Figure 6.

IRE1 and PERK-dependent pathways cooperate to generate cGAS/STING activating dsDNA release. During ER stress, the UPR activates PERK and IRE1 pathways. PERK induces the expression of CHOP and Bim, which influence mitochondrial integrity. IRE1 endonuclease activation results in the translation of the full length XBP1 transcription factor and thus induction of iNOS. Together, these 2 pathways both contribute to the ER stress-induced increase in cytosolic dsDNA, which may serve as a nominal stimulus for cGAS/STING dependent IFN-β induction. Bak/Bax placement within this schematic (in gray) derive from the literature (52), whereas black font molecules were addressed in this study. This Figure was made using BioRender.