scholarly journals The E3 Ubiquitin Ligase Tripartite Motif 33 Is Essential for Cytosolic RNA–Induced NLRP3 Inflammasome Activation

2014 ◽  
Vol 193 (7) ◽  
pp. 3676-3682 ◽  
Author(s):  
Leiyun Weng ◽  
Hiroki Mitoma ◽  
Coline Tricot ◽  
Musheng Bao ◽  
Ying Liu ◽  
...  
Keyword(s):  
Ubiquitin Ligase ◽  
Nlrp3 Inflammasome ◽  
E3 Ubiquitin Ligase ◽  
Inflammasome Activation ◽  
Nlrp3 Inflammasome Activation ◽  
Tripartite Motif

scholarly journals Sequential ubiquitination of NLRP3 by RNF125 and Cbl-b limits inflammasome activation and endotoxemia

2020 ◽  
Vol 217 (4) ◽  
Author(s):  
Juan Tang ◽  
Sha Tu ◽  
Guoxin Lin ◽  
Hui Guo ◽  
Chengkai Yan ◽  
...  
Keyword(s):  
Ubiquitin Ligase ◽  
Lethal Dose ◽  
E3 Ubiquitin Ligase ◽  
Inflammasome Activation ◽  
Dependent Manner ◽  
Leucine Rich Repeat ◽  
Nlrp3 Inflammasome Activation ◽  
Repeat Domain ◽  
Nlrp3 Inflammasomes ◽  
Lrr Domain

Aberrant NLRP3 inflammasome activation contributes to the development of endotoxemia. The importance of negative regulation of NLRP3 inflammasomes remains poorly understood. Here, we show that the E3 ubiquitin ligase Cbl-b is essential for preventing endotoxemia induced by a sub-lethal dose of LPS via a caspase-11/NLRP3–dependent manner. Further studies show that NLRP3 undergoes both K63- and K48-linked polyubiquitination. Cbl-b binds to the K63-ubiquitin chains attached to the NLRP3 leucine-rich repeat domain (LRR) via its ubiquitin-associated region (UBA) and then targets NLRP3 at K496 for K48-linked ubiquitination and proteasome-mediated degradation. We also identify RNF125 as an additional E3 ubiquitin ligase that initiates K63-linked ubiquitination of the NLRP3 LRR domain. Therefore, NLRP3 is sequentially ubiquitinated by K63- and K48-linked ubiquitination, thus keeping the NLRP3 inflammasomes in check and restraining endotoxemia.

scholarly journals TRIM28 SUMOylates and stabilizes NLRP3 to facilitate inflammasome activation

2021 ◽  
Vol 12 (1) ◽  
Author(s):  
Ying Qin ◽  
Qi Li ◽  
Wenbo Liang ◽  
Rongzhen Yan ◽  
Li Tong ◽  
...  
Keyword(s):  
Posttranslational Modifications ◽  
Nlrp3 Inflammasome ◽  
Inflammasome Activation ◽  
Sumo Modification ◽  
Nlrp3 Inflammasome Activation ◽  
Sumo Ligase ◽  
Tripartite Motif ◽  
Nlrp3 Expression

AbstractThe cellular NLRP3 protein level is crucial for assembly and activation of the NLRP3 inflammasome. Various posttranslational modifications (PTMs), including phosphorylation and ubiquitination, control NLRP3 protein degradation and inflammasome activation; however, the function of small ubiquitin-like modifier (SUMO) modification (called SUMOylation) in controlling NLRP3 stability and subsequent inflammasome activation is unclear. Here, we show that the E3 SUMO ligase tripartite motif-containing protein 28 (TRIM28) is an enhancer of NLRP3 inflammasome activation by facilitating NLRP3 expression. TRIM28 binds NLRP3, promotes SUMO1, SUMO2 and SUMO3 modification of NLRP3, and thereby inhibits NLRP3 ubiquitination and proteasomal degradation. Concordantly, Trim28 deficiency attenuates NLRP3 inflammasome activation both in vitro and in vivo. These data identify a mechanism by which SUMOylation controls the cellular NLRP3 level and inflammasome activation, and reveal correlations and interactions of NLRP3 SUMOylation and ubiquitination during inflammasome activation.

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