Zhuo Xiaolong, Guo Xiao, Zhang Xiaoyan, Jing Guihua, Wang Yao, Chen Qiang, Jiang Qing, Liu Junjun, Zhang Chuanmao
Ministry of Education Key Laboratory of Cell Proliferation and Differentiation and State Key Laboratory of Membrane Biology, College of Life Sciences, Peking University, Beijing 100871, China.
Department of Biological Sciences, California State Polytechnic University, Pomona, CA 91768.
J Cell Biol. 2015 Aug 31;210(5):727-35. doi: 10.1083/jcb.201502044.
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.
在G2期到M期的转变过程中，一部分有丝分裂调节因子Plk1定位于动粒，并调节动粒-微管附着的起始，以实现染色体的正确排列。一旦实现动粒-微管附着，这部分Plk1会因泛素化作用而从动粒上被移除。然而，促进Plk1在动粒上定位并维持到中期的关键分子机制仍不清楚。我们报告称泛素特异性肽酶16（Usp16）在此过程中起关键作用。Usp16去除Plk1上的泛素，导致其与动粒定位蛋白（如BubR1）的相互作用增强，从而将Plk1保留在动粒上，以促进有丝分裂早期染色体的正确排列。Usp16的下调会导致Plk1泛素化增加，其在动粒上的定位减少。因此，我们的数据揭示了一种独特的机制，通过该机制Usp16促进Plk1在动粒上的定位和维持，以实现染色体的正确排列。
