4.7 Review

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

Journal

JOURNAL OF MOLECULAR BIOLOGY
Volume 434, Issue 6, Pages -

Publisher

ACADEMIC PRESS LTD- ELSEVIER SCIENCE LTD
DOI: 10.1016/j.jmb.2021.167257

Keywords

STING; vesicle trafficking; cell death; autophagy; NF-kB; type I IFN; infection; autoimmune disease; anti-tumor immunity; neurodegenetive disease

Funding

  1. NIH [AI161708]
  2. Cleveland Clinic

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This review article summarizes the important role of stimulator of interferon genes (STING) in infection, autoimmune disease, and cancer. It focuses on the evolutionary origin and molecular mechanisms of STING-mediated interferon-independent activities. The article highlights that STING not only produces interferons, but also functions as a hub that converts multiple environmental cues into diverse cellular responses. These findings provide new insights for the clinical testing of STING agonists in cancer and the treatment of STING-associated human diseases.
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 is not just a simple IFN-producing machine, rather, it functions as a hub that converts multiple environmental cues into diverse cellular responses . This expanded view of STING biology should guide future clinical testing of STING agonists in cancer and treatment of STING-associated human diseases.(c) 2021 Elsevier Ltd. All rights reserved.

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