Document Type
Article
Publication Date
12-1-2018
Abstract
The NLRP3 inflammasome responds to infection and tissue damage, and rapidly escalates the intensity of inflammation by activating interleukin (IL)-1β, IL-18 and cell death by pyroptosis. How the NLRP3 inflammasome is negatively regulated is poorly understood. Here we show that NLRP3 inflammasome activation is suppressed by sumoylation. NLRP3 is sumoylated by the SUMO E3-ligase MAPL, and stimulation-dependent NLRP3 desumoylation by the SUMO-specific proteases SENP6 and SENP7 promotes NLRP3 activation. Defective NLRP3 sumoylation, either by NLRP3 mutation of SUMO acceptor lysines or depletion of MAPL, results in enhanced caspase-1 activation and IL-1β release. Conversely, depletion of SENP7 suppresses NLRP3-dependent ASC oligomerisation, caspase-1 activation and IL-1β release. These data indicate that sumoylation of NLRP3 restrains inflammasome activation, and identify SUMO proteases as potential drug targets for the treatment of inflammatory diseases.
Recommended Citation
Barry, Rachael; John, Sidonie Wicky; Liccardi, Gianmaria; Tenev, Tencho; Jaco, Isabel; Chen, Chih-Hong; Choi, Justin; Kasperkiewicz, Paulina; Fernandes-Alnemri, Teresa; Alnemri, Emad S; Drag, Marcin; Chen, Yuan; and Meier, Pascal, "SUMO-mediated regulation of NLRP3 modulates inflammasome activity." (2018). Department of Biochemistry and Molecular Biology Faculty Papers. Paper 137.
https://jdc.jefferson.edu/bmpfp/137
Creative Commons License
This work is licensed under a Creative Commons Attribution 4.0 License.
PubMed ID
30069026
Language
English
Comments
This article has been peer reviewed. It is the author’s final published version in Nature Communications Volume 9, Issue 1, December 2018, Article number 3001.
The published version is available at https://doi.org/10.1038/s41467-018-05321-2. Copyright © Barry et al.