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PMID: 9725902 Published · ppublish English Journal Article Research Support, Non-U.S. Gov't

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

Molecular biology of the cell ·Vol. 9 ·No. 9 ·1998-09-00 ·Pages 2393-405

Nishizawa M, Kawasumi M, Fujino M, Toh-e A

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.

MeSH Terms
CDC28 Protein Kinase, S cerevisiae/metabolism Cyclin-Dependent Kinase Inhibitor Proteins Cyclin-Dependent Kinases/genetics,metabolism Cyclins/metabolism Enzyme Inhibitors/metabolism Fungal Proteins/genetics,metabolism Mutagenesis Phosphorylation Recombinant Fusion Proteins/genetics,metabolism Saccharomyces cerevisiae Proteins Transcription Factors/metabolism
Chemicals
Cyclin-Dependent Kinase Inhibitor Proteins Cyclins Enzyme Inhibitors Fungal Proteins Recombinant Fusion Proteins SIC1 protein, S cerevisiae Saccharomyces cerevisiae Proteins Transcription Factors PCL1 protein, S cerevisiae CDC28 Protein Kinase, S cerevisiae Cyclin-Dependent Kinases PHO85 protein, S cerevisiae
Authors & Affiliations
4 authors, click to expand affiliations / ORCID
Nishizawa M
Department of Microbiology, Keio University School of Medicine, Tokyo 160-8582, Japan. mas@mc.med.keio.ac.jp
Kawasumi M
Fujino M
Toh-e A
References (46)
46 references, click to expand
  1. The kin28 protein kinase is associated with a cyclin in Saccharomyces cerevisiae.
    J Mol Biol. 1993 Nov 20;234(2):307-10 PMID: 8230216
  2. CLB5 and CLB6, a new pair of B cyclins involved in DNA replication in Saccharomyces cerevisiae.
    Genes Dev. 1993 Jul;7(7A):1160-75 PMID: 8319908
  3. The B-type cyclin kinase inhibitor p40SIC1 controls the G1 to S transition in S. cerevisiae.
    Cell. 1994 Oct 21;79(2):233-44 PMID: 7954792
  4. Cell cycle control by a complex of the cyclin HCS26 (PCL1) and the kinase PHO85.
    Science. 1994 Nov 25;266(5189):1388-91 PMID: 7973730
  5. The PCL2 (ORFD)-PHO85 cyclin-dependent kinase complex: a cell cycle regulator in yeast.
    Science. 1994 Nov 25;266(5189):1391-5 PMID: 7973731
  6. Positive and negative transcriptional regulation by the yeast GAL11 protein depends on the structure of the promoter and a combination of cis elements.
    Mol Gen Genet. 1994 Nov 1;245(3):301-12 PMID: 7816040
  7. Functional domains of Pho81p, an inhibitor of Pho85p protein kinase, in the transduction pathway of Pi signals in Saccharomyces cerevisiae.
    Mol Cell Biol. 1995 Feb;15(2):997-1004 PMID: 7823964
  8. G1 cyclin-dependent activation of p34CDC28 (Cdc28p) in vitro.
    Proc Natl Acad Sci U S A. 1995 Feb 14;92(4):1182-6 PMID: 7862657
  9. Principles of CDK regulation.
    Nature. 1995 Mar 9;374(6518):131-4 PMID: 7877684
  10. A kinase-cyclin pair in the RNA polymerase II holoenzyme.
    Nature. 1995 Mar 9;374(6518):193-6 PMID: 7877695
  11. KIN28 encodes a C-terminal domain kinase that controls mRNA transcription in Saccharomyces cerevisiae but lacks cyclin-dependent kinase-activating kinase (CAK) activity.
    Mol Cell Biol. 1995 Jun;15(6):2983-92 PMID: 7760796
  12. The KIN28 gene is required both for RNA polymerase II mediated transcription and phosphorylation of the Rpb1p CTD.
    J Mol Biol. 1995 Jun 9;249(3):535-44 PMID: 7783209
  13. Roles and regulation of Cln-Cdc28 kinases at the start of the cell cycle of Saccharomyces cerevisiae.
    EMBO J. 1995 Oct 2;14(19):4803-13 PMID: 7588610
  14. Cyclin-dependent protein kinases: key regulators of the eukaryotic cell cycle.
    Bioessays. 1995 Jun;17(6):471-80 PMID: 7575488
  15. CLN3, not positive feedback, determines the timing of CLN2 transcription in cycling cells.
    Genes Dev. 1995 Nov 15;9(22):2780-94 PMID: 7590253
  16. Regulation of PHO4 nuclear localization by the PHO80-PHO85 cyclin-CDK complex.
    Science. 1996 Jan 12;271(5246):209-12 PMID: 8539622
  17. Linkage of replication to start by the Cdk inhibitor Sic1.
    Science. 1996 Apr 26;272(5261):560-2 PMID: 8614808
  18. Pho85p, a cyclin-dependent protein kinase, and the Snf1p protein kinase act antagonistically to control glycogen accumulation in Saccharomyces cerevisiae.
    Mol Cell Biol. 1996 Aug;16(8):4357-65 PMID: 8754836
  19. Cdc53 targets phosphorylated G1 cyclins for degradation by the ubiquitin proteolytic pathway.
    Cell. 1996 Aug 9;86(3):453-63 PMID: 8756727
  20. The cyclin-dependent kinase inhibitor p40SIC1 imposes the requirement for Cln G1 cyclin function at Start.
