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

Sanjeev Gupta, Zoltan Giricz, Alessandro Natoni, Neysan Donnelly, Shane Deegan, Eva Szegezdi, Afshin Samali

Research output: Contribution to journalArticle

15 Citations (Scopus)

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 languageEnglish
Pages (from-to)4023-4030
Number of pages8
JournalFEBS letters
Volume586
Issue number22
DOIs
Publication statusPublished - Nov 16 2012

Keywords

  • Apoptosis
  • ER stress
  • NOXA
  • PERK
  • Unfolded protein response

ASJC Scopus subject areas

  • Biophysics
  • Structural Biology
  • Biochemistry
  • Molecular Biology
  • Genetics
  • Cell Biology

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  • Cite this

    Gupta, S., Giricz, Z., Natoni, A., Donnelly, N., Deegan, S., Szegezdi, E., & Samali, A. (2012). NOXA contributes to the sensitivity of PERK-deficient cells to ER stress. FEBS letters, 586(22), 4023-4030. https://doi.org/10.1016/j.febslet.2012.10.002