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)

Proteins were isolated from the 40S ribosomal subunits of baby-hamster kidney fibroblasts and subjected to two-dimensional gel electrophoresis. When the cells were pretreated with cyclic AMP or 2-deoxyglucose a more basic derivative of ribosomal protein S3 or S3a was often observed, apparently similar to that previously reported to occur early in liver generation. This derivative was not a dephosphorylated form of protein S3, which protein does not appear to be phosphorylated in normal cells; nor did it correspond to the proteolytic fragment, S3b. It appears to be an oxidation product of protein S3 or S3a, as it can be eliminated by thorough reduction of the ribosomal protein before electrophoresis. In contrast with previous results with Krebs II ascites cells, starvation of baby-hamster kidney fibroblasts of glucose did not cause extensive phosphorylation of ribosomal protein S3.
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PMID:Phosphorylated and other modified forms of eukaryotic ribosomal protein S3 analysed by two-dimensional gel electrophoresis. 625 31

When exponentially growing cells of Tetrahymena pyriformis are transferred to a non-nutrient medium the loss of whole cell RNA, 90% of which is ribosomal RNA, exhibits biphasic kinetics, whereas whole cell protein is lost at a constant rate. The ratio RNA/protein declines during the first 5 h of starvation and then remains constant during the subsequent period of starvation. The synthesis of the majority of the ribosomal proteins is coordinately regulated during a nutritional shift-down. Exponentially growing cells devote 17% of their capacity for protein synthesis to the production of ribosomal proteins. Upon starvation this proportion is rapidly reduced 3.5-fold. In long-time-starved cells the absolute rate of ribosomal protein synthesis is only about 4.5% of that of exponentially growing cells. The synthesis of ribosomal RNA and ribosomal proteins appears tightly coupled during the transition from growth to starvation. In long-time-starved cells the synthesis of ribosomal RNA and ribosomal proteins are stoichiometrically balanced with no significant degradation of de novo synthesized ribosomal proteins.
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PMID:Regulation of ribosome synthesis in Tetrahymena pyriformis. 1. Coordination of synthesis of ribosomal proteins and ribosomal RNA during nutritional shift-down. 642 53

We have measured the levels of translatable total mRNA and ribosomal protein (r-protein) mRNAs in Tetrahymena pyriformis during nutritional shifts. After 15 min of starvation total mRNA is reduced 2-fold, and after 24 h 7.5-fold, relative to exponentially growing cells. Upon refeeding total mRNA increases rapidly reaching the level of exponentially growing cells after 2.5 h. The levels of the individual r-protein mRNAs are coordinately regulated throughout a starvation-refeeding cycle. The relative levels of r-protein mRNAs remain virtually unchanged during the first hour of starvation and then decrease gradually to 30% of the relative levels in exponentially growing cells. Following refeeding the relative levels of r-protein mRNAs increase 6-fold. Taking into account the changes in whole cell RNA, we have calculated that long-time-starved Tetrahymena cells contain only 4%, whereas cells after 3 h of refeeding contain 200% of the amount of r-protein mRNA in exponentially growing cells. The amount of r-protein mRNA thus increases 50-fold during the first 3 h of refeeding. A comparison between the relative levels of r-protein mRNAs and the relative rate of r-protein synthesis in vivo indicates that Tetrahymena employs a combination of control of translation and control of the level of r-protein mRNAs to ensure a rapid reduction in the rate of r-protein synthesis during the early period of starvation. In this period translation of r-protein mRNAs is preferentially inhibited. During refeeding the increase in the rate of r-protein synthesis parallels the increase in the abundance of r-protein mRNAs.
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PMID:Regulation of ribosome synthesis in Tetrahymena pyriformis. 3. Analysis by translation in vitro of RNA isolated during nutritional shift-down and nutritional shift-up. 642 55

