The Polo kinase Plk4 functions in centriole duplication

The Polo kinase Plk4 functions in centriole duplication
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DOI:
10.1038/ncb1320
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发表时间:
2005-11-01
影响因子:
21.3
通讯作者:
Nigg, EA
Nigg, EA
中科院分区:
生物学1区
文献类型:
--
作者:
Habedanck, R;Stierhof, YD;Nigg, EA

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人类polo样激酶1 (PLK1)及其功能同源物存在于其他真核生物中,在减数分裂和有丝分裂细胞分裂中具有多重关键作用(1,2)。相比之下,其他哺乳动物波罗科成员的功能在很大程度上仍然未知。Plk4是结构分歧最大的Polo家族成员;它在积极分裂的组织中表达最多,对小鼠胚胎发育至关重要(3)。在这里,我们确定Plk4是中心粒复制的关键调节因子。获得和失去功能的实验都表明,Plk4与Cdk2、CP110和Hs-SAS6合作,在细胞周期中中心体的精确复制是必需的。这些发现为Plk4在细胞增殖中的关键功能提供了一个有吸引力的解释,并对Polo激酶在肿瘤发生中的作用产生了影响。
The human Polo-like kinase 1 (PLK1) and its functional homologues that are present in other eukaryotes have multiple, crucial roles in meiotic and mitotic cell division(1,2). By contrast, the functions of other mammalian Polo family members remain largely unknown. Plk4 is the most structurally divergent Polo family member; it is maximally expressed in actively dividing tissues and is essential for mouse embryonic development(3). Here, we identify Plk4 as a key regulator of centriole duplication. Both gain- and loss-of-function experiments demonstrate that Plk4 is required - in cooperation with Cdk2, CP110 and Hs-SAS6 - for the precise reproduction of centrosomes during the cell cycle. These findings provide an attractive explanation for the crucial function of Plk4 in cell proliferation and have implications for the role of Polo kinases in tumorigenesis.