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Query: UMLS:C0038187 (starvation)
 24,951 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

TOR is the target of the immunosuppressant rapamycin and a key regulator of cell growth. It modulates diverse cellular processes in the cytoplasm and nucleus, including the expression of amino acid transporters, ribosomal RNAs and ribosomal proteins. Despite considerable recent progress, little is known about the spatial and temporal regulation of TOR signalling, particularly that leading into the nucleus. Here we show that Tor1 is dynamically distributed in the cytoplasm and nucleus in yeast. Tor1 nuclear localization is nutrient dependent and rapamycin sensitive: starvation or treatment with rapamycin causes Tor1 to exit from the nucleus. Tor1 nuclear localization is critical for 35S rRNA synthesis, but not for the expression of amino acid transporters and ribosomal protein genes. We show further that Tor1 is associated with 35S ribosomal DNA (rDNA) promoter chromatin in a rapamycin- and starvation-sensitive manner; this association is necessary for 35S rRNA synthesis and cell growth. These results indicate that the spatial regulation of TOR complex 1 (TORC1) might be involved in differential control of its target genes. TOR is known as a classic cytoplasmic kinase that mediates the cytoplasm-to-nucleus signalling by controlling the localization of transcription factors. Our data indicate that TOR might be more intimately involved in gene regulation than previously thought.
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PMID:Nutrient regulates Tor1 nuclear localization and association with rDNA promoter. 1690 Jan 1

The rpoZ gene for the omega subunit of Escherichia coli RNA polymerase constitutes single operon with the spoT gene, which is responsible for the maintenance of stringent response under nutrient starvation conditions. To identify the physiological role of the omega subunit, we compared the gene expression profile of wild-type Escherichia coli with that of an rpoZ deleted strain by microarray analysis using an E. coli DNA chip. Here we report on a set of genes which show changes in expression profile following the removal of rpoZ. We have seen that relA, which is responsible for the synthesis of the stringent factor ppGpp and many ribosomal proteins, exhibited noticeable changes in mRNA levels and were therefore further analyzed for their expression using a GFP/RFP two-fluorescent protein promoter assay vector. In the absence of rpoZ, the promoter for the relA gene was severely impaired, but the promoters from the ribosomal protein genes were not affected as much. Taking these results together we propose that the omega subunit is involved in regulation of the relA gene, but induction of the stringently controlled genes in the absence of rpoZ is, at least in part, attributable to a decrease in ppGpp level.
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PMID:The role of the omega subunit of RNA polymerase in expression of the relA gene in Escherichia coli. 1723 76

Nutrient starvation results in the interaction of Saccharomyces cerevisiae cells with each other and with surfaces. Adhesive growth requires the expression of the FLO11 gene regulated by the Ras/cAMP/cAMP-dependent protein kinase, the Kss1p/MAPK, and the Gcn4p/general amino acid control pathway, respectively. Proteomics two-dimensional DIGE experiments revealed post-transcriptionally regulated proteins in response to amino acid starvation including the ribosomal protein Cpc2p/Asc1p. This putative translational regulator is highly conserved throughout the eukaryotic kingdom and orthologous to mammalian RACK1. Deletion of CPC2/ASC1 abolished amino acid starvation-induced adhesive growth and impaired basal expression of FLO11 and its activation upon starvation in haploid cells. In addition, the diploid Flo11p-dependent pseudohyphal growth during nitrogen limitation was CPC2/ASC1-dependent. A more detailed analysis revealed that a CPC2/ASC1 deletion caused increased sensitivity to cell wall drugs suggesting that the gene is required for general cell wall integrity. Phosphoproteome and Western hybridization data indicate that Cpc2p/Asc1p affected the phosphorylation of the translational initiation factors eIF2 alpha and eIF4A and the ribosome-associated complex RAC. A crucial role of Cpc2p/Asc1p at the ribosomal interface coordinating signal transduction, translation initiation, and transcription factor formation was corroborated.
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PMID:The Saccharomyces homolog of mammalian RACK1, Cpc2/Asc1p, is required for FLO11-dependent adhesive growth and dimorphism. 1770 55

