Deubiquitination of NLRP3 by BRCC3 critically regulates inflammasome activity - PubMed

Affiliations

• PMID: 23246432
• DOI: 10.1016/j.molcel.2012.11.009

Free article

Deubiquitination of NLRP3 by BRCC3 critically regulates inflammasome activity

Bénédicte F Py et al. Mol Cell. 2013.

Free article

Abstract

NLRP3 is an important pattern recognition receptor involved in mediating inflammasome activation in response to viral and bacterial infections as well as various proinflammatory stimuli associated with tissue damage or malfunction. Upon activation, NLRP3 assembles a multimeric inflammasome complex comprising the adaptor ASC and the effector pro-caspase-1 to mediate the activation of caspase-1. Although NLRP3 expression is induced by the NF-κB pathway, the posttranscriptional molecular mechanism controlling the activation of NLRP3 remains elusive. Using both pharmacological and molecular approaches, we show that the activation of NLRP3 inflammasome is regulated by a deubiquitination mechanism. We further identify the deubiquitinating enzyme, BRCC3, as a critical regulator of NLRP3 activity by promoting its deubiquitination and characterizing NLRP3 as a substrate for the cytosolic BRCC3-containing BRISC complex. Our results elucidate a regulatory mechanism involving BRCC3-dependent NLRP3 regulation and highlight NLRP3 ubiquitination as a potential therapeutic target for inflammatory diseases.

Similar articles

• Vitamin D Receptor Inhibits NLRP3 Activation by Impeding Its BRCC3-Mediated Deubiquitination.

  Rao Z, Chen X, Wu J, Xiao M, Zhang J, Wang B, Fang L, Zhang H, Wang X, Yang S, Chen Y. Rao Z, et al. Front Immunol. 2019 Dec 4;10:2783. doi: 10.3389/fimmu.2019.02783. eCollection 2019. Front Immunol. 2019. PMID: 31866999 Free PMC article.

• Caspase-1 autoproteolysis is differentially required for NLRP1b and NLRP3 inflammasome function.

  Guey B, Bodnar M, Manié SN, Tardivel A, Petrilli V. Guey B, et al. Proc Natl Acad Sci U S A. 2014 Dec 2;111(48):17254-9. doi: 10.1073/pnas.1415756111. Epub 2014 Nov 17. Proc Natl Acad Sci U S A. 2014. PMID: 25404286 Free PMC article.

• The purinergic 2X7 receptor participates in renal inflammation and injury induced by high-fat diet: possible role of NLRP3 inflammasome activation.

  Solini A, Menini S, Rossi C, Ricci C, Santini E, Blasetti Fantauzzi C, Iacobini C, Pugliese G. Solini A, et al. J Pathol. 2013 Nov;231(3):342-53. doi: 10.1002/path.4237. Epub 2013 Sep 3. J Pathol. 2013. PMID: 23843215

• The role of mitochondria in NLRP3 inflammasome activation.

  Liu Q, Zhang D, Hu D, Zhou X, Zhou Y. Liu Q, et al. Mol Immunol. 2018 Nov;103:115-124. doi: 10.1016/j.molimm.2018.09.010. Epub 2018 Sep 21. Mol Immunol. 2018. PMID: 30248487 Review.

• NLRP3 Ubiquitination-A New Approach to Target NLRP3 Inflammasome Activation.

  Akther M, Haque ME, Park J, Kang TB, Lee KH. Akther M, et al. Int J Mol Sci. 2021 Aug 16;22(16):8780. doi: 10.3390/ijms22168780. Int J Mol Sci. 2021. PMID: 34445484 Free PMC article. Review.

Cited by

• Lipopolysaccharide Primes the NALP3 Inflammasome by Inhibiting Its Ubiquitination and Degradation Mediated by the SCFFBXL2 E3 Ligase.

  Han S, Lear TB, Jerome JA, Rajbhandari S, Snavely CA, Gulick DL, Gibson KF, Zou C, Chen BB, Mallampalli RK. Han S, et al. J Biol Chem. 2015 Jul 17;290(29):18124-18133. doi: 10.1074/jbc.M115.645549. Epub 2015 Jun 2. J Biol Chem. 2015. PMID: 26037928 Free PMC article.

• The Role of Deubiquitinating Enzymes in Acute Lung Injury and Acute Respiratory Distress Syndrome.

  Li T, Zou C. Li T, et al. Int J Mol Sci. 2020 Jul 8;21(14):4842. doi: 10.3390/ijms21144842. Int J Mol Sci. 2020. PMID: 32650621 Free PMC article. Review.

• Perception of self: distinguishing autoimmunity from autoinflammation.

  van Kempen TS, Wenink MH, Leijten EF, Radstake TR, Boes M. van Kempen TS, et al. Nat Rev Rheumatol. 2015 Aug;11(8):483-92. doi: 10.1038/nrrheum.2015.60. Epub 2015 May 12. Nat Rev Rheumatol. 2015. PMID: 25963881 Review.

• Inhibitors of NLRP3 Inflammasome Formation: A Cardioprotective Role for the Gasotransmitters Carbon Monoxide, Nitric Oxide, and Hydrogen Sulphide in Acute Myocardial Infarction.

  Payne FM, Dabb AR, Harrison JC, Sammut IA. Payne FM, et al. Int J Mol Sci. 2024 Aug 26;25(17):9247. doi: 10.3390/ijms25179247. Int J Mol Sci. 2024. PMID: 39273196 Free PMC article. Review.

• Mycobacterial EST12 activates a RACK1-NLRP3-gasdermin D pyroptosis-IL-1β immune pathway.

  Qu Z, Zhou J, Zhou Y, Xie Y, Jiang Y, Wu J, Luo Z, Liu G, Yin L, Zhang XL. Qu Z, et al. Sci Adv. 2020 Oct 23;6(43):eaba4733. doi: 10.1126/sciadv.aba4733. Print 2020 Oct. Sci Adv. 2020. PMID: 33097533 Free PMC article.

Publication types

MeSH terms

Substances

LinkOut - more resources

• Full Text Sources

  • Elsevier Science
  • HAL archives ouvertes

• Other Literature Sources

  • H1 Connect
  • The Lens - Patent Citations Database
  • scite Smart Citations

• Molecular Biology Databases

  • BioCyc
  • GlyGen glycoinformatics resource
  • Mouse Genome Informatics (MGI)

• Miscellaneous

  • NCI CPTAC Assay Portal