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)

Diploid yeast cells switch from mitosis to meiosis when starved of essential nutrients. While G1 cyclins play a key role in initiating the mitotic cell cycle, entry into meiosis depends on Ime1, a transcriptional activator regulated by both nutritional and cell-type signals. We show here that G1 cyclins downregulate IME1 transcription and prevent the accumulation of the Ime1 protein within the nucleus, which results in repression of early-meiotic gene expression. As G1-cyclin deficient cells do not require nutrient starvation to undergo meiosis, G1 cyclin would exert its role by transmitting essential nutritional signals to Ime1 function. The existence of a negative cross-talk mechanism between mitosis and meiosis may help explain why these two developmental options are incompatible in budding yeast.
 ...
PMID:G1 cyclins block the Ime1 pathway to make mitosis and meiosis incompatible in budding yeast. 988 89

The CPC2 gene of the budding yeast Saccharomyces cerevisiae encodes a G beta-like WD protein which is involved in regulating the activity of the general control activator Gcn4p. The CPC2 gene encodes a premRNA which is spliced and constitutively expressed in the presence or absence of amino acids. Loss of CPC2 gene function suppresses a deletion of the GCN2 gene encoding the general control sensor kinase, but not a deletion in the GCN4 gene. The resulting phenotype has resistance against amino-acid analogues. The Neurospora crassa cpc-2 and the rat RACK1 genes are homologues of CPC2 that complement the yeast cpc2 deletion. The cpc2 delta mutation leads to increased transcription of Gcn4p-dependent genes under non-starvation conditions without increasing GCN4 expression or the DNA binding activity of Gcn4p. Cpc2p-mediated transcriptional repression requires the Gcn4p transcriptional activator and a Gcn4p recognition element in the target promoter. Frameshift mutations resulting in a shortened G beta-like protein cause a different phenotype that has sensitivity against amino-acid analogues similar to a gcn2 deletion. Cpc2p seems to be part of an additional control of Gcn4p activity, independent of its translational regulation.
 ...
PMID:The WD protein Cpc2p is required for repression of Gcn4 protein activity in yeast in the absence of amino-acid starvation. 1004 25

Expression of the catalase-peroxidase of Caulobacter crescentus, a gram-negative member of the alpha subdivision of the Proteobacteria, is 50-fold higher in stationary-phase cultures than in exponential cultures. To identify regulators of the starvation response, Tn5 insertion mutants were isolated with reduced expression of a katG::lacZ fusion on glucose starvation. One insertion interrupted an open reading frame encoding a protein with significant amino acid sequence identity to TipA, a helix-turn-helix transcriptional activator in the response of Streptomyces lividans to the peptide antibiotic thiostrepton, and lesser sequence similarity to other helix-turn-helix regulators in the MerR family. The C. crescentus orthologue of tipA was named skgA (stationary-phase regulation of katG). Stationary-phase expression of katG was reduced by 70% in the skgA::Tn5 mutant, and stationary-phase resistance to hydrogen peroxide decreased by a factor of 10. Like the wild type, the skgA mutant exhibited starvation-induced cross-resistance to heat and acid shock, entered into the helical morphology that occurs after 9 to 12 days in stationary phase, and during exponential growth induced katG in response to hydrogen peroxide challenge. Expression of skgA increased 5- to 10-fold in late exponential phase. skgA is the first regulator of a starvation-induced stress response identified in C. crescentus. SkgA is not a global regulator of the stationary-phase stress response; its action encompasses the oxidative stress-hydrogen peroxide response but not acid or heat responses. Moreover, SkgA is not an alternative sigma factor, like RpoS, which controls multiple aspects of starvation-induced cross-resistance to stress in enteric bacteria. These observations raise the possibility that regulation of stationary-phase gene expression in this member of the alpha subdivision of the Proteobacteria is different from that in Escherichia coli and other members of the gamma subdivision.
 ...
PMID:Identification of a regulator that controls stationary-phase expression of catalase-peroxidase in Caulobacter crescentus. 1049 30

The IciA protein from Escherichia coli has been shown specifically to inhibit the in vitro initiation of chromosomal DNA replication. However, the in vivo role of IciA has not yet been established. In order to investigate the in vivo function of this protein, expression of the iciA gene was studied by monitoring the beta-galactosidase activity specified by an iciA promoter-lacZ fusion inserted into the chromosome. Among the conditions tested (carbon starvation, the stringent response, phosphate starvation, and the SOS response), only phosphate depletion increased iciA expression. Supplementation of phosphate-depleted cultures with inorganic phosphate reduced the beta-galactosidase activity to basal levels. Enhanced expression of iciA-lacZ was dependent upon the PhoB protein. PhoB is known to be a transcriptional activator of the Pho regulon, expression of which is activated during phosphate starvation. It was also found that the iciA promoter contains a PhoB protein-binding sequence, termed the Pho box, which is necessary for the activation of genes of the Pho regulon. These results suggest that the iciA gene is a member of the Pho regulon.
 ...
PMID:PhoB-dependent transcriptional activation of the iciA gene during starvation for phosphate in Escherichia coli. 1058 31

