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

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

Y-1 adrenal cells were cell cycle arrested by serum starvation to characterize a G0-->G1-->S transition in these cells. Cycle arrested Y-1 cells start to enter S phase 8h after serum feeding, reaching more than 90% cells synthesizing DNA by 24h. ACTH displays a dual effect in the G0-->G1-->S transition: 2h ACTH treatment stimulates DNA synthesis initiation, but longer treatments inhibit S phase entry. This dual effect of ACTH is similar to the antagonistic actions of PMA (phorbol-12-miristate-13-acetate) on the G0-->G1-->S transition. However ACTH and PMA are likely to have different mechanisms of action. ACTH inhibitory effect requires PKA, whereas PMA inhibitory effect is not dependent on PKA. ACTH induces the proto-oncogenes c-fos and c-jun, but inhibits the expression of the c-myc proto-oncogene. PMA, on the other hand, induces equally well c-fos, c-jun and c-myc. We hypothesize that ACTH promotes G0-->G1 transition by induction of c-fos and c-jun and blocks G1-->S transition by c-myc inhibition.
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PMID:Regulation of growth by ACTH in the Y-1 line of mouse adrenocortical cells. 896 86

When nutrients are depleted, Dictyostelium cells undergo cell cycle arrest and initiate a developmental program that ensures survival. The YakA protein kinase governs this transition by regulating the cell cycle, repressing growth-phase genes and inducing developmental genes. YakA mutants have a shortened cell cycle and do not initiate development. A suppressor of yakA that reverses most of the developmental defects of yakA- cells, but none of their growth defects was identified. The inactivated gene, pufA, encodes a member of the Puf protein family of translational regulators. Upon starvation, pufA- cells develop precociously and overexpress developmentally important proteins, including the catalytic subunit of cAMP-dependent protein kinase, PKA-C. Gel mobility-shift assays using a 200-base segment of PKA-C's mRNA as a probe reveals a complex with wild-type cell extracts, but not with pufA- cell extracts, suggesting the presence of a potential PufA recognition element in the PKA-C mRNA. PKA-C protein levels are low at the times of development when this complex is detectable, whereas when the complex is undetectable PKA-C levels are high. There is also an inverse relationship between PufA and PKA-C protein levels at all times of development in every mutant tested. Furthermore, expression of the putative PufA recognition elements in wild-type cells causes precocious aggregation and PKA-C overexpression, phenocopying a pufA mutation. Finally, YakA function is required for the decline of PufA protein and mRNA levels in the first 4 hours of development. We propose that PufA is a translational regulator that directly controls PKA-C synthesis and that YakA regulates the initiation of development by inhibiting the expression of PufA. Our work also suggests that Puf protein translational regulation evolved prior to the radiation of metazoan species.
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PMID:Starvation promotes Dictyostelium development by relieving PufA inhibition of PKA translation through the YakA kinase pathway. 1037 15

In fission yeast Schizosaccharomyces pombe, ammonium starvation induces a growth arrest, a cell cycle exit in G(1) and a further switch to meiosis. This process is regulated by the cAMP-dependent protein kinase and the Wis1-dependent MAP kinase cascade, and downstream transcription factors. In order to understand how cells adapt their genetic programme to the switch from mitotic cycling to starvation, a differential transcript analysis comparing mRNA from exponentially growing and ammonium-starved cells was performed. Genes repressed by this stimulus mainly concern cell growth, i.e. protein synthesis and global metabolism. Comparison of the expression of two of them, the ribosomal proteins Rps6 and TCTP, in many different growing conditions, evidenced a strong correlation, suggesting that their transcriptions are coordinately regulated. Nevertheless, by repeating the ammonium starvation on strains constitutively activated for the PKA pathway (Deltacgs1), or unable to activate the Wis1-dependent MAP kinase pathway (Deltawis1), or with both characteristics (Deltacgs1+Deltawis1), the transcriptional inhibition was found to be governed either by the PKA pathway, or by the Wis1 pathway, or by both. These results suggest that during the switch from exponential growth to ammonium starvation, cell homeostasis is maintained by downregulating the transcription of the most expressed genes by a PKA and a Wis1-dependent process. Accession Nos for the S30 and L14 ribosomal protein cDNA sequences are AJ2731 and AJ2732, respectively.
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PMID:Identification and transcription control of fission yeast genes repressed by an ammonium starvation growth arrest. 1062 Jul 72

