Cdk phosphorylation licenses Kif4A chromosome localization required for early mitotic progression  

作　　者：Zhixiong Dong Changjun Zhu Qimin Zhan Wei Jiang 

机构地区：[1]State Key Laboratory of Molecular Oncology, National Cancer Center/Cancer Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing 100021, China [2]Key Laboratory of Molecular and Cellular Systems Biology, Tianjin Normal University, Tianjin 300387, China [3]Tianjin Key Laboratory of Animal and Plant Resistance, College of Life Sciences, Tianjin Normal University, Tianjin 300387, China

出　　处：《Journal of Molecular Cell Biology》2018年第4期358-370,共13页分子细胞生物学报（英文版）

基　　金：This work was supported by CAMS Innovation Fund for Medical Sciences （CIFMS） （2016-12M-1-001）, the National Natural Science Foundation of China （31171299, 31271485, and 31301138）, the National Basic Research Program of China （2012CB910703）, and Tianjin Research Program of Application Foundation and Advanced Technology （12JC2DJC21400）. C.Z. is supported by Program for New Century Excellent Talents in University in China （NCET-11-1066）.

摘　　要：The chromokinesin Kif4A controls proper chromosome condensation, congression/alignment, and cytokinesis to ensure faithful genetic inheritance. Here, we report that Cdk phosphorylation of human Kif4A at T1161 licenses Kif4A chromosomal localization, which, in turn, controls Kif4A early mitotic function. Phosphorylated Kif4A （Kif4A^WT） or Cdk phospho-mimetic Kif4A mutant （Kif4A^TE） associated with chromosomes and condensin I （non-SMC subunit CAP-G and core subunit SMC2） to regulate chromosome condensation, spindle morphology, and chromosome congression/alignment in early mitosis. In contrast, Cdk non-phosphorylatable Kif4A mutant （Kif4A^TA） could neither localize on chromosomes nor associate with CAP-G and SMC2. Furthermore, Kif4A^TA could not rescue defective chromosome condensation, spindle morphology, or chromosome congression/alignment in cells depleted of endogenous Kif4A, which activated a mitotic checkpoint and delayed early mitotic progression. However, targeting Kif4A^TA to chromosomes by fusion of Kif4A^TA with Histone H1 resulted in restoration of chromosome and spindle functions of Kif4A, similar to Kif4A^WT and Kif4A^TE, in cells depleted of endogenous Kif4A. Thus, our results demonstrate that Cdk phosphorylation-licensed chromosomal localization of Kif4A plays a critical role in regulating early mitotic functions of Kif4A that are important for early mitotic progression.

关 键 词：Kif4A chromokinesin Cdk phosphorylation MITOSIS 

分 类 号：Q253[生物学—细胞生物学] Q343.2