Two studies discover new enzyme that acts as a sensor of innate immunity

Published on February 16, 2013 at 6:31 AM · No Comments

"Foreign DNA in the cytoplasm is a sign of attack by a virus, bacteria, or parasite," Dr. Chen said. "Host DNA that somehow leaks into the cytoplasm can trigger autoimmune conditions, like lupus, Sjogren's syndrome, and Aicardi-Goutiere's syndrome in humans."

In these studies, UTSW researchers identified a new sensor of innate immunity - the enzyme cyclic GMP-AMP synthase (cGAS) - that sounds a cellular alarm when it encounters DNA in the cytoplasm. After the enzyme detects and binds to the DNA, it catalyzes the formation of a compound called cyclic GMP-AMP (cGAMP), the compound never before seen in humans, Dr. Chen said.

The cGAMP functions as a second messenger that binds to an adaptor protein called STING, which activates a cell signaling cascade that in turn produces agents of inflammation: interferons and cytokines.

"Normally this pathway is important for immune defense against infections by microbial pathogens. However, when the immune system turns against host DNA, it can cause autoimmune diseases," Dr. Chen said. "Our discovery of cGAS as the DNA sensor provides an attractive target for the development of new drugs that might treat autoimmune diseases."

Source: UT Southwestern Medical Center

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