STING (Stimulator of Interferon Genes, also known as TMEM173, MITA, ERIS, and MPYS) is an adapter transmembrane protein that resides in the endoplasmic reticulum (ER). In eukaryotic cells, activation of STING occurs when double stranded DNA gains access to the cytosol. This pathway was originally uncovered in search for a mechanism by which DNA viruses could be sensed by the host immune system. STING pathway activation also can occur with certain bacterial and parasitic infections, and more recently has been described to occur under conditions when mammalian DNA itself can attain access to the cytosol. Cytosolic DNA is detected upon binding to the sensor cyclic-GMP-AMP synthase (cGAS, MB21D1), which catalyzes the synthesis of cyclic GMP-AMP (cGAMP) from guanosine triphosphate (GTP) and adenosine triphosphate (ATP). cGAMP functions as a second messenger that binds and activates STING. Upon binding of cGAMP, STING undergoes conformational changes that trigger its trafficking from the ER to the Golgi to perinuclear endosomes. Consequently, STING recruits tank-binding kinase 1 (TBK1) and is, in turn, phosphorylated by TBK1, which renders it accessible for the binding of the transcription factor interferon regulatory factor 3 (IRF3). TBK1 then phosphorylates IRF3 which translocates to the nucleus to drive transcription of IFN-β and other genes.

References

1.Leticia Corrales,et al. Clin Cancer Res. 2015 Nov 1; 21(21): 4774–4779.