two sites located upstream of the promoter that together constitute an enhancer. The cooperative binding facilitates the oligomerization of NR1-phosphate endowing it with the ATPase activity required for its ability to serve as transcriptional activator. We show here that these sites can be replaced by sequence-dependent superhelical inserts, lacking any homology to the nucleotide sequence of the enhancers. These superhelical inserts, irrespective of their chirality, are as effective as the paired sites in binding NR1-phosphate and in stimulating its oligomerization. We conclude that a specific sequence of nucleotides and the three-dimensional structure of DNA can determine its affinity for the NR1 activator protein capable of binding to DNA.
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PMID:A sequence-induced superhelical DNA segment serves as transcriptional enhancer. 785 2

The sensor kinase FixL and the response regulator FixJ induce the expression of the nitrogen fixation genes of Rhizobium meliloti in response to microaerobiosis, which is a characteristic feature of the plant root nodule interior where the bacteria fix nitrogen. The kinase activity of a purified, soluble derivative of the membrane-bound hemoprotein FixL, designated FixL*, is stimulated under low oxygen conditions, thus increasing FixJ-phosphate levels. FixJ-phosphate is a potent transcriptional activator of the nifA and fixK genes, the products of which, in turn, induce the expression of most if not all of the remaining nitrogen fixation genes. FixL* and FixL*-phosphate also dephosphorylate FixJ-phosphate, and this activity is depressed by low oxygen concentrations. In the current model, gene expression is reciprocally coordinated by the kinase and phosphatase activities of FixL according to changes in oxygen tension.
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PMID:Oxygen regulation of expression of nitrogen fixation genes in Rhizobium meliloti. 785 32

The two-component system sensor/response regulator pair, FixL/FixJ, controls the expression of Rhizobium meliloti nitrogen fixation (nif and fix) genes in response to changes in oxygen concentration. A truncated version of FixL, FixL*, is an oxygen-binding hemoprotein kinase that phosphorylates and dephosphorylates the nif and fix gene transcriptional activator, FixJ. Phosphorylation of FixJ is required for optimal transcriptional activation, and anaerobic conditions in vitro result in a substantial increase in the level of FixJ-phosphate. In this study, site-directed mutagenesis was carried out at histidine residues in FixL*. Mutant FixL* derivatives were purified and analyzed in vitro for their heme/oxygen binding properties and phosphorylation/dephosphorylation activities. Mutation of histidine 285, the putative autophosphorylation site, to glutamine results in the loss of FixL* phosphorylation activities. However, this mutant protein retains a substantial level of FixJ-phosphate dephosphorylation activity. Mutation of histidine 194 to asparagine results in the loss of heme binding and in the failure of FixL* to regulate its phosphorylation/dephosphorylation activities in response to changes in oxygen concentration. The FixL*H194N mutant protein also exhibits an increased FixJ phosphorylation activity under aerobic conditions. This study provides further evidence for the importance of the heme binding domain of FixL* in regulating FixJ phosphorylation and dephosphorylation activities in response to oxygen.
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PMID:The oxygen sensor protein, FixL, of Rhizobium meliloti. Role of histidine residues in heme binding, phosphorylation, and signal transduction. 789 Jun 34

The yeast Saccharomyces cerevisiae can use alternative nitrogen sources such as arginine, urea, allantoin, gamma-aminobutyrate, or proline when preferred nitrogen sources like glutamine, asparagine, or ammonium ions are unavailable in the environment. Utilization of alternative nitrogen sources requires the relief of nitrogen repression and induction of specific permeases and enzymes. The products of the GLN3 and URE2 genes are required for the appropriate transcription of many genes in alternative nitrogen assimilatory pathways. GLN3 appears to activate their transcription when good nitrogen sources are unavailable, and URE2 appears to repress their transcription when alternative nitrogen sources are not needed. The participation of nitrogen repression and the regulators GLN3 and URE2 in the proline utilization pathway was evaluated in this study. Comparison of PUT gene expression in cells grown in repressing or derepressing nitrogen sources, in the absence of the inducer proline, indicated that both PUT1 and PUT2 are regulated by nitrogen repression, although the effect on PUT2 is comparatively small. Recessive mutations in URE2 elevated expression of the PUT1 and PUT2 genes 5- to 10-fold when cells were grown on a nitrogen-repressing medium. Although PUT3, the proline utilization pathway transcriptional activator, is absolutely required for growth on proline as the sole nitrogen source, a put3 ure2 strain had somewhat elevated PUT gene expression, suggesting an effect of the ure2 mutation in the absence of the PUT3 product. PUT1 and PUT2 gene expression did not require the GLN3 activator protein for expression under either repressing or derepressing conditions. Therefore, regulation of the PUT genes by URE2 does not require a functional GLN3 protein. The effect of the ure2 mutation on the PUT genes is not due to increased internal proline levels. URE2 repression appears to be limited to nitrogen assimilatory systems and does not affect genes involved in carbon, inositol, or phosphate metabolism or in mating-type control and sporulation.
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PMID:Roles of URE2 and GLN3 in the proline utilization pathway in Saccharomyces cerevisiae. 789 26


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