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)

In Rhodobacter capsulatus, genes encoding enzymes of the Calvin-Benson-Bassham reductive pentose phosphate pathway are located in the cbb(I) and cbb(II) operons. Each operon contains a divergently transcribed LysR-type transcriptional activator (CbbR(I) and CbbR(II)) that regulates the expression of its cognate cbb promoter in response to an as yet unidentified effector molecule(s). Both CbbR(I) and CbbR(II) were purified, and the ability of a variety of potential effector molecules to induce changes in their DNA binding properties at their target promoters was assessed. The responses of CbbR(I) and CbbR(II) to potential effectors were not identical. In gel mobility shift assays, the affinity of both CbbR(I) and CbbR(II) for their target promoters was enhanced in the presence of ribulose-1,5-bisphosphate (RuBP), phosphoenolpyruvate, 3-phosphoglycerate, 2-phosphoglycolate. ATP, 2-phosphoglycerate, and KH(2)PO(4) were found to enhance only CbbR(I) binding, while fructose-1,6-bisphosphate enhanced the binding of only CbbR(II). The DNase I footprint of CbbR(I) was reduced in the presence of RuBP, while reductions in the CbbR(II) DNase I footprint were induced by fructose-1,6-bisphosphate, 3-phosphoglycerate, and KH(2)PO(4). The current in vitro results plus recent in vivo studies suggest that CbbR-mediated regulation of cbb transcription is controlled by multiple metabolic signals in R. capsulatus. This control reflects not only intracellular levels of Calvin-Benson-Bassham cycle metabolic intermediates but also the fixed (organic) carbon status and energy charge of the cell.
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PMID:Effector-mediated interaction of CbbRI and CbbRII regulators with target sequences in Rhodobacter capsulatus. 1554 75

Plants sense phosphate (Pi) deficiency and initiate signaling that controls adaptive responses necessary for Pi acquisition. Herein, evidence establishes that AtSIZ1 is a plant small ubiquitin-like modifier (SUMO) E3 ligase and is a focal controller of Pi starvation-dependent responses. T-DNA insertional mutated alleles of AtSIZ1 (At5g60410) cause Arabidopsis to exhibit exaggerated prototypical Pi starvation responses, including cessation of primary root growth, extensive lateral root and root hair development, increase in root/shoot mass ratio, and greater anthocyanin accumulation, even though intracellular Pi levels in siz1 plants were similar to wild type. AtSIZ1 has SUMO E3 ligase activity in vitro, and immunoblot analysis revealed that the protein sumoylation profile is impaired in siz1 plants. AtSIZ1-GFP was localized to nuclear foci. Steadystate transcript abundances of Pi starvation-responsive genes AtPT2, AtPS2, and AtPS3 were moderate but clearly greater in siz1 seedlings than in wild type, where Pi is sufficient. Pi starvation induced the expression of these genes to the same extent in siz1 and wild-type seedlings. However, two other Pi starvation-responsive genes, AtIPS1 and AtRNS1, are induced more slowly in siz1 seedlings by Pi limitation. PHR1, a MYB transcriptional activator of AtIPS1 and AtRNS1, is an AtSIZ1 sumoylation target. These results indicate that AtSIZ1 is a SUMO E3 ligase and that sumoylation is a control mechanism that acts both negatively and positively on different Pi deficiency responses.
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PMID:The Arabidopsis SUMO E3 ligase SIZ1 controls phosphate deficiency responses. 1589 20

Growth of Sinorhizobium meliloti under Pi-limiting conditions induced expression of the major H2O2-inducible catalase (HPII) gene (katA) in this organism. This transcription required the PhoB transcriptional regulator and initiated from a promoter that was distinct from the OxyR-dependent promoter which activates katA transcription in response to addition of H2O2. In N2-fixing root nodules, katA was transcribed from the OxyR- and not the PhoB-dependent promoter. This is consistent with the accumulation of reactive oxygen species (ROS) in nodules and also indicates that bacteroids within nodules are not Pi-limited. Pi-limited growth also induced expression of catalase genes in Agrobacterium tumefaciens (HPI) and Pseudomonas aeruginosa (PA4236-HPI) suggesting that this may be a widespread phenomenon. The response is not a general stress response as in both S. meliloti and P. aeruginosa increased transcription is mediated by the phosphate responsive transcriptional activator PhoB. The phenotypic consequences of this response were demonstrated in S. meliloti by the dramatic increase in H2O2 resistance of wild type but not phoB mutant cells upon growth in Pi-limiting media. Our data indicate that in S. meliloti, katA and other genes whose products are involved in protection from oxidative stress are induced upon Pi-limitation. These observations suggest that as part of the response to Pi-limitation, S. meliloti, P. aeruginosa and A. tumefaciens have evolved a capacity to increase their resistance to oxidative stress. Whether this capacity evolved because Pi-starved cells generate more ROS or whether the physiological changes that occur in the cells in response to Pi-starvation render them more sensitive to ROS remains to be established.
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PMID:Phosphate limitation induces catalase expression in Sinorhizobium meliloti, Pseudomonas aeruginosa and Agrobacterium tumefaciens. 1623 34

