Aurora-A and an interacting activator, the LIM protein Ajuba, are required for mitotic commitment in human cells

被引:538
|
作者
Hirota, T
Kunitoku, N
Sasayama, T
Marumoto, T
Zhang, DW
Nitta, M
Hatakeyama, K
Saya, H
机构
[1] Kumamoto Univ, Grad Sch Med Sci, Dept Tumor Genet & Biol, Kumamoto 8608556, Japan
[2] Niigata Univ, Grad Sch Med & Dent Sci, Dept Surg, Niigata 9518510, Japan
关键词
D O I
10.1016/S0092-8674(03)00642-1
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
Aurora family kinases contribute to regulation of mitosis. Using RNA interference in synchronized HeLa cells, we now show that Aurora-A is required for mitotic entry. We found that initial activation of Aurora-A in late G2 phase of the cell cycle is essential for recruitment of the cyclin B1-Cdk1 complex to centrosomes, where it becomes activated and commits cells to mitosis. A two-hybrid screen identified the LIM protein Ajuba as an Aurora-A binding protein. Ajuba and Aurora-A interact in mitotic cells and become phosphorylated as they do so. In vitro analyses revealed that Ajuba induces the autophosphorylation and consequent activation of Aurora-A. Depletion of Ajuba prevented activation of Aurora-A at centrosomes in late G2 phase and inhibited mitotic entry. Overall, our data suggest that Ajuba is an essential activator of Aurora-A in mitotic commitment.
引用
收藏
页码:585 / 598
页数:14
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