Usp16 regulates kinetochore localization of Plk1 to promote proper chromosome alignment in mitosis.
Usp16 regulates kinetochore localization of Plk1 to promote proper chromosome alignment in mitosis.
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Usp16 调节 Plk1 的动粒定位，以促进有丝分裂中正确的染色体排列。
DOI：
10.1083/jcb.201502044
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发表时间：
2015-08-31
期刊：
影响因子：
--
通讯作者：
Zhang C
中科院分区：
文献类型：
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作者：
Zhuo X;Guo X;Zhang X;Jing G;Wang Y;Chen Q;Jiang Q;Liu J;Zhang C
CDK 1和Plk 1依次磷酸化并激活Usp 16，Usp 16反过来使Plk 1去泛素化，以维持激酶的动粒定位并促进有丝分裂中正确的染色体排列。在G2到M期的过渡，有丝分裂调节Plk 1的一部分定位到着丝粒和调节启动着丝粒微管附件正确的染色体排列。一旦实现动粒-微管附着，Plk 1的这一部分就会因遍在化而从动粒中去除。然而，促进Plk 1在着丝粒上的定位和维持直到中期的关键分子机制仍然不清楚。我们报告说，泛素特异性肽酶16（Usp 16）在这一过程中起着关键作用。Usp 16去泛素化Plk 1，导致与着丝粒定位的蛋白质如BubR 1的相互作用增强，从而将Plk 1保留在着丝粒上，以促进早期有丝分裂中正确的染色体排列。Usp 16的下调导致Plk 1的泛素化增加和动粒定位减少。因此，我们的数据揭示了一种独特的机制，通过这种机制，Usp 16促进了Plk 1在着丝粒上的定位和维持，以进行正确的染色体比对。
CDK1 and Plk1 sequentially phosphorylate and activate Usp16, which in turn deubiquitinates Plk1 to maintain the kinase’s kinetochore localization and promote proper chromosome alignment in mitosis. During the G2 to M phase transition, a portion of mitotic regulator Plk1 localizes to the kinetochores and regulates the initiation of kinetochore–microtubule attachments for proper chromosome alignment. Once kinetochore–microtubule attachment is achieved, this portion of Plk1 is removed from the kinetochores as a result of ubiquitination. However, the crucial molecular mechanism that promotes the localization and the maintenance of Plk1 on the kinetochores until metaphase is still unclear. We report that ubiquitin-specific peptidase 16 (Usp16) plays a key role during this process. Usp16 deubiquitinates Plk1, resulting in an enhanced interaction with kinetochore-localized proteins such as BubR1, and thereby retains Plk1 on the kinetochores to promote proper chromosome alignment in early mitosis. Down-regulation of Usp16 causes increased ubiquitination and decreased kinetochore localization of Plk1. Thus, our data unveil a unique mechanism by which Usp16 promotes the localization and maintenance of Plk1 on the kinetochores for proper chromosome alignment.