Mitotic activation of the kinase Aurora-A requires its binding partner Bora

Mitotic activation of the kinase Aurora-A requires its binding partner Bora
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DOI:
10.1016/j.devcel.2006.06.002
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发表时间:
2006-08-01
期刊:
影响因子:
11.8
通讯作者:
Knoblich, Juergen A.
Knoblich, Juergen A.
中科院分区:
生物学1区
文献类型:
--
作者:
Hutterer, Andrea;Berdnik, Daniela;Knoblich, Juergen A.

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蛋白激酶Aurora-A是有丝分裂过程中中心体成熟、纺锤体组装和不对称蛋白定位所必需的。在这里,我们描述了Bora的鉴定,Bora是一种在有丝分裂开始时激活Aurora-A所需的保守蛋白。在果蝇周围神经系统中,bora突变体在不对称细胞分裂过程中有缺陷,与在aurora-A中观察到的缺陷相同。此外,bora的过表达可以挽救由aurora-A突变引起的缺陷。Bora在脊椎动物中是保守的,果蝇和人类Bora都可以与Auroral-A结合并在体外激活激酶。在间期细胞中,Bora是一种核蛋白,但在进入有丝分裂时,Bora被排除在细胞核之外,并以Cdc 2依赖的方式易位到细胞质中。我们提出了一个模型,其中Cdc 2的激活启动Bora释放到细胞质中,在那里它可以结合并激活Aurora-A。
The protein kinase Aurora-A is required for centrosome maturation, spindle assembly, and asymmetric protein localization during mitosis. Here, we describe the identification of Bora, a conserved protein that is required for the activation of Aurora-A at the onset of mitosis. In the Drosophila peripheral nervous system, bora mutants have defects during asymmetric cell division identical to those observed in aurora-A. Furthermore, overexpression of bora can rescue defects caused by mutations in aurora-A. Bora is conserved in vertebrates, and both Drosophila and human Bora can bind to Auroral-A and activate the kinase in vitro. In interphase cells, Bora is a nuclear protein, but upon entry into mitosis, Bora is excluded from the nucleus and translocates into the cytoplasm in a Cdc2-dependent manner. We propose a model in which activation of Cdc2 initiates the release of Bora into the cytoplasm where it can bind and activate Aurora-A.