Involvement of calcineurin‐dependent degradation of Yap1p in Ca 2+ ‐induced G 2 cell‐cycle regulation in Saccharomyces cerevisiae

The Ca 2+ ‐activated pathways in Saccharomyces cerevisiae induce a delay in the onset of mitosis through the activation of Swe1p, a negative regulatory kinase that inhibits the Cdc28p/Clb complex. We isolated the YAP1 gene as a multicopy suppressor of calcium sensitivity owing to the loss of ZDS1 , a negative regulator of SWE1 and CLN2 gene expression. YAP1 deletion on a zds1 Δ background exacerbated the Ca 2+ ‐related phenotype. Yap1p was degraded in a calcineurin‐dependent manner when cells were exposed to calcium. In yap1 Δ cells, the expression level of the RPN4 gene encoding a transcription factor for the subunits of the ubiquitin–proteasome system was diminished. The deletion of YAP1 gene or RPN4 gene led to the accumulation of Swe1p and Cln2p. Yap1p was a substrate of calcineurin in vivo and in vitro . The calcineurin‐mediated Yap1p degradation seems to be a long adaptive response that assures a G 2 delay in response to a stress that causes the activation of the calcium signalling pathways.