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

EMBO J. 2005 Jun 15;24(12):2194-204. doi: 10.1038/sj.emboj.7600683. Epub 2005 May 26.

Abstract

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.

Publication types

  • Research Support, N.I.H., Intramural
  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • CDC28 Protein Kinase, S cerevisiae / metabolism
  • Cell Cycle Proteins / metabolism*
  • Mitosis / physiology
  • Phosphorylation
  • Phosphotransferases / metabolism*
  • Protein Kinases / metabolism
  • Protein Serine-Threonine Kinases
  • Protein Tyrosine Phosphatases / physiology
  • Protein-Arginine N-Methyltransferases
  • Protein-Tyrosine Kinases / metabolism*
  • RNA-Binding Proteins
  • Saccharomyces cerevisiae Proteins / metabolism*
  • Saccharomyces cerevisiae Proteins / physiology
  • Saccharomycetales / enzymology
  • Saccharomycetales / physiology*
  • ras-GRF1

Substances

  • CDC25 protein, S cerevisiae
  • CEF1 protein, S cerevisiae
  • Cell Cycle Proteins
  • RNA-Binding Proteins
  • Saccharomyces cerevisiae Proteins
  • ras-GRF1
  • Protein-Arginine N-Methyltransferases
  • HSL7 protein, S cerevisiae
  • Phosphotransferases
  • Protein Kinases
  • SWE1 protein, S cerevisiae
  • Protein-Tyrosine Kinases
  • HSL1 protein, S cerevisiae
  • Protein Serine-Threonine Kinases
  • CDC28 Protein Kinase, S cerevisiae
  • Protein Tyrosine Phosphatases