No Longer A One-Trick Pony: STING Signaling Activity Beyond Interferon.

Abstract

Stimulator of interferon genes (STING) plays an important role in infection, autoimmune disease and cancer. STING-mediated type I interferon (IFN) signaling is well recognized and extensively studied. Several IFN-independent activities of STING were also discovered in recent years and their physiological importance has begun to be appreciated. Here, we review recent advance in the evolutionary origin and molecular mechanisms of STING-mediated IFN-independent activities. New insights from these studies suggest that STING functions as a hub that converts multiple environmental cues into diverse cellular responses rather than acts as a simple IFN-producing machine. This expanded view of STING biology should guide future clinical testing of STING agonists and treatment of STING-associated human diseases.