Cizmecioglu Onur, Warnke Silke, Arnold Marc, Duensing Stefan, Hoffmann Ingrid
Cell cycle Control and Carcinogenesis (F045), German Cancer Research Center (DKFZ), Heidelberg, Germany.
Cell Cycle. 2008 Nov 15;7(22):3548-55. doi: 10.4161/cc.7.22.7071. Epub 2008 Nov 26.
In mammalian cells, the centrosome consists of a pair of centrioles and amorphous pericentriolar material. The centrosome duplicates once per cell cycle. Polo like kinases (Plks) perform crucial functions in cell cycle progression and during mitosis. The polo-like kinase-2, Plk2, is activated near the G(1)/S phase transition, and plays an important role in the reproduction of centrosomes. In this study, we show that the polo-box of Plk2 is required both for association to the centrosome and centriole duplication. Mutation of critical sites in the Plk2 polo-box prevents centrosomal localization and impairs centriole duplication. Plk2 is localized to centrosomes during early G(1) phase where it only associates to the mother centriole and then distributes equally to both mother and daughter centrioles at the onset of S phase. Furthermore, our results imply that Plk2 mediated centriole duplication is dependent on Plk4 function. In addition, we find that siRNA-mediated downregulation of Plk2 leads to the formation of abnormal mitotic spindles confirming that Plk2 may have a function in the reproduction of centrioles.
在哺乳动物细胞中,中心体由一对中心粒和无定形的中心粒外周物质组成。中心体在每个细胞周期复制一次。类Polo激酶(Plks)在细胞周期进程和有丝分裂过程中发挥关键作用。类Polo激酶2(Plk2)在G(1)/S期转换附近被激活,并在中心体复制中起重要作用。在本研究中,我们表明Plk2的Polo框对于其与中心体的结合及中心粒复制都是必需的。Plk2的Polo框中关键位点的突变会阻止其定位于中心体,并损害中心粒复制。在G(1)早期阶段,Plk2定位于中心体,此时它仅与母中心粒结合,然后在S期开始时均匀分布到母中心粒和子中心粒。此外,我们的结果表明Plk2介导的中心粒复制依赖于Plk4的功能。另外,我们发现siRNA介导的Plk2表达下调会导致异常有丝分裂纺锤体的形成,这证实Plk2可能在中心粒复制中发挥作用。