Through genome-wide transcript analysis of a reference strain and two recombinant Saccharomyces cerevisiae strains with different rates of galactose uptake, we obtained information about the global transcriptional response to metabolic engineering of the GAL gene regulatory network. One of the recombinant strains overexpressed the gene encoding the transcriptional activator Gal4, and in the other strain the genes encoding Gal80, Gal6, and Mig1, which are negative regulators of the GAL system, were deleted. Even though the galactose uptake rates were significantly different in the three strains, we surprisingly did not find any significant changes in the expression of the genes encoding the enzymes catalyzing the first steps of the pathway (i.e., the genes encoding Gal2, Gal1, Gal7, and Gal10). We did, however, find that PGM2, encoding the major isoenzyme of phosphoglucomutase, was slightly up-regulated in the two recombinant strains with higher galactose uptake rates. This indicated that PGM2 is a target for overexpression in terms of increasing the flux through the Leloir pathway, and through overexpression of PGM2 the galactose uptake rate could be increased by 70% compared to that of the reference strain. Based on our findings, we concluded that phosphoglucomutase plays a key role in controlling the flux through the Leloir pathway, probably due to increased conversion of glucose-1-phosphate to glucose-6-phosphate. This conclusion was supported by measurements of sugar phosphates, which showed that there were increased concentrations of glucose-6-phosphate, galactose-6-phosphate, and fructose-6-phosphate in the strain construct overexpressing PGM2.
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PMID:Improvement of galactose uptake in Saccharomyces cerevisiae through overexpression of phosphoglucomutase: example of transcript analysis as a tool in inverse metabolic engineering. 1626 70

The molecular response of Shewanella oneidensis MR-1 to variations in extracellular pH was investigated based on genomewide gene expression profiling. Microarray analysis revealed that cells elicited both general and specific transcriptome responses when challenged with environmental acid (pH 4) or base (pH 10) conditions over a 60-min period. Global responses included the differential expression of genes functionally linked to amino acid metabolism, transcriptional regulation and signal transduction, transport, cell membrane structure, and oxidative stress protection. Response to acid stress included the elevated expression of genes encoding glycogen biosynthetic enzymes, phosphate transporters, and the RNA polymerase sigma-38 factor (rpoS), whereas the molecular response to alkaline pH was characterized by upregulation of nhaA and nhaR, which are predicted to encode an Na+/H+ antiporter and transcriptional activator, respectively, as well as sulfate transport and sulfur metabolism genes. Collectively, these results suggest that S. oneidensis modulates multiple transporters, cell envelope components, and pathways of amino acid consumption and central intermediary metabolism as part of its transcriptome response to changing external pH conditions.
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PMID:Transcriptome profiling of Shewanella oneidensis gene expression following exposure to acidic and alkaline pH. 1645 48

The Aspergillus nidulans xprG gene is involved in the regulation of extracellular proteases. A plasmid which complemented the xprG2 mutation was shown to carry the phoG gene, reported to encode an acid phosphatase. Two phoGDelta mutants were constructed and were identical in phenotype to an xprG2 mutant. Null mutants were unable to use protein as a carbon or nitrogen source, have lost a repressible acid phosphatase and have pale conidial color. XprG shows similarity to the Ndt80 transcriptional activator, which regulates the expression of genes during meiosis in Saccharomyces cerevisiae. The xprG1 gain-of-function mutant contains a missense mutation in the region encoding the putative DNA-binding domain. The response to carbon, nitrogen, sulfur, and phosphate limitation is altered in xprG(-) mutants suggesting that XprG is involved in a general response to starvation. Ndt80 may also be involved in sensing nutritional status and control of commitment to meiosis in S. cerevisiae.
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PMID:The Aspergillus nidulans xprG (phoG) gene encodes a putative transcriptional activator involved in the response to nutrient limitation. 1646 24

Grixazone (GX), which is a diffusible yellow pigment containing a phenoxazinone chromophore, is one of the secondary metabolites under the control of A-factor (2-isocapryloyl-3R-hydroxymethyl-gamma-butyrolactone) in Streptomyces griseus. GX production is also induced by phosphate starvation. The whole biosynthesis gene cluster for GX was cloned and characterized. The gene cluster consisting of 13 genes contained six transcriptional units, griT, griSR, griR, griAB, griCDEFG, and griJIH. During cultivation in a phosphate-depleted medium, the six promoters were activated in the order (i) griR, (ii) griC and griJ, and (iii) griT, griS, and griA. Disruption of griR, which encodes a SARP family transcriptional regulator, abolished the transcriptional activation of all other genes in the cluster. In addition, ectopic expression of griR from a constitutively active promoter resulted in GX overproduction even in the absence of AdpA, a key transcriptional activator in the A-factor regulatory cascade, and in the presence of phosphate at a high concentration. GriR monomers bound direct repeat sequences in the griC and griJ promoters in a cooperative manner. Therefore, the early active genes (griCDEFG and griJIH), all of which, except for griG (which encodes a transporter-like protein), encode the GX biosynthesis enzymes, were directly activated by GriR. The transcription of griR was greatly reduced in the presence of phosphate at a high concentration and was hardly detected in the absence of AdpA. These findings showed that both A-factor and phosphate depletion signals were required for griR transcription and both signals were transmitted to the GX biosynthesis genes solely via the griR promoter.
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PMID:A-factor and phosphate depletion signals are transmitted to the grixazone biosynthesis genes via the pathway-specific transcriptional activator GriR. 1733 80

