泛素特异性蛋白酶2的生理功能及调控机制

Physiological functions and regulatory mechanisms of ubiquitin specific protease 2

泛素特异性蛋白酶2(ubiquitin specific peptidase 2,USP2)是去泛素化酶家族(deubiquitylating enzymes,DUBs)的重要成员,通过特异性去除靶蛋白的泛素化修饰,阻碍靶蛋白的降解,从而调控机体各项生理过程。USP2通过可变剪切产生USP2-45和USP2-69,这两种变体在各种生理过程中发挥的作用不尽相同。该文详细梳理了USP2-45和USP2-69在肿瘤发生、葡萄糖代谢、神经性疾病、骨骼肌分化、细胞凋亡以及雄性生殖等多种病理/生理过程中的作用,并进一步探讨了USP2与生物钟系统之间的互作机制,为深入解析USP2的生理功能以及生物钟调控Usp2转录的分子机制提供参考借鉴。

Ubiquitin specific peptidase 2(USP2)is an important member of deubiquitylating enzymes(DUBs)family.USP2 impedes the degradation of its target proteins by specifically removing the ubiquitin modification,thereby regulating various physiological processes of living organisms.There are two main variants of USP2formed by alternative splicing,namely USP2-45 and USP2-69,which play different roles in various physiological processes.This article summarizes the roles of USP2-45 and USP2-69 in diverse pathological/physiological processes,including tumorigenesis,glucose metabolism,neurological diseases,skeletal muscle differentiation,cell apoptosis,and male reproduction.In addition,the interaction mechanisms between USP2 and circadian clock system are further discussed.Collectively,this paper provides a reference for in-depth analysis of the physiological functions of USP2 and the molecular mechanisms on circadian clock regulating Usp2 transcription.