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

The STING-TBK1 complex is a central signaling assembly in the innate immune system, formed when the Stimulator of Interferon Genes (STING) protein recruits TANK-binding kinase 1 (TBK1) upon activation by cytosolic DNA [1, 3]. This interaction typically occurs at the Golgi apparatus following STING's translocation from the endoplasmic reticulum in response to cyclic dinucleotides like cGAMP [6, 10]. Once the complex is formed, TBK1 phosphorylates the C-terminal tail of STING and the transcription factor IRF3, which then translocates to the nucleus to induce the expression of type I interferons and pro-inflammatory cytokines [4, 13]. This pathway is essential for host defense against viral and bacterial pathogens and plays a pivotal role in cancer immunosurveillance by promoting the maturation of dendritic cells and the priming of T cells [3, 12]. Conversely, aberrant or chronic activation of the STING-TBK1 complex is linked to various autoinflammatory and autoimmune conditions, such as Aicardi-Goutières syndrome and STING-associated vasculopathy with onset in infancy (SAVI) [1, 16]. Consequently, the complex is a high-priority therapeutic target, with STING agonists being developed as cancer immunotherapies and TBK1 or STING inhibitors being explored for the treatment of chronic inflammatory and autoimmune diseases [2, 9].

Other names

STING-TBK1 complexSTING-TBK1-IRF3 complexTMEM173-TBK1 complexStimulator of interferon genes-TANK-binding kinase 1 complexMITA-TBK1 complexERIS-TBK1 complexMPYS-TBK1 complex

The complex is modulated through two primary strategies: agonism and inhibition. STING agonists (e.g., cGAMP analogs) promote the formation and activation of the STING-TBK1 complex to induce type I interferons for antitumor immunity [3, 4]. Conversely, inhibitors target the complex by either blocking the kinase activity of TBK1, inhibiting STING's ability to oligomerize, or directly disrupting the protein-protein interaction between STING and TBK1 (e.g., Idronoxil) to treat autoimmune and inflammatory diseases [1, 9].