Granzyme A from cytotoxic lymphocytes cleaves GSDMB to trigger pyroptosis in target cells

作者：Zhiwei Zhou, Huabin He, Kun Wang, Xuyan Shi, Yupeng Wang, Ya Su, Yao Wang, Da Li, Wang Liu, Yongliang Zhang, Lianjun Shen, Weidong Han, Lin Shen, Jingjin Ding, Feng Shao · 发表于：Science · 年份：2020 · DOI：10.1126/science.aaz7548 · 被引用次数：1333 · 研究领域：Inflammasome and immune disorders、Gout, Hyperuricemia, Uric Acid、Neutrophil, Myeloperoxidase and Oxidative Mechanisms

Granzyme A lights a fire Cytotoxic T cells and natural killer cells use several strategies to kill infected or transformed cells. One such pathway entails the delivery of a family of serine proteases called granzymes to target cells through perforin-mediated pores to induce a form of programmed cell death called apoptosis. Zhou et al. show that granzyme A cleaves and activates gasdermin B (GSDMB), a central player in the highly inflammatory cell death process known as pyroptosis (see the Perspective by Nicolai and Raulet). GSDMB expression was highly expressed in some tissues and could be up-regulated by interferon-γ. Enforced expression of GSDMB in cancer cells enhanced tumor clearance in a mouse model, suggesting that this pathway may be a target for future cancer immunotherapies. Science , this issue p. eaaz7548 ; see also p. 943