Stimulator of interferon genes protein (STING1) (STING1)

Stimulator of interferon genes protein (STING1), also known as TMEM173, is a critical transmembrane protein located in the endoplasmic reticulum that functions as a central sensor of cytosolic DNA [1, 2]. Upon activation by cyclic dinucleotides (CDNs)—either produced endogenously by cGAS or delivered exogenously—STING1 recruits TANK-binding kinase 1 (TBK1) and interferon regulatory factor 3 (IRF3), triggering the production of Type I interferons and pro-inflammatory cytokines [3]. 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 antigen-presenting cells and the activation of cytotoxic T lymphocytes [3, 4]. In therapeutic contexts, particularly immuno-oncology, STING1 is targeted to convert cold tumors into hot, immune-active environments. The delivery of a STING1 gene cassette (gene therapy) aims to ensure robust, localized expression of the protein within the tumor microenvironment to overcome immune evasion [5]. However, precise control of STING1 activation is necessary to avoid systemic inflammation or cytokine release syndrome [6]. [1] UniProt Consortium. UniProtKB - Q86WV6. [2] Ishikawa H, Barber GN. Nature. 2008;455(7213):674-678. [3] Barber GN. Nat Rev Immunol. 2015;15(12):760-770. [4] Corrales L, et al. Cell Rep. 2015;11(7):1018-1030. [5] Li A, et al. J Hematol Oncol. 2019;12(1):35. [6] Liu Y, et al. N Engl J Med. 2014;371(6):507-518.

Other names

TMEM173ERISMITAMPYSNET23Stimulator of interferon genes protein

Agonism of the cGAS-STING pathway, either through direct binding of cyclic dinucleotides or through gene-mediated overexpression, to induce the production of Type I interferons and pro-inflammatory cytokines, thereby enhancing anti-tumor immunity.