Please use this identifier to cite or link to this item: https://doi.org/10.1126/science.aay2002
Title: Enteroviral 3C protease activates the human NLRP1 inflammasome in airway epithelia.
Authors: Robinson, Kim S
Teo, Daniel Eng Thiam 
Tan, Kai Sen 
Toh, Gee Ann
Ong, Hsiao Hui 
Lim, Chrissie Kaishi
Lay, Kenneth
Au, Bijin Veonice
Lew, Tian Sheng
Chu, Justin Jang Hann 
Chow, Vincent Tak Kwong 
Wang, De Yun 
Zhong, Franklin L
Reversade, Bruno 
Issue Date: 22-Oct-2020
Publisher: American Association for the Advancement of Science (AAAS)
Citation: Robinson, Kim S, Teo, Daniel Eng Thiam, Tan, Kai Sen, Toh, Gee Ann, Ong, Hsiao Hui, Lim, Chrissie Kaishi, Lay, Kenneth, Au, Bijin Veonice, Lew, Tian Sheng, Chu, Justin Jang Hann, Chow, Vincent Tak Kwong, Wang, De Yun, Zhong, Franklin L, Reversade, Bruno (2020-10-22). Enteroviral 3C protease activates the human NLRP1 inflammasome in airway epithelia.. Science : eaay2002-eaay2002. ScholarBank@NUS Repository. https://doi.org/10.1126/science.aay2002
Abstract: 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 NLRP1 is activated by 3C proteases (3Cpros) of enteroviruses, such as human rhinovirus (HRV). 3Cpros directly cleave human NLRP1 at a single site between Glu130 and Gly131. This cleavage triggers N-glycine-mediated degradation of the autoinhibitory NLRP1 N-terminal fragment via the cullinZER1/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 IL-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.
Source Title: Science
URI: https://scholarbank.nus.edu.sg/handle/10635/181931
ISSN: 00368075
10959203
DOI: 10.1126/science.aay2002
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