The serine/threonine kinase Nek6 is required for cell cycle progression through mitosis

被引:89
作者
Yin, MJ [1 ]
Shao, LH [1 ]
Voehringer, D [1 ]
Smeal, T [1 ]
Jallal, B [1 ]
机构
[1] SUGEN Inc, San Francisco, CA 94080 USA
关键词
D O I
10.1074/jbc.M308080200
中图分类号
Q5 [生物化学]; Q7 [分子生物学];
学科分类号
071010 ; 081704 ;
摘要
The Aspergillus nidulans protein NIMA ((n) under bar ever (i) under barn (m) under bar itosis, gene (A) under bar) is a protein kinase required for the initiation of mitosis, whereas its inactivation is necessary for mitotic exit. Here, we demonstrate that human NIMA-related kinase 6 (Nek6) is required for mitotic progression of human cells. Nek6 is phosphorylated and activated during M phase. Inhibition of Nek6 function by either overexpression of an inactive Nek6 mutant or elimination of endogenous Nek6 by siRNA arrests cells in M phase and triggers apoptosis. Time-lapse recording of the cell cycle progression of cells expressing kinase-inactive Nek6 reveals mitotic arrest at the metaphase stage prior to cells entering apoptosis. In contrast to NIMA and the closely related mammalian Nek2 kinase, which regulate centrosome function and separation, our data demonstrate an important function for Nek6 during mitosis and suggest that Nek6 kinase is required for metaphase-anaphase transition.
引用
收藏
页码:52454 / 52460
页数:7
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