Virus-triggered ubiquitination of TRAF3/6 by cIAP1/2 is essential for induction of interferon-beta (IFN-beta) and cellular antiviral response

  • J Biol Chem. 2010 Mar 26;285(13):9470-9476. doi: 10.1074/jbc.M109.071043.
Ai-Ping Mao  1 ,  Shu Li  1 ,  Bo Zhong  1 ,  Ying Li  1 ,  Jie Yan  1 ,  Qi Li  1 ,  Chengwen Teng  1 ,  Hong-Bing Shu  2
Affiliations
  • 1. College of Life Sciences, Wuhan University, Wuhan 430072, China.
  • 2. College of Life Sciences, Wuhan University, Wuhan 430072, China. Electronic address: [email protected].
PMID: 20097753 DOI: 10.1074/jbc.M109.071043
Abstract

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.