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Query: UNIPROT:P51532 (transcriptional activator)
 6,546 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

The nitrogen-regulated genes and operons of the Ntr regulon of Escherichia coli are activated by the enhancer-binding transcriptional activator NRI approximately P (NtrC approximately P). Here, we examined the activation of the glnA, glnK, and nac promoters as cells undergo the transition from growth on ammonia to nitrogen starvation and examined the amplification of NRI during this transition. The results indicate that the concentration of NRI is increased as cells become starved for ammonia, concurrent with the activation of Ntr genes that have less- efficient enhancers than does glnA. A diauxic growth pattern was obtained when E. coli was grown on a low concentration of ammonia in combination with arginine as a nitrogen source, consistent with the hypothesis that Ntr genes other than glnA become activated only upon amplification of the NRI concentration.
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PMID:Activation of the glnA, glnK, and nac promoters as Escherichia coli undergoes the transition from nitrogen excess growth to nitrogen starvation. 1221 22

The transcriptional activator protein Gcn4p increases the transcription of many genes that code for amino acid synthesis genes during amino acid starvation in Saccharomyces cerevisiae. Here we showed that after the disruption of C-GCN4, a homolog in Candida maltosa of GCN4 in S. cerevisiae, formed pseudohyphae in minimal medium. This is the first report that a GCN4 homolog is involved in the control of morphological transition.
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PMID:Pseudohyphal growth in a dimorphic yeast, Candida maltosa, after disruption of the C-GCN4 gene, a homolog of Saccharomyces cerevisiae GCN4. 1240 Jun 94

To characterize the metabolic role of peroxisomes in yeast cells under physiological conditions, we performed a comprehensive meta-analysis of published microarray data. Previous studies of yeast peroxisomes have mainly been focused on the function of peroxisomes under extreme conditions, such as growth on oleate or methanol as the sole carbon source, and may therefore not be representative of the normal physiological role of yeast peroxisomes. Surprisingly, our analysis of the microarray data reveals that the only pathway responding to peroxisome deficiency in mid-log phase is lysine biosynthesis, whereas classical peroxisomal pathways such as beta-oxidation are unaffected. We show that the upregulation of lysine biosynthesis genes in peroxisome-deficient yeasts shares many characteristics with the physiological response to lysine starvation. We provide data that suggest that this is the result of a "pathological" stimulation of the Lys14p transcriptional activator by the pathway intermediate aminoadipate semialdehyde. Mistargeting of the peroxisomal lysine pathway to the cytosol increases the active concentration of aminoadipate semialdehyde, which is no longer contained in the peroxisome and can now activate Lys14p at much lower levels than in wild-type yeasts. This is the first well-documented example of pathway misregulation in response to peroxisome deficiency and will be useful in understanding the phenotypic details of human peroxisome-deficient patients (Zellweger syndrome).
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PMID:Loss of compartmentalization causes misregulation of lysine biosynthesis in peroxisome-deficient yeast cells. 1247 98

The non-proteinogenic amino acid, alpha-aminoadipate, defines the biosynthetic branch-point of lysine and penicillin biosynthesis in the filamentous fungus, Aspergillus nidulans. Regulation of both pathways was analysed in response to amino acid limitation. The lysF-encoded homoaconitase acts upstream of the alpha-aminoadipate branch point, whereas the lysA gene product, saccharopine dehydrogenase, catalyses the ultimate step of the lysine-specific branch. The lysA gene from A. nidulans was identified and isolated. Amino acid starvation resulted in significantly increased transcription of lysA but not lysF. Starvation-dependent changes in transcription levels of lysA were dependent on the presence of the central transcriptional activator of the cross-pathway control (CPCA). The effect of amino acid starvation under penicillin-producing conditions was analysed in A. nidulans strains with reporter genes for the penicillin-biosynthesis genes, acvA and ipnA, and genetically altered activity of the cross-pathway control. Overproduction of CPCA decreased expression of ipnAand acvA reporter genes and even more drastically reduced penicillin production. This work suggests that, upon amino acid starvation, the cross-pathway control overrules secondary metabolite biosynthesis and favours the metabolic flux towards amino acids instead of penicillin in A. nidulans.
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PMID:Impact of the cross-pathway control on the regulation of lysine and penicillin biosynthesis in Aspergillus nidulans. 1258 72

