Elongation factor 2 diphthamide is critical for translation of two IRES-dependent protein targets, XIAP and FGF2, under oxidative stress conditions

Sandro Argüelles, Simonetta Camandola, Roy G. Cutler, Antonio Ayala, Mark P. Mattson

Research output: Contribution to journalArticle

Abstract

Elongation factor-2 (eEF2) catalyzes the movement of the ribosome along the mRNA. A single histidine residue in eEF2 (H715) is modified to form diphthamide. A role for eEF2 in the cellular stress response is highlighted by the fact that eEF2 is sensitive to oxidative stress and that it must be active to drive the synthesis of proteins that help cells to mitigate the adverse effects of oxidative stress. Many of these proteins are encoded by mRNAs containing a sequence called an "internal ribosomal entry site" (IRES). Under high oxidative stress conditions diphthamide-deficient cells were significantly more sensitive to cell death. These results suggest that diphthamide may play a role in protection against the degradation of eEF2. This protection is especially important in those situations in which eEF2 is necessary for the reprogramming of translation from global to IRES synthesis. Indeed, we found that the expression of X-linked inhibitor of apoptosis (XIAP) and fibroblast growth factor 2 (FGF2), two proteins synthesized from mRNAs with IRESs that promote cell survival, is deregulated in diphthamide-deficient cells. Our findings therefore suggest that eEF2 diphthamide controls the selective translation of IRES-dependent protein targets XIAP and FGF2, critical for cell survival under conditions of oxidative stress.

Original languageEnglish (US)
Pages (from-to)131-138
Number of pages8
JournalFree Radical Biology and Medicine
Volume67
DOIs
StatePublished - 2014

Fingerprint

X-Linked Inhibitor of Apoptosis Protein
Peptide Elongation Factor 2
Oxidative stress
Fibroblast Growth Factor 2
Oxidative Stress
Apoptosis
Proteins
Messenger RNA
Cell Survival
Cells
Cell death
Ribosomes
Histidine
Cell Death
diphthamide
Degradation

Keywords

  • Diphthamide
  • Eukaryotic elongation factor-2
  • FGF-2
  • Free radicals
  • Internal ribosomal entry site
  • Lipid peroxidation
  • XIAP

ASJC Scopus subject areas

  • Biochemistry
  • Physiology (medical)
  • Medicine(all)

Cite this

Elongation factor 2 diphthamide is critical for translation of two IRES-dependent protein targets, XIAP and FGF2, under oxidative stress conditions. / Argüelles, Sandro; Camandola, Simonetta; Cutler, Roy G.; Ayala, Antonio; Mattson, Mark P.

In: Free Radical Biology and Medicine, Vol. 67, 2014, p. 131-138.

Research output: Contribution to journalArticle

Argüelles, Sandro ; Camandola, Simonetta ; Cutler, Roy G. ; Ayala, Antonio ; Mattson, Mark P. / Elongation factor 2 diphthamide is critical for translation of two IRES-dependent protein targets, XIAP and FGF2, under oxidative stress conditions. In: Free Radical Biology and Medicine. 2014 ; Vol. 67. pp. 131-138.
@article{d876da3b888944d5b7ac02a182724981,
title = "Elongation factor 2 diphthamide is critical for translation of two IRES-dependent protein targets, XIAP and FGF2, under oxidative stress conditions",
abstract = "Elongation factor-2 (eEF2) catalyzes the movement of the ribosome along the mRNA. A single histidine residue in eEF2 (H715) is modified to form diphthamide. A role for eEF2 in the cellular stress response is highlighted by the fact that eEF2 is sensitive to oxidative stress and that it must be active to drive the synthesis of proteins that help cells to mitigate the adverse effects of oxidative stress. Many of these proteins are encoded by mRNAs containing a sequence called an {"}internal ribosomal entry site{"} (IRES). Under high oxidative stress conditions diphthamide-deficient cells were significantly more sensitive to cell death. These results suggest that diphthamide may play a role in protection against the degradation of eEF2. This protection is especially important in those situations in which eEF2 is necessary for the reprogramming of translation from global to IRES synthesis. Indeed, we found that the expression of X-linked inhibitor of apoptosis (XIAP) and fibroblast growth factor 2 (FGF2), two proteins synthesized from mRNAs with IRESs that promote cell survival, is deregulated in diphthamide-deficient cells. Our findings therefore suggest that eEF2 diphthamide controls the selective translation of IRES-dependent protein targets XIAP and FGF2, critical for cell survival under conditions of oxidative stress.",
keywords = "Diphthamide, Eukaryotic elongation factor-2, FGF-2, Free radicals, Internal ribosomal entry site, Lipid peroxidation, XIAP",
author = "Sandro Arg{\"u}elles and Simonetta Camandola and Cutler, {Roy G.} and Antonio Ayala and Mattson, {Mark P.}",
year = "2014",
doi = "10.1016/j.freeradbiomed.2013.10.015",
language = "English (US)",
volume = "67",
pages = "131--138",
journal = "Free Radical Biology and Medicine",
issn = "0891-5849",
publisher = "Elsevier Inc.",