Pseudohyphal differentiation in the budding yeast Saccharomyces cerevisiae is induced in diploid cells in response to nitrogen starvation and abundant fermentable carbon source. Filamentous growth requires at least two signaling pathways: the pheromone responsive MAP kinase cascade and the Gpa2p-cAMP-PKA signaling pathway. Recent studies have established a physical and functional link between the Galpha protein Gpa2 and the G protein-coupled receptor homolog Gpr1. We report here that the Gpr1 receptor is required for filamentous and haploid invasive growth and regulates expression of the cell surface flocculin Flo11. Epistasis analysis supports a model in which the Gpr1 receptor regulates pseudohyphal growth via the Gpa2p-cAMP-PKA pathway and independently of both the MAP kinase cascade and the PKA related kinase Sch9. Genetic and physiological studies indicate that the Gpr1 receptor is activated by glucose and other structurally related sugars. Because expression of the GPR1 gene is known to be induced by nitrogen starvation, the Gpr1 receptor may serve as a dual sensor of abundant carbon source (sugar ligand) and nitrogen starvation. In summary, our studies reveal a novel G protein-coupled receptor senses nutrients and regulates the dimorphic transition to filamentous growth via a Galpha protein-cAMP-PKA signal transduction cascade.
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PMID:The G protein-coupled receptor gpr1 is a nutrient sensor that regulates pseudohyphal differentiation in Saccharomyces cerevisiae. 1065 15

The influence of the cAMP-signalling pathway on the metabolism of trehalose in Neurospora crassa was investigated. The changes in intracellular trehalose concentration were measured in two mutants affected in components of the cAMP-signalling pathway: cr-1 (crisp-1), deficient in adenylyl cyclase activity, and mcb (microcyclic conidiation), deficient in the regulatory subunit of PKA. Rapid mobilisation of intracellular trehalose in the wild-type occurred, either at the onset of germination, or after a heat shock, and by carbon starvation. Mutant cr-1 failed to mobilise trehalose at germination, but behaved almost normally after a heat shock, or during carbon starvation. On the other hand, the levels of trehalose in mcb fell to values much lower than in the wild-type at germination, but accumulated trehalose normally during a heat shock. These results are consistent with the involvement of cAMP in the activation of the neutral trehalase at the onset of germination. However, the control of the enzyme under the other physiological conditions which also promote mobilisation of intracellular trehalose was apparently independent of cAMP-signalling.
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PMID:Mobilisation of trehalose in mutants of the cyclic AMP signalling pathway, cr-1 (CRISP-1) and mcb (microcycle conidiation), of Neurospora crassa. 1135 72

Haploid Saccharomyces cerevisiae cells growing on media lacking glucose but containing high concentrations of carbon sources such as fructose, galactose, raffinose, and ethanol exhibit enhanced agar invasion. These carbon sources also promote diploid filamentous growth in response to nitrogen starvation. The enhanced invasive and filamentous growth phenotypes are suppressed by the addition of glucose to the media and require the Snf1 kinase. Mutations in the PGI1 and GND1 genes encoding carbon source utilization enzymes confer enhanced invasive growth that is unaffected by glucose but requires active Snf1. Carbon source does not modulate FLO11 flocculin expression, but enhanced polarized bud site selection is necessary for invasion on certain carbon sources. Interestingly, deletion of SNF1 blocks invasion without affecting bud site selection. Snf1 is also required for formation of spokes and hubs in multicellular mats. To examine glucose repression of invasive growth more broadly, we performed genome-wide microarray expression analysis in wild-type cells growing on glucose and galactose, and snf1 Delta cells on galactose. SNF1 probably mediates glucose repression of multiple genes potentially involved in invasive and filamentous growth. FLO11-independent cell-cell attachment, cell wall integrity, and/or polarized growth are affected by carbon source metabolism. In addition, derepression of cell cycle genes and signalling via the cAMP-PKA pathway appears to depend upon SNF1 activity during growth on galactose.
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PMID:Depression of Saccharomyces cerevisiae invasive growth on non-glucose carbon sources requires the Snf1 kinase. 1212 56

