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  • The EMBO Journal (2005) 24, 2194 - 2204
  • doi:10.1038/sj.emboj.7600683

Published online: 26 May 2005

Concerted mechanism of Swe1/Wee1 regulation by multiple kinases in budding yeast

Satoshi Asano1,a, Jung-Eun Park1,a, Krisada Sakchaisri1,2, Li-Rong Yu3, Sukgil Song4, Porntip Supavilai2, Timothy D Veenstra3 and Kyung S Lee1

  1. Laboratory of Metabolism, Center for Cancer Research, National Cancer Institute, NIH, Bethesda, MD, USA
  2. Department of Pharmacology, Faculty of Science, Mahidol University, Bangkok, Thailand
  3. Laboratory of Proteomics and Analytical Technologies, NCI-Frederick, Frederick, MD, USA
  4. College of Pharmacy, Chungbuk National University, South Korea

Correspondence to:

Kyung S Lee, Laboratory of Metabolism, National Cancer Institute, NIH, 9000 Rockville Pike, Bldg 37, Room 3118, Bethesda, MD 20892, USA. Tel.: +1 301 496 9635; Fax: +1 301 496 8419; E-mail: kyunglee@mail.nih.gov

aThese authors contributed equally to this work

Received 11 November 2004; Accepted 21 April 2005

In eukaryotes, entry into mitosis is induced by cyclin B-bound Cdk1, which is held in check by the protein kinase, Wee1. In budding yeast, Swe1 (Wee1 ortholog) is targeted to the bud neck through Hsl1 (Nim1-related kinase) and its adaptor Hsl7, and is hyperphosphorylated prior to ubiquitin-mediated degradation. Here, we show that Hsl1 and Hsl7 are required for proper localization of Cdc5 (Polo-like kinase homolog) to the bud neck and Cdc5-dependent Swe1 phosphorylation. Mitotic cyclin (Clb2)-bound Cdc28 (Cdk1 homolog) directly phosphorylated Swe1 and this modification served as a priming step to promote subsequent Cdc5-dependent Swe1 hyperphosphorylation and degradation. Clb2-Cdc28 also facilitated Cdc5 localization to the bud neck through the enhanced interaction between the Clb2-Cdc28-phosphorylated Swe1 and the polo-box domain of Cdc5. We propose that the concerted action of Cdc28/Cdk1 and Cdc5/Polo on their common substrates is an evolutionarily conserved mechanism that is crucial for effectively triggering mitotic entry and other critical mitotic events.

  • Keywords:

    • budding yeast,
    • Cdc5,
    • Cdc28,
    • G2/M transition,
    • Swe1