}

TY - JOUR

T1 - Elongation factor 2 diphthamide is critical for translation of two IRES-dependent protein targets, XIAP and FGF2, under oxidative stress conditions

AU - Argüelles, Sandro

AU - Camandola, Simonetta

AU - Cutler, Roy G.

AU - Ayala, Antonio

AU - Mattson, Mark P.

PY - 2014

Y1 - 2014

N2 - Elongation factor-2 (eEF2) catalyzes the movement of the ribosome along the mRNA. A single histidine residue in eEF2 (H715) is modified to form diphthamide. A role for eEF2 in the cellular stress response is highlighted by the fact that eEF2 is sensitive to oxidative stress and that it must be active to drive the synthesis of proteins that help cells to mitigate the adverse effects of oxidative stress. Many of these proteins are encoded by mRNAs containing a sequence called an "internal ribosomal entry site" (IRES). Under high oxidative stress conditions diphthamide-deficient cells were significantly more sensitive to cell death. These results suggest that diphthamide may play a role in protection against the degradation of eEF2. This protection is especially important in those situations in which eEF2 is necessary for the reprogramming of translation from global to IRES synthesis. Indeed, we found that the expression of X-linked inhibitor of apoptosis (XIAP) and fibroblast growth factor 2 (FGF2), two proteins synthesized from mRNAs with IRESs that promote cell survival, is deregulated in diphthamide-deficient cells. Our findings therefore suggest that eEF2 diphthamide controls the selective translation of IRES-dependent protein targets XIAP and FGF2, critical for cell survival under conditions of oxidative stress.

AB - Elongation factor-2 (eEF2) catalyzes the movement of the ribosome along the mRNA. A single histidine residue in eEF2 (H715) is modified to form diphthamide. A role for eEF2 in the cellular stress response is highlighted by the fact that eEF2 is sensitive to oxidative stress and that it must be active to drive the synthesis of proteins that help cells to mitigate the adverse effects of oxidative stress. Many of these proteins are encoded by mRNAs containing a sequence called an "internal ribosomal entry site" (IRES). Under high oxidative stress conditions diphthamide-deficient cells were significantly more sensitive to cell death. These results suggest that diphthamide may play a role in protection against the degradation of eEF2. This protection is especially important in those situations in which eEF2 is necessary for the reprogramming of translation from global to IRES synthesis. Indeed, we found that the expression of X-linked inhibitor of apoptosis (XIAP) and fibroblast growth factor 2 (FGF2), two proteins synthesized from mRNAs with IRESs that promote cell survival, is deregulated in diphthamide-deficient cells. Our findings therefore suggest that eEF2 diphthamide controls the selective translation of IRES-dependent protein targets XIAP and FGF2, critical for cell survival under conditions of oxidative stress.

KW - Diphthamide

KW - Eukaryotic elongation factor-2

KW - FGF-2

KW - Free radicals

KW - Internal ribosomal entry site

KW - Lipid peroxidation

KW - XIAP

UR - http://www.scopus.com/inward/record.url?scp=84888125439&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=84888125439&partnerID=8YFLogxK

U2 - 10.1016/j.freeradbiomed.2013.10.015

DO - 10.1016/j.freeradbiomed.2013.10.015

M3 - Article

C2 - 24140707

AN - SCOPUS:84888125439

VL - 67

SP - 131

EP - 138

JO - Free Radical Biology and Medicine

JF - Free Radical Biology and Medicine

SN - 0891-5849

ER -