The pathogenic fungus Candida albicans has a dimorphic transition in various environmental conditions. Many regulatory factors and several transduction pathways have been identified in controlling filamentous growth. G(1) cyclins Cln1 and Cln2 have been reported as involved in the control of morphogenesis in Saccharomyces cerevisiae. Diploid cln1/cln1 and cln2/cln2 strains completely lost the ability to form pseudohyphae. A C. albicans genomic DNA library was introduced into cln1/cln1 and cln2/cln2 mutants to screen genes which could complement its filamentous growth defect. In this screening a BEM1 homolog, CaBEM1, was identified. The CaBEM1 gene has an ORF of 1 899 bp, encoding a putative protein of 632 amino acids. The CaBem1 protein shares highest homology in amino acids with Bem1 (38%) of S. cerevisiae and Scd2 (32%) of Schizosaccharomyces pombe. Sequence analysis showed that the CaBem1 contains two N-terminal SH3 domains, a PX domain and a C-terminal PB1 domain. It is believed these domains are required for binding to proteins involved in polarized growth in S. cerevisiae and S. pombe. Ectopic expression of the CaBEM1 gene in diploid S. cerevisiae suppressed defects in filamentous growth of some mutants under nitrogen starvation conditions. This suppression bypassed MAPK pathway and cAMP/PKA pathway in filamentous growth. These results suggest that the CaBem1 protein may be a downstream component of these two signal transduction pathways of filament formation.
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PMID:[Cloning of Candida albicans CaBEM1 and its role in filamentous growth of Saccharomyces cerevisiae]. 1219 55

Mesangial cell proliferation is an early event in several progressive renal diseases. When mesangial cells in culture are rendered quiescent by serum starvation and subsequently stimulated to proliferate, induction of c-fos is an early indicator of entry into the cell cycle. Several heparin-sensitive signals transduce these events. We have examined the potential roles of CaMK and PKA. Selective stimulation of CaMK with Ca(2+) ionophores and of PKA with forskolin or dibutyryl cAMP both result in induction of c-fos mRNA. CaMK but not PKA signaling is suppressed by low concentrations of heparin. Cross talk between the pathways has been demonstrated in some cells, with evidence of CaMK phosphorylating cAMP response element binding protein (CREB) at an inhibitory site and PKA suppressing CaMK-dependent signaling. However, in the present study, both pathways phosphorylated CREB on Ser(133) and induced c-fos in an additive manner. Serum, ionomycin, and forskolin all caused a rapid decline in cyclin D1 levels, but only serum effected a subsequent increase, indicative of cell cycle progression. We conclude that, in human mesangial cells, CaMK and PKA can both contribute to cell cycle entry, and, although induction of c-fos by CaMK requires active PKA, neither pathway antagonizes or synergizes c-fos induction by the other.
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PMID:Ca(2+)/calmodulin-dependent and cAMP-dependent kinases in induction of c-fos in human mesangial cells. 1237 63

Successful adaptation to starvation in mammals depends heavily on the regulated mobilization of fatty acids from triacylglycerols stored in adipose tissue. Although it has long been recognized that cyclic AMP represents the critical second messenger and hormone-sensitive lipase (HSL)**Abbreviations used in this paper: ADRP, adipocyte differentiation-related protein; HSL, hormone-sensitive lipase; PKA, protein kinase A; TAG, triacylglycerol. the rate-determining enzyme for lipolysis, simple activation of the enzyme has failed to account for the robust augmentation of fatty release in response to physiological agonists. In this issue, Sztalryd et al. (2003) provide convincing support to the notion that the subcellular compartmentalization of lipase also regulates lipolysis, and, more importantly, that proteins other than HSL are localized to the lipid droplet and are indispensable for its optimal hydrolysis.
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PMID:Lipolysis: more than just a lipase. 1281 Jun 97


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