Yeast protein kinase GCN2 stimulates the translation of transcriptional activator GCN4 by phosphorylating eIF2alpha in response to amino acid starvation. Kinase activation requires binding of uncharged tRNA to a histidyl tRNA synthetase-related domain in GCN2. Phosphorylation of serine 577 (Ser 577) in GCN2 by another kinase in vivo inhibits GCN2 function in rich medium by reducing tRNA binding activity. We show that rapamycin stimulates eIF2alpha phosphorylation by GCN2, with attendant induction of GCN4 translation, while reducing Ser 577 phosphorylation in nonstarved cells. The alanine 577 (Ala 577) mutation in GCN2 (S577A) dampened the effects of rapamycin on eIF2alpha phosphorylation and GCN4 translation, suggesting that GCN2 activation by rapamycin involves Ser 577 dephosphorylation. Rapamycin regulates the phosphorylation of Ser 577 and eIF2alpha by inhibiting the TOR pathway. Rapamycin-induced dephosphorylation of Ser 577, eIF2alpha phosphorylation, and induction of GCN4 all involve TAP42, a regulator of type 2A-related protein phosphatases. Our results add a new dimension to the regulation of protein synthesis by TOR proteins and demonstrate cross-talk between two major pathways for nutrient control of gene expression in yeast.
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PMID:Translational control by TOR and TAP42 through dephosphorylation of eIF2alpha kinase GCN2. 1265 28

Initiation of meiosis in Saccharomyces cerevisiae is regulated by mating type and nutritional conditions that restrict meiosis to diploid cells grown under starvation conditions. Specifically, meiosis occurs in MATa/MATalpha cells shifted to nitrogen depletion media in the absence of glucose and the presence of a nonfermentable carbon source. These conditions lead to the expression and activation of Ime 1, the master regulator of meiosis. IME1 encodes a transcriptional activator recruited to promoters of early meiosis-specific genes by association with the DNA-binding protein, Ume6. Under vegetative growth conditions these genes are silent due to recruitment of the Sin3/Rpd3 histone deacetylase and Isw2 chromatin remodeling complexes by Ume6. Transcription of these meiotic genes occurs following histone acetylation by Gcn5. Expression of the early genes promote entry into the meiotic cycle, as they include genes required for premeiotic DNA synthesis, synapsis of homologous chromosomes, and meiotic recombination. Two of the early meiosis specific genes, a transcriptional activator, Ndt80, and a CDK2 homologue, Ime2, are required for the transcription of middle meiosis-specific genes that are involved with nuclear division and spore formation. Spore maturation depends on late genes whose expression is indirectly dependent on Ime1, Ime2, and Ndt80. Finally, phosphorylation of Imel by Ime2 leads to its degradation, and consequently to shutting down of the meiotic transcriptional cascade. This review is focusing on the regulation of gene expression governing initiation and progression through meiosis.
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PMID:Transcriptional regulation of meiosis in budding yeast. 1272 50

In response to environmental stress, cells induce a program of gene expression designed to remedy cellular damage or, alternatively, induce apoptosis. In this report, we explore the role of a family of protein kinases that phosphorylate eukaryotic initiation factor 2 (eIF2) in coordinating stress gene responses. We find that expression of activating transcription factor 3 (ATF3), a member of the ATF/CREB subfamily of basic-region leucine zipper (bZIP) proteins, is induced in response to endoplasmic reticulum (ER) stress or amino acid starvation by a mechanism requiring eIF2 kinases PEK (Perk or EIF2AK3) and GCN2 (EIF2AK4), respectively. Increased expression of ATF3 protein occurs early in response to stress by a mechanism requiring the related bZIP transcriptional regulator ATF4. ATF3 contributes to induction of the CHOP transcriptional factor in response to amino acid starvation, and loss of ATF3 function significantly lowers stress-induced expression of GADD34, an eIF2 protein phosphatase regulatory subunit implicated in feedback control of the eIF2 kinase stress response. Overexpression of ATF3 in mouse embryo fibroblasts partially bypasses the requirement for PEK for induction of GADD34 in response to ER stress, further supporting the idea that ATF3 functions directly or indirectly as a transcriptional activator of genes targeted by the eIF2 kinase stress pathway. These results indicate that ATF3 has an integral role in the coordinate gene expression induced by eIF2 kinases. Given that ATF3 is induced by a very large number of environmental insults, this study supports involvement of eIF2 kinases in the coordination of gene expression in response to a more diverse set of stress conditions than previously proposed.
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PMID:Activating transcription factor 3 is integral to the eukaryotic initiation factor 2 kinase stress response. 1472 79

