Stimulator of interferon genes (STING) - Axis inhibition protein 1 (AXIN1) interaction (STING-AXIN1)

The STING pathway via AXIN-1–STING interaction is a critical regulatory mechanism in the innate immune system where the scaffold protein Axis inhibition protein 1 (AXIN1) facilitates the activation of the Stimulator of Interferon Genes (STING) (UniProt: Q86WV6, O15169). While AXIN1 is traditionally known for its role in the Wnt/beta-catenin pathway, it has been identified as a positive regulator of the cGAS-STING axis by acting as a bridge that promotes the recruitment of TANK-binding kinase 1 (TBK1) to STING (Li et al., Nature Communications, 2020). This interaction is vital for the phosphorylation of STING and the subsequent induction of Type I interferons and pro-inflammatory cytokines, which are essential for antiviral defense and anti-tumor immunity (Barber, Nature Reviews Immunology, 2015). In oncology, the STING-AXIN1 interaction is a target for enhancing the efficacy of immunotherapies, as AXIN1 deficiency can lead to immune evasion by impairing the sensing of cytosolic DNA. Conversely, overactivation of this axis may contribute to the pathogenesis of autoinflammatory diseases. Therapeutic strategies currently focus on STING agonists like ADU-S100, though small molecules that stabilize AXIN1, such as Tankyrase inhibitors, are being explored for their potential to modulate this pathway indirectly. This target represents a promising avenue for developing treatments that can convert cold tumors into hot tumors by stimulating innate immune recognition.

Other names

TMEM173-AXIN1 interactionAXIN1-STING axisSTING-AXIN1 complexAXIN1-mediated STING activation

AXIN1 serves as a molecular scaffold that facilitates the recruitment of TANK-binding kinase 1 (TBK1) to the Stimulator of Interferon Genes (STING) upon activation by cyclic dinucleotides. This interaction is essential for the phosphorylation of STING at Ser366, which triggers the downstream IRF3 signaling pathway and the induction of Type I interferons (Li et al., Nature Communications, 2020).