Edagawa et al. has previously shown that the PERK-ATF4-CHOP pathway mediates DR4 and DR5 activation in an ATF3/CHOP-dependent manner when TP53 is functionally lost or deleted [54], a characteristic signature of numerous cancers Moreover, DR4/5 induction can also be regulated via the IRE1α/TRAIL arm of the UPR by interacting with phosphorylated C-Jun, forming a complex and regulates DR4/5 transcriptional activity [55]. The gene discussed is ERN1; the disease is cancer.