title: TRIM11 Suppresses AIM2 Inflammasome by Degrading AIM2 via p62-Dependent Selective Autophagy.
abstract: The AIM2 inflammasome is a key cytosolic signaling complex that is activated by double-stranded DNA, leading to the maturation of proinflammatory cytokines such as interleukin-1β (IL-1β) and IL-18. Dysregulated AIM2 inflammasome activity is associated with human inflammatory diseases and cancers, suggesting that its activity must be tightly regulated. However, the precise molecular mechanisms that control AIM2 levels and activity are still poorly understood. Here, we report tripartite motif 11 (TRIM11) as a key negative regulator of the AIM2 inflammasome. Upon DNA virus infection, TRIM11 binds to AIM2 via its PS domain and undergoes auto-polyubiquitination at K458 to promote an association between TRIM11 and the autophagic cargo receptor p62 to mediate AIM2 degradation via selective autophagy. These findings identify a role for TRIMs in AIM2 inflammasome activation where TRIM11 acts as a secondary receptor to deliver AIM2 to the autophagosomes for degradation in a p62-dependent manner.
authors: Key Laboratory of Gene Engineering of the Ministry of Education, State Key Laboratory of Biocontrol, School of Life Sciences, Sun Yat-sen University, Guangzhou 510275, PRC.
authors: Tao
authors: T
authors: Liu
authors: Key Laboratory of Gene Engineering of the Ministry of Education, State Key Laboratory of Biocontrol, School of Life Sciences, Sun Yat-sen University, Guangzhou 510275, PRC; Center for Inflammation and Epigenetics, Houston Methodist Research Institute, Houston, TX 77030, USA.
authors: Qin
authors: Q
authors: Tang
authors: Key Laboratory of Gene Engineering of the Ministry of Education, State Key Laboratory of Biocontrol, School of Life Sciences, Sun Yat-sen University, Guangzhou 510275, PRC.
authors: Kunpeng
authors: K
authors: Liu
authors: Zhongshan School of Medicine, Sun Yat-sen University, Guangzhou 510275, PRC.
authors: Weihong
authors: W
authors: Xie
authors: Key Laboratory of Gene Engineering of the Ministry of Education, State Key Laboratory of Biocontrol, School of Life Sciences, Sun Yat-sen University, Guangzhou 510275, PRC.
authors: Xin
authors: X
authors: Liu
authors: Key Laboratory of Gene Engineering of the Ministry of Education, State Key Laboratory of Biocontrol, School of Life Sciences, Sun Yat-sen University, Guangzhou 510275, PRC.
authors: Huishan
authors: H
authors: Wang
authors: Center for Inflammation and Epigenetics, Houston Methodist Research Institute, Houston, TX 77030, USA. Electronic address: rwang3@houstonmethodist.org.
authors: Rong-Fu
authors: RF
authors: Wang
authors: Key Laboratory of Gene Engineering of the Ministry of Education, State Key Laboratory of Biocontrol, School of Life Sciences, Sun Yat-sen University, Guangzhou 510275, PRC; Collaborative Innovation Center of Cancer Medicine, Sun Yat-sen University, Guangzhou 510275, PRC. Electronic address: cuij5@mail.sysu.edu.cn.
authors: Jun
authors: J
authors: Cui
mesh_terms: D000818:Animals; D000071182:Autophagosomes / Q000187:drug effects / Q000276:immunology* / Q000378:metabolism; D001343:Autophagy; D001665:Binding Sites; D002460:Cell Line; D003587:Cytomegalovirus / Q000254:growth & development / Q000276:immunology; D004268:DNA-Binding Proteins / Q000235:genetics* / Q000276:immunology; D005786:Gene Expression Regulation; D057809:HEK293 Cells; D006367:HeLa Cells; D018259:Herpesvirus 1, Human / Q000254:growth & development / Q000276:immunology; D054884:Host-Pathogen Interactions; D006801:Humans; D058847:Inflammasomes / Q000187:drug effects / Q000276:immunology* / Q000378:metabolism; D008070:Lipopolysaccharides / Q000494:pharmacology; D008264:Macrophages / Q000187:drug effects / Q000276:immunology* / Q000821:virology; D051379:Mice; D008810:Mice, Inbred C57BL; D011070:Poly I-C / Q000494:pharmacology; D011485:Protein Binding; D059748:Proteolysis; D000071456:Sequestosome-1 Protein / Q000235:genetics* / Q000276:immunology; D015398:Signal Transduction; D000070584:Tripartite Motif Proteins / Q000235:genetics* / Q000276:immunology; D044767:Ubiquitin-Protein Ligases / Q000235:genetics* / Q000276:immunology
chemical_list: C410167:AIM2 protein, human; D004268:DNA-Binding Proteins; D058847:Inflammasomes; D008070:Lipopolysaccharides; C099718:SQSTM1 protein, human; D000071456:Sequestosome-1 Protein; D000070584:Tripartite Motif Proteins; C510874:TRIM11 protein, human; D044767:Ubiquitin-Protein Ligases; D011070:Poly I-C
keywords: AIM2 inflammasome; TRIM11; p62; protein degradation; selective autophagy