@article{f22ff9c030a94718ba73d324d114a08f,
title = "Peli1 facilitates NLRP3 inflammasome activation by mediating ASC ubiquitination",
abstract = "Inflammasomes are crucial for innate immunity against infections and, when deregulated, also contribute to inflammatory diseases. Here, we identify a critical function of the E3 ubiquitin ligase Peli1 in regulating the activation of NLRP3 inflammasome. Peli1 deficiency impairs induction of interleukin-1β (IL-1β) secretion by different NLRP3 inducers, but not by inducers of the Aim2, NLRP1, and NLRC4 inflammasomes. Peli1-deficient mice have alleviated peritonitis induction by alum and display increased resistance to lipopolysaccharide (LPS) endotoxin shock, coupled with decreased serum concentration of IL-1β. Peli1 is required for NLRP3-induced caspase-1 activation and IL-1β maturation. Mechanistically, Peli1 conjugates K63 ubiquitin chain to lysine 55 of the inflammasome adaptor apoptosis-associated speck-like protein containing a caspase recruitment domain (ASC), which in turn facilitates ASC/NLRP3 interaction and ASC oligomerization, thereby contributing to inflammasome activation. Peli1 deficiency impairs the ubiquitination of ASC and inhibits inflammasome activation. Our findings establish Peli1 as an important inflammasome regulator and suggest a mechanism by which Peli1 mediates inflammatory responses.",
keywords = "ASC, Peli1, inflammasome, ubiquitination",
author = "Lingyun Zhang and Ko, {Chun Jung} and Yanchuan Li and Zuliang Jie and Lele Zhu and Xiaofei Zhou and Xiaoping Xie and Tianxiao Gao and Ting Liu and Xuhong Cheng and Sun, {Shao Cong}",
note = "Funding Information: We thank the Knockout Mouse Project (KOMP) and the European Conditional Mouse Mutagenesis Program (EUCOMM) for the Peli1-targeted mice and BEI Resources for iBMDMs. This work was supported by grants from the National Institutes of Health ( AI104519 and AI057555 ). This study also used the NIH/NCI -supported resources under award number P30CA016672 at The MD Anderson Cancer Center. T.G. was a visiting student supported by a scholarship from the China Scholarship Council (grant 201906380080 ). Funding Information: We thank the Knockout Mouse Project (KOMP) and the European Conditional Mouse Mutagenesis Program (EUCOMM) for the Peli1-targeted mice and BEI Resources for iBMDMs. This work was supported by grants from the National Institutes of Health (AI104519 and AI057555). This study also used the NIH/NCI-supported resources under award number P30CA016672 at The MD Anderson Cancer Center. T.G. was a visiting student supported by a scholarship from the China Scholarship Council (grant 201906380080). Lingyun Zhang and Chun-Jung Ko designed and performed research, analyzed data, and prepared the figures; Chun-Jung Ko wrote the manuscript; Yanchuan Li, Zuliang Jie, Lele Zhu, Xiaofei Zhou, Xiaoping Xie, and Tianxiao Gao assisted with animal experiments, sample processing, and/or data analysis; Ting Liu performed experiments; Xuhong Cheng assisted with animal experiments; and Shao-Cong Sun supervised the work and wrote the manuscript. X.X. is presently an employee of AbbVie, a company headquartered in Lake County, IL, although his contribution to this work was made while he was employed at the University of Texas MD Anderson Cancer Center. The remaining authors declare no competing interests. Publisher Copyright: {\textcopyright} 2021 The Author(s)",
year = "2021",
month = oct,
day = "26",
doi = "10.1016/j.celrep.2021.109904",
language = "English (US)",
volume = "37",
journal = "Cell Reports",
issn = "2211-1247",
publisher = "Cell Press",
number = "4",
}