Journal
NATURE REVIEWS IMMUNOLOGY
Volume 20, Issue 3, Pages 143-157Publisher
NATURE PUBLISHING GROUP
DOI: 10.1038/s41577-019-0228-2
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Funding
- Swiss National Science Foundation [175576]
- European Research Council [ERC-2013-CoG 614578, ERC-2017-CoG 770988]
- Sociedad Espanola de Reumatologia Pediatrica, Ministerio de Economia, Industria y Competitividad-Fondo Europeo de Desarrollo Regional [SAF2017-88276-R]
- Fundacion Seneca [20859/PI/18]
- China NSFC [81788101]
- MOST of China [2017YFA0505900, 2016YFA0501500]
- Chinese Academy of Sciences [XDB08020202]
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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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