Department of Pathology, Case Western Reserve University, Cleveland, OH, United States.
Department of Pathology, Case Western Reserve University, Cleveland, OH, United States.
Adv Immunol. 2023;158:75-106. doi: 10.1016/bs.ai.2023.03.002. Epub 2023 Apr 11.
Gasdermins are effectors of pyroptosis downstream of diverse signaling pathways. Emerging evidence suggests that a number of post-translational modifications regulate the function of gasdermins in pyroptosis, a highly inflammatory form of cell death, and lytic or non-lytic secretion of intracellular contents. These include processing by different caspases and other proteases that may activate or suppress pyroptosis, ubiquitination by a bacterial E3 ligase that suppresses pyroptosis as an immune evasion mechanism, modifications at Cys residues in mammalian or microbial gasdermins that promote or inhibit pyroptosis, and potential phosphorylation that represses pyroptosis. Such diverse regulatory mechanisms by host and microbial proteases, ubiquitin ligases, acyltransferases, kinases and phosphatases may underlie the divergent physiological and pathological functions of gasdermins, and furnish opportunities for therapeutic targeting of gasdermins in infectious diseases and inflammatory disorders.
Gasdermins 是多种信号通路下游细胞焦亡的效应蛋白。有研究表明，多种翻译后修饰调控着 Gasdermins 在细胞焦亡（一种高度炎症的细胞死亡形式）和细胞内物质的裂解或非裂解分泌中的功能。这些修饰包括不同半胱天冬酶和其他蛋白酶的加工，它们可能激活或抑制细胞焦亡；细菌 E3 连接酶的泛素化，这是一种免疫逃避机制，抑制细胞焦亡；哺乳动物或微生物 Gasdermins 中 Cys 残基的修饰，促进或抑制细胞焦亡；以及可能的磷酸化，抑制细胞焦亡。宿主和微生物蛋白酶、泛素连接酶、酰基转移酶、激酶和磷酸酶的这些不同调控机制可能是 Gasdermins 具有不同生理和病理功能的基础，并为在传染病和炎症性疾病中靶向 Gasdermins 提供了机会。