In Caulobacter crescentus, stalk biosynthesis is regulated by cell cycle cues and by extracellular phosphate concentration. Phosphate-starved cells undergo dramatic stalk elongation to produce stalks as much as 30 times as long as those of cells growing in phosphate-rich medium. To identify genes involved in the control of stalk elongation, transposon mutants were isolated that exhibited a long-stalk phenotype irrespective of extracellular phosphate concentration. The disrupted genes were identified as homologues of the high-affinity phosphate transport genes pstSCAB of Escherichia coli. In E. coli, pst mutants have a constitutively expressed phosphate (Pho) regulon. To determine if stalk elongation is regulated by the Pho regulon, the Caulobacter phoB gene that encodes the transcriptional activator of the Pho regulon was cloned and mutated. While phoB was not required for stalk synthesis or for the cell cycle timing of stalk synthesis initiation, it was required for stalk elongation in response to phosphate starvation. Both pstS and phoB mutants were deficient in phosphate transport. When a phoB mutant was grown with limiting phosphate concentrations, stalks only increased in length by an average of 1.4-fold compared to the average 9-fold increase in stalk length of wild-type cells grown in the same medium. Thus, the phenotypes of phoB and pst mutants were opposite. phoB mutants were unable to elongate stalks during phosphate starvation, whereas pst mutants made long stalks in both high- and low-phosphate media. Analysis of double pst phoB mutants indicated that the long-stalk phenotype of pst mutants was dependent on phoB. In addition, analysis of a pstS-lacZ transcriptional fusion showed that pstS transcription is dependent on phoB. These results suggest that the signal transduction pathway that stimulates stalk elongation in response to phosphate starvation is mediated by the Pst proteins and the response regulator PhoB.
 ...
PMID:Regulation of stalk elongation by phosphate in Caulobacter crescentus. 1062 78

Gcn4, a yeast transcriptional activator that promotes the expression of amino acid and purine biosynthesis genes, is rapidly degraded in rich medium. Here we report that SCF(CDC4), a recently characterized protein complex that acts in conjunction with the ubiquitin-conjugating enzyme Cdc34 to degrade cell cycle regulators, is also necessary for the degradation of the transcription factor Gcn4. Degradation of Gcn4 occurs throughout the cell cycle, whereas degradation of the known cell cycle substrates of Cdc34/SCF(CDC4) is cell cycle regulated. Gcn4 ubiquitination and degradation are regulated by starvation for amino acids, whereas the degradation of the cell cycle substrates of Cdc34/SCF(CDC4) is unaffected by starvation. We further show that unlike the cell cycle substrates of Cdc34/SCF(CDC4), which require phosphorylation by the kinase Cdc28, Gcn4 degradation requires the kinase Pho85. We identify the critical target site of Pho85 on Gcn4; a mutation of this site stabilizes the protein. A specific Pho85-Pcl complex that is able to phosphorylate Gcn4 on that site is inactive under conditions under which Gcn4 is stable. Thus, Cdc34/SCF(CDC4) activity is constitutive, and regulation of the stability of its various substrates occurs at the level of their phosphorylation.
 ...
PMID:Degradation of the transcription factor Gcn4 requires the kinase Pho85 and the SCF(CDC4) ubiquitin-ligase complex. 1071 9

Phosphorylation of the alpha subunit of eukaryotic initiation factor 2 (eIF-2alpha) is a well-characterized mechanism regulating protein synthesis in response to environmental stresses. In the yeast Saccharomyces cerevisiae, starvation for amino acids induces phosphorylation of eIF-2alpha by Gcn2 protein kinase, leading to elevated translation of GCN4, a transcriptional activator of more than 50 genes. Uncharged tRNA that accumulates during amino acid limitation is proposed to activate Gcn2p by associating with Gcn2p sequences homologous to histidyl-tRNA synthetase (HisRS) enzymes. Given that eIF-2alpha phosphorylation in mammals is induced in response to both carbohydrate and amino acid limitations, we addressed whether activation of Gcn2p in yeast is also controlled by different nutrient deprivations. We found that starvation for glucose induces Gcn2p phosphorylation of eIF-2alpha and stimulates GCN4 translation. Induction of eIF-2alpha phosphorylation by Gcn2p during glucose limitation requires the function of the HisRS-related domain but is largely independent of the ribosome binding sequences of Gcn2p. Furthermore, Gcn20p, a factor required for Gcn2 protein kinase stimulation of GCN4 expression in response to amino acid starvation, is not essential for GCN4 translational control in response to limitation for carbohydrates. These results indicate there are differences between the mechanisms regulating Gcn2p activity in response to amino acid and carbohydrate deficiency. Gcn2p induction of GCN4 translation during carbohydrate limitation enhances storage of amino acids in the vacuoles and facilitates entry into exponential growth during a shift from low-glucose to high-glucose medium. Gcn2p function also contributes to maintenance of glycogen levels during prolonged glucose starvation, suggesting a linkage between amino acid control and glycogen metabolism.
 ...
PMID:Glucose limitation induces GCN4 translation by activation of Gcn2 protein kinase. 1073 73

