Fig. 3: IKK and TBK1 functions in the liver.

Canonical NF-κB signaling is mediated by the IKKα/IKKβ/IKKγ complex upon proinflammatory cytokine (TNF-α or IL-1β) or lipopolysaccharide stimulus. This complex induces the phosphorylation-mediated degradation of IκB, which leads to NF-κB activation. Furthermore, LTβ, CD40L, and BAFF stimulate NIK phosphorylation, thereby promoting IKKα phosphorylation and downstream signaling via the RelB:p52 complex. On the other hand, TBK1 is phosphorylated via STING or MAVS activation upon viral infection, which promotes IRF3 activation for the type I IFN response. Additionally, inactive TBK1 promotes FA oxidation in hepatocytes.