title: The E3 ubiquitin ligase tripartite motif 33 is essential for cytosolic RNA-induced NLRP3 inflammasome activation.
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.
authors.affiliation: Baylor Institute for Immunology Research, Baylor Research Institute, Baylor Scott and White Health, Dallas, TX 75204;
authors.forename: Leiyun
authors.initials: L
authors.lastname: Weng
authors.affiliation: Baylor Institute for Immunology Research, Baylor Research Institute, Baylor Scott and White Health, Dallas, TX 75204;
authors.forename: Hiroki
authors.initials: H
authors.lastname: Mitoma
authors.affiliation: Baylor Institute for Immunology Research, Baylor Research Institute, Baylor Scott and White Health, Dallas, TX 75204;
authors.forename: Coline
authors.initials: C
authors.lastname: Trichot
authors.affiliation: Baylor Institute for Immunology Research, Baylor Research Institute, Baylor Scott and White Health, Dallas, TX 75204;
authors.forename: Coline
authors.initials: C
authors.lastname: Tricot
authors.affiliation: Baylor Institute for Immunology Research, Baylor Research Institute, Baylor Scott and White Health, Dallas, TX 75204;
authors.forename: Musheng
authors.initials: M
authors.lastname: Bao
authors.affiliation: Baylor Institute for Immunology Research, Baylor Research Institute, Baylor Scott and White Health, Dallas, TX 75204;
authors.forename: Ying
authors.initials: Y
authors.lastname: Liu
authors.affiliation: Baylor Institute for Immunology Research, Baylor Research Institute, Baylor Scott and White Health, Dallas, TX 75204; Immunobiology and Transplant Research, Houston Methodist Hospital and Houston Methodist Research Institute, Texas Medical Center, Houston, TX 77030; and zzhang@houstonmethodist.org liuyo@medimmune.com.
authors.forename: Zhiqiang
authors.initials: Z
authors.lastname: Zhang
authors.affiliation: Baylor Institute for Immunology Research, Baylor Research Institute, Baylor Scott and White Health, Dallas, TX 75204; MedImmune, LLC, Gaithersburg, MD 20878 zzhang@houstonmethodist.org liuyo@medimmune.com.
authors.forename: Yong-Jun
authors.initials: YJ
authors.lastname: Liu
mesh_terms: D002352:Carrier Proteins / Q000235:genetics / Q000276:immunology*; D020170:Caspase 1 / Q000235:genetics / Q000276:immunology; D045744:Cell Line, Tumor; D053487:DEAD-box RNA Helicases / Q000235:genetics / Q000276:immunology; D055785:Gene Knockdown Techniques; D057809:HEK293 Cells; D006801:Humans; D058847:Inflammasomes / Q000235:genetics / Q000276:immunology*; D053583:Interleukin-1beta / Q000235:genetics / Q000276:immunology; D008264:Macrophages / Q000166:cytology / Q000276:immunology*; D009000:Monocytes / Q000166:cytology / Q000276:immunology*; D000071199:NLR Family, Pyrin Domain-Containing 3 Protein; D012330:RNA, Double-Stranded / Q000235:genetics / Q000276:immunology*; D014157:Transcription Factors / Q000235:genetics / Q000276:immunology*; D054875:Ubiquitination / Q000235:genetics / Q000276:immunology
chemical_list: D002352:Carrier Proteins; C508585:IL1B protein, human; D058847:Inflammasomes; D053583:Interleukin-1beta; D000071199:NLR Family, Pyrin Domain-Containing 3 Protein; C453881:NLRP3 protein, human; D012330:RNA, Double-Stranded; C511956:TRIM33 protein, human; D014157:Transcription Factors; D020170:Caspase 1; C568925:DHX33 protein, human; D053487:DEAD-box RNA Helicases