UMR6061-CNRS, Institut de Génétique et Développement de Rennes, Université de Rennes I, Rennes, France.
PLoS One. 2011 Jan 31;6(1):e14600. doi: 10.1371/journal.pone.0014600.
CDK11(p58) is a mitotic protein kinase, which has been shown to be required for different mitotic events such as centrosome maturation, chromatid cohesion and cytokinesis.
METHODOLOGY/PRINCIPAL FINDINGS: In addition to these previously described roles, our study shows that CDK11(p58) inhibition induces a failure in the centriole duplication process in different human cell lines. We propose that this effect is mediated by the defective centrosomal recruitment of proteins at the onset of mitosis. Indeed, Plk4 protein kinase and the centrosomal protein Cep192, which are key components of the centriole duplication machinery, showed reduced levels at centrosomes of mitotic CDK11-depleted cells. CDK11(p58), which accumulates only in the vicinity of mitotic centrosomes, directly interacts with the centriole-associated protein kinase Plk4 that regulates centriole number in cells. In addition, we show that centriole from CDK11 defective cells are not able to be over duplicated following Plk4 overexpression.
CONCLUSION/SIGNIFICANCE: We thus propose that CDK11 is required for centriole duplication by two non-mutually-exclusive mechanisms. On one hand, the observed duplication defect could be caused indirectly by a failure of the centrosome to fully maturate during mitosis. On the other hand, CDK11(p58) could also directly regulate key centriole components such as Plk4 during mitosis to trigger essential mitotic centriole modifications, required for centriole duplication during subsequent interphase.
CDK11（p58）是一种有丝分裂蛋白激酶，已被证明在不同的有丝分裂事件中是必需的，如中心体成熟、染色单体黏合和胞质分裂。
方法/主要发现：除了这些先前描述的作用外，我们的研究表明，CDK11（p58）抑制会导致不同人类细胞系中心体复制过程失败。我们提出，这种效应是由有丝分裂起始时中心体募集蛋白的缺陷介导的。事实上，Plk4 蛋白激酶和中心体蛋白 Cep192，它们是中心体复制机制的关键组成部分，在有丝分裂 CDK11 耗尽细胞的中心体中显示出降低的水平。仅在有丝分裂中心体附近积累的 CDK11（p58）与调节细胞中中心体数量的中心体相关蛋白激酶 Plk4 直接相互作用。此外，我们还表明，CDK11 缺陷细胞的中心体在 Plk4 过表达后不能被过度复制。
结论/意义：因此，我们提出 CDK11 通过两种非互斥的机制来促进中心体复制。一方面，观察到的复制缺陷可能是由于中心体在有丝分裂期间不能完全成熟而间接引起的。另一方面，CDK11（p58）也可以在有丝分裂期间直接调节 Plk4 等关键中心体成分，触发有丝分裂中心体必需的修饰，这对于随后的间期中心体复制是必需的。
