Aurora-A and an interacting activator, the LIM protein Ajuba, are required for mitotic commitment in human cells
Aurora-A and an interacting activator, the LIM protein Ajuba, are required for mitotic commitment in human cells
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DOI：
10.1016/s0092-8674(03)00642-1
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发表时间：
2003-09-05
期刊：
影响因子：
64.5
通讯作者：
Saya, H
中科院分区：
文献类型：
--
作者：
Hirota, T;Kunitoku, N;Saya, H
极光激酶家族对有丝分裂的调控起作用。我们在同步化的海拉细胞中利用RNA干扰技术，现在表明极光激酶A是有丝分裂进入所必需的。我们发现细胞周期G2期晚期极光激酶A的初始激活对于细胞周期蛋白B1 - 细胞周期蛋白依赖性激酶1复合物募集到中心体是必不可少的，在此处该复合物被激活并促使细胞进入有丝分裂。一个双杂交筛选鉴定出LIM蛋白Ajuba是一种极光激酶A结合蛋白。Ajuba和极光激酶A在有丝分裂细胞中相互作用，并且在相互作用时被磷酸化。体外分析显示Ajuba诱导极光激酶A的自身磷酸化以及随之而来的激活。Ajuba的缺失阻止了G2期晚期极光激酶A在中心体的激活，并抑制了有丝分裂的进入。总体而言，我们的数据表明Ajuba是有丝分裂启动过程中极光激酶A的一个关键激活因子。
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.