title: Subcellular localization of the cyclin dependent kinase inhibitor Sic1 is modulated by the carbon source in budding yeast.
abstract: The cyclin dependent kinase inhibitor Sic1 and the cyclin Clb5 are essential regulators of the cyclin dependent kinase Cdc28 during the G1 to S transition in budding yeast. Yeast enters S phase after ubiquitin-mediated degradation of Sic1, an event triggered by Cln1, 2-Cdc28 mediated phosphorylation. We recently showed that Sic1 is involved in carbon source modulation of the critical cell size required to enter S phase. Here we show that the amount and sub-cellular localization of Sic1 are also carbon source-modulated. We identify a bipartite nuclear localization sequence responsible for nuclear localization of Sic1 and for correct cell cycle progression in a carbon-source dependent manner. Similarly to Cip/Kip proteins-Sic1 mammalian counterparts-Sic1 facilitates nuclear accumulation of its cognate cyclin, since cytoplasmic building-up of Clb5 is observed upon switching off expression of the SIC1 gene. Our data indicate a previously unrecognized inhibitor/activator dual role for Sic1 and put it among key molecules whose activity is regulated by their nuclear-cytoplasmic localization.
authors.affiliation: Department of Biotechnology and Biosciences, University of Milano-Bicocca, Milan, Italy.
authors.forename: Riccardo L
authors.initials: RL
authors.lastname: Rossi
authors.forename: Vittoria
authors.initials: V
authors.lastname: Zinzalla
authors.forename: Andrea
authors.initials: A
authors.lastname: Mastriani
authors.forename: Marco
authors.initials: M
authors.lastname: Vanoni
authors.forename: Lilia
authors.initials: L
authors.lastname: Alberghina
mesh_terms: D021581:Active Transport, Cell Nucleus; D017489:CDC28 Protein Kinase, S cerevisiae / Q000378:metabolism; D002244:Carbon / Q000378:metabolism*; D002453:Cell Cycle / Q000502:physiology; D002467:Cell Nucleus / Q000378:metabolism; D019926:Cyclin B / Q000378:metabolism; D050756:Cyclin-Dependent Kinase Inhibitor Proteins; D018844:Cyclin-Dependent Kinases / Q000037:antagonists & inhibitors*; D015966:Gene Expression Regulation, Fungal / Q000235:genetics; D008954:Models, Biological; D019913:Nuclear Localization Signals / Q000737:chemistry; D021381:Protein Transport; D011993:Recombinant Fusion Proteins / Q000378:metabolism; D029701:Saccharomyces cerevisiae Proteins / Q000737:chemistry / Q000378:metabolism*; D004718:Saccharomycetales / Q000166:cytology / Q000378:metabolism*; D013997:Time Factors
chemical_list: C076558:CLB5 protein, S cerevisiae; D019926:Cyclin B; D050756:Cyclin-Dependent Kinase Inhibitor Proteins; D019913:Nuclear Localization Signals; D011993:Recombinant Fusion Proteins; C086926:SIC1 protein, S cerevisiae; D029701:Saccharomyces cerevisiae Proteins; D002244:Carbon; D017489:CDC28 Protein Kinase, S cerevisiae; D018844:Cyclin-Dependent Kinases