Involvement of calcineurin-dependent degradation of Yap1p in Ca2+-induced G2 cell-cycle regulation in Saccharomyces cerevisiae.
The Ca2+-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 zds1delta background exacerbated the Ca2+-related phenotype. Yap1p was degraded in a calcineurin-dependent manner when cells were exposed to calcium. In yap1delta 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 G2 delay in response to a stress that causes the activation of the calcium signalling pathways.
Yokoyama
Hiroshi
H
Department of Molecular Biotechnology, Graduate School of Advanced Sciences of Matter, Hiroshima University, Higashi-Hiroshima 739-8530, Japan.
Mizunuma
Masaki
M
Okamoto
Michiyo
M
Yamamoto
Josuke
J
Hirata
Dai
D
Miyakawa
Tokichi
T
D019703:Calcineurin / Q000378:metabolism / Q000502:physiology*; D002118:Calcium / Q000502:physiology*; D018797:Cell Cycle Proteins / Q000096:biosynthesis / Q000378:metabolism; D016213:Cyclins / Q000096:biosynthesis / Q000378:metabolism; D016195:G2 Phase / Q000502:physiology*; D011505:Protein-Tyrosine Kinases / Q000096:biosynthesis / Q000378:metabolism; D012441:Saccharomyces cerevisiae / Q000166:cytology* / Q000378:metabolism*; D029701:Saccharomyces cerevisiae Proteins / Q000096:biosynthesis / Q000378:metabolism*; D013312:Stress, Physiological / Q000502:physiology; D014157:Transcription Factors / Q000378:metabolism*; D015854:Up-Regulation / Q000502:physiology
C082721:CLN2 protein, S cerevisiae; D018797:Cell Cycle Proteins; D016213:Cyclins; D029701:Saccharomyces cerevisiae Proteins; D014157:Transcription Factors; C086677:YAP1 protein, S cerevisiae; C099685:SWE1 protein, S cerevisiae; D011505:Protein-Tyrosine Kinases; D019703:Calcineurin; D002118:Calcium