Molecular analysis of cell cycle regulation by Ca^<2+>

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We investigated molecular mechanism of G2/M cell cycle regulation by Ca^<2+> signal in Saccharomyces cerevisiae. We isolated mutants with a defect in the Ca^<2+> signaling pathway linked to cell cycle regulation. The mutants were classified to 14 complementation groups.(1) csz7 mutant was analyzed in detail. The scz7 mutation was identified as an allele of MCK1 that encodes a GSK-3 family protein kinase highly conserved among eukaryotes. It was found that Mck1 was involved in the Ca^<2+>-induced destabilization of Hsl1, Negative regulator of Swe1 through the ubiquitin-proteasome pathway. We further revealed the detailed mechanism by which Hsl1 abundance is regulated.(2) scz6 mutant was analyzed in detail. The scz6 mutation was identified as an allele of PKC1 that encodes a unique protein kinase C in the yeast. Interestingly, the scz6 mutation suppressed Ca^<2+> sensitive growth and Ca^<2+>-induced polarized bud growth, but not G2 cell cycle delay. We found a novel pathway of Pkc1, in which Pkc1 plays an important role in the regulation of the transcription of SWE1 And the G1 cyclin CLN1, in addition to the previously characterized pathway that activates the Mpk1 MAP kinase pathway. The transcription factor Swi4 was implicated in the transcriptional regulation of CLN1 and SWE1.scz5 mutant was analyzed in detail. The scz5 mutation was identified as an allele of PDR5 that encodes an ABC transporter implicated in multidrug resistance in the yeast. Pdr5 was suggested to be responsible for Ca^<2+> uptake.