PathwayStep811 p-IRF7 dimer interacts with coactivator CBP/p300 Formation of VAF (virus-activated factor) complex VAF/pIRF7:CBP/p300 binds the promoters of type-I IFN genes Recruitment of IRF7 to TRAF6 Recruitment of TBK1/IKK epsilon complex to TANK:TRAF6 Recruitment of TANK to TRAF6 Recruitment of TRAF6/TRAF2 to IPS-1 Phosphorylation and release of IRF7 Dimerization of p-IRF7 Translocation of p-IRF7:p-IRF7 to nucleus PathwayStep6942 PathwayStep6943 PathwayStep6944 PathwayStep6945 PathwayStep6946 PathwayStep6947 PathwayStep6941 PathwayStep6940 PathwayStep6760 PathwayStep6761 Expression of Interferon-alpha and beta TRAF6 mediated IRF7 activation Authored: Garapati, P V, 2010-08-02 Edited: Garapati, P V, 2010-08-02 Pubmed19479062 Reactome Database ID Release 43933541 Reactome, http://www.reactome.org ReactomeREACT_24938 Reviewed: Kawai, T, Akira, S, 2010-10-30 TRAF6 is crucial for both RIG-I- and MDA5-mediated antiviral responses. The absence of TRAF6 resulted in enhanced viral replication and a significant reduction in the production of type I IFNs and IL6 after infection with RNA virus. Activation of NF-kB and IRF7, but not that of IRF3, was significantly impaired during RIG-like helicases (RLHs) signaling in the absence of TRAF6. TRAF6-induced activation of IRF is likely to be specific for IRF7, while TRAF3 is thought to activate both IRF3 and IRF7. These results strongly suggest that the TRAF6- and TRAF3-dependent pathways are likely to bifurcate at IPS-1, but to converge later at IRF7 in order to co-operatively induce sufficient production of type I IFNs during RLH signaling.