Entry into mitosis in eukaryotic organisms is regulated by an intricate network of kinases and phosphatases that coordinately bring about reorganization of various subcellular structures. A key regulatory component for this event is the conserved cyclin B-bound Cdc2. In fission yeast and higher eukaryotes, Cdc2 is phosphorylated at Tyr15 and negatively regulated by Wee1, an event that is reversed by the activity of Cdc25C phosphatase. These critical steps at mitotic entry appear to be largely conserved throughout evolution. Studies on the G2/M regulation in genetically-amenable organisms such as budding yeast have provided valuable insights into how eukaryotic organisms bring about timely activation of cyclin B-Cdc2 activity prior to mitotic entry. In budding yeast, Swe1 (Wee1 ortholog) negatively regulates mitotic Clb (collectively for the B-type cyclins - Clb1, Clb2, Clb3, and Clb4) associated-Cdc28 (Cdc2 homolog) by phosphorylating the equivalent Tyr19 residue, a modification that is reversed by Mih1 (Cdc25 ortholog). We previously showed that Cla4 (PAK homolog) and Cdc5 (Polo homolog) phosphorylate Swe1 in a step-wise manner. Our recent study found that Hsl1 (Nim1 ortholog) and Hsl7, which are critical for Swe1 localization to the bud-neck, are also required for proper localization of Cdc5 to the bud-neck and the Cdc5-dependent Swe1 phosphorylation. Mitotic Clb-bound Cdc28, but not G1 or S cyclin-bound Cdc28, directly phosphorylated Swe1 and this phosphorylation step appears to be important to prime Swe1 for the subsequent Cdc5-dependent Swe1 phosphorylation. We would like to further investigate the mechanism of how Hsl1 and Hsl7 cooperate with multi-kinases (Cla4, Cdc28, and Cdc5) to facilitate Swe1 hyperphosphorylation and subsequent degradation prior to mitotic entry. Our current model is that Swe1 functions as a nodal point to integrate multi-kinase-dependent signals that license passage into mitosis.
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| Asano, Satoshi; Park, Jung-Eun; Sakchaisri, Krisada et al. (2005) Concerted mechanism of Swe1/Wee1 regulation by multiple kinases in budding yeast. EMBO J 24:2194-204 |
| Sakchaisri, Krisada; Asano, Satoshi; Yu, Li-Rong et al. (2004) Coupling morphogenesis to mitotic entry. Proc Natl Acad Sci U S A 101:4124-9 |
| Park, Chong Jin; Song, Sukgil; Lee, Philip R et al. (2003) Loss of CDC5 function in Saccharomyces cerevisiae leads to defects in Swe1p regulation and Bfa1p/Bub2p-independent cytokinesis. Genetics 163:21-33 |
