کد مقاله | کد نشریه | سال انتشار | مقاله انگلیسی | نسخه تمام متن |
---|---|---|---|---|
2047894 | 1074044 | 2012 | 8 صفحه PDF | دانلود رایگان |
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.
Journal: FEBS Letters - Volume 586, Issue 22, 16 November 2012, Pages 4023–4030