title: Phosphorylation of sic1, a cyclin-dependent kinase (Cdk) inhibitor, by Cdk including Pho85 kinase is required for its prompt degradation.
abstract: In the yeast Saccharomyces cerevisiae, Sic1, an inhibitor of Clb-Cdc28 kinases, must be phosphorylated and degraded in G1 for cells to initiate DNA replication, and Cln-Cdc28 kinase appears to be primarily responsible for phosphorylation of Sic1. The Pho85 kinase is a yeast cyclin-dependent kinase (Cdk), which is not essential for cell growth unless both CLN1 and CLN2 are absent. We demonstrate that Pho85, when complexed with Pcl1, a G1 cyclin homologue, can phosphorylate Sic1 in vitro, and that Sic1 appears to be more stable in pho85Delta cells. Three consensus Cdk phosphorylation sites present in Sic1 are phosphorylated in vivo, and two of them are required for prompt degradation of the inhibitor. Pho85 and other G1 Cdks appear to phosphorylate Sic1 at different sites in vivo. Thus at least two distinct Cdks can participate in phosphorylation of Sic1 and may therefore regulate progression through G1.
authors.affiliation: Department of Microbiology, Keio University School of Medicine, Tokyo 160-8582, Japan. mas@mc.med.keio.ac.jp
authors.forename: M
authors.initials: M
authors.lastname: Nishizawa
authors.forename: M
authors.initials: M
authors.lastname: Kawasumi
authors.forename: M
authors.initials: M
authors.lastname: Fujino
authors.forename: A
authors.initials: A
authors.lastname: Toh-e
mesh_terms: D017489:CDC28 Protein Kinase, S cerevisiae / Q000378:metabolism; D050756:Cyclin-Dependent Kinase Inhibitor Proteins; D018844:Cyclin-Dependent Kinases / Q000235:genetics / Q000378:metabolism*; D016213:Cyclins / Q000378:metabolism; D004791:Enzyme Inhibitors / Q000378:metabolism*; D005656:Fungal Proteins / Q000235:genetics / Q000378:metabolism*; D016296:Mutagenesis; D010766:Phosphorylation; D011993:Recombinant Fusion Proteins / Q000235:genetics / Q000378:metabolism; D029701:Saccharomyces cerevisiae Proteins; D014157:Transcription Factors / Q000378:metabolism
chemical_list: D050756:Cyclin-Dependent Kinase Inhibitor Proteins; D016213:Cyclins; D004791:Enzyme Inhibitors; D005656:Fungal Proteins; D011993:Recombinant Fusion Proteins; C086926:SIC1 protein, S cerevisiae; D029701:Saccharomyces cerevisiae Proteins; D014157:Transcription Factors; C070839:PCL1 protein, S cerevisiae; D017489:CDC28 Protein Kinase, S cerevisiae; D018844:Cyclin-Dependent Kinases; C058605:PHO85 protein, S cerevisiae