New Auroras on the Roles of the Chromosomal Passenger Complex in Cytokinesis: Implications for Cancer Therapies.
New Auroras on the Roles of the Chromosomal Passenger Complex in Cytokinesis: Implications for Cancer Therapies.
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DOI：
10.3389/fonc.2015.00221
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发表时间：
2015
影响因子：
4.7
通讯作者：
Capalbo L
中科院分区：
文献类型：
--
作者：
D'Avino PP;Capalbo L
由激酶组分Aurora B、支架亚基内着丝粒蛋白Borealin和Survivin组成的染色体乘客复合物（CPC）是细胞分裂的关键调节剂。它控制着多个事件，从前期的染色体浓缩到两个子细胞的最终分离或分裂。然而，CPC在中期的基本功能一直阻碍着对其在胞质分裂中作用的准确研究。近年来，针对Aurora B的小分子抑制剂的开发以及化学遗传学等先进技术的使用为研究CPC在细胞分裂末期的功能提供了新的方法。本文就CPC在卵裂沟、纺锤体和中间体组装中的作用作一综述。我们还将讨论这个复杂的关键功能，在控制终止时间，以防止终止时，落后的染色质存在于切割位点，从而避免形成遗传异常的子细胞。最后，我们提供了我们的观点，如何利用潜在的治疗应用抑制CPC活性在癌细胞胞质分裂。
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.