The E3 ubiquitin ligase TRIM31 attenuates NLRP3 inflammasome activation by promoting proteasomal degradation of NLRP3

• DOI: 10.1038/ncomms13727
• Publication Date: 2016-12-08T10:08:56Z
• Authors: Hui Song; Bingyu Liu; Wanwan Huai; Zhongxia Yu; Wenwen Wang; Jing Zhao; Lihui Han; Guosheng Jiang; Lining Zhang; Chengjiang Gao; Wei Zhao
• Keywords: Lipopolysaccharides; 0301 basic medicine; Proteasome Endopeptidase Complex; Inflammasomes; Science; Ubiquitin-Protein Ligases; Interleukin-1beta; Primary Cell Culture; Peritonitis; Article; Tripartite Motif Proteins; 03 medical and health sciences; NLR Family, Pyrin Domain-Containing 3 Protein; Animals; Polyubiquitin; Mice, Knockout; Q; Dextran Sulfate; Ubiquitination; Nuclear Proteins; Colitis; 3. Good health; Mice, Inbred C57BL; Alum Compounds; Female; Carrier Proteins

The NLRP3 inflammasome has a fundamental role in host defence against microbial pathogens and its deregulation may cause diverse inflammatory diseases. protein expression is rate-limiting step for activation, thus must be tightly controlled to maintain immune homeostasis avoid detrimental effects. However, how regulated remains largely unknown. In this study, we identify E3 ubiquitin ligase TRIM31 as feedback suppressor of inflammasome. directly binds NLRP3, promotes K48-linked polyubiquitination proteasomal degradation NLRP3. Consequently, deficiency enhances activation aggravates alum-induced peritonitis vivo. Furthermore, attenuates the severity dextran sodium sulfate (DSS)-induced colitis, an bowel diseases model which possesses protective roles. Thus, our research describes mechanism by limits activity under physiological conditions suggests potential therapeutic target intervention related