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 yeast, glucose depletion elicits a quick response in the transcription of stress-related genes. The main transcriptional activator that orchestrates this response is Msn2, whose nuclear localization and DNA binding are negatively controlled by the cAMP-dependent protein kinase (PKA). Msn2 activation by sudden glucose depletion correlates with a fast but transient decrease in phosphorylation of several sites in its nuclear localization signal (NLS). Here we show that protein phosphatase 1 (PP1) is the direct antagonist of PKA-dependent phosphorylation at the Msn2 nuclear import domain and therefore a potential mediator of glucose starvation signals that target this transcription factor. Apart from PKA, the protein kinase Snf1 can also directly modify one of the Msn2 phosphorylation sites (S582) and thereby repress Msn2 function. Consequently, in snf1 mutants, rephosphorylation of the NLS happens to be much slower during prolonged starvation. Thus, a second, Reg1-dependent form of PP1 indirectly influences Msn2 functionality by modulating Snf1 kinase activation and repression. Different activities of PP1 are therefore involved in shaping induction and adaptation of the transcriptional stress response during acute glucose starvation.
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PMID:A dual role for PP1 in shaping the Msn2-dependent transcriptional response to glucose starvation. 1628 Oct 53

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

The movement of ammonium across biological membranes is mediated in both prokaryotes and eukaryotes by ammonium transport proteins (AMT/MEP) that constitute a family of related sequences. We have previously identified two ammonium permeases in Aspergillus nidulans, encoded by the meaA and mepA genes. Here we show that meaA is expressed in the presence of ammonium, consistent with the function of MeaA as the main ammonium transporter required for optimal growth on ammonium as a nitrogen source. In contrast, mepA, which encodes a high-affinity ammonium permease, is expressed only under nitrogen-limiting or starvation conditions. We have identified two additional AMT/MEP-like genes in A. nidulans, namely, mepB, which encodes a second high-affinity ammonium transporter expressed only in response to complete nitrogen starvation, and mepC, which is expressed at low levels under all nitrogen conditions. The MepC gene product is more divergent than the other A. nidulans AMT/MEP proteins and is not thought to significantly contribute to ammonium uptake under normal conditions. Remarkably, the expression of each AMT/MEP gene under all nitrogen conditions is regulated by the global nitrogen regulatory GATA factor AreA. Therefore, AreA is also active under nitrogen-sufficient conditions, along with its established role as a transcriptional activator in response to nitrogen limitation.
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PMID:Differential expression of Aspergillus nidulans ammonium permease genes is regulated by GATA transcription factor AreA. 1646 64

The Drosophila methuselah (mth) mutant has an approximately 35 percent increase in average lifespan, and enhanced resistance to various forms of stress, including starvation, high temperature, and dietary paraquat. To examine the transcriptional regulation of mth, we used luciferase assays employing Drosophila S2 cells. Two positive control elements were found at -542 to -272 (PE1) and +28 to +217 (PE2), where putative binding sites for transcription factors including Dorsal (Dl) were identified. Cotransfection of a Dl expression plasmid with a mth-luciferase reporter plasmid resulted in decreased reporter activity. PE1 and PE2, the minimal elements for strong promoter activity, were required for maximal repression by Dl protein. The N-terminal Rel homology domain (RHD) of Dl was not sufficient for repression of mth. We demonstrated by chromatin affinity precipitation (ChAP) assays in S2 cells that Dl bound to the putative PE1 binding site. Unexpectedly, semi-quantitative RT-PCR analysis revealed that the level of mth transcripts was reduced in dl flies. However, the in vivo result support the view that mth expression is regulated by dl, since it is well known that Dl functions as both a transcriptional activator and repressor depending on what other transcription factors are present. These findings suggest that both innate immunity and resistance to stress are controlled by Dl protein.
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PMID:Transcriptional regulation of the methuselah gene by dorsal protein in Drosophila melanogaster. 1668 22

Nonself recognition during somatic growth is an essential and ubiquitous phenomenon in both prokaryotic and eukaryotic species. In filamentous fungi, nonself recognition is also important during vegetative growth. Hyphal fusion between genetically dissimilar individuals results in rejection of heterokaryon formation and in programmed cell death of the fusion compartment. In filamentous fungi, such as Neurospora crassa, nonself recognition and heterokaryon incompatibility (HI) are regulated by genetic differences at het loci. In N. crassa, mutations at the vib-1 locus suppress nonself recognition and HI mediated by genetic differences at het-c/pin-c, mat, and un-24/het-6. vib-1 is a homolog of Saccharomyces cerevisiae NDT80, which is a transcriptional activator of genes during meiosis. For this study, we determined that vib-1 encodes a nuclear protein and showed that VIB-1 localization varies during asexual reproduction and during HI. vib-1 is required for the expression of genes involved in nonself recognition and HI, including pin-c, tol, and het-6; all of these genes encode proteins containing a HET domain. vib-1 is also required for the production of downstream effectors associated with HI, including the production of extracellular proteases upon carbon and nitrogen starvation. Our data support a model in which mechanisms associated with starvation and nonself recognition/HI are interconnected. VIB-1 is a major regulator of responses to nitrogen and carbon starvation and is essential for the expression of genes involved in nonself recognition and death in N. crassa.
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PMID:VIB-1 is required for expression of genes necessary for programmed cell death in Neurospora crassa. 1701 38

