炎性小体中ASC斑点形成机理及调控机制  

Advances in formation and regulation of ASC-speck in inflammasome activation-A review

作　　者：方仁东[1] 巫芮 申艳娜[2] 

机构地区：[1]西南大学动物科技学院,重庆400715 [2]天津医科大学医学检验学院,天津300203

出　　处：《微生物学报》2016年第9期1406-1414,共9页Acta Microbiologica Sinica

基　　金：国家自然科学基金(31400762;81101222);中央高校基本科研业务费专项(XDJK2015B002;SWU114032);重庆市科委专项(cstc2015shmszx80010);天津市自然科学基金(15JCYBJC49700)~~

摘　　要：在一系列微生物感染及内外源性刺激物的作用下,细胞质中多种蛋白复合物组装成炎性小体,其主要功能是活化半胱天冬酶-1,引起一系列促炎细胞因子的分泌和半胱天冬酶-1依赖性的细胞死亡。凋亡相关斑点样蛋白(ASC)是炎性小体中连接胞浆内受体和半胱天冬酶-1的接头蛋白,在炎性小体活化中ASC聚集成大分子的二聚体,被称为ASC斑点(ASC-speck)。ASC斑点的形成对半胱天冬酶-1的活化至关重要,调控ASC斑点的形成是炎性小体相关疾病的治疗和预防的新途径。本文从ASC斑点形成的分子机理,以及磷酸化、泛素化和去泛素化、离子通道等方面,对近年来ASC斑点的调控机制相关的研究进展进行综合评述,总结了ASC斑点的形成机理及主要调控机制,最后结合作者相关研究成果和观点对该领域的研究前景进行了展望。Under the effects of a series of microbial infection and endogenous or exogenous stimuli, inflammasomes are assembled as multiple protein complexes in the cytoplasm, which mainly contain pattern recognition receptors （PRRs）, apoptosis-associated speck-like protein containing a CARD （ASC）, and pro-caspase-1. The inflammasomes are the platform for caspase-1 activation and subsequent proinflammatory cytokines secretion, and caspase-1 dependent cell death as well. As a key adaptor protein, ASC concatenates PRRs and pro-caspase-1 in the cytoplasm. During inflammasome activation, ASC molecules assemble into large molecule dimers, which is called ASC-speck. The formation of ASC-speck is critical for caspase-1 activation, and ASC-speck becomes a target for the therapy and prevention of inflammatory diseases. In this review, advances in molecular mechanism of ASC-speck formation and the regulation systems for ASC-speck are summarized from the aspects of phosphorylation, ubiquitination and iron channels etc. Finally, the research prospects in this field are discussed.

关 键 词：炎性小体 ASC斑点 半胱天冬酶-1 半胱天冬酶募集结构域 

分 类 号：R364[医药卫生—病理学]