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

Afshin Samali; Sanjeev Gupta

doi:10.1016/j.febslet.2012.10.002

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

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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.

Original language	English (Ireland)
Pages (from-to)	4023-4030
Number of pages	8
Journal	Febs Letters
Volume	586
Issue number	22
DOIs	https://doi.org/10.1016/j.febslet.2012.10.002
Publication status	Published - 1 Nov 2012

Keywords

Apoptosis
ER stress
NOXA
PERK
Unfolded protein response

Authors (Note for portal: view the doc link for the full list of authors)

Authors
Gupta S, Giricz Z, Natoni A, Donnelly N, Deegan S, Szegezdi E, Samali A
Gupta, S,Giricz, Z,Natoni, A,Donnelly, N,Deegan, S,Szegezdi, E,Samali, A

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10.1016/j.febslet.2012.10.002

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title = "NOXA contributes to the sensitivity of PERK-deficient cells to ER stress.",

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.",

keywords = "Apoptosis, ER stress, NOXA, PERK, Unfolded protein response",

author = "Afshin Samali and Sanjeev Gupta",

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doi = "10.1016/j.febslet.2012.10.002",

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AU - Samali, Afshin

AU - Gupta, Sanjeev

PY - 2012/11/1

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N2 - 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.

AB - 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.

KW - Apoptosis

KW - ER stress

KW - NOXA

KW - PERK

KW - Unfolded protein response

UR - https://www.scopus.com/pages/publications/84868564773

U2 - 10.1016/j.febslet.2012.10.002

DO - 10.1016/j.febslet.2012.10.002

M3 - Article

VL - 586

SP - 4023

EP - 4030

JO - Febs Letters

JF - Febs Letters

IS - 22

ER -

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

Abstract

Keywords

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