Cell Cycle Control and Carcinogenesis, German Cancer Research Center (DKFZ), 69120 Heidelberg, Germany.
J Cell Biol. 2010 Nov 15;191(4):731-9. doi: 10.1083/jcb.201007107. Epub 2010 Nov 8.
Both gain and loss of function studies have identified the Polo-like kinase Plk4/Sak as a crucial regulator of centriole biogenesis, but the mechanisms governing centrosome duplication are incompletely understood. In this study, we show that the pericentriolar material protein, Cep152, interacts with the distinctive cryptic Polo-box of Plk4 via its N-terminal domain and is required for Plk4-induced centriole overduplication. Reduction of endogenous Cep152 levels results in a failure in centriole duplication, loss of centrioles, and formation of monopolar mitotic spindles. Interfering with Cep152 function prevents recruitment of Plk4 to the centrosome and promotes loss of CPAP, a protein required for the control of centriole length in Plk4-regulated centriole biogenesis. Our results suggest that Cep152 recruits Plk4 and CPAP to the centrosome to ensure a faithful centrosome duplication process.
功能获得和缺失研究均表明，Polo 样激酶 Plk4/Sak 是中心体生物发生的关键调节因子，但调控中心体复制的机制尚不完全清楚。在这项研究中，我们发现，中心粒周围物质蛋白 Cep152 通过其 N 端结构域与 Plk4 的独特隐性 Polo 盒相互作用，并且是 Plk4 诱导的中心粒过度复制所必需的。内源性 Cep152 水平的降低导致中心粒复制失败、中心粒丢失和形成单极有丝分裂纺锤体。干扰 Cep152 的功能会阻止 Plk4 向中心体的募集，并促进 CPAP 的丢失，CPAP 是 Plk4 调控的中心体生物发生中控制中心体长度所必需的蛋白。我们的结果表明，Cep152 将 Plk4 和 CPAP 招募到中心体，以确保中心体复制过程的忠实进行。
