Roles of Yap1p in the Ca2+-induced G2 cell-cycle regulation.
Hiroshi Yokoyama, Masaki Mizunuma, Dai Hirata, Tokichi Miyakawa
Graduate School of ADSM, Hiroshima University, 1-3-1, Higashi-Hiroshima, 739-8530, Japan
The Ca2+-activated pathways of Saccharomyces cerevisiae, through the activation of calcineurin and the Mpk1 MAP kinase pathway, induce a delay in the onset of mitosis by the activation of Swe1, a negative regulatory kinase that inhibits the Cdc28/Clb complex. In a screen for high dosage suppressors of the lethality of delta cnb1 delta mpk1 strain, we found that YAP1 gene acts in cell-cycle regulation at the downstream of the Ca2+ signaling pathways. The strain lacking ZDS1, a negative regulator of the expression of SWE1 gene in G2, exhibits various Ca2+-related phenotypes, such as growth defect, polarized bud growth and cell-cycle delay in G2. The overexpression of the YAP1 gene suppressed the Ca2+ phenotypes, while the deletion of the YAP1 gene exacerbated these phenotypes. The effects of the YAP1 gene were suppressed by the deletion of the SWE1 gene, suggesting that Yap1p functions through the regulation of Swe1p. When activated by Ca2+, Yap1p is involved in promoting the onset of mitosis by the inhibition of Swe1p. In delta yap1 strain, the Swe1p protein level, but not the SWE1 mRNA level, was elevated compared to that of wild-type strain, suggesting that Yap1p affects on Swe1p at post-transcriptional level. Yap1p was degraded by the Pep4p protease in a manner dependent on calcineurin. These results suggested that Yap1p is down-regulated by calcineurin, and the Yap1p function may be important for the exit from mitosis.
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