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 developed a high-resolution "genome array" for the study of gene expression and regulation in Escherichia coli. This array contains on average one 25-mer oligonucleotide probe per 30 base pairs over the entire genome, with one every 6 bases for the intergenic regions and every 60 bases for the 4,290 open reading frames (ORFs). Twofold concentration differences can be detected at levels as low as 0.2 messenger RNA (mRNA) copies per cell, and differences can be seen over a dynamic range of three orders of magnitude. In rich medium we detected transcripts for 97% and 87% of the ORFs in stationary and log phases, respectively. We found that 1, 529 transcripts were differentially expressed under these conditions. As expected, genes involved in translation were expressed at higher levels in log phase, whereas many genes known to be involved in the starvation response were expressed at higher levels in stationary phase. Many previously unrecognized growth phase-regulated genes were identified, such as a putative receptor (b0836) and a 30S ribosomal protein subunit (S22), both of which are highly upregulated in stationary phase. Transcription of between 3,000 and 4,000 predicted ORFs was observed from the antisense strand, indicating that most of the genome is transcribed at a detectable level. Examples are also presented for high-resolution array analysis of transcript start and stop sites and RNA secondary structure.
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PMID:RNA expression analysis using a 30 base pair resolution Escherichia coli genome array. 1110 97

The rplK gene of Corynebacterium glutamicum ATCC13032 comprises 438 nucleotides and encodes a protein of 145 amino acids with a molecular mass of 15.3 kDa. The amino acid sequence revealed extensive similarities to the large ribosomal subunit protein L11 from several Gram-positive and Gram-negative bacteria. The C. glutamicum rplK gene is located downstream of secE, representing part of the protein export apparatus, and of nusG, encoding a transcription antiterminator protein. The rplK gene is followed by an ORF homologous to rplA encoding the 50S ribosomal protein L1. Northern analysis revealed that transcription of the rplK-rplA cluster resulted in two different transcripts of 1.5 and 0.6 kb. The 1.5 kb transcript corresponds to the entire rplK-rplA cluster and the short transcript originates from the rplK gene. A C. glutamicum rplK mutant strain carrying a 12 bp in-frame deletion within rplK, which resulted in the loss of the tetrapeptide Pro-Ala-Leu-Gly in the L11 protein, was constructed. The mutant failed to accumulate (p)ppGpp in response to amino acid starvation and exhibited an increased tolerance to the antibiotic thiostrepton. Evidently, the C. glutamicum rplK gene is required for (p)ppGpp accumulation upon nutritional starvation.
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PMID:A Corynebacterium glutamicum mutant with a defined deletion within the rplK gene is impaired in (p)ppGpp accumulation upon amino acid starvation. 1123 76

Inorganic polyphosphate (polyP), a polymer of hundreds of phosphate (Pi) residues, accumulates in Escherichia coli in response to stresses, including amino acid starvation. Here we show that the adenosine 5'-triphosphate-dependent protease Lon formed a complex with polyP and degraded most of the ribosomal proteins, including S2, L9, and L13. Purified S2 also bound to polyP and formed a complex with Lon in the presence of polyP. Thus, polyP may promote ribosomal protein degradation by the Lon protease, thereby supplying the amino acids needed to respond to starvation.
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PMID:Role of inorganic polyphosphate in promoting ribosomal protein degradation by the Lon protease in E. coli. 1147 88

