Mizunuma M, Hirata D, Miyaoka R, Miyakawa T

Department of Molecular Biotechnology, Graduate School of Advanced Sciences of Matter, Hiroshima University, Higashi-Hiroshima 739-8526, Japan.

The Ca2+-activated pathways of Saccharomyces cerevisiae induce a delay in the onset of mitosis through the activation of Swe1, a negative regulatory kinase that inhibits the Cdc28-Clb complex. Calcineurin and Mpk1 activate Swe1 at the transcriptional and post-translational level, respectively, and both pathways are essential for the cell cycle delay. Our genetic screening identified the MCK1 gene, which encodes a glycogen synthetase kinase-3 family protein kinase, as a component of the Ca2+ signaling pathway. Genetic analyses indicated that Mck1 functions downstream of the Mpk1 pathway and down-regulates Hsl1, an inhibitory kinase of Swe1. In medium with a high concentration of Ca2+, Hsl1 was delocalized from the bud neck and destabilized in a manner dependent on both calcineurin and Mck1. Calcineurin was required for the dephosphorylation of autophosphorylated Hsl1. The E3 ubiquitin ligase complex SCF(Cdc4), but not the anaphase-promoting complex (APC), was essential for Hsl1 destabilization. The Ca2+-activated pathway may play a role in the rapid inactivation of Hsl1 at the cell cycle stage(s) when APC activity is low.

Mesh Terms:
Calcineurin, Calcium, Calcium Signaling, Calcium-Calmodulin-Dependent Protein Kinases, Cell Cycle Proteins, Cell Division, Down-Regulation, Enzyme Activation, Epistasis, Genetic, F-Box Proteins, Flow Cytometry, Fungal Proteins, G2 Phase, Gene Expression Regulation, Enzymologic, Gene Expression Regulation, Fungal, Genes, Fungal, Glycogen Synthase Kinase 3, Ligases, Mitogen-Activated Protein Kinases, Models, Biological, Mutation, Peptide Synthases, Protein Kinases, Protein-Serine-Threonine Kinases, Protein-Tyrosine Kinases, RNA, Fungal, SKP Cullin F-Box Protein Ligases, Saccharomyces cerevisiae, Saccharomyces cerevisiae Proteins, Transcription, Genetic, Ubiquitin-Protein Ligase Complexes, Ubiquitin-Protein Ligases

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