期刊
FREE RADICAL BIOLOGY AND MEDICINE
卷 67, 期 -, 页码 131-138出版社
ELSEVIER SCIENCE INC
DOI: 10.1016/j.freeradbiomed.2013.10.015
关键词
Eukaryotic elongation factor-2; Diphthamide; Lipid peroxidation; XIAP; FGF-2; Internal ribosomal entry site; Free radicals
资金
- Ministerio de Educacion, Cultura y Deporte of Spain [EX2009-0918]
- Ministerio de Ciencia e Innovacion [BFU 2010-20882]
- Intramural Research Program of the National Institute on Aging
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. Published by Elsevier Inc.
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