TRAF3 binds both IPS‑1 and downstream interferon regulatory factor 3/7 (IRF3/7) kinases TBK1 and IKK‑epsilon (IKKi, IKBKE) and thus serves as a critical link between RIG‑I/MDA5 adaptors and downstream regulatory kinases important for interferon regulatory factor (IRF) activation (Oganesyan et al).
SIKE (Suppressor of IKK-epsilon) interacts with IKBKE and TBK1. SIKE is associated with TBK1 under physiological conditions and dissociated from TBK1 upon viral infection. Overexpression of SIKE disrupted the interactions of IKBKE or TBK1 with RIG‑I (DDX58).
SARS-CoV-1 M protein prevents the formation of the TRAF3:TANK:TBK1/IKBKE complex and thereby inhibits TBK1/IKBKE-dependent activation of IRF3/IRF7 transcription factors (Siu KL et al. 2009).