Premium
SUMO1 SUMOylates and SENP3 deSUMOylates NLRP3 to orchestrate the inflammasome activation
Author(s) -
Shao Luyao,
Liu Yan,
Wang Wenbiao,
Li Aixin,
Wan Pin,
Liu Weiyong,
Shereen Muhammad Adnan,
Liu Fang,
Zhang Wen,
Tan Quiping,
Wu Kailang,
Liu Yingle,
Wu Jianguo
Publication year - 2020
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fj.201901653r
Subject(s) - inflammasome , sumo protein , secretion , chemistry , microbiology and biotechnology , innate immune system , caspase 1 , cleavage (geology) , aim2 , ubiquitin , biochemistry , biology , receptor , paleontology , fracture (geology) , gene
The NLRP3 inflammasome regulates innate immune and inflammatory responses by promoting caspase1‐dependent induction of pro‐inflammatory cytokines. However, aberrant inflammasome activation causes diverse diseases, and thus inflammasome activity must be tightly controlled. Here, we reveal a molecular mechanism underlying the regulation of NLRP3 inflammasome. NLRP3 interacts with SUMO‐conjugating enzyme (UBC9), which subsequently promotes small ubiquitin‐like modifier 1 (SUMO1) to catalyze NLRP3 SUMOylation at residue Lys 204 . SUMO1‐catalyzed SUMOylation of NLRP3 facilitates ASC oligomerization, inflammasome activation, and interleukin‐1β secretion. Moreover, this study also reveals that SUMO‐specific protease 3 (SENP3) is required for the deSUMOylation of NLRP3. Interestingly, SENP3 deSUMOylates NLRP3 to attenuate ASC recruitment and speck formation, the NLRP3 inflammasome activation, as well as IL‐1β cleavage and secretion. In conclusion, we reveal that SUMO1‐catalyzed SUMOylation and SENP3‐mediated deSUMOylation of NLRP3 orchestrate the inflammasome activation.