D'Avino Pier Paolo, Capalbo Luisa
Department of Pathology, University of Cambridge , Cambridge , UK.
Front Oncol. 2015 Oct 14;5:221. doi: 10.3389/fonc.2015.00221. eCollection 2015.
The chromosomal passenger complex (CPC), composed of a kinase component, Aurora B, the scaffolding subunit inner centromeric protein, Borealin, and Survivin, is a key regulator of cell division. It controls multiple events, from chromosome condensation in prophase to the final separation or abscission of the two daughter cells. The essential functions of the CPC during metaphase, however, have always hindered an accurate study of its role during cytokinesis. The recent development of small molecule inhibitors against Aurora B and the use of elegant technologies such as chemical genetics have offered new approaches to study the functions of the CPC at the end of cell division. Here, we review the recent findings about the roles of the CPC in controlling the assembly of the cleavage furrow, central spindle, and midbody. We will also discuss the crucial function of this complex in controlling abscission timing in order to prevent abscission when lagging chromatin is present at the cleavage site, thereby avoiding the formation of genetically abnormal daughter cells. Finally, we offer our perspective on how to exploit the potential therapeutic applications of inhibiting CPC activity during cytokinesis in cancer cells.
染色体乘客复合体(CPC)由激酶成分极光激酶B、支架亚基着丝粒内蛋白、博瑞林和生存素组成,是细胞分裂的关键调节因子。它控制着多个事件,从前期的染色体凝聚到两个子细胞的最终分离或脱离。然而,CPC在中期的基本功能一直阻碍着对其在胞质分裂过程中作用的准确研究。针对极光激酶B的小分子抑制剂的最新研发以及化学遗传学等精湛技术的应用,为研究细胞分裂末期CPC的功能提供了新方法。在此,我们综述了关于CPC在控制分裂沟、中央纺锤体和中间体组装方面作用的最新发现。我们还将讨论该复合体在控制脱离时间方面的关键功能,以便在分裂位点存在滞后染色质时防止脱离,从而避免形成基因异常的子细胞。最后,我们就如何在癌细胞的胞质分裂过程中利用抑制CPC活性的潜在治疗应用提出了我们的观点。