Ludwig Institute for Cancer Research, University of California, San Diego, La Jolla, CA 92093, USA.
Mol Biol Cell. 2012 May;23(10):1838-45. doi: 10.1091/mbc.E11-12-1043. Epub 2012 Mar 28.
Centrioles organize the centrosome, and accurate control of their number is critical for the maintenance of genomic integrity. Centrioles duplicate once per cell cycle, and duplication is coordinated by Polo-like kinase 4 (Plk4). We previously demonstrated that Plk4 accumulation is autoregulated by its own kinase activity. However, loss of heterozygosity of Plk4 in mouse embryonic fibroblasts has been proposed to cause cytokinesis failure as a primary event, leading to centrosome amplification and gross chromosomal abnormalities. Using targeted gene disruption, we show that human epithelial cells with one inactivated Plk4 allele undergo neither cytokinesis failure nor increase in centrosome amplification. Plk4 is shown to localize exclusively at the centrosome, with none in the spindle midbody. Substantial depletion of Plk4 by small interfering RNA leads to loss of centrioles and subsequent spindle defects that lead to a modest increase in the rate of cytokinesis failure. Therefore, Plk4 is a centriole-localized kinase that does not directly regulate cytokinesis.
中心体由中心粒组成，准确控制其数量对于维持基因组完整性至关重要。中心粒在细胞周期中复制一次，其复制由 Polo 样激酶 4（Plk4）协调。我们之前证明 Plk4 的积累受到其自身激酶活性的自我调节。然而，有人提出，在小鼠胚胎成纤维细胞中，Plk4 的杂合性缺失可能导致胞质分裂失败作为主要事件，从而导致中心体扩增和染色体异常。使用靶向基因敲除，我们表明，一个 Plk4 等位基因失活的人上皮细胞既不会发生胞质分裂失败，也不会增加中心体扩增。Plk4 被证明仅定位于中心体，纺锤体中间体中没有 Plk4。用小干扰 RNA 大量消耗 Plk4 会导致中心粒丢失，随后出现纺锤体缺陷，导致胞质分裂失败率适度增加。因此，Plk4 是一种定位于中心粒的激酶，它不直接调节胞质分裂。
