F-box proteins and cancer: an update from functional and regulatory mechanism to therapeutic clinical prospects
Dinesh Singh Tekcham, Di Chen, Yu Liu, Ting Ling, Yi Zhang, Huan Chen, Wen Wang, Wuxiyar Otkur, Huan Qi, Tian Xia, Xiaolong Liu, Hai‐long Piao, Hongxu Liu
Abstract
E3 ubiquitin ligases play a critical role in cellular mechanisms and cancer progression. F-box protein is the core component of the SKP1-cullin 1-F-box (SCF)-type E3 ubiquitin ligase and directly binds to substrates by various specific domains. According to the specific domains, F-box proteins are further classified into three sub-families: 1) F-box with leucine rich amino acid repeats (FBXL); 2) F-box with WD 40 amino acid repeats (FBXW); 3) F-box only with uncharacterized domains (FBXO). Here, we summarize the substrates of F-box proteins, discuss the important molecular mechanism and emerging role of F-box proteins especially from the perspective of cancer development and progression. These findings will shed new light on malignant tumor progression mechanisms, and suggest the potential role of F-box proteins as cancer biomarkers and therapeutic targets for future cancer treatment.