The transcriptional activator Zap1 induces target gene expression in response to zinc deficiency. We demonstrate that during zinc starvation, Zap1 is required for the repression of ADH1 expression. ADH1 encodes the major zinc-dependent alcohol dehydrogenase that is utilized during fermentation. During zinc starvation, Zap1 binds upstream of the activator Rap1 and induces an intergenic RNA transcript, ZRR1. ZRR1 expression leads to the transient displacement of Rap1 from the ADH1 promoter resulting in ADH1 repression. Using a microarray-based approach, we screened for additional genes repressed by Zap1 intergenic transcripts. We found that ADH3, the major mitochondrial alcohol dehydrogenase, is regulated in a manner similar to ADH1. Thus, during zinc deficiency, Zap1 mediates the repression of two of the most abundant zinc-requiring enzymes.
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PMID:Repression of ADH1 and ADH3 during zinc deficiency by Zap1-induced intergenic RNA transcripts. 1713 54

Hexokinases catalyse the first step in glucose metabolism and play a role in glucose sensing in mammals, plants and fungi. We describe a new class of hexokinases that appear to be solely regulatory in function. The Aspergillus nidulans hxkD gene (formerly named xprF) encodes a hexokinase-like protein. We constructed hxkDDelta gene disruption mutants which showed increased levels of extracellular protease in response to carbon starvation. The hxkDDelta mutations are not completely recessive, indicating that the level of the gene product is critical. Transcript levels of hxkD increase during carbon starvation and this response is not dependent on functional HxkD. A gene encoding a second atypical hexokinase (HxkC) was identified. The hxkCDelta gene disruption mutant exhibits a phenotype similar, but not identical, to hxkDDelta mutants. As with hxkD, mutations in hxkC are suppressed by loss-of-function mutations in xprG, which encodes a putative transcriptional activator involved in the response to nutrient limitation. We show that GFP-tagged HxkD was found only in nuclei suggesting a regulatory role for HxkD. GFP-tagged HxkC was associated with mitochondria. Homologs of hxkC and hxkD are conserved in multi-cellular fungi. Genes encoding atypical hexokinases are present in many genome sequence databases. Thus, non-catalytic hexokinases may be widespread.
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PMID:Characterization of regulatory non-catalytic hexokinases in Aspergillus nidulans. 1722 29

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

A yeast transcriptional activator, Gcn4p, induces the expression of genes that are involved in amino acid and purine biosynthetic pathways under amino acid starvation. Gcn4p has an acidic activation domain in the central region and a bZIP domain in the C-terminus that is divided into the DNA-binding motif and dimerization leucine zipper motif. In order to identify amino acids in the DNA-binding motif of Gcn4p which are involved in transcriptional activation, we constructed mutant libraries in the DNA-binding motif through an innovative application of random mutagenesis. Mutant library made by oligonucleotides which were mutated randomly using the Poisson distribution showed that the actual mutation frequency was in good agreement with expected values. This method could save the time and effort to create a mutant library with a predictable mutation frequency. Based on the studies using the mutant libraries constructed by the new method, the specific residues of the DNA-binding domain in Gcn4p appear to be involved in the transcriptional activities on a conserved binding site.
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PMID:A new method for the construction of a mutant library with a predictable occurrence rate using Poisson distribution. 1742 60

When iron is scarce, Bacillus subtilis expresses genes involved in the synthesis and uptake of the siderophore bacillibactin (BB) and uptake systems to pirate other microbial siderophores. Here, we demonstrate that transcriptional induction of the feuABCybbA operon, encoding the Fe-BB uptake system, is mediated by Btr (formerly YbbB), which is encoded by the immediately upstream gene. Btr contains an AraC-type DNA binding domain fused to a substrate binding protein (SBP) domain related to FeuA, the SBP for Fe-BB uptake. When cells are iron-limited, the Fur-mediated repression of btr is relieved and Btr binds to a conserved direct repeat sequence adjacent to feuA to activate transcription. If BB is present, Btr further activates feuA expression. Btr binds with high affinity to both apo-BB and Fe-BB, and the resulting complex displays a significantly increased efficacy as a transcriptional activator relative to Btr alone. Btr can also activate transcription in response to the structurally similar siderophore enterobactin, although genetic analyses indicate that the two siderophores make distinct interactions with the Btr substrate binding domain. Thus, the FeuABC transporter is optimally expressed under conditions of iron starvation, when Fur-mediated repression is relieved, and in the presence of its cognate substrate.
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PMID:Substrate induction of siderophore transport in Bacillus subtilis mediated by a novel one-component regulator. 1772 65


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