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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。
In a series of microbial infections and exogenous stimuli, the cytoplasm of a variety of protein complexes assembled into inflammatory bodies, its main function is to activate caspase-1, causing a series of pro-inflammatory cytokines Secretion and caspase-1-dependent cell death. Apoptosis-associated speckle-like proteins (ASCs) are adapter proteins in the inflammasome that connect the intracytoplasmic receptors and caspase-1, and ASC aggregates into macromolecular dimers during inflammasome activation, It is called ASC-speck. The formation of ASC spots is crucial for the activation of caspase-1, and the regulation of the formation of ASC spots is a new approach for the treatment and prevention of inflammatory corpus-related diseases. In this paper, we summarize the research progress on the regulation mechanism of ASC spots in recent years from the molecular mechanism of ASC spots formation, phosphorylation, ubiquitination and de-ubiquitination, ion channels and so on, and summarize the formation mechanism of ASC spots And the main regulation and control mechanism. Finally, the research prospects in this field are prospected in the light of the author’s relevant research findings and perspectives.