MAVS recruits multiple ubiquitin E3 ligases to activate antiviral signaling cascades

Siqi Liu, Jueqi Chen, Xin Cai, Jiaxi Wu, Xiang Chen, You Tong Wu, Lijun Sun, Zhijian J. Chen

Research output: Contribution to journalArticle

151 Citations (Scopus)

Abstract

RNA virus infections are detected by the RIG-I family of receptors, which induce type-I interferons through the mitochondrial protein MAVS. MAVS forms large prion-like polymers that activate the cytosolic kinases IKK and TBK1, which in turn activate NF-κB and IRF3, respectively, to induce interferons. Here we show that MAVS polymers recruit several TRAF proteins, including TRAF2, TRAF5, and TRAF6, through distinct TRAF-binding motifs. Mutations of these motifs that disrupted MAVS binding to TRAFs abrogated its ability to activate IRF3. IRF3 activation was also abolished in cells lacking TRAF2, 5, and 6. These TRAF proteins promoted ubiquitination reactions that recruited NEMO to the MAVS signaling complex, leading to the activation of IKK and TBK1. These results delineate the mechanism of MAVS signaling and reveal that TRAF2, 5, and 6, which are normally associated with NF-κB activation, also play a crucial role in IRF3 activation in antiviral immune responses.

Original languageEnglish (US)
Article numbere00785
JournaleLife
Volume2013
Issue number2
DOIs
StatePublished - Aug 14 2013

Fingerprint

TNF Receptor-Associated Factor 2
Ubiquitin-Protein Ligases
Tumor Necrosis Factor Receptor-Associated Peptides and Proteins
Antiviral Agents
Chemical activation
TNF Receptor-Associated Factor 5
RNA Virus Infections
Polymers
TNF Receptor-Associated Factor 6
Interferon Type I
Prions
Ubiquitination
Mitochondrial Proteins
Interferons
Phosphotransferases
Viruses
Mutation
RNA

ASJC Scopus subject areas

  • Biochemistry, Genetics and Molecular Biology(all)
  • Immunology and Microbiology(all)
  • Medicine(all)
  • Neuroscience(all)

Cite this

MAVS recruits multiple ubiquitin E3 ligases to activate antiviral signaling cascades. / Liu, Siqi; Chen, Jueqi; Cai, Xin; Wu, Jiaxi; Chen, Xiang; Wu, You Tong; Sun, Lijun; Chen, Zhijian J.

In: eLife, Vol. 2013, No. 2, e00785, 14.08.2013.

Research output: Contribution to journalArticle

Liu, Siqi ; Chen, Jueqi ; Cai, Xin ; Wu, Jiaxi ; Chen, Xiang ; Wu, You Tong ; Sun, Lijun ; Chen, Zhijian J. / MAVS recruits multiple ubiquitin E3 ligases to activate antiviral signaling cascades. In: eLife. 2013 ; Vol. 2013, No. 2.
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