Fig. 3
A proposed STING SMOCs model reconciling the TBK1-IRF3 and NF-κB activation. a STING–TBK1–IRF3 complex activates IRF3 and induces IFN production in a STING C-terminal tail-dependent way. b Activated STING polymerizes and recruits essential adaptors like TRAFs, NEMO, and IKKβ, beyond the STING–TBK1–IRF3 complex. Ubiquitination chains are covalently linked to various components of these SMOCs and stabilize the complex. A positive feedback loop exits between TBK1 and IKKβ to assure full activation of NF-κB, which may not depend on the STING C-terminal tail but require TBK1. Enigmatic mechanisms of STAT6 and MAPKs activation could also originate in this complex. cGAMP cyclic GMP–AMP, IFN interferon, IKKβ inhibitor of NF-κB kinase beta, IRF3 interferon regulatory factor 3, NEMO NF-κB essential modifier, PolyUb polyubiquitin chain, STING stimulator of interferon genes, SMOCs supramolecular organizing centres, TBK1 TANK-binding kinase 1, TRAFs tumor necrosis factor receptor-associated factors
