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

Laboratory of Metabolism, Center for Cancer Research, National Cancer Institute, NIH, Bethesda, MD 20892, USA.
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.
Mesh Terms:
CDC28 Protein Kinase, S cerevisiae, Cell Cycle Proteins, Mitosis, Phosphorylation, Phosphotransferases, Protein Kinases, Protein Tyrosine Phosphatases, Protein-Arginine N-Methyltransferases, Protein-Serine-Threonine Kinases, Protein-Tyrosine Kinases, RNA-Binding Proteins, Saccharomyces cerevisiae Proteins, Saccharomycetales
EMBO J. Jun. 15, 2005; 24(12);2194-204 [PUBMED:15920482]
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