Stimulator of interferon genes protein (STING)-TANK-binding kinase 1 (TBK1) complex (STING-TBK1 complex)

The Stimulator of interferon genes protein (STING)-TANK-binding kinase 1 (TBK1) complex is a critical signaling assembly in the cGAS-STING pathway, essential for the induction of innate immune responses to cytosolic DNA. Upon activation by cyclic dinucleotides like cGAMP, STING translocates from the endoplasmic reticulum to the Golgi, where its C-terminal tail recruits TBK1 (Liu et al., 2015, Science; Tanaka & Chen, 2012, Science Signaling). This interaction facilitates the phosphorylation of STING and the transcription factor IRF3 by TBK1, ultimately triggering the production of Type I interferons and pro-inflammatory cytokines (Motwani et al., 2019, Nature Reviews Genetics). In oncology, this complex is a major therapeutic target, with STING agonists being developed to promote its formation and stimulate anti-tumor immunity (Decout et al., 2021, Nature Reviews Immunology). Conversely, overactivation of the STING-TBK1 complex is implicated in autoinflammatory diseases such as STING-associated vasculopathy with onset in infancy (SAVI) and systemic lupus erythematosus, leading to research into inhibitors that disrupt this specific protein-protein interface (Barber, 2015, Nature Reviews Immunology). Targeting the complex directly or its individual components allows for the modulation of the immune system in both cancer and inflammatory contexts.

Other names

TMEM173-TBK1 complexSTING-TBK1 signalosomeSTING-TBK1 interaction

Agonism of STING to induce complex formation or inhibition of TBK1 to prevent complex-mediated signaling.