Concerted mechanism of Swe1/Wee1 regulation by multiple kinases in budding yeast.
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.
Asano
Satoshi
S
Laboratory of Metabolism, Center for Cancer Research, National Cancer Institute, NIH, Bethesda, MD 20892, USA.
Park
Jung-Eun
JE
Sakchaisri
Krisada
K
Yu
Li-Rong
LR
Song
Sukgil
S
Supavilai
Porntip
P
Veenstra
Timothy D
TD
Lee
Kyung S
KS
D017489:CDC28 Protein Kinase, S cerevisiae / Q000378:metabolism; D018797:Cell Cycle Proteins / Q000378:metabolism*; D008938:Mitosis / Q000502:physiology; D010766:Phosphorylation; D010770:Phosphotransferases / Q000378:metabolism*; D011494:Protein Kinases / Q000378:metabolism; D017346:Protein Serine-Threonine Kinases; D017027:Protein Tyrosine Phosphatases / Q000502:physiology; D011484:Protein-Arginine N-Methyltransferases; D011505:Protein-Tyrosine Kinases / Q000378:metabolism*; D016601:RNA-Binding Proteins; D029701:Saccharomyces cerevisiae Proteins / Q000378:metabolism* / Q000502:physiology; D004718:Saccharomycetales / Q000201:enzymology / Q000502:physiology*; D020666:ras-GRF1
C542351:CDC25 protein, S cerevisiae; C513239:CEF1 protein, S cerevisiae; D018797:Cell Cycle Proteins; D016601:RNA-Binding Proteins; D029701:Saccharomyces cerevisiae Proteins; D020666:ras-GRF1; D011484:Protein-Arginine N-Methyltransferases; C120666:HSL7 protein, S cerevisiae; D010770:Phosphotransferases; D011494:Protein Kinases; C099685:SWE1 protein, S cerevisiae; D011505:Protein-Tyrosine Kinases; C106494:HSL1 protein, S cerevisiae; D017346:Protein Serine-Threonine Kinases; D017489:CDC28 Protein Kinase, S cerevisiae; D017027:Protein Tyrosine Phosphatases