Habedanck Robert, Stierhof York-Dieter, Wilkinson Christopher J, Nigg Erich A
Department of Cell Biology, Max-Planck-Institute for Biochemistry, Am Klopferspitz 18, D-82152 Martinsried, Germany.
Nat Cell Biol. 2005 Nov;7(11):1140-6. doi: 10.1038/ncb1320.
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. 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. 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.
人类的Polo样激酶1（PLK1）及其在其他真核生物中存在的功能同源物在减数分裂和有丝分裂细胞分裂中具有多种关键作用。相比之下，其他哺乳动物Polo家族成员的功能在很大程度上仍不清楚。Plk4是结构上差异最大的Polo家族成员；它在活跃分裂的组织中表达最高，对小鼠胚胎发育至关重要。在这里，我们确定Plk4是中心粒复制的关键调节因子。功能获得和功能丧失实验均表明，在细胞周期中，Plk4与Cdk2、CP110和Hs-SAS6协同作用，是中心体精确复制所必需的。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具有启示意义。
