Ordered proteolysis in anaphase inactivates Plk1 to contribute to proper mitotic exit in human cells.

Ordered proteolysis in anaphase inactivates Plk1 to contribute to proper mitotic exit in human cells.
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DOI:
10.1083/jcb.200309035
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发表时间:
2004-01-19
期刊:
The Journal of cell biology
影响因子:
--
通讯作者:
Pines J
Pines J
中科院分区:
其他
文献类型:
--
作者:
Lindon C;Pines J

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我们已经发现,在人类细胞退出有丝分裂的过程中,关键的有丝分裂调节因子显示出不同的降解模式。使用活细胞蛋白质降解实验,我们发现其中两个调节因子,Polo-like kinase1(Plk1)和Aurora A,在后期促进复合体/环体(APC/C)从结合CDc20转换到CDH1后,在不同的时间被降解。因此,除了从cdc20到cdh1的转换外,还发生了一些事件,控制了体内APC/CCdh1底物的蛋白分解。我们已经在Plk1中确定了一个假定的破坏框,它是Plk1在后期降解所必需的,并检测了不可降解的Plk1对有丝分裂退出的影响。我们的结果表明,Plk1蛋白降解有助于Plk1在后期失活,这是适当控制有丝分裂退出和胞质分裂所必需的。我们的实验揭示了APC/C介导的蛋白分解在人类细胞退出有丝分裂中的作用。
We have found that key mitotic regulators show distinct patterns of degradation during exit from mitosis in human cells. Using a live-cell assay for proteolysis, we show that two of these regulators, polo-like kinase 1 (Plk1) and Aurora A, are degraded at different times after the anaphase-promoting complex/cyclosome (APC/C) switches from binding Cdc20 to Cdh1. Therefore, events in addition to the switch from Cdc20 to Cdh1 control the proteolysis of APC/CCdh1 substrates in vivo. We have identified a putative destruction box in Plk1 that is required for degradation of Plk1 in anaphase, and have examined the effect of nondegradable Plk1 on mitotic exit. Our results show that Plk1 proteolysis contributes to the inactivation of Plk1 in anaphase, and that this is required for the proper control of mitotic exit and cytokinesis. Our experiments reveal a role for APC/C-mediated proteolysis in exit from mitosis in human cells.
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