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

Gupta, Sanjeev and Giricz, Zoltán and Natoni, Alessandro and Donnelly, Neysan and Deegan, Shane and Szegezdi, Eva and Samali, Afshin (2012) NOXA contributes to the sensitivity of PERK-deficient cells to ER stress. FEBS letters, 586 (22). pp. 4023-30. ISSN 1873-3468

Preview

Text NOXA.pdf Download (1MB) | Preview

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.

Actions (login required)

Edit Item