York Biomedical Research Institute, University of York, Heslington, York, U.K.
Department of Biology, University of York, Heslington, York, U.K.
Biochem Soc Trans. 2021 Jun 30;49(3):1311-1324. doi: 10.1042/BST20200986.
Innate immune responses are tightly regulated by various pathways to control infections and maintain homeostasis. One of these pathways, the inflammasome pathway, activates a family of cysteine proteases called inflammatory caspases. They orchestrate an immune response by cleaving specific cellular substrates. Canonical inflammasomes activate caspase-1, whereas non-canonical inflammasomes activate caspase-4 and -5 in humans and caspase-11 in mice. Caspases are highly specific enzymes that select their substrates through diverse mechanisms. During inflammation, caspase activity is responsible for the secretion of inflammatory cytokines and the execution of a form of lytic and inflammatory cell death called pyroptosis. This review aims to bring together our current knowledge of the biochemical processes behind inflammatory caspase activation, substrate specificity, and substrate signalling.
先天免疫反应受多种途径的严格调控，以控制感染并维持体内平衡。其中一条途径是炎症小体途径，它激活了一组称为炎性半胱天冬酶的胱氨酸蛋白酶。它们通过切割特定的细胞底物来协调免疫反应。经典炎症小体激活半胱天冬酶-1，而非经典炎症小体在人类中激活半胱天冬酶-4 和 -5，而在小鼠中激活半胱天冬酶-11。半胱天冬酶是高度特异的酶，通过多种机制选择其底物。在炎症过程中，半胱天冬酶的活性负责炎症细胞因子的分泌以及一种称为细胞焦亡的溶酶体和炎症性细胞死亡形式的执行。这篇综述旨在汇集我们目前对炎症性半胱天冬酶激活、底物特异性和底物信号转导背后的生化过程的认识。
