DOI: 10.7554/elife.00785. MAVS recruits multiple ubiquitin E3 ligases to activate antiviral signaling cascades

MAVS recruits multiple ubiquitin E3 ligases to activate antiviral signaling cascades

10.7554/elife.00785

Crossref journal-article

eLife Sciences Publications, Ltd

eLife (4374)

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.

Bibliography

Liu, S., Chen, J., Cai, X., Wu, J., Chen, X., Wu, Y.-T., Sun, L., & Chen, Z. J. (2013). MAVS recruits multiple ubiquitin E3 ligases to activate antiviral signaling cascades. ELife, 2. CLOCKSS.

Authors 8

Siqi Liu (first)
Jueqi Chen (additional)
Xin Cai (additional)
Jiaxi Wu (additional)
Xiang Chen (additional)
You-Tong Wu (additional)
Lijun Sun (additional)
Zhijian J Chen (additional)

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Dates

Type	When
Created	12 years ago (Aug. 15, 2013, 1:53 p.m.)
Deposited	1 year, 10 months ago (Oct. 11, 2023, 8:40 p.m.)
Indexed	2 days ago (Aug. 30, 2025, 12:46 p.m.)
Issued	12 years ago (Aug. 14, 2013)
Published	12 years ago (Aug. 14, 2013)
Published Online	12 years ago (Aug. 14, 2013)

Funders 10

National Institutes of Health 10.13039/100000002
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gov (National government)
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Region: Americas
pri (Trusts, charities, foundations (both public and private))
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pri (Research institutes and centers)
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National Institutes of Health 10.13039/100000002
Region: Americas
gov (National government)
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1. GM63692
Cancer Prevention and Research Institute of Texas 10.13039/100004917
Region: Americas
gov (National government)
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Welch Foundation 10.13039/100000928
Region: Americas
pri (Trusts, charities, foundations (both public and private))
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pri (Research institutes and centers)
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gov (National government)
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BibTeX

@article{Liu_2013, title={MAVS recruits multiple ubiquitin E3 ligases to activate antiviral signaling cascades}, volume={2}, ISSN={2050-084X}, url={http://dx.doi.org/10.7554/elife.00785}, DOI={10.7554/elife.00785}, journal={eLife}, publisher={eLife Sciences Publications, Ltd}, author={Liu, Siqi and Chen, Jueqi and Cai, Xin and Wu, Jiaxi and Chen, Xiang and Wu, You-Tong and Sun, Lijun and Chen, Zhijian J}, year={2013}, month=aug }

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  "abstract": "<jats:p>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-\u03baB 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-\u03baB activation, also play a crucial role in IRF3 activation in antiviral immune responses.</jats:p>",
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        "name": "publication_history",
        "label": "Publication History"
      }
    },
    {
      "value": "2013-07-01",
      "order": 1,
      "name": "accepted",
      "label": "Accepted",
      "group": {
        "name": "publication_history",
        "label": "Publication History"
      }
    },
    {
      "value": "2013-08-14",
      "order": 2,
      "name": "published",
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      "group": {
        "name": "publication_history",
        "label": "Publication History"
      }
    }
  ],
  "article-number": "e00785"
}