The E3 Ubiquitin Ligase Tripartite Motif 33 Is Essential for Cytosolic RNA–Induced NLRP3 Inflammasome Activation
- 1 October 2014
- journal article
- Published by The American Association of Immunologists in The Journal of Immunology
- Vol. 193 (7), 3676-3682
- https://doi.org/10.4049/jimmunol.1401448
Abstract
NLRP3 is a key component of caspase-activating macromolecular protein complexes called inflammasomes. It has been found that DHX33 is a cytosolic dsRNA sensor for the NLRP3 inflammasome, which induces caspase-1–dependent production of IL-1β and IL-18 upon activation. However, how the cytosolic dsRNAs induce the interaction between DHX33 and the NLRP3 inflammasome remains unknown. In this study, we report that TRIM33, a member of the tripartite motif (TRIM) family, can bind DHX33 directly and induce DHX33 ubiquitination via the lysine 218 upon dsRNA stimulation. Knocking down of TRIM33 abolished the dsRNA-induced NLRP3 inflammasome activation in both THP-1–derived macrophages and human monocyte-derived macrophages. The ubiquitination of DHX33 by TRIM33 is lysine 63 specific and is required for the formation of the DHX33–NLRP3 inflammasome complex.Keywords
This publication has 37 references indexed in Scilit:
- Oxidized Mitochondrial DNA Activates the NLRP3 Inflammasome during ApoptosisImmunity, 2012
- Transcription intermediary factor 1γ is a tumor suppressor in mouse and human chronic myelomonocytic leukemiaJCI Insight, 2011
- Transcription cofactors TRIM24, TRIM28, and TRIM33 associate to form regulatory complexes that suppress murine hepatocellular carcinomaProceedings of the National Academy of Sciences of the United States of America, 2011
- Activation of the NLRP3 inflammasome by intracellular poly I:CFEBS Letters, 2010
- TIF1γ Controls Erythroid Cell Fate by Regulating Transcription ElongationCell, 2010
- Involvement of the AIM2, NLRC4, and NLRP3 Inflammasomes in Caspase-1 Activation by Listeria monocytogenesJournal of Clinical Immunology, 2010
- The InflammasomesCell, 2010
- Inactivation of TIF1γ Cooperates with KrasG12D to Induce Cystic Tumors of the PancreasPLoS Genetics, 2009
- TRIM25 RING-finger E3 ubiquitin ligase is essential for RIG-I-mediated antiviral activityNature, 2007
- The cytoplasmic body component TRIM5α restricts HIV-1 infection in Old World monkeysNature, 2004