TREX1 cytosolic DNA degradation correlates with autoimmune disease and cancer immunity

Abstract

The N-terminal domain of Three Prime Repair Exonuclease 1 (TREX1) is catalytically active and can degrade dsDNA or ssDNA in the cytosol, whereas the C-terminal domain is primarily involved in protein localization. TREX1 deficiency induces cytosolic DNA accumulation as well as activation of the cGAS-STING-IFN signaling pathway, which results in tissue inflammation and autoimmune diseases. Furthermore, TREX1 expression in cancer immunity can be adaptively regulated to promote tumor proliferation, making it a promising therapeutic target.