上睑下垂
效应器
程序性细胞死亡
溶解循环
细胞毒性T细胞
细胞生物学
生物
免疫学
细胞凋亡
化学
生物化学
体外
病毒
作者
Petr Brož,Pablo Pelegrı́n,Feng Shao
出处
期刊:Nature Reviews Immunology
[Springer Nature]
日期:2019-11-05
卷期号:20 (3): 143-157
被引量:888
标识
DOI:10.1038/s41577-019-0228-2
摘要
The gasdermins are a family of recently identified pore-forming effector proteins that cause membrane permeabilization and pyroptosis, a lytic pro-inflammatory type of cell death. Gasdermins contain a cytotoxic N-terminal domain and a C-terminal repressor domain connected by a flexible linker. Proteolytic cleavage between these two domains releases the intramolecular inhibition on the cytotoxic domain, allowing it to insert into cell membranes and form large oligomeric pores, which disrupts ion homeostasis and induces cell death. Gasdermin-induced pyroptosis plays a prominent role in many hereditary diseases and (auto)inflammatory disorders as well as in cancer. In this Review, we discuss recent developments in gasdermin research with a focus on mechanisms that control gasdermin activation, pore formation and functional consequences of gasdermin-induced membrane permeabilization. The gasdermin family of proteins has the capacity to form pores in the membrane, causing a pro-inflammatory lytic type of cell death called pyroptosis, This Review provides a comprehensive overview of the gasdermin family, the mechanisms that control their activation and their role in inflammatory disorders and cancer.
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