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Title:
The E3 ubiquitin ligase TRIM31 attenuates NLRP3 inflammasome activation by promoting proteasomal degradation of NLRP3 | Nature Communications
Description:
The NLRP3 inflammasome has a fundamental role in host defence against microbial pathogens and its deregulation may cause diverse inflammatory diseases. NLRP3 protein expression is a rate-limiting step for inflammasome activation, thus its expression must be tightly controlled to maintain immune homeostasis and avoid detrimental effects. However, how NLRP3 expression is regulated remains largely unknown. In this study, we identify E3 ubiquitin ligase TRIM31 as a feedback suppressor of NLRP3 inflammasome. TRIM31 directly binds to NLRP3, promotes K48-linked polyubiquitination and proteasomal degradation of NLRP3. Consequently, TRIM31 deficiency enhances NLRP3 inflammasome activation and aggravates alum-induced peritonitis in vivo. Furthermore, TRIM31 deficiency attenuates the severity of dextran sodium sulfate (DSS)-induced colitis, an inflammatory bowel diseases model in which NLRP3 possesses protective roles. Thus, our research describes a mechanism by which TRIM31 limits NLRP3 inflammasome activity under physiological conditions and suggests TRIM31 as a potential therapeutic target for the intervention of NLRP3 inflammasome related diseases. The NLRP3 inflammasome controls the response of the host to pathogens; precise regulation is required to limit autoimmune diseases. Here, the authors identify the E3 ligase TRIM31 that aids the ubiquitin-mediated proteasomal degradation of NLRP3, which may be a therapeutic target for alleviating disease.
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Keywords {🔍}
trim, nlrp, inflammasome, fig, expression, article, activation, macrophages, cells, google, scholar, analysis, degradation, mice, cas, ilβ, protein, deficiency, mouse, lps, immunoblot, ubiquitin, peritoneal, ubiquitination, data, immune, nature, colitis, activity, supplementary, cell, ligase, klinked, caspase, hekt, transfected, proteasomal, experiments, inflammatory, diseases, effects, regulation, tnfα, thp, model, atp, pathway, secretion, extracts, colon,
Topics {✒️}
nature portfolio privacy policy il-1β-triggered nf-κb activation advertising n-terminal ring-finger domain research identify trim31 c-terminal coiled-coil domain pro-interleukin-1β protein complexes anti-il-1β p31&p17 nature 481 nature social media ros/mapk/nf-κb signaling elisa kits ha-tagged k48-linked ubiquitin scientific investigation board c-terminal coiled-coil nf-κb reporter plasmid 0/ reprints key research ha-tagged k63-linked ubiquitin dextran sodium sulfate dextran sulfate sodium japan aggravates alum-induced peritonitis research describes n-terminal ring domain full size image enhanced il-1β secretion tnf-α-induced nlrp3 expression dss-induced mucosal damage e3 ligase activity promotes k48-linked polyubiquitination sds–polyacrylamide gel electrophoresis exacerbated dss-induced colitis aggravated alum-induced peritonitis k48-linked polyubiquitination leads il-1β secretion stimulated subsequent il-1β secretion agonists-induced nlrp3 expression acute dss-induced colitis nfκb-mediated signaling pathway trim31-mediated nlrp3 polyubiquitination aryl hydrocarbon receptor dds-induced colitis model research promotes k48-linked ubiquitination mediating lysosome-dependent degradation wnt/β-catenin pathway dss-induced colitis model
Questions {❓}
- A role for the NLRP3 inflammasome in metabolic diseases--did Warburg miss inflammation?
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headline:The E3 ubiquitin ligase TRIM31 attenuates NLRP3 inflammasome activation by promoting proteasomal degradation of NLRP3
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description:The NLRP3 inflammasome has a fundamental role in host defence against microbial pathogens and its deregulation may cause diverse inflammatory diseases. NLRP3 protein expression is a rate-limiting step for inflammasome activation, thus its expression must be tightly controlled to maintain immune homeostasis and avoid detrimental effects. However, how NLRP3 expression is regulated remains largely unknown. In this study, we identify E3 ubiquitin ligase TRIM31 as a feedback suppressor of NLRP3 inflammasome. TRIM31 directly binds to NLRP3, promotes K48-linked polyubiquitination and proteasomal degradation of NLRP3. Consequently, TRIM31 deficiency enhances NLRP3 inflammasome activation and aggravates alum-induced peritonitis in vivo. Furthermore, TRIM31 deficiency attenuates the severity of dextran sodium sulfate (DSS)-induced colitis, an inflammatory bowel diseases model in which NLRP3 possesses protective roles. Thus, our research describes a mechanism by which TRIM31 limits NLRP3 inflammasome activity under physiological conditions and suggests TRIM31 as a potential therapeutic target for the intervention of NLRP3 inflammasome related diseases. The NLRP3 inflammasome controls the response of the host to pathogens; precise regulation is required to limit autoimmune diseases. Here, the authors identify the E3 ligase TRIM31 that aids the ubiquitin-mediated proteasomal degradation of NLRP3, which may be a therapeutic target for alleviating disease.
