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

Gupta, Sanjeev and Giricz, Zoltan 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

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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.

Item Type: Article
Subjects: Q Science / természettudomány > Q1 Science (General) / természettudomány általában
Depositing User: Dr. Zoltán Giricz
Date Deposited: 09 Sep 2015 09:26
Last Modified: 09 Sep 2015 09:26
URI: http://real.mtak.hu/id/eprint/16550

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