The prnD-prnB intergenic region regulates the divergent transcription of the genes encoding proline oxidase and the major proline transporter. Eight nucleosomes are positioned in this region. Upon induction, the positioning of these nucleosomes is lost. This process depends on the specific transcriptional activator PrnA but not on the general GATA factor AreA. Induction of prnB but not prnD can be elicited by amino acid starvation. A specific nucleosomal pattern in the prnB proximal region is associated with this process. Under conditions of induction by proline, metabolite repression depends on the presence of both repressing carbon (glucose) and nitrogen (ammonium) sources. Under these repressing conditions, partial nucleosomal positioning is observed. This depends on the CreA repressor's binding to two specific cis-acting sites. Three conditions (induction by the defective PrnA80 protein, induction by amino acid starvation, and induction in the presence of an activated CreA) result in similar low transcriptional activation. Each results in a different nucleosome pattern, which argues strongly for a specific effect of each signal on nucleosome positioning. Experiments with trichostatin A suggest that both default nucleosome positioning and partial positioning under induced-repressed conditions depend on deacetylated histones.
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PMID:Chromatin rearrangements in the prnD-prnB bidirectional promoter: dependence on transcription factors. 1487 45

In the yeast Saccharomyces cerevisiae, starvation for amino acids induces phosphorylation of the alpha subunit of eukaryotic initiation factor 2alpha by Gcn2 protein kinase, leading to elevated translation of GCN4. Gcn4p is a transcriptional activator of hundreds of genes involved in remedying nutrient deprivation. In addition to a conserved kinase domain, Gcn2p has a regulatory region homologous to histidyl tRNA synthetase enzymes that binds uncharged tRNA that accumulates during amino acid starvation. Flanking the carboxyl terminus of the histidyl-tRNA synthetase-related domain is a region spanning 162 residues that participates in the activation of the protein kinase. Gel filtration and chemical cross-linking analysis of the recombinant carboxyl-terminal Gcn2 protein revealed that this region is a stable homodimer that is highly resistant to high concentrations of salt. Residue alterations in three hydrophobic segments and one segment with a proposed amphipathic alpha-helix in this Gcn2p carboxyl terminus blocked oligomerization, supporting the role of hydrophobic interactions in the dimerization interface of Gcn2p. Introduction of residue substitutions that impaired dimerization into the full-length protein prevented the ability of Gcn2p to phosphorylate its substrate eukaryotic initiation factor-2alpha and induce GCN4 translational expression in yeast cells subjected to a variety of stresses including amino acid limitation or exposure to rapamycin or high levels of NaCl. This latter stress can be overcome by addition of increasing amounts of K+ ions, indicating that the Na+/K+ ion balance is central to this stress induction. We conclude that dimerization involving hydrophobic segments in the carboxyl-terminal region is required for activation of Gcn2p in response to a multitude of stresses.
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PMID:Dimerization is required for activation of eIF2 kinase Gcn2 in response to diverse environmental stress conditions. 1501 Apr 61

We have cloned and characterized the Aspergillus fumigatus cpcA gene encoding the transcriptional activator of the cross-pathway control system of amino acid biosynthesis. cpcA encodes a functional orthologue of Saccharomyces cerevisiae Gcn4p. The coding sequence of the 2.2 kb transcript is preceded by two short upstream open reading frames, the larger one being well conserved among Aspergilli. Deletion strains in which either the coding sequence or the entire locus are replaced by a bifunctional dominant marker are impaired in their cross-pathway control response upon amino acid starvation, as demonstrated by analyses of selected reporter genes and specific enzymatic activities. In a murine model of pulmonary aspergillosis, cpcAdelta strains display attenuated virulence. Pathogenicity is restored to wild-type levels in strains with reconstitution of the genomic locus. Competitive mixed infection experiments additionally demonstrate that cpcAdelta strains are less able to survive in vivo than their wild-type progenitor. Our data suggest that specific stress conditions are encountered by A. fumigatus within the mammalian host and that the fungal cross-pathway control system plays a significant role in pulmonary aspergillosis.
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PMID:The Aspergillus fumigatus transcriptional activator CpcA contributes significantly to the virulence of this fungal pathogen. 1510 84


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