Viral infection causes activation of transcription factors NF-κB 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-κB as well as IFN-β 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.
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Published in Journal of Biological Chemistry, Volume 285, Issue 13, 2010, pages 9470-9476.
© 2010 by The American Society for Biochemistry and Molecular Biology, Inc. This is an Open Access article under the CC BY license.
Mao, A.-P., Li, S., Zhong, B., Li, Y., Yan, J., Li, Q., Teng, C., & Shu, H.-B. (2010). Virus-triggered ubiquitination of TRAF3/6 by CIAP1/2 is essential for induction of interferon-β (IFN-β) and cellular antiviral response. Journal of Biological Chemistry, 285(13), 9470–9476. https://doi.org/10.1074/jbc.m109.071043