Saccharomyces cerevisiae Ime2 phosphorylates Sic1 at multiple PXS/T sites but is insufficient to trigger Sic1 degradation

Author:

Sedgwick Chantelle1,Rawluk Matthew1,Decesare James1,Raithatha Sheetal1,Wohlschlegel James2,Semchuk Paul3,Ellison Michael3,Yates John2,Stuart David1

Affiliation:

1. Department of Biochemistry, 561 Medical Sciences Building, University of Alberta, Edmonton, AB, T6G 2H7, Canada

2. The Scripps Research Institute, 10550 North Torrey Pines Road, La Jolla, CA, 92037 U.S.A.

3. Institute for Biomolecular Design, 367 Medical Sciences Building, University of Alberta, Edmonton AB, T6G 2H7, Canada

Abstract

The initiation of DNA replication in Saccharomyces cerevisiae depends upon the destruction of the Clb–Cdc28 inhibitor Sic1. In proliferating cells Cln–Cdc28 complexes phosphorylate Sic1, which stimulates binding of Sic1 to SCFCdc4 and triggers its proteosome mediated destruction. During sporulation cyclins are not expressed, yet Sic1 is still destroyed at the G1-/S-phase boundary. The Cdk (cyclin dependent kinase) sites are also required for Sic1 destruction during sporulation. Sic1 that is devoid of Cdk phosphorylation sites displays increased stability and decreased phosphorylation in vivo. In addition, we found that Sic1 was modified by ubiquitin in sporulating cells and that SCFCdc4 was required for this modification. The meiosis-specific kinase Ime2 has been proposed to promote Sic1 destruction by phosphorylating Sic1 in sporulating cells. We found that Ime2 phosphorylates Sic1 at multiple sites in vitro. However, only a subset of these sites corresponds to Cdk sites. The identification of multiple sites phosphorylated by Ime2 has allowed us to propose a motif for phosphorylation by Ime2 (PXS/T) where serine or threonine acts as a phospho-acceptor. Although Ime2 phosphorylates Sic1 at multiple sites in vitro, the modified Sic1 fails to bind to SCFCdc4. In addition, the expression of Ime2 in G1 arrested haploid cells does not promote the destruction of Sic1. These data support a model where Ime2 is necessary but not sufficient to promote Sic1 destruction during sporulation.

Publisher

Portland Press Ltd.

Subject

Cell Biology,Molecular Biology,Biochemistry

Reference43 articles.

1. The role of p34 kinases in the G1 to S-phase transition;Reed;Annu. Rev. Cell Biol.,1992

2. Control of the yeast cell cycle by the Cdc28 protein kinase;Nasmyth;Curr. Opin. Cell Biol.,1993

3. CDK Inhibitors: positive and negative regulators of G1 progression;Sherr;Genes Dev.,1999

4. Molecular and Cellular Biology of the Yeast Saccharomyces cerevisiae;Lew,1997

5. The B-type cyclin kinase inhibitor p40SIC1 controls the G1/S transition in Saccharomyces cerevisiae;Schwob;Cell,1994

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