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. (c) 2012 Published by Elsevier B.V. on behalf of the Federation of European Biochemical Societies.
NOXA contributes to the sensitivity of PERK-deficient cells to ER stress / Gupta, Sanjeev; Giricz, Zoltan; Natoni, Alessandro; Donnelly, Neysan; Deegan, Shane; Szegezdi, Eva; Samali, Afshin. - In: FEBS LETTERS. - ISSN 0014-5793. - 586:22(2012), pp. 4023-4030. [10.1016/j.febslet.2012.10.002]
NOXA contributes to the sensitivity of PERK-deficient cells to ER stress
Natoni, AlessandroInvestigation
;
2012
Abstract
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. (c) 2012 Published by Elsevier B.V. on behalf of the Federation of European Biochemical Societies.I documenti in IRIS sono protetti da copyright e tutti i diritti sono riservati, salvo diversa indicazione.
