Involvement of calcineurin‐dependent degradation of Yap1p in Ca2+‐induced G2 cell‐cycle regulation in Saccharomyces cerevisiae
Involvement of calcineurin‐dependent degradation of Yap1p in Ca2+‐induced G2 cell‐cycle regulation in Saccharomyces cerevisiae
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DOI：
10.1038/sj.embor.7400647
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发表时间：
2006-05
期刊：
影响因子：
7.7
通讯作者：
H. Yokoyama;Masaki Mizunuma;Michiyo Okamoto;J. Yamamoto;D. Hirata;T. Miyakawa
中科院分区：
文献类型：
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作者：
H. Yokoyama;Masaki Mizunuma;Michiyo Okamoto;J. Yamamoto;D. Hirata;T. Miyakawa
酵母中的Ca 2+激活途径通过激活Swe 1 p（一种抑制Cdc 28 p/Clb复合物的负调节激酶）诱导有丝分裂开始延迟。由于ZDS 1的缺失，我们分离出了YAP 1基因，该基因是一个钙敏感性的多拷贝抑制基因，ZDS 1是SWE 1和CLN 2基因表达的负调控因子。当细胞暴露于钙时，Yap 1 p以钙调磷酸酶依赖性方式降解。在yap 1 Δ细胞中，编码泛素-蛋白酶体系统亚基转录因子的RPN 4基因的表达水平降低。YAP 1和RPN 4基因的缺失导致了Swe 1 p和Cln 2 p的积累。Yap 1 p是钙调神经磷酸酶在体内和体外的底物。钙调神经磷酸酶介导的Yap 1 p降解似乎是一种长期的适应性反应，它确保了G2延迟响应导致钙信号通路激活的应激。
The Ca2+‐activated pathways inSaccharomyces cerevisiaeinduce a delay in the onset of mitosis through the activation of Swe1p, a negative regulatory kinase that inhibits the Cdc28p/Clb complex. We isolated theYAP1gene as a multicopy suppressor of calcium sensitivity owing to the loss ofZDS1, a negative regulator ofSWE1andCLN2gene expression.YAP1deletion on azds1Δ background exacerbated the Ca2+‐related phenotype. Yap1p was degraded in a calcineurin‐dependent manner when cells were exposed to calcium. Inyap1Δ cells, the expression level of theRPN4gene encoding a transcription factor for the subunits of the ubiquitin–proteasome system was diminished. The deletion ofYAP1gene orRPN4gene led to the accumulation of Swe1p and Cln2p. Yap1p was a substrate of calcineurinin vivoandin vitro. The calcineurin‐mediated Yap1p degradation seems to be a long adaptive response that assures a G2delay in response to a stress that causes the activation of the calcium signalling pathways.