    Proc Natl Acad Sci U S A. 1996 Jul 23;93(15):7772-6 PMID: 8755551
  21. A family of cyclin-like proteins that interact with the Pho85 cyclin-dependent kinase.
    Mol Cell Biol. 1997 Mar;17(3):1212-23 PMID: 9032248
  22. SIC1 is ubiquitinated in vitro by a pathway that requires CDC4, CDC34, and cyclin/CDK activities.
    Mol Biol Cell. 1997 Aug;8(8):1427-37 PMID: 9285816
  23. Phosphorylation of Sic1p by G1 Cdk required for its degradation and entry into S phase.
    Science. 1997 Oct 17;278(5337):455-60 PMID: 9334303
  24. F-box proteins are receptors that recruit phosphorylated substrates to the SCF ubiquitin-ligase complex.
    Cell. 1997 Oct 17;91(2):209-19 PMID: 9346238
  25. A complex of Cdc4p, Skp1p, and Cdc53p/cullin catalyzes ubiquitination of the phosphorylated CDK inhibitor Sic1p.
    Cell. 1997 Oct 17;91(2):221-30 PMID: 9346239
  26. Swi5 controls a novel wave of cyclin synthesis in late mitosis.
    Mol Biol Cell. 1998 Apr;9(4):945-56 PMID: 9529390
  27. A quantitative cytochemical investigation of the relationship between cell mass and initiation of DNA synthesis in mouse fibroblasts in vitro.
    Exp Cell Res. 1965 Oct;40(1):12-20 PMID: 5838935
  28. Isolation and characterization of acid phosphatase mutants in Saccharomyces cerevisiae.
    J Bacteriol. 1973 Feb;113(2):727-38 PMID: 4570606
  29. Genetic control of the cell division cycle in yeast.
    Science. 1974 Jan 11;183(4120):46-51 PMID: 4587263
  30. Sequential gene function in the initiation of Saccharomyces cerevisiae DNA synthesis.
    J Mol Biol. 1974 Apr 15;84(3):445-61 PMID: 4618856
  31. Sequences that regulate the divergent GAL1-GAL10 promoter in Saccharomyces cerevisiae.
    Mol Cell Biol. 1984 Aug;4(8):1440-8 PMID: 6092912
  32. Negative regulators of the PHO system in Saccharomyces cerevisiae: isolation and structural characterization of PHO85.
    Nucleic Acids Res. 1987 Dec 23;15(24):10299-309 PMID: 3320965
  33. Control of the yeast cell cycle is associated with assembly/disassembly of the Cdc28 protein kinase complex.
    Cell. 1988 Sep 23;54(7):1061-72 PMID: 3046752
  34. An essential G1 function for cyclin-like proteins in yeast.
    Cell. 1989 Dec 22;59(6):1127-33 PMID: 2574633
  35. IRA2, a second gene of Saccharomyces cerevisiae that encodes a protein with a domain homologous to mammalian ras GTPase-activating protein.
    Mol Cell Biol. 1990 Aug;10(8):4303-13 PMID: 2164637
  36. Use of T7 RNA polymerase to direct expression of cloned genes.
    Methods Enzymol. 1990;185:60-89 PMID: 2199796
  37. The role of CDC28 and cyclins during mitosis in the budding yeast S. cerevisiae.
    Cell. 1991 Apr 5;65(1):145-61 PMID: 1849457
  38. Transcriptional activation of CLN1, CLN2, and a putative new G1 cyclin (HCS26) by SWI4, a positive regulator of G1-specific transcription.
    Cell. 1991 Sep 6;66(5):1015-26 PMID: 1832336
  39. The role of SWI4 and SWI6 in the activity of G1 cyclins in yeast.
    Cell. 1991 Sep 6;66(5):995-1013 PMID: 1832338
  40. Cloning, nucleotide sequence, and regulation of MET14, the gene encoding the APS kinase of Saccharomyces cerevisiae.
    Mol Gen Genet. 1991 Sep;229(1):96-108 PMID: 1654509
  41. CLB5: a novel B cyclin from budding yeast with a role in S phase.
    Genes Dev. 1992 Sep;6(9):1695-706 PMID: 1387626
  42. Cyclin-B homologs in Saccharomyces cerevisiae function in S phase and in G2.
    Genes Dev. 1992 Nov;6(11):2021-34 PMID: 1427070
  43. An inhibitor of p34CDC28 protein kinase activity from Saccharomyces cerevisiae.
    Science. 1993 Jan 8;259(5092):216-9 PMID: 8421781
  44. Comparison of the Saccharomyces cerevisiae G1 cyclins: Cln3 may be an upstream activator of Cln1, Cln2 and other cyclins.
    EMBO J. 1993 May;12(5):1955-68 PMID: 8387915
  45. Control of the yeast cell cycle by the Cdc28 protein kinase.
    Curr Opin Cell Biol. 1993 Apr;5(2):166-79 PMID: 8507488
  46. Phosphorylation of the transcription factor PHO4 by a cyclin-CDK complex, PHO80-PHO85.
    Science. 1994 Feb 25;263(5150):1153-6 PMID: 8108735
Article Info
Journal
Molecular biology of the cell
Abbr.
Mol Biol Cell
ISSN
1059-1524
DOI
10.1091/mbc.9.9.2393
Email
mas@mc.med.keio.ac.jp
Published
1998-09-00
Pages
2393-405
Language
English
Region
United States
NLM ID
9201390
PMCID
PMC25506
Subset
IM
External Links
PubMed source DOI: 10.1091/mbc.9.9.2393 PMC Full Text View journal details
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