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- Title
Interferon-ainduction through Toll-like receptors involves a direct interaction of IRF7 with MyD88 and TRAF6.
- Authors
Taro Kawai; Shintaro Sato; Ishii, Ken J.; Coban, Cevayir; Hemmi, Hiroaki; Yamamoto, Masahiro; Terai, Kenta; Matsuda, Michiyuki; Inoue, Jun-ichiro; Uematsu, Satoshi; Takeuchi, Osamu; Akira, Shizuo
- Abstract
Toll-like receptors (TLRs) are involved in the recognition of microbial pathogens. A subset of TLRs, TLR7, TLR8 and TLR9, induces antiviral responses by producing interferon-a (lFN-α). Production of lFN-α is dependent on the Toll-interleukin-1 receptor domain-containing adaptor MyD88. Here we show that MyD88 formed a complex with the transcription factor IRF7 but not with IRF3. The death domain of MyD88 interacted with an inhibitory domain of IRF7, and this interaction resulted in activation of the lFN-α-dependent promoters. Furthermore, the adaptor molecule TRAF6 also bound and activated IRF7. Ubiquitin ligase activity of TRAF6 was required for IRF7 activation. These results indicate that TLR-mediated IFN-α induction requires the formation of a complex consisting of MyD88, TRAF6 and IRF7 as well as TRAF6-dependent ubiquitination.
- Publication
Nature Immunology, 2004, Vol 5, Issue 10, p1061
- ISSN
1529-2908
- Publication type
Academic Journal
- DOI
10.1038/ni1118