Cyclic GMP-AMP Synthase in Cancer Prevention. 2023

Weidong Chen, and Ga-Eun Lee, and Dohyun Jeung, and Jiin Byun, and Wu Juan, and Yong-Yeon Cho
BK21-Four, College of Pharmacy, The Catholic University of Korea.

Cyclic GMP-AMP (cGAMP), synthesized by cGAMP synthase (cGAS), serves as a secondary messenger that modulates various cellular processes, including cell proliferation, cell death, immune response, and inflammation. cGAS is activated upon detecting cytoplasmic DNA, which may originate from damaged genomic and mitochondrial DNA or from viral and bacterial infections. The presence of DNA in the cytoplasm can trigger a substantial inflammatory reaction and cytokine production via the cGAS-STING signaling pathway. Consequently, specific inhibitors targeting this pathway hold significant potential as chemopreventive agents. In this review, we explore the potential effectiveness of modulating cGAS activity. We discuss the role of cGAMP, the mechanism of action for distinguishing between self and foreign DNA, and the possible functions of cGAS within the nucleus.

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