Predicted highly expressed (PHX) genes are characterized for the completely sequenced genomes of the four fast-growing bacteria Escherichia coli, Haemophilus influenzae, Vibrio cholerae, and Bacillus subtilis. Our approach to ascertaining gene expression levels relates to codon usage differences among certain gene classes: the collection of all genes (average gene), the ensemble of ribosomal protein genes, major translation/transcription processing factors, and genes for polypeptides of chaperone/degradation complexes. A gene is predicted highly expressed (PHX) if its codon frequencies are close to those of the ribosomal proteins, major translation/transcription processing factor, and chaperone/degradation standards but strongly deviant from the average gene codon frequencies. PHX genes identified by their codon usage frequencies among prokaryotic genomes commonly include those for ribosomal proteins, major transcription/translation processing factors (several occurring in multiple copies), and major chaperone/degradation proteins. Also PHX genes generally include those encoding enzymes of essential energy metabolism pathways of glycolysis, pyruvate oxidation, and respiration (aerobic and anaerobic), genes of fatty acid biosynthesis, and the principal genes of amino acid and nucleotide biosyntheses. Gene classes generally not PHX include most repair protein genes, virtually all vitamin biosynthesis genes, genes of two-component sensor systems, most regulatory genes, and most genes expressed in stationary phase or during starvation. Members of the set of PHX aminoacyl-tRNA synthetase genes contrast sharply between genomes. There are also subtle differences among the PHX energy metabolism genes between E. coli and B. subtilis, particularly with respect to genes of the tricarboxylic acid cycle. The good agreement of PHX genes of E. coli and B. subtilis with high protein abundances, as assessed by two-dimensional gel determination, is verified. Relationships of PHX genes with stoichiometry, multifunctionality, and operon structures are also examined. The spatial distribution of PHX genes within each genome reveals clusters and significantly long regions without PHX genes.
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PMID:Characterizations of highly expressed genes of four fast-growing bacteria. 1148 55

Coordinate regulation of the ribosomal protein genes is entrusted to a number of signal transduction pathways that can abruptly induce or silence the ribosomal genes. We have uncovered a cellular model system, which selectively induces the ribosomal protein S25 gene in hepatoma cells that are stressed by nutrient deprivation. Our results indicate that p53 along with two other identified proteins, MTF-1 and La, post-transcriptionally regulate the synthesis of the S25 protein by controlling the nuclear export of the stress-induced S25 mRNA. This system is unique in that the nuclear-retained S25 mRNA is exported to the cytosol only upon replenishment or alternatively after prolonged starvation to participate in a p53-mediated apoptotic sequence of events. This p53-dependent survival or death pathway involves a previously unreported protein relationship among these three actors, one of which, MTF-1, has not yet been shown to have RNA-binding characteristics.
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PMID:Ribosomal protein S25 mRNA partners with MTF-1 and La to provide a p53-mediated mechanism for survival or death. 1174 12

The essential, rapamycin-sensitive TOR kinases regulate a diverse set of cell growth-related readouts in response to nutrients. Thus, the yeast TOR proteins function as nutrient sensors, in particular as sensors of nitrogen and possibly carbon. However, the nutrient metabolite(s) that acts upstream of TOR is unknown. We investigated the role of glutamine, a preferred nitrogen source and a key intermediate in yeast nitrogen metabolism, as a possible regulator of TOR. We show that the glutamine synthetase inhibitor L-methionine sulfoximine (MSX) specifically provokes glutamine depletion in yeast cells. MSX-induced glutamine starvation caused nuclear localization and activation of the TOR-inhibited transcription factors GLN3, RTG1, and RTG3, all of which mediate glutamine synthesis. The MSX-induced nuclear localization of GLN3 required the TOR-controlled, type 2A-related phosphatase SIT4. Other TOR-controlled transcription factors, GAT1/NIL1, MSN2, MSN4, and an unknown factor involved in the expression of ribosomal protein genes, were not affected by glutamine starvation. These findings suggest that the TOR pathway senses glutamine. Furthermore, as glutamine starvation affects only a subset of TOR-controlled transcription factors, TOR appears to discriminate between different nutrient conditions to elicit a response appropriate to a given condition.
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PMID:The TOR-controlled transcription activators GLN3, RTG1, and RTG3 are regulated in response to intracellular levels of glutamine. 1199 79

1. When the methionine-requiring mutant 58-161 of Escherichia coli was starved of methionine, ribonucleic acid was made in the absence of protein synthesis. 2. Most of this ribonucleic acid was similar to that found in ribosomes but was contained in particles differing from ribosomes both in sedimentation coefficient and in chromatographic behaviour on diethylaminoethylcellulose. 3. When methionine was added to a starved culture, the ribonucleic acid synthesized during starvation was almost completely undegraded as growth resumed. A transient loss of 5-10% could be largely attributed to breakdown of messenger ribonucleic acid accumulated during starvation. 4. After the addition of methionine, ribosomes were formed from the particles, and during this period preferential synthesis of ribosomal protein took place. 5. It is suggested that under these conditions the direct synthesis of ribosomes from the particles may occur.
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PMID:THE SYNTHESIS OF RIBOSOMES BY A MUTANT OF ESCHERICHIA COLI. 1434 92

