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

Zhiwei Zhou(Chinese Academy of Medical Sciences & Peking Union Medical College), Huabin He(Peking University), Kun Wang(National Institute of Biological Sciences, Beijing), Xuyan Shi(National Institute of Biological Sciences, Beijing), Yupeng Wang(Chinese Academy of Medical Sciences & Peking Union Medical College), Ya Su(National Institute of Biological Sciences, Beijing), Yao Wang(Chinese Academy of Medical Sciences & Peking Union Medical College), Da Li(National Institute of Biological Sciences, Beijing), Wang Liu(Chinese Academy of Medical Sciences & Peking Union Medical College), Yongliang Zhang(Ustar Biotechnologies (China)), Lianjun Shen(Peking University), Weidong Han(Chinese PLA General Hospital), Lin Shen(Peking University), Jingjin Ding(Chinese Academy of Sciences), Feng Shao(Chinese Academy of Sciences)
Science
April 16, 2020
10.1126/science.aaz7548
Cited by 1,297

Abstract

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

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