遗传
遺傳
유전
Hereditas
2015年
9期
911-917
,共7页
线性泛素化修饰%LUBAC复合体%NF-κB信号通路%HOIP
線性汎素化脩飾%LUBAC複閤體%NF-κB信號通路%HOIP
선성범소화수식%LUBAC복합체%NF-κB신호통로%HOIP
Linear ubiquitin modification%LUBAC complex%NF-κB signaling pathways%HOIP
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。
蛋白質汎素化脩飾過程在調節各種細胞生物學功能的過程中髮揮瞭非常重要的作用，如細胞週期進程、DNA 損傷脩複、信號轉導和各種蛋白質膜定位等。汎素化脩飾可分為多聚汎素化脩飾和單汎素化脩飾。多聚汎素化脩飾繫統可以通過對底物連接不同類型的多汎素化鏈調節蛋白質的功能。多聚汎素化脩飾中已知7種汎素鏈連接方式均為汎素內賴氨痠連接方式。近幾年髮現瞭第8種類型的汎素鏈連接形式即線性汎素化，其汎素鏈的連接方式是由汎素甲硫氨痠的氨基基糰與另一汎素甘氨痠的羧基基糰相連形成汎素鏈標記。目前研究錶明線性汎素化脩飾在先天性免疫和炎癥反應等多箇過程中髮揮著非常重要的作用。募集線性汎素鏈的汎素連接酶E3被稱為LUBAC複閤體，其組成底物以及其活性調控機製和功能所知甚少。本文綜述瞭募集線性汎素化鏈的汎素連接酶、去汎素化酶、底物等活性調控機製及其在先天性免疫等多箇領域中的功能，分析瞭後續研究方嚮，以期為相關研究提供參攷。
단백질범소화수식과정재조절각충세포생물학공능적과정중발휘료비상중요적작용，여세포주기진정、DNA 손상수복、신호전도화각충단백질막정위등。범소화수식가분위다취범소화수식화단범소화수식。다취범소화수식계통가이통과대저물련접불동류형적다범소화련조절단백질적공능。다취범소화수식중이지7충범소련련접방식균위범소내뢰안산련접방식。근궤년발현료제8충류형적범소련련접형식즉선성범소화，기범소련적련접방식시유범소갑류안산적안기기단여령일범소감안산적최기기단상련형성범소련표기。목전연구표명선성범소화수식재선천성면역화염증반응등다개과정중발휘착비상중요적작용。모집선성범소련적범소련접매E3피칭위LUBAC복합체，기조성저물이급기활성조공궤제화공능소지심소。본문종술료모집선성범소화련적범소련접매、거범소화매、저물등활성조공궤제급기재선천성면역등다개영역중적공능，분석료후속연구방향，이기위상관연구제공삼고。
Protein ubiquitination plays vital roles in regulating various cytobiological processes such as cell cycle pro-gression, 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.
