Ludwig Institute for Cancer Research, Department of Cellular and Molecular Medicine, University of California, San Diego, La Jolla, CA, USA.
Cell Cycle. 2010 Jul 15;9(14):2731-6. doi: 10.4161/cc.9.14.12184. Epub 2010 Jul 27.
In interphase and mitosis, centrosomes play a major role in the spatial organization of the microtubule network. Alterations in centrosome number and structure are associated with genomic instability and occur in many cancers. Centrosome duplication is controlled by centriole replication. In most dividing animal cells, centrioles duplicate only once per cell cycle at a site adjacent to existing centrioles. The conserved protein kinase Polo-like kinase 4 (Plk4) has a key role in controlling centriole biogenesis. Overexpression of Plk4 drives centrosome amplification and is associated with tumorigenesis in flies. By contrast, haploinsufficiency of Plk4 promotes cytokinesis failure, leading to an increased incidence of tumors in mice. Recent studies have shown that Plk4 is a low abundance protein whose stability is linked to the activity of the enzyme. We discuss how this autoregulatory feedback loop acts to limit the damaging effects caused by too much or too little Plk4.
在间期中和有丝分裂中，中心体在微管网络的空间组织中起主要作用。中心体数量和结构的改变与基因组不稳定性有关，发生在许多癌症中。中心体的复制由中心粒复制控制。在大多数有丝分裂的动物细胞中，中心粒在细胞周期中仅在与现有中心粒相邻的位置复制一次。保守的蛋白激酶 Polo 样激酶 4（Plk4）在控制中心粒发生中起关键作用。Plk4 的过表达驱动中心体扩增，并与果蝇的肿瘤发生有关。相比之下，Plk4 的杂合不足会促进胞质分裂失败，导致小鼠肿瘤的发生率增加。最近的研究表明，Plk4 是一种低丰度的蛋白质，其稳定性与酶的活性有关。我们讨论了这种自调节反馈环如何作用以限制过多或过少的 Plk4 造成的破坏性影响。
