Division of Translational Medicine, Wadsworth Center, New York State Department of Health, Albany, NY 12201-0509, USA.
Curr Biol. 2010 Jul 27;20(14):1277-82. doi: 10.1016/j.cub.2010.05.050. Epub 2010 Jun 17.
Supernumerary centrioles lead to abnormal mitosis, which in turn promotes tumorigenesis. Thus, centriole duplication must be coordinated with the cell cycle to ensure that the number of centrioles in the cell doubles precisely during each cell cycle. However, in some transformed cells, centrioles undergo multiple rounds of duplication (reduplication) during prolonged interphase. Mechanisms responsible for centriole reduplication are poorly understood. Here, we report that centrioles reduplicate consistently in cancerous and nontransformed human cells during G2 arrests and that this reduplication requires the activity of Polo-like kinase 1 (Plk1). We also find that a cell's ability to reduplicate centrioles during S arrests depends on the presence of activated (Thr210-phosphorylated) Plk1 at the centrosome. In the absence of activated Plk1, nascent procentrioles remain associated with mother centrioles, which prevents centriole reduplication. In contrast, if Plk1(pT210) appears at the centrosome, procentrioles mature, disengage from mother centrioles, and ultimately duplicate. Plk1 activity is not required for the assembly of procentrioles, however. Thus, the role of Plk1 is to coordinate the centriole duplication cycle with the cell cycle. Activation of Plk1 during late S/G2 induces procentriole maturation, and after this point, the centriole cycle can be completed autonomously, even in the absence of cell-cycle progression.
额外的中心粒导致异常有丝分裂,进而促进肿瘤发生。因此,中心粒的复制必须与细胞周期相协调,以确保细胞在每个细胞周期中精确地将中心粒数量加倍。然而,在一些转化细胞中,中心粒在间期延长时会经历多次复制(重复复制)。负责中心粒重复复制的机制尚不清楚。在这里,我们报告在 G2 期阻滞期间,癌细胞和非转化的人类细胞中的中心粒一致地进行重复复制,并且这种重复复制需要 Polo 样激酶 1(Plk1)的活性。我们还发现,细胞在 S 期阻滞时复制中心粒的能力取决于中心体上激活的(Thr210 磷酸化)Plk1 的存在。在缺乏激活的 Plk1 的情况下,新生的中心粒仍然与母中心粒相关联,这阻止了中心粒的重复复制。相比之下,如果 Plk1(pT210)出现在中心体上,中心粒成熟,与母中心粒脱离,最终复制。然而,Plk1 活性不是中心粒组装所必需的。因此,Plk1 的作用是将中心粒复制周期与细胞周期相协调。Plk1 在晚期 S/G2 期间的激活诱导中心粒成熟,在此之后,即使没有细胞周期进展,中心粒周期也可以自主完成。