XPO1/CRM1介导的核质运输与疾病治疗

XPO1/CRM1-mediated nucleocytoplasmic transport and disease therapy

蛋白质在细胞中的定位和分布非常重要,蛋白质的错误定位或者异常调节将会导致各种疾病的产生,包括癌症、炎症、自身免疫性疾病等。XPO1(又称CRM1)是核输出蛋白受体importinβ家族的重要成员,主要负责一些肿瘤抑制蛋白、生长调节蛋白如p53、p21、FOXO、PI3K/AKT、Wnt/β-catenin、AP-1和NF-κB等的核输出,通过小分子化合物来调节XPO1介导的特异性蛋白质的核输出,从而恢复一些重要蛋白质在核内的正常分布及功能,是治疗相关疾病的一种有效方法。本综述介绍XPO1介导的核输出机制以及靶向核输出蛋白XPO1治疗疾病的研究进展。

The localization and adjustment of protein in each cell is very important. Aberrant localization or regulation of protein will lead to a variety of diseases, including cancer, inflammation, autoimmune diseases, etc. XPO1 （also referred as CRM1） is a key member of the importin β superfamily of nuclear transport recep- tors. CRM1 controls the transport of a number of tumor suppressor proteins and growth regulatory proteins including p53, p21, FOXO, PI3K/AKT, Wnt/β-catenin, AP-1 and NF-KB, etc. The mislocation of key regu- lator proteins during the pathogenesis of human diseases can be restored by the treatment of XPO1 inhibitors or modulators. This review is to introduce XPOl-mediated transport machinery and the research progress of treating the disease targeting XPO1.