In Saccharomyces cerevisiae, the levels of ribosomal protein mRNAs are regulated coordinately. Vegetative strains carrying the temperature-sensitive rna2 mutation exhibit a dramatic decrease in the levels of most ribosomal protein mRNAs at the restrictive temperature. Similarly, in wild-type cells induced to sporulate by nitrogen starvation, there is a fivefold reduction in the relative synthesis rate of ribosomal proteins. Using Northern gel analysis and cloned ribosomal protein genes, we compared the way in which ribosomal protein mRNA is affected under these two conditions. In vegetative rna2 cells, incubation at 34 degrees C led to the disappearance of ribosomal protein mRNAs and the accumulation of higher-molecular-weight precursor RNAs. A different phenotype was observed during sporulation. Although sporulating conditions led to a significant reduction in the relative abundance of ribosomal protein mRNA, there was no detectable accumulation of precursor RNAs even in rna2/rna2 diploids at 34 degrees C. A suppressor of rna2 and of other rna mutations, SRN1, at least partially relieved the block in the splicing of the ribosomal protein 51 intron in vegetative rna2 cells but did not detectably affect the level of ribosomal protein mRNA in sporulating cells. We concluded that the rna2 mutation and sporulation conditions affected ribosomal protein mRNA metabolism in two quite different ways. In vegetative cells the mutant rna2 effected a block which occurred primarily in post-transcriptional processing, whereas in sporulating cells the ribosomal protein mRNA levels were decreased by some other mechanism, presumably a change in the relative rate of transcription or mRNA turnover. Furthermore, the data suggest that the mutation rna2 has no additional effect on ribosomal protein mRNA metabolism in sporulating cells.
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PMID:Sporulation and rna2 lower ribosomal protein mRNA levels by different mechanisms in Saccharomyces cerevisiae. 675 16

Amino acid starvation of a variety of different types of cells has been reported to induce protein degradation and also specific mistranslation. For certain amino acid starvations, the mistranslated protein, which contains specific amino acid substitutions, can be separated and quantified by two-dimensional polyacrylamide gel electrophoresis. In this paper, I show that this specifically mistranslated protein, made during amino acid starvation, does not seem to be preferentially degraded during continued starvation or renewed growth. Specifically mistranslated ribosomal protein is also assembled into ribosomes in the same proportion that it is made. These results imply that the amino acid substitutions apparently made (lysine for asparagine or glutamine or histidine) do not lead to proteins recognized as grossly "abnormal" by the cell's proteolysis systems.
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PMID:Mistranslated protein in Escherichia coli. 702 69

Tetrahymena thermophila cells transferred from growth medium into a dilute salt (starvation) medium shortly (approximately 6-8 hrs) become more resistant to the in vivo inhibitory effects of the antibiotics cycloheximide, tetracycline and emetine. They also be come more sensitive to the inhibitory effects of paromomycin and anisomycin. By comparing ribosomes from growing and starved cells we have found that for at least two of these drugs differences between growing cell and starved cell ribosomes exist with respect to drug-ribosome interactions. In addition, we found that isolated monosomic ribosomes from starved cells are more resistant to thermal denaturation than are monosomic ribosomes from growing cells. The kinetics of all these changes following transfer of growing cells to starvation medium is the same and correlates with a change in the extent of phosphorylation of a single small subunit ribosomal protein. As judged by our in vitro assays, enzymatic removal of this phosphate converts "starved cell" ribosomes into "growing cell" ribosomes. We have extended these studies to show that the phenomenon of drug adaptation in Tetrahymena, at least with respect to cycloheximide, is associated with this ribosome phosphorylation.
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PMID:Regulation of ribosome phosphorylation and antibiotic sensitivity in Tetrahymena thermophila: A correlation. 732 42

By differential hybridization, we identified a number of genes in Saccharomyces cerevisiae that are activated by addition of cyclic AMP (cAMP) to cAMP-depleted cells. A majority, but not all, of these genes encode ribosomal proteins. While expression of these genes is also induced by addition of the appropriate nutrient to cells starved for a nitrogen source or for a sulfur source, the pathway for nutrient activation of ribosomal protein gene transcription is distinct from that of cAMP activation: (i) cAMP-mediated transcriptional activation was blocked by prior addition of an inhibitor of protein synthesis whereas nutrient-mediated activation was not, and (ii) cAMP-mediated induction of expression occurred through transcriptional activation whereas nutrient-mediated induction was predominantly a posttranscriptional response. Transcriptional activation of the ribosomal protein gene RPL16A by cAMP is mediated through a upstream activation sequence element consisting of a pair of RAP1 binding sites and sequences between them, suggesting that RAP1 participates in the cAMP activation process. Since RAP1 protein decays during starvation for cAMP, regulation of ribosomal protein genes under these conditions may directly relate to RAP1 protein availability. These results define additional critical targets of the cAMP-dependent protein kinase, suggest a mechanism to couple ribosome production to the metabolic activity of the cell, and emphasize that nutrient regulation is independent of the RAS/cAMP pathway.
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PMID:Nutrient availability and the RAS/cyclic AMP pathway both induce expression of ribosomal protein genes in Saccharomyces cerevisiae but by different mechanisms. 776 Aug 15

