Figure 1

A model depicting the mechanisms of Tax-mediated IKK/NF-κB activation. 1. Tax dimerizes with each other and binds to NEMO to recruit two IKK complexes and also an E2 ubiquitin conjugating enzyme and an E3 ubiquitin ligase to form the Taxisome; 2. Some Tax and NEMO proteins within the Taxisome are polyubiquitinated via ubiquitin lysine 63 (K63) by the E2 ubiquitin conjugating enzyme and E3 ubiquitin ligase; 3. K63-linked ubiquitination of Tax and/or NEMO leads to catalytic activation of IKK1 and IKK2 within the Taxisome via two alternative mechanisms: K63-linked polyubiquitin chains either act as the platform to recruit IKKK to phosphorylate the activation loops of IKK1 and IKK2, or interact with each other and the components within the Taxisome to cause structural alterations of the Taxisome and trans-autophosphorylation of IKK1 and IKK2; 4a. Activated IKK2 and IKK1 respectively phosphorylate IκBs and RelA, leading to canonical NF-κB activation; 4b. Activated IKK1 is selectively recruited by Tax (through NEMO) into the p100 complex to phosphorylate p100, resulting in non-canonical NF-κB activation (see text for details and other possible or alternative mechanisms involved in the activation of IKK/NF-κB by Tax).