期刊
SCIENCE
卷 370, 期 6521, 页码 1182-+出版社
AMER ASSOC ADVANCEMENT SCIENCE
DOI: 10.1126/science.aay2002
关键词
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资金
- Agency for Science, Technology and Research (GODAFIT Strategic Positioning Fund)
- National Medical Research Council, Singapore [NMRC/OFYIRG/0046/2017]
- Concern Foundation's Conquer Cancer Now Award
- National Research Foundation, Singapore
- the EAACI Research Fellowship, 2019
- A*STAR Investigatorship
- Senior NRF Investigatorship
- EMBO Young Investigatorship
Immune sensor proteins are critical to the function of the human innate immune system. The full repertoire of cognate triggers for human immune sensors is not fully understood. Here, we report that human NACHT, LRR, and PYD domains-containing protein 1 (NLRP1) is activated by 3C proteases (3Cpros) of enteroviruses, such as human rhinovirus (HRV). 3Cpros directly cleave human NLRP1 at a single site between Glu(130) and Gly(131). This cleavage triggers N-glycine-mediated degradation of the autoinhibitory NLRP1 N-terminal fragment via the cullin(ZER1/ZYG11B) complex, which liberates the activating C-terminal fragment. Infection of primary human airway epithelial cells by live human HRV triggers NLRP1-dependent inflammasome activation and interleukin-18 secretion. Our findings establish 3Cpros as a pathogen-derived trigger for the human NLRP1 inflammasome and suggest that NLRP1 may contribute to inflammatory diseases of the airway.
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