While the core splicing machinery is highly conserved between budding yeast and mammals, the absence of alternative splicing in Saccharomyces cerevisiae raises the fundamental question of why introns have been retained in approximately 5% of the 6000 genes. Because ribosomal protein-encoding genes (RPGs) are highly overrepresented in the set of intron-containing genes, we tested the hypothesis that splicing of these transcripts would be regulated under conditions in which translation is impaired. Using a microarray-based strategy, we find that, within minutes after the induction of amino acid starvation, the splicing of the majority of RPGs is specifically inhibited. In response to an unrelated stress, exposure to toxic levels of ethanol, splicing of a different group of transcripts is inhibited, while the splicing of a third set is actually improved. We propose that regulation of splicing, like transcription, can afford rapid and specific changes in gene expression in response to the environment.
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PMID:Rapid, transcript-specific changes in splicing in response to environmental stress. 1788 58

Escherichia coli has a PhoR-PhoB two-component regulatory system to detect and respond to the changes of environmental phosphate concentration. For the E. coli W3110 strain growing under phosphate-limiting condition, the changes of global gene expression levels were investigated by using DNA microarray analysis. The expression levels of some genes that are involved in phosphate metabolism were increased as phosphate became limited, whereas those of the genes involved in ribosomal protein or amino acid metabolism were decreased, owing to the stationary phase response. The upregulated genes could be divided into temporarily and permanently inducible genes by phosphate starvation. At the peak point showing the highest expression levels of the phoB and phoR genes under phosphate-limiting condition, the phoB- and/or phoR-dependent regulatory mechanisms were investigated in detail by comparing the gene expression levels among the wild-type and phoB and/or phoR mutant strains. Overall, the phoB mutation was epistatic over the phoR mutation. It was found that PhoBR and PhoB were responsible for the upregulation of the phosphonate or glycerol phosphate metabolism and high-affinity phosphate transport system, respectively. These results show the complex regulation by the PhoR-PhoB two-component regulatory system in E. coli.
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PMID:Transcriptome analysis of phosphate starvation response in Escherichia coli. 1805 55

MicroRNAs (miRNAs) are small RNAs that function as posttranscriptional regulators of gene expression. miRNAs affect a variety of signaling pathways, and impaired miRNA regulation may contribute to the development of cancer and other diseases. Here we show that miRNA miR-10a interacts with the 5' untranslated region of mRNAs encoding ribosomal proteins to enhance their translation. miR-10a alleviates translational repression of the ribosomal protein mRNAs during amino acid starvation and is required for their translational induction following anisomycin treatment or overexpression of RAS. We show that miR-10a binds immediately downstream of the regulatory 5'TOP motif and that the 5'TOP regulatory complex and miR-10a are functionally interconnected. The results show that miR-10a may positively control global protein synthesis via the stimulation of ribosomal protein mRNA translation and ribosome biogenesis and hereby affect the ability of cells to undergo transformation.
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PMID:MicroRNA-10a binds the 5'UTR of ribosomal protein mRNAs and enhances their translation. 1849 49

The protein kinase Sch9 is proposed to be a downstream effector of TORC1 that is required for activation of ribosome biogenesis and repression of entry into G(0). However, Sch9 apparently functions antagonistically to TORC1, when considering the induction of several stress defence genes that are normally repressed by TORC1. To further investigate the relationship between Sch9 and TORC1, we compared the rapamycin-induced transcriptional responses in an sch9Delta mutant and the isogenic wild type. The data indicate that Sch9 is necessary for proper integration of the rapamycin-induced stress signal, i.e. in sch9Delta cells, typical effects of rapamycin-like repression of ribosomal protein genes and induction of stress response genes are diminished or abolished. Moreover, they reveal for the first time a direct link between Sch9 and nitrogen metabolism. A sch9Delta mutant has an increased basal activation of targets of the general amino acid control pathway and of the nitrogen discrimination pathway, including the ammonium permease MEP2 and the amino acid permease GAP1. The mutant also shows enhanced expression of the transcription factor Gcn4 required for amino acid biosynthesis. Our data favour a model in which (1) the role of Sch9 in the general stress response switches depending on TORC1 activity and (2) Sch9 and TORC1 have independent and additive effects on genes induced upon nitrogen and amino acid starvation.
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PMID:Genome-wide expression analysis reveals TORC1-dependent and -independent functions of Sch9. 1875 43

