去泛素化酶USP14对铁死亡的调控作用

The regulation of deubiquitinase USP14 in ferroptosis

铁死亡是一种依赖铁的新型非凋亡细胞死亡形式,在调节细胞代谢、细胞命运决定以及疾病的发生和发展中扮演着关键角色。去泛素化酶14(ubiquitin-specific protease 14,USP14)作为泛素-蛋白酶体和自噬途径的重要调节因子,除了参与细胞周期、免疫反应、信号转导等经典生命活动的调节,对铁死亡相关途径的关键蛋白发挥了精细调控作用。USP14作为一个潜在的抗肿瘤药物靶点,目前已经有一系列靶向抑制剂被开发出来。本文主要综述了USP14的活性调控机制、在铁死亡相关疾病中的生理作用以及其小分子抑制剂的研究进展,并对相关研究中的问题和挑战进行了深入探讨,旨在为未来的研究提供新的方向和策略。

Ferroptosis is a novel form of non-apoptotic cell death that is dependent on iron. An increasing number of studies indicate that ferroptosis plays a key role in regulating cell metabolism, cell fate determination, and the occurrence and development of various diseases. As an important regulator of ubiquitinproteasome and autophagy pathways, ubiquitin-specific protease 14(USP14) not only participates in the regulation of many classic life activities such as cell cycle, immune response, signal transduction and autophagy, but recent studies have also shown that it exerts fine regulatory effect on key proteins in ferroptosisrelated pathways. USP14 is a potential anti-tumor drug target, and a series of targeted inhibitors have been developed. This review mainly summarizes the regulation mechanism of USP14 activity, physiological role in ferroptosis-related diseases and small molecule inhibitors of USP14. It also conducts an in-depth discussion of the issues and challenges in related research, aiming to provide new directions and strategies for future studies.