极光激酶将染色体分离和细胞分裂与癌症易感性联系起来。

Aurora kinases link chromosome segregation and cell division to cancer susceptibility.

作者信息

Meraldi Patrick, Honda Reiko, Nigg Erich A

机构信息

Massachusetts Institute of Technology, Dept. of Biology, 77 Massachusetts Ave., Cambridge, MA 02139, USA.

出版信息

Curr Opin Genet Dev. 2004 Feb;14(1):29-36. doi: 10.1016/j.gde.2003.11.006.

DOI:10.1016/j.gde.2003.11.006

PMID:15108802

Abstract

Aurora kinases play critical roles in chromosome segregation and cell division. They are implicated in the centrosome cycle, spindle assembly, chromosome condensation, microtubule-kinetochore attachment, the spindle checkpoint and cytokinesis. Aurora kinases are regulated through phosphorylation, the binding of specific partners and ubiquitin-dependent proteolysis. Several Aurora substrates have been identified and their roles are being elucidated. The deregulation of Aurora kinases impairs spindle assembly, checkpoint function and cell division, causing missegregation of individual chromosomes or polyploidization accompanied by centrosome amplification. Aurora kinases are frequently overexpressed in cancers and the identification of Aurora A as a cancer-susceptibility gene provides a strong link between mitotic errors and carcinogenesis.

摘要

极光激酶在染色体分离和细胞分裂中发挥着关键作用。它们参与中心体周期、纺锤体组装、染色体凝聚、微管-动粒附着、纺锤体检查点和胞质分裂。极光激酶通过磷酸化、特定伴侣的结合以及泛素依赖性蛋白水解来调节。已经鉴定出几种极光激酶的底物，并且它们的作用正在被阐明。极光激酶的失调会损害纺锤体组装、检查点功能和细胞分裂，导致个别染色体的错误分离或多倍体化，并伴有中心体扩增。极光激酶在癌症中经常过度表达，并且将极光A鉴定为癌症易感基因，这为有丝分裂错误与致癌作用之间提供了强有力的联系。