Cell-size homeostasis entails a fundamental balance between growth and division. The budding yeast Saccharomyces cerevisiae establishes this balance by enforcing growth to a critical cell size prior to cell cycle commitment (Start) in late G1 phase. Nutrients modulate the critical size threshold, such that cells are large in rich medium and small in poor medium. Here, we show that two potent negative regulators of Start, Sfp1 and Sch9, are activators of the ribosomal protein (RP) and ribosome biogenesis (Ribi) regulons, the transcriptional programs that dictate ribosome synthesis rate in accord with environmental and intracellular conditions. Sfp1 and Sch9 are required for carbon-source modulation of cell size and are regulated at the level of nuclear localization and abundance, respectively. Sfp1 nuclear concentration responds rapidly to nutrient and stress conditions and is regulated by the Ras/PKA and TOR signaling pathways. In turn, Sfp1 influences the nuclear localization of Fhl1 and Ifh1, which bind to RP gene promoters. Starvation or the absence of Sfp1 causes Fhl1 and Ifh1 to localize to nucleolar regions, concomitant with reduced RP gene transcription. These findings suggest that nutrient signals set the critical cell-size threshold via Sfp1 and Sch9-mediated control of ribosome biosynthetic rates.
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PMID:A dynamic transcriptional network communicates growth potential to ribosome synthesis and critical cell size. 1546 58

Regulation of ribosome biogenesis is central to the control of cell growth. In rapidly growing yeast cells, ribosomal protein (RP) genes account for approximately one-half of all polymerase II transcription-initiation events, yet these genes are markedly and coordinately downregulated in response to a number of environmental stress conditions, or during the transition from fermentation to respiration. Although several conserved signalling pathways (TOR, RAS/protein kinase A and protein kinase C) impinge upon RP gene transcription, little is known about how initiation at these genes is controlled. Rap1 (refs 6, 7) and more recently Fhl1 (ref. 8) were shown to bind upstream of many RP genes. Here we show that the essential protein Ifh1 binds to and activates many RP gene promoters under optimal growth conditions in Saccharomyces cerevisiae. Ifh1 is recruited to RP gene promoters through the forkhead-associated domain of Fhl1. Ifh1 binding decreases when RP genes are downregulated either by TOR inhibition or nutrient depletion, and is restored after release from starvation or upon regulated induction of IFH1 expression. These findings indicate a central role for Ifh1 and Fhl1 in RP gene regulation.
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PMID:Growth-regulated recruitment of the essential yeast ribosomal protein gene activator Ifh1. 1561 69

Although conjugation of overexpressed GABARP to phospholipid has been reported during starvation-induced autophagy, it is unclear whether endogenous GABARAP-phospholipid conjugation is also activated under starvation conditions. We observed little accumulation of GABARAP-phospholipid conjugate (GABARAP-PL) in mouse liver and kidney under starvation conditions, whereas endogenous LC3-phospholipid conjugate (LC3-II) accumulated. A small amount of endogenous GABARAP-PL was observed in the heart, independent of starvation. In rapamycin-treated HEK293 cells, there was little accumulation of endogenous GABARAP-PL, even in the presence of lysosomal protease-inhibitors, whereas there was significant accumulation of endogenous LC3-II, together with inactivation of the mTor kinase-signaling pathway. In HeLa and C2C12 cells, GABARAP-PL accumulation in the presence of lysosomal protease inhibitors was independent of starvation-induced autophagy, whereas LC3-II accumulation was significant during starvation-induced autophagy. Interestingly, we observed activation of lysosomal turnover of GABARAP-PL during the differentiation of C2C12 cells to myotubes, along with increased lysosomal turnover of LC3-II. Under these conditions, S6 ribosomal protein was still phosphorylated, suggesting that the mTor kinase-signaling pathway is active during the differentiation of C2C12 cells to myotubes, in contrast to starvation-induced autophagy. These results indicated that lysosomal turnover of GABARAP-PL was activated during the differentiation of C2C12 cells to myotubes without inactivation of the mTor kinase-signaling pathway, whereas little lysosomal turnover of GABARAP-PL was activated during starvation-induced autophagy.
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PMID:Lysosomal turnover of GABARAP-phospholipid conjugate is activated during differentiation of C2C12 cells to myotubes without inactivation of the mTor kinase-signaling pathway. 1688 Jul 29


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