Stimulator of interferon genes

Stimulator of interferon genes (STING), also known as transmembrane protein 173 (TMEM173), is a protein that in humans is encoded by the TMEM173 gene. STING plays a crucial role in the innate immune response to viral and bacterial infections, as well as in the regulation of the type I interferon pathway. This protein is involved in the recognition of cytosolic DNA and the activation of the transcription factor IRF3, leading to the production of interferon.

Function

STING is located in the endoplasmic reticulum and is activated upon binding to cyclic dinucleotides (CDNs), molecules that are often produced during microbial infections or generated in the cytosol of the host cell upon detection of DNA. Once activated, STING undergoes a conformational change and translocates from the endoplasmic reticulum to the Golgi apparatus. This translocation is essential for the recruitment of TANK-binding kinase 1 (TBK1) and the subsequent phosphorylation and activation of interferon regulatory factor 3 (IRF3). Activated IRF3 then translocates to the nucleus, where it induces the expression of type I interferons and other inflammatory cytokines.

Clinical Significance

Mutations in the TMEM173 gene have been associated with a range of autoimmune and autoinflammatory diseases, including STING-associated vasculopathy with onset in infancy (SAVI). Patients with SAVI exhibit symptoms such as systemic inflammation, skin lesions, and interstitial lung disease. This highlights the critical role of STING in controlling immune responses and maintaining immune homeostasis.

Furthermore, the STING pathway has been identified as a potential target for cancer immunotherapy. Activation of STING in tumor cells can lead to an antitumor immune response, making it a promising target for the development of new cancer treatments.

Research

Research on STING is focused on understanding its role in the innate immune response and its potential as a therapeutic target. Studies are exploring how STING signaling can be modulated to treat autoimmune diseases, cancer, and infectious diseases. Additionally, the development of small molecule STING agonists and antagonists is an area of active investigation.

See Also

• Innate immune system
• Interferon
• Autoimmune disease
• Cancer immunotherapy