Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0038187 (starvation)
 24,951 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

We have previously shown that nucleosome loss, obtained by repressing histone H4 mRNA synthesis, activates otherwise inactive PHO5, GAL1, and CYC1 gene promoters (fused to the bacterial beta-galactosidase [lacZ] reporter gene) to moderate levels of activity (approximately 2 to 15% of fully induced levels). We now report that nucleosome loss activates the expression of two additional promoters that are normally induced by independent mechanisms: CUP1 (induced by heavy-metal toxicity) and HIS3 (induced by amino acid starvation). Surprisingly, the level of CUP1-lacZ and HIS3-lacZ activation by nucleosome loss approximates fully induced levels of transcription. These CUP1 and HIS3 promoter activities are increased similarly from either episomal or genomic constructs. Our results emphasize the universality of the mechanism by which nucleosome loss activates yeast promoters. Moreover, a comparison of absolute levels of activation for different promoters suggests that activation by nucleosome loss results in a relatively constant level of activation, while levels obtained by normal induction vary considerably. These data argue that nucleosome loss may play a uniquely dominant role in the regulation of certain promoters.
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PMID:Nucleosome loss activates CUP1 and HIS3 promoters to fully induced levels in the yeast Saccharomyces cerevisiae. 154 16

The GCD1 gene product of Saccharomyces cerevisiae has been implicated in the coordination of the cell cycle with the general control of amino acid biosynthesis (M. Wolfner et al., J. Mol. Biol. 96:273-290, 1975). Strains containing the gcd1-1 allele constitutively express the amino acid biosynthetic genes at the induced levels normally found only during conditions of amino acid starvation. In addition, gcd1-1 strains do not grow at high temperatures because under these conditions they are unable to proceed beyond the START step of the cell division cycle. We have cloned and sequenced the GCD1 gene and examined various aspects of cellular metabolism in order to elucidate its role(s) in regulating gene expression and the cell cycle. GCD1 encodes a 1.7 kb RNA whose expression is not regulated as a function of amino acid starvation. Overexpression of this RNA does not affect the regulation of amino acid biosynthetic genes or cell growth. GCD1 is an essential gene because cells containing a gcd1-HIS3 disruption are unable to grow. The essential function of GCD1 may be involved in protein synthesis because a gcd1-1 strain incorporates low levels of 35S-methionine into protein when cells are shifted to the restrictive temperature. GCD1 encodes a protein of 511 amino acids whose predicted sequence does not exhibit significant homology to any other known proteins and appears too large to be a ribosomal protein. We suggest that GCD1 encodes a component of the normal protein synthesis machinery that is involved in the translational regulation of GCN4, a protein that coordinately activates the transcription of amino acid biosynthetic genes. GCD1 may also be part of a sensing mechanism in which cells monitor the protein synthesis capacity prior to initiating a new cell division cycle.
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PMID:Molecular characterization of GCD1, a yeast gene required for general control of amino acid biosynthesis and cell-cycle initiation. 305 Aug 97

The yeast GCN4 gene product is necessary for the transcriptional induction of many amino acid biosynthetic genes in response to conditions of amino acid starvation. We synthesized radioactively pure GCN4 protein by in vitro translation of mRNA produced by in vitro transcription with SP6 RNA polymerase. GCN4 protein binds specifically to the 20 bp region of the HIS3 gene that is critical for transcriptional regulation in vivo and contains the TGACTC sequence common to coregulated genes. A synthetic GCN4 mutant protein lacking the 40 C-terminal amino acids fails to bind DNA; this correlates with a gcn4 mutant gene that is nonfunctional in vivo. Finally, GCN4 protein binds to the promoter regions of coordinately regulated genes, but not to analogous regions of other genes. We suggest that GCN4 protein is a specific transcription factor, and we describe a molecular model for the general control of amino acid biosynthetic genes.
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PMID:GCN4 protein, synthesized in vitro, binds HIS3 regulatory sequences: implications for general control of amino acid biosynthetic genes in yeast. 390 51

UV irradiation of mammalian cells activates AP-1 through a Ras-dependent pathway, independently of DNA damage. We show that the yeast S. cerevisiae has a remarkably similar UV response involving the AP-1 factor Gcn4, which is distinct from the DNA damage response. Transcriptional activation of HIS3 and HIS4 by Gcn4 is triggered by UV irradiation in a Ras-dependent fashion. Moreover, resistance of yeast to UV irradiation is correlated with the level of Ras activity and Gcn4 function. Like mammalian cells in which activated Ras leads to increased c-Jun synthesis and phosphorylation, the effects in yeast involve increased translation of GCN4 mRNA and a posttranslational event. However, this effect on GCN4 translation is different from the response to amino acid or purine starvation. Therefore, a UV signaling pathway involving Ras and AP-1 is an ancient and universal mechanism involved in protection against damage to cellular components other than DNA.
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PMID:The UV response involving the Ras signaling pathway and AP-1 transcription factors is conserved between yeast and mammals. 818 Oct 58

The SUD1 gene was identified during a hunt for mutants that are able to express an sta1 gene (encoding an extracellular glucoamylase) lacking an upstream activation sequence (UAS) for transcription. A null allele of sud1 alleviated the transcriptional defect of the UAS-less sta1 and also suppressed mutations in trans-acting genes (GAM1/SNF2 and GAM3/ADR6) required for transcription of STA1. The mutation also increased expression from various core promoters (CYC1, CUP1, HIS3, PUT1, and PUT2), suggesting that the SUD1 protein is a global transcriptional regulator that plays a negative role at or near the TATA element. However, the SUD1 function was ineffective on promoters containing a UAS from either STA1 or GAL10 under derepressed conditions. The sud1 mutation suppressed the salt-sensitive cell growth phenotype caused by elevated levels of the TATA-binding protein (SPT15), further suggesting a transcriptional role for SUD1. sud1 cells showed additional pleiotropic phenotypes: temperature-sensitive (ts) growth, reduced efficiencies of sporulation, and sensitivity to heat shock and nitrogen starvation. The SUD1 gene is predicted to encode a 64 kDa, hydrophilic protein.
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PMID:Isolation and characterization of the SUD1 gene, which encodes a global repressor of core promoter activity in Saccharomyces cerevisiae. 826 36

We report here the identification of a novel multiprotein bridging factor type 1 from the apicomplexan Cryptosporidium parvum (CpMBF1), one of the opportunistic pathogens in AIDS patients. In slime molds, insects, and humans, MBF1-regulated systems have been associated with cell differentiation, which indicates that CpMBF1 could be responsible for the activation of similar systems in C. parvum during its complex life cycle. Because of the difficulties and high cost in obtaining sufficient and purified C. parvum material for molecular and biochemical analyses, well-characterized yeast genetic systems may be useful for investigating the functions of C. parvum genes. In this study, the function of CpMBF1 as an interconnecting element between a DNA-binding regulator and TATA-box-binding protein (TBP) was confirmed using a yeast complementation assay. Under conditions of histidine starvation, an MBF1-deficient strain of Saccharomyces cerevisiae was unable to activate the HIS3 gene, which encodes imidazoleglycerol-phosphate dehydratase (IGPDH), and thus became sensitive to 3-amino triazole, an inhibitor of this enzyme. Upon introduction of parasite CpMBF1 into S. cerevisiae, 3-amino triazole resistance of the MBF1-deficient strain was restored to wild-type levels, and Northern blot analysis revealed that CpMBF1 was able to activate HIS3 transcription in response to histidine starvation.
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PMID:Cryptosporidium parvum: functional complementation of a parasite transcriptional coactivator CpMBF1 in yeast. 1116 72