Once activated, IPS-1 recruits TRAFs (TNF receptor associated factor protein family members) to the RIG-1/MDA5 receptor complex. TRAF3 and TRAF6 act as a scaffold for the assembly of the signaling complex composed of TBK1/ IKK epsilon, leading to the activation of transcription factors IRF3 and IRF7. TRAF6-induced activation of IRF is likely to be specific for IRF7, while TRAF3 is thought to activate both IRF3 and IRF7 [Konno H et al 2009, Oganesyan G et al 2006].
Transient transfection experiments in human embryonic kidney (HEK) 293 cells revealed that TRAF6 associates with IPS-1, TBK1, IKKi and TANK [Konno H et al 2009]. TRAF3 was also shown to form complexes with IPS-1, TBK1 and IKKi [Oganesyan G et al 2006, Alff PJ et al 2008, Saha SK et al 2006]