Virus-triggered ubiquitination of TRAF3/6 by cIAP1/2 is essential for induction of interferon-beta (IFN-beta) and cellular antiviral response.
Viral infection causes activation of transcription factors NF-kappaB and IRF3, which collaborate to induce type I interferons (IFNs) and cellular antiviral response. Here we show that knockdown of the E3 ubiquitin ligases cIAP1 and cIAP2 markedly inhibited virus-triggered activation of IRF3 and NF-kappaB as well as IFN-beta induction. Knockdown of ... cIAP1 and cIAP2 also inhibited cytoplasmic dsRNA-triggered cellular antiviral response. Endogenous coimmunoprecipitation experiments indicated that viral infection caused recruitment of cIAP1 and cIAP2 to TRAF3, TRAF6, and VISA. Furthermore, we demonstrated that cIAP1- and cIAP2-mediated virus-triggered ubiquitination of TRAF3 and TRAF6. These findings suggest that virus-triggered ubiquitination of TRAF3 and TRAF6 by cIAP1 and cIAP2 is essential for type I IFN induction and cellular antiviral response.
Mesh Terms:
Antiviral Agents, Cytoplasm, Cytosol, Humans, Inhibitor of Apoptosis Proteins, Interferon-beta, NF-kappa B, RNA Interference, RNA, Double-Stranded, Signal Transduction, TNF Receptor-Associated Factor 3, TNF Receptor-Associated Factor 6, Ubiquitin-Protein Ligases
Antiviral Agents, Cytoplasm, Cytosol, Humans, Inhibitor of Apoptosis Proteins, Interferon-beta, NF-kappa B, RNA Interference, RNA, Double-Stranded, Signal Transduction, TNF Receptor-Associated Factor 3, TNF Receptor-Associated Factor 6, Ubiquitin-Protein Ligases
J. Biol. Chem.
Date: Mar. 26, 2010
PubMed ID: 20097753
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