NOXA contributes to the sensitivity of PERK-deficient cells to ER stress

PKR-like ER kinase (PERK) deficient mouse embryonic fibroblasts (MEFs) are hypersensitive to ER stress-induced apoptosis. However, the molecular determinants of increased sensitivity of PERK−/− MEFs are not clearly understood. Here we show that induction of several Unfolded Protein Response (UPR) target genes is attenuated in PERK−/− MEFs. We also report elevated expression of the BH3-only protein, NOXA in PERK−/− MEFs. Further, shRNA-mediated knockdown of NOXA rescued the hypersensitivity of PERK−/− MEFs to ER stress-induced apoptosis. Taken together our results suggest that compromised induction of UPR and increased NOXA expression contributes to hypersensitivity of PERK−/− MEFs to ER stress-induced apoptosis.

► PERK−/− MEFs are hypersensitive to ER stress-induced apoptosis. ► Increased oxidative stress leads to increased expression of NOXA in PERK−/− MEFs. ► Increased NOXA expression contributes to hypersensitivity of PERK−/− MEFs.