Phosphorylation of sic1, a cyclin-dependent kinase (Cdk) inhibitor, by Cdk including Pho85 kinase is required for its prompt degradation. 1998

M Nishizawa, and M Kawasumi, and M Fujino, and A Toh-e
Department of Microbiology, Keio University School of Medicine, Tokyo 160-8582, Japan. mas@mc.med.keio.ac.jp

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.

UI MeSH Term Description Entries
D010766 Phosphorylation The introduction of a phosphoryl group into a compound through the formation of an ester bond between the compound and a phosphorus moiety. Phosphorylations
D011993 Recombinant Fusion Proteins Recombinant proteins produced by the GENETIC TRANSLATION of fused genes formed by the combination of NUCLEIC ACID REGULATORY SEQUENCES of one or more genes with the protein coding sequences of one or more genes. Fusion Proteins, Recombinant,Recombinant Chimeric Protein,Recombinant Fusion Protein,Recombinant Hybrid Protein,Chimeric Proteins, Recombinant,Hybrid Proteins, Recombinant,Recombinant Chimeric Proteins,Recombinant Hybrid Proteins,Chimeric Protein, Recombinant,Fusion Protein, Recombinant,Hybrid Protein, Recombinant,Protein, Recombinant Chimeric,Protein, Recombinant Fusion,Protein, Recombinant Hybrid,Proteins, Recombinant Chimeric,Proteins, Recombinant Fusion,Proteins, Recombinant Hybrid
D004791 Enzyme Inhibitors Compounds or agents that combine with an enzyme in such a manner as to prevent the normal substrate-enzyme combination and the catalytic reaction. Enzyme Inhibitor,Inhibitor, Enzyme,Inhibitors, Enzyme
D005656 Fungal Proteins Proteins found in any species of fungus. Fungal Gene Products,Fungal Gene Proteins,Fungal Peptides,Gene Products, Fungal,Yeast Proteins,Gene Proteins, Fungal,Peptides, Fungal,Proteins, Fungal
D014157 Transcription Factors Endogenous substances, usually proteins, which are effective in the initiation, stimulation, or termination of the genetic transcription process. Transcription Factor,Factor, Transcription,Factors, Transcription
D016213 Cyclins A large family of regulatory proteins that function as accessory subunits to a variety of CYCLIN-DEPENDENT KINASES. They generally function as ENZYME ACTIVATORS that drive the CELL CYCLE through transitions between phases. A subset of cyclins may also function as transcriptional regulators. Cyclin
D016296 Mutagenesis Process of generating a genetic MUTATION. It may occur spontaneously or be induced by MUTAGENS. Mutageneses
D017489 CDC28 Protein Kinase, S cerevisiae A protein kinase encoded by the Saccharomyces cerevisiae CDC28 gene and required for progression from the G1 PHASE to the S PHASE in the CELL CYCLE. CDC28 protein, S cerevisiae,p34cdc28 Kinase, S cerevisiae
D050756 Cyclin-Dependent Kinase Inhibitor Proteins A group of cell cycle proteins that negatively regulate the activity of CYCLIN/CYCLIN-DEPENDENT KINASE complexes. They inhibit CELL CYCLE progression and help control CELL PROLIFERATION following GENOTOXIC STRESS as well as during CELL DIFFERENTIATION. CIP-KIP Cyclin-Dependent Kinase Inhibitors,INK4 Cyclin-Dependent Kinase Inhibitors,CDKI Proteins,CIP-KIP CDKI Proteins,CIP-KIP CKI Proteins,CKI Proteins,Cyclin-Kinase Inhibitor Proteins,INK4 CDKI Proteins,INK4 CKI Proteins,Inhibitors of Cyclin-Dependent Kinase 4 Proteins,CDKI Proteins, CIP-KIP,CDKI Proteins, INK4,CIP KIP CDKI Proteins,CIP KIP CKI Proteins,CIP KIP Cyclin Dependent Kinase Inhibitors,CKI Proteins, CIP-KIP,CKI Proteins, INK4,Cyclin Dependent Kinase Inhibitor Proteins,Cyclin Kinase Inhibitor Proteins,INK4 Cyclin Dependent Kinase Inhibitors,Inhibitor Proteins, Cyclin-Kinase,Inhibitors of Cyclin Dependent Kinase 4 Proteins
D018844 Cyclin-Dependent Kinases Protein kinases that control cell cycle progression in all eukaryotes and require physical association with CYCLINS to achieve full enzymatic activity. Cyclin-dependent kinases are regulated by phosphorylation and dephosphorylation events. Cyclin-Dependent Kinase,Cyclin-Dependent Protein Kinase,cdk Proteins,Cyclin-Dependent Protein Kinases,Cyclin Dependent Kinase,Cyclin Dependent Kinases,Cyclin Dependent Protein Kinase,Cyclin Dependent Protein Kinases,Kinase, Cyclin-Dependent,Kinase, Cyclin-Dependent Protein,Protein Kinase, Cyclin-Dependent

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