气候变化领域集成服务门户(CCPortal): Granzyme A from cytotoxic lymphocytes cleaves GSDMB to trigger pyroptosis in target cells

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DOI	10.1126/science.aaz7548
	Granzyme A from cytotoxic lymphocytes cleaves GSDMB to trigger pyroptosis in target cells
	Zhou Z.; He H.; Wang K.; Shi X.; Wang Y.; Su Y.; Wang Y.; Li D.; Liu W.; Zhang Y.; Shen L.; Han W.; Shen L.; Ding J.; Shao F.
发表日期	2020
ISSN	0036-8075
卷号	368 期号:6494
英文摘要	Cytotoxic lymphocyte-mediated immunity relies on granzymes. Granzymes are thought to kill target cells by inducing apoptosis, although the underlying mechanisms are not fully understood. Here, we report that natural killer cells and cytotoxic T lymphocytes kill gasdermin B (GSDMB)-positive cells through pyroptosis, a form of proinflammatory cell death executed by the gasdermin family of poreforming proteins. Killing results from the cleavage of GSDMB by lymphocyte-derived granzyme A (GZMA), which unleashes its pore-forming activity. Interferon-g (IFN-g) up-regulates GSDMB expression and promotes pyroptosis. GSDMB is highly expressed in certain tissues, particularly digestive tract epithelia, including derived tumors. Introducing GZMA-cleavable GSDMB into mouse cancer cells promotes tumor clearance in mice. This study establishes gasdermin-mediated pyroptosis as a cytotoxic lymphocyte-killing mechanism, which may enhance antitumor immunity. © 2020 American Association for the Advancement of Science. All rights reserved.
关键词	cell cell component cytology enzyme enzyme activity gene expression immunity tumor Mus gamma interferon granzyme GSDMB protein, human GZMA protein, human pore forming cytotoxic protein tumor protein animal Bagg albino mouse chemistry cytotoxic T lymphocyte enzymology genetics HEK293 cell line human immunology metabolism mouse natural killer cell neoplasm pathology protein degradation protein domain pyroptosis transgenic mouse Animals Granzymes HEK293 Cells Humans Interferon-gamma Killer Cells, Natural Mice Mice, Inbred BALB C Mice, Transgenic Neoplasm Proteins Neoplasms Pore Forming Cytotoxic Proteins Protein Domains Proteolysis Pyroptosis T-Lymphocytes, Cytotoxic
语种	英语
来源机构	Science
文献类型	期刊论文
条目标识符	http://gcip.llas.ac.cn/handle/2XKMVOVA/133468
推荐引用方式 GB/T 7714	Zhou Z.,He H.,Wang K.,et al. Granzyme A from cytotoxic lymphocytes cleaves GSDMB to trigger pyroptosis in target cells[J]. Science,2020,368(6494).
APA	Zhou Z..,He H..,Wang K..,Shi X..,Wang Y..,...&Shao F..(2020).Granzyme A from cytotoxic lymphocytes cleaves GSDMB to trigger pyroptosis in target cells.,368(6494).
MLA	Zhou Z.,et al."Granzyme A from cytotoxic lymphocytes cleaves GSDMB to trigger pyroptosis in target cells".368.6494(2020).