Phosphate import is required for the growth of mycobacteria and is regulated by environmental inorganic phosphate (P(i)) concentrations, although the mechanism of this regulation has not been characterized. The expression of genes involved in P(i) acquisition is frequently regulated by two-component regulatory systems (2CRs) consisting of a sensor histidine kinase and a DNA-binding response regulator. In this work, we have identified the senX3-regX3 2CR as a P(i)-dependent regulator of genes involved in phosphate acquisition in Mycobacterium smegmatis. Characterization of senX3 mutants with different PhoA phenotypes suggests a dual role for SenX3 as a phosphatase or a phosphodonor for the response regulator RegX3, depending upon P(i) availability. Expression of PhoA activity required phosphorylation of RegX3, consistent with a role for phosphorylated RegX3 (RegX3 approximately P) as a transcriptional activator of phoA. Furthermore, purified RegX3 approximately P bound to promoter sequences from phoA, senX3, and the high-affinity phosphate transporter component pstS, demonstrating direct transcriptional control of all three genes. DNase I footprinting and primer extension analyses have further defined the DNA-binding region and transcriptional start site within the phoA promoter. A DNA motif consisting of an inverted repeat was identified in each of the promoters bound by RegX3 approximately P. Based upon our findings, we propose a model for P(i)-regulated gene expression mediated by SenX3-RegX3 in mycobacteria.
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PMID:The two-component regulatory system senX3-regX3 regulates phosphate-dependent gene expression in Mycobacterium smegmatis. 1752 10

The actinomycete Nonomuraea sp. strain ATCC 39727 produces the glycopeptide A40926, the precursor of the novel antibiotic dalbavancin. Previous studies have shown that phosphate limitation results in enhanced A40926 production. The A40926 biosynthetic gene (dbv) cluster, which consists of 37 genes, encodes two putative regulators, Dbv3 and Dbv4, as well as the response regulator (Dbv6) and the sensor-kinase (Dbv22) of a putative two-component system. Reverse transcription-PCR (RT-PCR) and real-time RT-PCR analysis revealed that the dbv14-dbv8 and the dbv30-dbv35 operons, as well as dbv4, were negatively influenced by phosphate. Dbv4 shows a putative helix-turn-helix DNA-binding motif and shares sequence similarity with StrR, the transcriptional activator of streptomycin biosynthesis in Streptomyces griseus. Dbv4 was expressed in Escherichia coli as an N-terminal His(6)-tagged protein. The purified protein bound the dbv14 and dbv30 upstream regions but not the region preceding dbv4. Bbr, a Dbv4 ortholog from the gene cluster for the synthesis of the glycopeptide balhimycin, also bound to the dbv14 and dbv30 upstream regions, while Dbv4 bound appropriate regions from the balhimycin cluster. Our results provide new insights into the regulation of glycopeptide antibiotics, indicating that the phosphate-controlled regulator Dbv4 governs two key steps in A40926 biosynthesis: the biosynthesis of the nonproteinogenic amino acid 3,5-dihydroxyphenylglycine and critical tailoring reactions on the heptapeptide backbone.
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PMID:Phosphate-controlled regulator for the biosynthesis of the dalbavancin precursor A40926. 1787 36

In an effort to identify novel components of the PHO regulon in Saccharomyces cerevisiae, we have isolated and characterized suppressors of the Pho(-) phenotype associated with deletion of the Pho4 transcriptional activator. Here we report that either a defective form of the Rsp5 E3 ubiquitin ligase or deletion of the End3 component of the endocytic pathway restores growth of the pho4 Delta mutant in the presence of limiting inorganic phosphate (P i). The spa1-1 suppressor allele of RSP5 encodes a phenylalanine-to-valine replacement at position 748 (F748V) within the catalytic HECT domain of Rsp5. Consistent with suppression due to impaired ubiquitin ligase activity, the heat-sensitive growth defect of the spa1-1 mutant is suppressed either by overexpression of ubiquitin or by osmotic stabilization. Western blot analyses revealed that the cellular levels of the Pho87 and Pho91 low affinity P i are markedly increased in the spa1-1 mutant, yet Pho84 high affinity P i transporter levels are unaffected. Furthermore, Pho87 and Pho91 are ubiquitinated in vivo in an Rsp5-dependent manner, and the Pho+ phenotype of the spa1-1 suppressor is dependent upon Pho87 and Pho91. We conclude that turnover of the low affinity P i transporters is initiated by Rsp5-mediated ubiquitination followed by internalization and degradation by the endocytic pathway.
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PMID:The Rsp5 E3 ligase mediates turnover of low affinity phosphate transporters in Saccharomyces cerevisiae. 1816 38


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