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在错误的时间出现在错误的地点:细胞周期蛋白定位错误是否会引发致癌转化?

In the wrong place at the wrong time: does cyclin mislocalization drive oncogenic transformation?

机构信息

Vernalis (R&D), Granta Park, Great Abington, Cambridge CB21 6GB, UK.

出版信息

Nat Rev Cancer. 2013 Mar;13(3):201-8. doi: 10.1038/nrc3468. Epub 2013 Feb 7.

Abstract

Cyclin-dependent kinases (CDKs) are regulated by both cyclin abundance and cyclin localization. Increased cyclin expression in cancer was first observed two decades ago, and its role in pathogenesis has been investigated in great depth. This Opinion article focuses on the spatial deregulation of cyclin expression and its potential link to oncogenesis. It describes the contexts in which particular cyclins have been reported to be mislocalized in neoplasia, reviews the mechanisms underlying the dynamic subcellular localization of CDK-cyclin complexes in normal cells, and discusses how these controls can be disrupted in cancer. It also outlines the mechanisms by which cyclin mislocalization might disrupt cell cycle control and interfere with faithful chromosome segregation. Finally, it discusses the extent to which cyclin mislocalization might facilitate tumorigenesis in human cancer.

摘要

细胞周期蛋白依赖性激酶(CDKs)受细胞周期蛋白丰度和细胞周期蛋白定位的调节。二十年前首次观察到癌症中细胞周期蛋白表达增加,其在发病机制中的作用已被深入研究。本文观点主要集中在细胞周期蛋白表达的空间失调及其与肿瘤发生的潜在联系上。它描述了特定细胞周期蛋白在肿瘤中报道的定位错误的情况,综述了 CDK-细胞周期蛋白复合物在正常细胞中动态亚细胞定位的机制,并讨论了这些控制在癌症中是如何被破坏的。它还概述了细胞周期蛋白定位错误可能破坏细胞周期控制并干扰染色体正确分离的机制。最后,它讨论了细胞周期蛋白定位错误在多大程度上可能促进人类癌症的发生。

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