title: The Yeast GSK-3 Homologue Mck1 Is a Key Controller of Quiescence Entry and Chronological Lifespan.
abstract: Upon starvation for glucose or any other core nutrient, yeast cells exit from the mitotic cell cycle and acquire a set of G0-specific characteristics to ensure long-term survival. It is not well understood whether or how cell cycle progression is coordinated with the acquisition of different G0-related features during the transition to stationary phase (SP). Here, we identify the yeast GSK-3 homologue Mck1 as a key regulator of G0 entry and reveal that Mck1 acts in parallel to Rim15 to activate starvation-induced gene expression, the acquisition of stress resistance, the accumulation of storage carbohydrates, the ability of early SP cells to exit from quiescence, and their chronological lifespan. FACS and microscopy imaging analyses indicate that Mck1 promotes mother-daughter cell separation and together with Rim15, modulates cell size. This indicates that the two kinases coordinate the transition-phase cell cycle, cell size and the acquisition of different G0-specific features. Epistasis experiments place MCK1, like RIM15, downstream of RAS2 in antagonising cell growth and activating stress resistance and glycogen accumulation. Remarkably, in the ras2∆ cells, deletion of MCK1 and RIM15 together, compared to removal of either of them alone, compromises respiratory growth and enhances heat tolerance and glycogen accumulation. Our data indicate that the nutrient sensor Ras2 may prevent the acquisition of G0-specific features via at least two pathways. One involves the negative regulation of the effectors of G0 entry such as Mck1 and Rim15, while the other likely to involve its functions in promoting respiratory growth, a phenotype also contributed by Mck1 and Rim15.
authors.affiliation: Cambridge Systems Biology Centre and Department of Biochemistry, University of Cambridge, Cambridge, United Kingdom.
authors.forename: Zhenzhen
authors.initials: Z
authors.lastname: Quan
authors.affiliation: Cambridge Systems Biology Centre and Department of Biochemistry, University of Cambridge, Cambridge, United Kingdom.
authors.forename: Lu
authors.initials: L
authors.lastname: Cao
authors.affiliation: Cambridge Systems Biology Centre and Department of Biochemistry, University of Cambridge, Cambridge, United Kingdom.
authors.forename: Yingzhi
authors.initials: Y
authors.lastname: Tang
authors.affiliation: Graduate school of Chinese Academy of Agricultural Sciences, Zhongguancun, Beijing, PR China.
authors.forename: Yanchun
authors.initials: Y
authors.lastname: Yan
authors.affiliation: Cambridge Systems Biology Centre and Department of Biochemistry, University of Cambridge, Cambridge, United Kingdom.
authors.forename: Stephen G
authors.initials: SG
authors.lastname: Oliver
authors.affiliation: Cambridge Systems Biology Centre and Department of Biochemistry, University of Cambridge, Cambridge, United Kingdom.
authors.forename: Nianshu
authors.initials: N
authors.lastname: Zhang
mesh_terms: D002453:Cell Cycle; D038362:Glycogen Synthase Kinase 3 / Q000235:genetics / Q000378:metabolism*; D011494:Protein Kinases / Q000235:genetics / Q000378:metabolism; D012441:Saccharomyces cerevisiae / Q000166:cytology / Q000235:genetics*; D029701:Saccharomyces cerevisiae Proteins / Q000235:genetics / Q000378:metabolism*; D013312:Stress, Physiological; D018631:ras Proteins / Q000235:genetics / Q000378:metabolism
chemical_list: D029701:Saccharomyces cerevisiae Proteins; D011494:Protein Kinases; C410736:Rim15 protein, S cerevisiae; D038362:Glycogen Synthase Kinase 3; C068124:MCK1 protein, S cerevisiae; C489015:RAS2 protein, S cerevisiae; D018631:ras Proteins