Translation of ribosomal protein (rp) mRNA is selectively repressed in mouse erythroleukemia (MEL) cells, which cease to proliferate upon differentiation, and in NIH 3T3 cells, for which growth is arrested by either serum starvation, contact inhibition, or treatment with the DNA polymerase inhibitor, aphidicolin. The efficiency of translation of rp mRNAs correlates with the expression of the gene encoding the cap binding protein, eIF-4E, as indicated by the fact that the abundance of the corresponding mRNA and protein also fluctuates in a growth-dependent manner. To examine the hypothesis that eIF-4E plays a role in regulation of the translation efficiency of rp mRNAs, we utilized an NIH 3T3-derived eIF-4E-overexpressing cell line. These cells overproduce eIF-4E to the extent that even under conditions of growth arrest, the abundance of the respective protein in its active (phosphorylated) form is higher than that found in exponentially growing NIH 3T3 cells. Nevertheless, this surplus amount of eIF-4E does not prevent the translational repression of rp mRNAs when the growth of these cells is arrested by blocking DNA synthesis with aphidicolin or hydroxyurea. In complementary experiments we used an in vitro translation system to compare the competitive potential of mRNAs, containing the translational cis-regulatory element (5' terminal oligopyrimidne tract) and mRNAs lacking such a motif, for the cap binding protein. Our results demonstrate that both types of mRNAs, regardless of their translational response to growth arrest, exhibit similar sensitivity to the cap analogue m7G(5')ppp(5')G. It appears, therefore, that the presence of the regulatory sequence at the 5' terminus of rp mRNAs does not lessen its competitive potential for the cap binding protein and that the growth-dependent decrease in the activity of eIF-4E does not play a key role in the repression of translation of rp mRNAs.
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PMID:Overexpression of initiation factor eIF-4E does not relieve the translational repression of ribosomal protein mRNAs in quiescent cells. 778 16

Yeast ribosomal protein genes are coordinately regulated as a function of cell growth; RNA levels decrease during amino acid starvation but increase following a carbon source upshift. Binding sites for RAP1, a multifunctional transcription factor, are present in nearly all ribosomal protein genes and are associated with growth rate regulation. We show that ribosomal protein mRNA levels are increased twofold in strains that have constitutively high levels of cyclic AMP-dependent protein kinase (protein kinase A [PKA]) activity. The PKA-dependent induction requires RAP1 binding sites, and it reflects increased transcriptional activation by RAP1. Growth-regulated transcription of ribosomal protein genes strongly depends on the ability to regulate PKA activity. Cells with constitutively high PKA levels do not show the transcriptional decrease in response to amino acid starvation. Conversely, in cells with constitutively low PKA activity, ribosomal protein mRNAs levels are lower and largely uninducible upon carbon source upshift. We suggest that modulation of RAP1 transcriptional activity by PKA accounts for growth-regulated expression of ribosomal protein genes.
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PMID:Protein kinase A mediates growth-regulated expression of yeast ribosomal protein genes by modulating RAP1 transcriptional activity. 811 23

An amino acid starvation-induced mRNA, increased up to 4-fold in the absence of amino acids, was identified previously as rat 60 S subunit ribosomal protein L17. The data presented here demonstrate that among ribosomal proteins, L17, as well as the smaller subunit ribosomal protein S25, are uniquely regulated by amino acid deprivation of cells; the increase in L17 and S25 mRNA content in response to substrate starvation is not shared by the 11 other ribosomal proteins tested. When rat Fao hepatoma cells were incubated in the presence of actinomycin D, the L17 mRNA level decayed below the basal level, regardless of medium amino acid content, and nuclear run-off assays confirmed that nutrient starvation leads to enhanced transcription of the L17 ribosomal protein gene. Likewise, the induction of S25 mRNA also was prevented in the presence of actinomycin D. Furthermore, the induction of L17 and S25 mRNA content was blocked by cycloheximide, demonstrating the requirement for a newly synthesized protein in the signaling pathway. Northern analysis with RNA isolated from cytoplasmic, polysomal, and nuclear enriched fractions indicated that the starvation-dependent increase in the S25 and L17 mRNAs is retained within the nucleus and not is available for translation. Amino acid refeeding of the cells caused the translocation of the stored nuclear mRNAs to the polysomal fraction.
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PMID:Nuclear retention of the induced mRNA following amino acid-dependent transcriptional regulation of mammalian ribosomal proteins L17 and S25. 814 59


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