A Quantitative Model for Ordered Cdk Substrate Dephosphorylation during Mitotic Exit
A Quantitative Model for Ordered Cdk Substrate Dephosphorylation during Mitotic Exit
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DOI：
10.1016/j.cell.2011.09.047
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发表时间：
2011-11-11
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：
Bouchoux, Celine;Uhlmann, Frank
姐妹染色单体在后期开始分裂后，有丝分裂的退出包括一系列有序的事件。被细胞周期蛋白依赖性激酶（Cdk）磷酸化的许多有丝分裂底物的去磷酸化被认为导致有丝分裂退出，但有丝分裂退出事件的时间顺序是如何实现的尚不清楚。在这里，我们使用出芽酵母显示，Cdk底物的去磷酸化参与顺序有丝分裂退出事件发生有序的时间。我们测试了不同的模型，通过体内调节Cdk和Cdk对抗磷酸酶Cdc14的活性来实现排序，以及通过体外Cdk底物磷酸化和去磷酸化的动力学分析。我们的研究结果表明，在有丝分裂退出过程中，磷酸酶与激酶比例的逐渐变化是由Cdk底物读出的，Cdk底物在不同的阈值下通过去磷酸化做出反应。这为细胞周期进程的定量模型提供了一个例子和机制解释。
After sister chromatid splitting at anaphase onset, exit from mitosis comprises an ordered series of events. Dephosphorylation of numerous mitotic substrates, which were phosphorylated by cyclin-dependent kinase (Cdk), is thought to bring about mitotic exit, but how temporal ordering of mitotic exit events is achieved is poorly understood. Here, we show, using budding yeast, that dephosphorylation of Cdk substrates involved in sequential mitotic exit events occurs with ordered timing. We test different models of how ordering might be achieved by modulating Cdk and Cdk-counteracting phosphatase Cdc14 activities in vivo, as well as by kinetic analysis of Cdk substrate phosphorylation and dephosphorylation in vitro. Our results suggest that the gradual change of the phosphatase to kinase ratio over the course of mitotic exit is read out by Cdk substrates that respond by dephosphorylation at distinct thresholds. This provides an example and a mechanistic explanation for a quantitative model of cell-cycle progression.