中文摘要：

泛素蛋白酶系统对于维持细胞正常生理功能具有重要作用，Fbw7是E3泛素连接酶的底物结合单位，参与泛素化降解与细胞增殖、分化、凋亡有关的重要分子，其调控异常在肿瘤细胞中极为常见。Fbw7调控的底物包括一系列促癌分子和癌症相关转录因子，被认为是重要的抑癌分子。比如Fbw7可以通过调控Cyclin E、c-Myc、Aurora A减少因细胞周期异常而造成的染色体不稳，通过调控p63、Mcl1 来影响细胞损伤修复并增加细胞凋亡，通过调控TGFβ、mTOR抑制肿瘤转移，再者可以通过对 Notch和Bcl2家族分子的调控增加肿瘤细胞对化疗的敏感性。因此稳定Fbw7的表达可以抑制肿瘤表型的产生和发展，本文就 Fbw7结构功能、突变机制，调控通路及其在肿瘤发生发展中的作用进行综述。

英文摘要：

Ubiquifin proteasome system is physically essential to normal cell functions. Fbw7 is a subunit of E3 ligase specifically binding to a series of substrates to promote their lysosomal degradation, the regulation of which is commonly mutated in tumors. Most substrates of Fbw7 are dominant oncogenes, including Cyclin E, c-Myc, Notch, Aurora A, and Mcll, which intensively regulate cell cyc!e, DNA repair, metastasis as well as chemoresistance. Therefore, Fbw7 targeting intervention can inhibit malignant transformation of cells. This review focuses on the biological functions, genetic alterations and regulation networks of Fbw7 in order to highlight its role in tumor progression.