Original Article

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Cdk phosphorylation licenses Kif4A chromosome localization required for early mitotic progression Free
Zhixiong Dong 1,2,3,† , Changjun Zhu 1,2,3,†,* , Qimin Zhan 1, and Wei Jiang 1,2,3,*
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
These authors contributed equally to this work. *Correspondence to:Wei Jiang, E-mail: wjiang6138@cicams.ac.cn; Changjun Zhu, E-mail: skyzcj@tjnu.edu.cn
J Mol Cell Biol, Volume 10, Issue 4, August 2018, 358-370,  https://doi.org/10.1093/jmcb/mjy033
Keyword: Kif4A, chromokinesin, Cdk phosphorylation, mitosis

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 (Kif4AWT) or Cdk phospho-mimetic Kif4A mutant (Kif4ATE) 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 (Kif4ATA) could neither localize on chromosomes nor associate with CAP-G and SMC2. Furthermore, Kif4ATA 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 Kif4ATA to chromosomes by fusion of Kif4ATA with Histone H1 resulted in restoration of chromosome and spindle functions of Kif4A, similar to Kif4AWT and Kif4ATE, 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.