线性泛素化修饰研究进展

蛋白质泛素化修饰过程在调节各种细胞生物学功能的过程中发挥了非常重要的作用,如细胞周期进程、DNA损伤修复、信号转导和各种蛋白质膜定位等。泛素化修饰可分为多聚泛素化修饰和单泛素化修饰。多聚泛素化修饰系统可以通过对底物连接不同类型的多泛素化链调节蛋白质的功能。多聚泛素化修饰中已知7种泛素链连接方式均为泛素内赖氨酸连接方式。近几年发现了第8种类型的泛素链连接形式即线性泛素化,其泛素链的连接方式是由泛素甲硫氨酸的氨基基团与另一泛素甘氨酸的羧基基团相连形成泛素链标记。目前研究表明线性泛素化修饰在先天性免疫和炎症反应等多个过程中发挥着非常重要的作用。募集线性泛素链的泛素连接酶E3被称为LUBAC复合体,其组成底物以及其活性调控机制和功能所知甚少。本文综述了募集线性泛素化链的泛素连接酶、去泛素化酶、底物等活性调控机制及其在先天性免疫等多个领域中的功能,分析了后续研究方向,以期为相关研究提供参考。

Research progress in linear ubiquitin modification

Protein ubiquitination plays vital roles in regulating various cytobiological processes such as cell cycle progression, DNA damage repair, signal transduction and membrane localization of various proteins. Moreover, proteins can be modified by single ubiquitin molecules (monoubiquitination) or ubiquitin chains (polyubiquitination). Polyubiquitination regulates protein function by linking different types of polyubiquitin chains to substrates. All the 7 known linkage types of polyubiquitination are inter-ubiquitin linkages formed through lysine residues. In recent years, the eighth ubiquitin linkage type, linear ubiquitination in which the linkages are formed between the amino group of methionine residues of ubiquitin and the carboxy group of glycine residues of another, has been identified. Studies have shown that linear ubiquitination plays very important roles in various processes including innate immunity and inflammatory reactions. The ubiquitin ligase E3 that recruits linear ubiquitin chains is called linear ubiquitin chain assembly complex (LUBAC), however, little is known about its constitutive substrates, activity regulation and functions. Here we reviewed the mechanism of activity regulation of ubiquitin ligases, deubiquitinating enzymes and substrates as well as their roles in multiple areas including innate immunity, and also analyzed future directions to provide references for relevant studies.