泛素连接酶SCF~(FBW7)调控的靶蛋白研究进展

FBW7(F-box and WD repeat domain-containing7,FBW7)为F-box蛋白家族成员,是SCF型泛素连接酶复合物的底物识别蛋白,介导细胞内多种蛋白质经泛素-蛋白酶体途径降解。FBW7通过靶向降解多种癌蛋白如Mcl-1、Notch、HIF-1α、Cyclin E和KFL5等,参与调控细胞增殖、分化、凋亡及肿瘤转移等多种生物学过程。作为一种肿瘤抑制蛋白,FBW7基因突变或缺失存在于多种人类肿瘤中,如白血病、乳腺癌、卵巢癌、胆管癌等,并在这些肿瘤的发生和发展中发挥重要作用。因此,针对FBW7的深入研究有助于理解肿瘤的发生发展机制以及开发肿瘤治疗新方案。本文就FBW7调控的癌蛋白研究进展作一综述。

Progress onUbiquitin-proteinEnzyme SCFFBW7RegulatingTarget Proteins

FBW7(F-box and WD repeat domain-containing7, FBW7) is a member of F - box protein family, seving as a substrate recognition unit of the SCF ubiquitin protein enzyme complex. FBW7 mediates the ubiquitylation of several oncoproteins, like Mcl-1, Notch, HIF-1alpha, Cyclin E and KFL5, and promotes their degradation via the ubiquitin - proteasome pathway. Therefore , FBW7 plays a key role in regulating a variety of biological processes such as cell cycle progression, cell proliferation, differentiation, apoptosis and tumor metastasis. As a tumor suppressor, gene deletion or mutations of FBW7 have been identified in various types of human tumor including leukemia, breast cancer, ovarian cancer and bile duct carcinoma. Therefore, research into FBW7 is of vital importance for a better understanding of tumorigenesis and cancer progression, and for developing novel targets for cancer therapy. This review summarizes the progression on the ubiquitin-protein enzyme SCFFBW7regulating oncoproteins.