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Nutrient limitations alter cell division control and chromosome segregation through growth-related kinases and phosphatases

The G0 Cell Unit, Okinawa Institute of Science and Technology Promotion Corporation, Tancha 1919-1, Onna, Okinawa 904-0412, Japan.
Philosophical Transactions of The Royal Society B Biological Sciences (Impact Factor: 6.31). 12/2011; 366(1584):3508-20. DOI: 10.1098/rstb.2011.0124
Source: PubMed

ABSTRACT In dividing fission yeast Schizosaccharomyces pombe cells, the balance between Wee1 kinase and Cdc25 phosphatase which control the cyclin-dependent kinase (CDK) at the G2-M transition determines the rod-shaped cell length. Under nitrogen source starvation or glucose limitation, however, cell size determination is considerably modulated, and cell size shortening occurs for wild-type cells. For several mutants of kinases or phosphatases, including CDK, target of rapamycin complex (TORC) 1 and 2, stress-responsive mitogen-activated protein kinase (MAPK) Sty1/Spc1, MAPK kinase Wis1, calcium- and calmodulin-dependent protein kinase kinase-like Ssp1, and type 2A and 2A-related phosphatases inhibitor Sds23, this cell shortening does not normally occur. In tor1 and ssp1 mutants, cell elongation is observed. Sds23 that binds to and inhibits 2A and 2A-related phosphatases is synergistic with Ssp1 in the cell size determination and survival under low glucose and nitrogen source. Tor2 (TORC1) is required for growth, whereas Tor1 (TORC2) is needed for determining division size according to different nutrient conditions. Surprisingly, in growth-diminished tor2 mutant or rapamycin-treated cells, the requirement of separase/Cut1-securin/Cut2 essential for chromosome segregation is greatly alleviated. By contrast, defects of tor1 with secruin/cut2 or overproduction of Cut1 are additive. While Tor1 and Tor2 are opposite in their apparent functions, both may actually coordinate cell division with growth in response to the changes in nutrients.

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    • "). Nitrogen starvation (or NS) induces sexual development in homothallic strains or heterothallic strains when mating partners are available (Yanagida et al. 2011). On the other hand, NS induces entry into a dormant state or at G0-phase in heterothallic strains when mating partners are not available (Yanagida et al. 2011). To investigate whether the sexual development-defective kinase-deletion strains would also exhibit defect in NS-induced G0-arrest (hereafter G0-arrest), all kinase-deletion strains were subjected to assays for competence of G0-arrest. "
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    ABSTRACT: Nitrogen starvation (NS) induces sexual development when mating partners are available or enter into quiescent state (G0) in heterothallic background in fission yeast. However, little is known whether the two processes share common signaling molecules or cells defective in the two processes share common transcriptional signatures. To address these questions, we first assessed 77 kinase-deletion strains for NS-induced G0-arrest phenotypes. Our result indicated that 10 out of 77 kinase-deletion strains exhibited defect in G0-arrest, only 3 of which were defective in sexual development based on a previous study, suggesting that the two processes hardly share common signaling components. We subsequently performed transcriptional profiling analysis. Our result indicated that NS-induced transcriptional change was so robust that it prevailed the alteration by individual kinase-deletion alleles. Based on comparison between kinase-deletion strains proficient and deficient in sexual development or G0-arrest, we identified subsets of genes that were associated with sexual development-deficient or G0-arrest-deficient kinase-deletion strains. Multiple pairing analyses allowed grouping of functional related kinases. Furthermore, we showed that Pka1-mediated pathways were required for upregulation of NS-induced genes upon NS and downregulation of the same set of genes under the N-replete conditions. Taken together, our analyses indicate that sexual development and NS-induced G0-arrest are unrelated; and sexual development-deficient and G0-arrest-deficient kinase-deletion strains possess distinct transcriptional signatures. We propose that Pka1 is a key regulator of nitrogen metabolic pathways and Pka1-mediated signaling pathways play roles in regulation of NS-induced genes under both N-depleted and N-replete conditions.
    Molecular Genetics and Genomics 12/2014; 290(3). DOI:10.1007/s00438-014-0966-6 · 2.83 Impact Factor
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    • "For several mutants of kinases including Tor1, Sty1, Wis1, Cdc2, Cdc13 and Ssp1, this cell shortening does not normally occur (Kawai et al., 2001; Petersen and Nurse, 2007; Yanagida et al., 2011). Thus, resulting long rod-shaped sty1 and wis1 mutant cells displayed an abnormally expanded nucleus, whereas other mutants (cdc2, cdc13 and ssp1) also revealed rod-shaped cells, but maintained a normal-sized nucleus (Yanagida et al., 2011). On the other hand, previous studies revealed that eIF2a phosphorylation can promote changes in gene expression through preferential translation of stress response genes. "
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    Journal of Cell Science 05/2013; 126(14). DOI:10.1242/jcs.118067 · 5.33 Impact Factor
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    Open Biology 11/2011; 1(3):110007. DOI:10.1098/rsob.110007 · 4.56 Impact Factor
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