The devH gene was identified in a screen for Anabaena sp. strain PCC 7120 sequences whose transcripts increase in abundance during a heterocyst development time course. The product of devH contains a helix-turn-helix motif similar to the DNA binding domain of members of the cyclic AMP receptor protein family, and the protein is most closely related to the cyanobacterial transcriptional activator NtcA. devH transcripts are barely detectable in vegetative cells and are induced approximately fivefold after nitrogen starvation. This induction is absent in the two developmental mutants hetR and ntcA. The gene is expressed as monocistronic transcripts with multiple 5' termini, and the approximately 500-bp region 5' to devH was shown to have promoter activity in vivo. The devH gene was insertionally inactivated by the integration of plasmid sequences within the open reading frame. Nitrogen starvation of the devH mutant induces heterocysts of wild-type morphology, but the mutant is inviable in the absence of fixed nitrogen and unable to reduce acetylene aerobically.
 ...
PMID:Characterization of devH, a gene encoding a putative DNA binding protein required for heterocyst function in Anabaena sp. strain PCC 7120. 1085 91

Amino acid limitation results in impaired sexual fruit body formation in filamentous fungi such as Aspergillus nidulans. The starvation signal is perceived by the cross-pathway regulatory network controlling the biosynthesis of translational precursors and results in increased expression of a transcriptional activator encoded by a c-Jun homologue. In the presence of amino acids, the gene product of the mammalian RACK1 homologue cpcB is required to repress the network. Growth under amino acid starvation conditions permits the initiation of the sexual developmental programme of the fungus, but blocks fruit body formation before completion of meiosis. Accordingly, arrest at this defined control point results in microcleistothecia filled with hyphae. Addition of amino acids results in release of the block and completion of development to mature ascospores. The same developmental block is induced by either overexpression of c-Jun homologues or deletion of the RACK1 homologue cpcB of A. nidulans in the presence of amino acids. Therefore, the amino acid starvation signal regulates sexual development through the network that also controls the amino acid biosynthetic genes. Expression of the RACK1 gene suppresses the block in development caused by a deletion of cpcB. These data illuminate a connection between metabolism and sexual development in filamentous fungi.
 ...
PMID:c-Jun and RACK1 homologues regulate a control point for sexual development in Aspergillus nidulans. 1093 3

Schizosaccharomyces pombe ste11 encodes a high-mobility group family transcriptional activator that is pivotal in sexual development. Transcription of ste11 is induced by starvation of nutrients via a decrease of the cAMP-dependent protein kinase (PKA) activity. Here we report the identification of a novel transcription factor, Rst2p, that directly regulates ste11 expression. Cells in which the rst2 gene was disrupted expressed ste11 poorly and were sterile, and this sterility could be suppressed by artificial expression of ste11. Disruption of rst2 suppressed hypermating and hypersporulation in the PKA-null mutant, whereas overexpression of rst2 induced sexual development in the PKA-activated mutant. Cloning analysis indicated that Rst2p was a Cys(2)His(2) zinc-finger protein carrying 567 amino acid residues. Rst2p could bind specifically to a stress response element-like cis element located in the ste11 promoter region, which was important for ste11 expression. Meanwhile, transcription of ste11 was reduced significantly by a defective mutation in itself. An artificial supply of functional Ste11p circumvented this reduction. A complete Ste11p-binding motif (TR box) found in the promoter region was necessary for the full expression of ste11, suggesting that Ste11p is involved in the activation of ste11. We conclude that transcription of ste11 is under autoregulation in addition to control through the PKA-Rst2p pathway.
 ...
PMID:A zinc-finger protein, Rst2p, regulates transcription of the fission yeast ste11(+) gene, which encodes a pivotal transcription factor for sexual development. 1098 11


<< Previous 1 2 3 4 5 6 7 8 9 10 Next >>