Many cell surface-associated, divalent cation-regulated proteins are immunogenic, and some of them confer protection against the bacterial species from which they are derived. In this work, two Streptococcus suis divalent cation uptake regulator genes controlling zinc/manganese and iron uptake (adcR and fur, respectively) were inactivated in order to study the protective capacities of their cell surface-associated proteins. The results obtained showed overexpression of a set of immunogenic proteins (including members of the pneumococcal histidine triad family previously reported to confer protection against streptococcal pathogens) in S. suis adcR mutant cell surface extracts. Likewise, genes encoding zinc transporters, putative virulence factors and a ribosomal protein paralogue related to zinc starvation appeared to be derepressed in this mutant strain. Moreover, protection assays in mice showed that although neither adcR- nor fur-regulated cell surface-associated proteins were sufficient to confer protection in mice, the combination of both adcR- and fur-regulated cell surface-associated proteins is able to confer significant protection (50 %, P=0.038) against a challenge to mice vaccinated with them.
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PMID:Protective capacities of cell surface-associated proteins of Streptococcus suis mutants deficient in divalent cation-uptake regulators. 1937 68

TORC1 is a central regulator of cell growth in response to amino acid availability, yet little is known about how it is regulated. Here, we performed a reverse genetic screen in yeast for genes necessary to inactivate TORC1. The screen consisted of monitoring the expression of a TORC1 sensitive GFP-based transcriptional reporter in all yeast deletion strains using flow cytometry. We find that in response to amino acid starvation, but not to carbon starvation or rapamycin treatment, cells lacking NPR2 and NPR3 fail to fully (1) activate transcription factors Gln3/Gat1, (2) dephosphorylate TORC1 effector Npr1, and (3) repress ribosomal protein gene expression. Both mutants show proliferation defects only in media containing a low quality nitrogen source, such as proline or ammonia, whereas no defects are evident when cells are grown in the presence of glutamine or peptone mixture. Proliferation defects in npr2Delta and npr3Delta cells can be completely rescued by artificially inhibiting TORC1 by rapamycin, demonstrating that overactive TORC1 in both strains prevents their ability to adapt to an environment containing a low quality nitrogen source. A biochemical purification of each demonstrates that Npr2 and Npr3 form a heterodimer, and this interaction is evolutionarily conserved since the human homologs of NPR2 and NPR3 (NPRL2 and NPRL3, respectively) also co-immunoprecipitate. We conclude that, in yeast, the Npr2/3 complex mediates an amino acid starvation signal to TORC1.
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PMID:A genome-wide screen for regulators of TORC1 in response to amino acid starvation reveals a conserved Npr2/3 complex. 1952 2

Sexual differentiation in Schizosaccharomyces pombe is triggered by nutrient starvation and is downregulated by cAMP. Screening programs have identified the moc1/sds23, moc2/ded1, moc3 and moc4/zfs1 genes as inducers of sexual differentiation, even in the presence of elevated levels of cAMP. To investigate possible interactions among Moc1, Moc2, Moc3 and Moc4 proteins, we first screened for individual Moc-interacting proteins using the yeast two-hybrid system and verified the interactions with other Moc proteins. Using this screening process, Cpc2 and Rpl32-2 were highlighted as factors involved in interactions with multiple Moc proteins. Cpc2 interacted with Moc1, Moc2 and Moc3, whereas the ribosomal protein Rpl32-2 interacted with all Moc proteins in the two-hybrid system. Physical interactions of Cpc2 with Moc1, Moc2 and Rpl32-2, and of Rpl32-2 with Moc2 were confirmed by coimmunoprecipitation. In addition, using Blue Native/PAGE, we revealed that each Moc protein exists as a large complex. Overexpression of Moc1, Moc2, Moc3, Moc4 and Rpl32-2 resulted in the efficient induction of a key transcription factor Ste11, suggesting that all proteins tested are positive regulators of Ste11. Considering that Moc2/Ded1 is a general translation factor and that Cpc2 associates with many ribosomal proteins, including Rpl32-2, it is possible that a large Moc-mediated complex, detected in this study, may act as a translational regulator involved in the control of sexual differentiation in S. pombe through the induction of Ste11.
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PMID:A large complex mediated by Moc1, Moc2 and Cpc2 regulates sexual differentiation in fission yeast. 1968 1


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