Usp16 regulates kinetochore localization of Plk1 to 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.
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.
Xiaolong
X
Zhuo
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.
Xiao
X
Guo
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.
Xiaoyan
X
Zhang
Department of Biological Sciences, California State Polytechnic University, Pomona, CA 91768.
Guihua
G
Jing
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.
Yao
Y
Wang
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.
Qiang
Q
Chen
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.
Qing
Q
Jiang
Department of Biological Sciences, California State Polytechnic University, Pomona, CA 91768 zhangcm@pku.edu.cn junjunliu@cpp.edu.
Junjun
J
Liu
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 zhangcm@pku.edu.cn junjunliu@cpp.edu.
Chuanmao
C
Zhang
D018797:Cell Cycle Proteins / Q000037:antagonists & inhibitors / Q000378:metabolism*; D045744:Cell Line, Tumor; D020090:Chromosome Segregation / Q000235:genetics* / Q000502:physiology; D002875:Chromosomes / Q000378:metabolism; D057809:HEK293 Cells; D006367:HeLa Cells; D006801:Humans; D018386:Kinetochores / Q000378:metabolism*; D008870:Microtubules / Q000378:metabolism; D008938:Mitosis / Q000187:drug effects / Q000235:genetics*; D015739:Nocodazole / Q000494:pharmacology; D010766:Phosphorylation; D017346:Protein Serine-Threonine Kinases / Q000037:antagonists & inhibitors / Q000378:metabolism*; D011518:Proto-Oncogene Proteins / Q000037:antagonists & inhibitors / Q000378:metabolism*; D011621:Pteridines / Q000494:pharmacology; D034622:RNA Interference; D034741:RNA, Small Interfering; D043222:Ubiquitin Thiolesterase / Q000235:genetics / Q000378:metabolism*; D054875:Ubiquitination; D000097869:Polo-Like Kinase 1
D018797:Cell Cycle Proteins; D015739:Nocodazole; D017346:Protein Serine-Threonine Kinases; D011518:Proto-Oncogene Proteins; D011621:Pteridines; D034741:RNA, Small Interfering; D043222:Ubiquitin Thiolesterase; D000097869:Polo-Like Kinase 1; C518477:BI 2536; C118778:USP16 protein, human; C584277:BUB1 protein, human