A20 is a potent inhibitor of TLR3-and Sendai virus-induced activation of NF-kappa B and ISRE and IFN-beta promoter

作者：Wang YY; Li LY; Han KJ; Zhai ZH; Shu HB^*

来源：FEBS LETTERS, 2004, 576(1-2): 86-90.

DOI：10.1016/j.febslet.2004.08.071

• toll-like receptor 3
• IFN-beta
• interferon-stimulated response element
• NF-kappa B
• A20

Toll-like receptor 3 (TLR3) recognizes dsRNA generated during viral infection and activation of TLR3 results in induction of type I interferons (IFNs) and cellular anti-viral response. TLR3 is associated with a TIR domain-containing adapter protein TRIF, which activates distinct downstream pathways leading to activation of NF-kappaB and ISRE sites in the promoters of type I IFNs. We show here that A20, a NF-kappaB-inducible zinc finger protein that has been demonstrated to be an inhibitor of TNF-induced NF-kappaB activation and a physiological suppressor of inflammatory response, potently inhibited TLR3- and Sendai virus-mediated activation of ISRE and NF-kappaB and IFN-beta promoter in reporter gene assays. A20 also inhibited TRIF-, but not its downstream signaling components TBK1-, IKKbeta-, and IKKepsilon-mediated activation of ISRE and NF-kappaB and IFN-beta promoter. Moreover, A20 interacted with TRIF in co-inummoprecipitation experiments. Finally, expression of A20 could be induced at protein level by Sendai virus infection. These data suggest that A20 targets TRIF to inhibit TLR3-mediated induction of IFN-beta transcription and functions as a feedback negative regulator for TLR3 signaling and cellular anti-viral response.

• 出版日期2004-10-8
• 单位北京大学