Fig. 8: Mechanistic model for CYB5R3-induced lung cancer cell death.

In lung cancer cells, CYB5R3 is downregulated, and CYB5R3 overexpression promotes cell death by inducing ER stress and ROS generation. CYB5R3 activates the PERK-ATF4-CHOP and IRE1α-JNK pathways through ADP-ribosylation mediated by PARP16. ROS generation induced by CYB5R3 activates caspase-9-dependent cell death.