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防止非整倍体:有丝分裂检查点蛋白的作用

Preventing aneuploidy: the contribution of mitotic checkpoint proteins.

作者信息

Suijkerbuijk Saskia J E, Kops Geert J P L

机构信息

Department of Physiological Chemistry, UMC Utrecht, Universiteitsweg 100, 3584 CG Utrecht, The Netherlands.

出版信息

Biochim Biophys Acta. 2008 Sep;1786(1):24-31. doi: 10.1016/j.bbcan.2008.04.001. Epub 2008 Apr 22.

Abstract

Aneuploidy, an abnormal number of chromosomes, is a trait shared by most solid tumors. Chromosomal instability (CIN) manifested as aneuploidy might promote tumorigenesis and cause increased resistance to anti-cancer therapies. The mitotic checkpoint or spindle assembly checkpoint is a major signaling pathway involved in the prevention of CIN. We review current knowledge on the contribution of misregulation of mitotic checkpoint proteins to tumor formation and will address to what extent this contribution is due to chromosome segregation errors directly. We propose that both checkpoint and non-checkpoint functions of these proteins contribute to the wide array of oncogenic phenotypes seen upon their misregulation.

摘要

非整倍体,即染色体数量异常,是大多数实体瘤共有的特征。表现为非整倍体的染色体不稳定性(CIN)可能促进肿瘤发生并导致对抗癌治疗的耐药性增加。有丝分裂检查点或纺锤体组装检查点是参与预防CIN的主要信号通路。我们综述了关于有丝分裂检查点蛋白调控异常对肿瘤形成的作用的现有知识,并将探讨这种作用在多大程度上直接归因于染色体分离错误。我们提出,这些蛋白的检查点和非检查点功能都导致了其调控异常时出现的广泛致癌表型。

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