Downregulation of PP2ACdc-95 phosphatase by separase initiates mitotic exit in budding yeast
Downregulation of PP2ACdc-95 phosphatase by separase initiates mitotic exit in budding yeast
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DOI：
10.1016/j.cell.2006.03.038
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发表时间：
2006-05-19
期刊：
影响因子：
64.5
通讯作者：
Uhlmann, Frank
中科院分区：
文献类型：
--
作者：
Queralt, Ethel;Lehane, Chris;Uhlmann, Frank
在有丝分裂后期，高有丝分裂周期蛋白依赖性激酶(CDK)的活性被下调，以促进有丝分裂的退出。为此，在萌芽酵母中，CDK对抗磷酸酶CDC14被激活。在中期，CDC14被其抑制剂Net1保持在核仁中不活跃。在后期，依赖于CDK和Polo的Net1的磷酸化被认为释放了活性的CDC14。当有丝分裂酶活性开始下降时，NETL是如何在后期被特异性磷酸化的，仍然没有解释。在这里，我们证明了PP2A(CDC55)磷酸酶在中期保持NETL的低磷酸化。姐妹染色单体分离蛋白分离酶在细胞分裂后期被激活，与PP2A(CDC55)相互作用并下调，从而促进依赖CDK的NETL的磷酸化。PP2A(CDC55)的下调也促进了Bfa1的磷酸化，有助于激活“有丝分裂退出网络”，该网络在CDK活性下降时维持CDC14。这些发现使我们能够提出一种新的定量模型来描述发芽酵母中有丝分裂的存在。
After anaphase, the high mitotic cyclin-dependent kinase (Cdk) activity is downregulated to promote exit from mitosis. To this end, in the budding yeast S. cerevisiae, the Cdk counteracting phosphatase Cdc14 is activated. In metaphase, Cdc14 is kept inactive in the nucleolus by its inhibitor Net1. During anaphase, Cdk- and Polo-dependent phosphorylation of Net1 is thought to release active Cdc14. How Netl is phosphorylated specifically in anaphase, when mitotic kinase activity starts to decline, has remained unexplained. Here, we show that PP2A(Cdc55) phosphatase keeps Netl under-phosphorylated in metaphase. The sister chromatid-separating protease separase, activated at anaphase onset, interacts with and down regulates PP2A(Cdc55) , thereby facilitating Cdk dependent Netl phosphorylation. PP2A(CdC55) downregulation also promotes phosphorylation of Bfa1, contributing to activation of the "mitotic exit network" that sustains Cdc14 as Cdk activity declines. These findings allow us to present a new quantitative model for mitotic exit in budding yeast.