Kovacs Stephen B, Miao Edward A
Department of Microbiology and Immunology, Lineberger Comprehensive Cancer Center, and Center for Gastrointestinal Biology and Disease, University of North Carolina at Chapel Hill, Chapel Hill, NC 27599, USA.
Department of Microbiology and Immunology, Lineberger Comprehensive Cancer Center, and Center for Gastrointestinal Biology and Disease, University of North Carolina at Chapel Hill, Chapel Hill, NC 27599, USA.
Trends Cell Biol. 2017 Sep;27(9):673-684. doi: 10.1016/j.tcb.2017.05.005. Epub 2017 Jun 12.
Pyroptosis is a form of lytic programmed cell death initiated by inflammasomes, which detect cytosolic contamination or perturbation. This drives activation of caspase-1 or caspase-11/4/5, which cleave gasdermin D, separating its N-terminal pore-forming domain (PFD) from the C-terminal repressor domain (RD). The PFD oligomerizes to form large pores in the membrane that drive swelling and membrane rupture. Gasdermin D is one of six (in humans) gasdermin family members; several other gasdermins have also been shown to form pores that cause pyroptosis after cleavage to activate their PFDs. One of these, gasdermin E, is activated by caspase-3 cleavage. We review our current understanding of pyroptosis as well as current knowledge of the gasdermin family.
细胞焦亡是一种由炎性小体引发的溶解性程序性细胞死亡形式，炎性小体能检测胞质污染或扰动。这促使半胱天冬酶-1或半胱天冬酶-11/4/5激活，后者切割gasdermin D，将其N端成孔结构域（PFD）与C端抑制结构域（RD）分离。PFD寡聚化在膜上形成大孔，导致细胞肿胀和膜破裂。Gasdermin D是（人类）六种gasdermin家族成员之一；其他几种gasdermin也已被证明在切割后形成孔道，激活其PFD，从而导致细胞焦亡。其中一种gasdermin E由半胱天冬酶-3切割激活。我们综述了目前对细胞焦亡的理解以及对gasdermin家族的现有认识。