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name:Key Laboratory of Infection and Immunity of Shandong Province, Shandong University School of Medicine, Jinan, China
type:PostalAddress
type:Organization
name:Zhongxia Yu
affiliation:
name:Shandong University School of Medicine
address:
name:Department of Immunology, Shandong University School of Medicine, Jinan, China
type:PostalAddress
type:Organization
name:Key Laboratory of Infection and Immunity of Shandong Province, Shandong University School of Medicine
address:
name:Key Laboratory of Infection and Immunity of Shandong Province, Shandong University School of Medicine, Jinan, China
type:PostalAddress
type:Organization
name:Wenwen Wang
affiliation:
name:Shandong University School of Medicine
address:
name:Department of Immunology, Shandong University School of Medicine, Jinan, China
type:PostalAddress
type:Organization
name:Key Laboratory of Infection and Immunity of Shandong Province, Shandong University School of Medicine
address:
name:Key Laboratory of Infection and Immunity of Shandong Province, Shandong University School of Medicine, Jinan, China
type:PostalAddress
type:Organization
name:Jing Zhao
affiliation:
name:Shandong University School of Medicine
address:
name:Department of Immunology, Shandong University School of Medicine, Jinan, China
type:PostalAddress
type:Organization
name:Key Laboratory of Infection and Immunity of Shandong Province, Shandong University School of Medicine
address:
name:Key Laboratory of Infection and Immunity of Shandong Province, Shandong University School of Medicine, Jinan, China
type:PostalAddress
type:Organization
name:Lihui Han
affiliation:
name:Shandong University School of Medicine
address:
name:Department of Immunology, Shandong University School of Medicine, Jinan, China
type:PostalAddress
type:Organization
name:Key Laboratory of Infection and Immunity of Shandong Province, Shandong University School of Medicine
address:
name:Key Laboratory of Infection and Immunity of Shandong Province, Shandong University School of Medicine, Jinan, China
type:PostalAddress
type:Organization
name:Guosheng Jiang
affiliation:
name:Institute of Basic Medicine, Shandong Academy of Medical Sciences
address:
name:Institute of Basic Medicine, Shandong Academy of Medical Sciences, Jinan, China
type:PostalAddress
type:Organization
name:Lining Zhang
affiliation:
name:Shandong University School of Medicine
address:
name:Department of Immunology, Shandong University School of Medicine, Jinan, China
type:PostalAddress
type:Organization
name:Key Laboratory of Infection and Immunity of Shandong Province, Shandong University School of Medicine
address:
name:Key Laboratory of Infection and Immunity of Shandong Province, Shandong University School of Medicine, Jinan, China
type:PostalAddress
type:Organization
name:Chengjiang Gao
affiliation:
name:Shandong University School of Medicine
address:
name:Department of Immunology, Shandong University School of Medicine, Jinan, China
type:PostalAddress
type:Organization
name:Key Laboratory of Infection and Immunity of Shandong Province, Shandong University School of Medicine
address:
name:Key Laboratory of Infection and Immunity of Shandong Province, Shandong University School of Medicine, Jinan, China
type:PostalAddress
type:Organization
email:[email protected]
name:Wei Zhao
affiliation:
name:Shandong University School of Medicine
address:
name:Department of Immunology, Shandong University School of Medicine, Jinan, China
type:PostalAddress
type:Organization
name:Key Laboratory of Infection and Immunity of Shandong Province, Shandong University School of Medicine
address:
name:Key Laboratory of Infection and Immunity of Shandong Province, Shandong University School of Medicine, Jinan, China
type:PostalAddress
type:Organization
email:[email protected]
PostalAddress:
name:Department of Immunology, Shandong University School of Medicine, Jinan, China
name:Key Laboratory of Infection and Immunity of Shandong Province, Shandong University School of Medicine, Jinan, China
name:Department of Immunology, Shandong University School of Medicine, Jinan, China
name:Key Laboratory of Infection and Immunity of Shandong Province, Shandong University School of Medicine, Jinan, China
name:Department of Immunology, Shandong University School of Medicine, Jinan, China
name:Key Laboratory of Infection and Immunity of Shandong Province, Shandong University School of Medicine, Jinan, China
name:Department of Immunology, Shandong University School of Medicine, Jinan, China
name:Key Laboratory of Infection and Immunity of Shandong Province, Shandong University School of Medicine, Jinan, China
name:Department of Immunology, Shandong University School of Medicine, Jinan, China
name:Key Laboratory of Infection and Immunity of Shandong Province, Shandong University School of Medicine, Jinan, China
name:Department of Immunology, Shandong University School of Medicine, Jinan, China
name:Key Laboratory of Infection and Immunity of Shandong Province, Shandong University School of Medicine, Jinan, China
name:Department of Immunology, Shandong University School of Medicine, Jinan, China
name:Key Laboratory of Infection and Immunity of Shandong Province, Shandong University School of Medicine, Jinan, China
name:Institute of Basic Medicine, Shandong Academy of Medical Sciences, Jinan, China
name:Department of Immunology, Shandong University School of Medicine, Jinan, China
name:Key Laboratory of Infection and Immunity of Shandong Province, Shandong University School of Medicine, Jinan, China
name:Department of Immunology, Shandong University School of Medicine, Jinan, China
name:Key Laboratory of Infection and Immunity of Shandong Province, Shandong University School of Medicine, Jinan, China
name:Department of Immunology, Shandong University School of Medicine, Jinan, China
name:Key Laboratory of Infection and Immunity of Shandong Province, Shandong University School of Medicine, Jinan, China
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