English
español
Please use this identifier to cite or link to this item:
http://hdl.handle.net/10261/49166
Share/Impact:
Statistics |
![]() ![]() ![]() |
|
|
Visualizar otros formatos: MARC | Dublin Core | RDF | ORE | MODS | METS | DIDL | DATACITE | |||
|
Title: | Prolyl hydroxylase-dependent modulation of eukaryotic elongation factor 2 activity and protein translation in acute hypoxia |
Authors: | Romero-Ruiz, Antonio; Bautista, Lucía; Navarro, Virginia; Heras-Garvin, Antonio ![]() ![]() ![]() ![]() |
Keywords: | AMP Kinase Hydroxylase Hypoxia Phosphatase Phosphorylation Translation Elongation Factors |
Issue Date: | 3-Feb-2012 |
Publisher: | American Society for Biochemistry and Molecular Biology |
Citation: | Journal of Biological Chemistry 287(12): 9651-9658 (2012) |
Abstract: | Early adaptive responses to hypoxia are essential for cell survival, but their nature and underlying mechanisms are poorly known. We have studied the post-transcriptional changes in the proteome of mammalian cells elicited by acute hypoxia and found that phosphorylation of eukaryotic elongation factor 2 (eEF2), a ribosomal translocase whose phosphorylation inhibits protein synthesis, is under the precise and reversible control of O2 tension. Upon exposure to hypoxia, phosphorylation of eEF2 at Thr56 occurred rapidly (<15 min) and resulted in modest translational arrest, a fundamental homeostatic response to hypoxia that spares ATP and thus facilitates cell survival. Acute inhibitory eEF2 phosphorylation occurred without ATP depletion or AMP kinase activation. Furthermore, eEF2 phosphorylation was mimicked by prolyl hydroxylase (PHD) inhibition with dimethyloxalylglycine or by selective PHD2 siRNA silencing but was independent of hypoxia-inducible factor α stabilization. Moreover, overexpression of PHD2 blocked hypoxic accumulation of phosphorylated eEF2. Therefore, our findings suggest that eEF2 phosphorylation status (and, as a consequence, translation rate) is controlled by PHD2 activity. They unravel a novel pathway for cell adaptation to hypoxia that could have pathophysiologic relevance in tissue ischemia and cancer. |
Description: | 24 páginas, 8 figuras, 2 tablas. |
Publisher version (URL): | http://dx.doi.org/10.1074/jbc.M111.299180 |
URI: | http://hdl.handle.net/10261/49166 |
DOI: | 10.1074/jbc.M111.299180 |
ISSN: | 0021-9258 |
E-ISSN: | 1083-351X |
Appears in Collections: | (IBIS) Artículos |
Files in This Item:
File | Description | Size | Format | |
---|---|---|---|---|
Romero-Ruiz et al 2012.pdf | 4,56 MB | Adobe PDF | ![]() View/Open |
Show full item record
Review this work
Review this work
Related articles:
WARNING: Items in Digital.CSIC are protected by copyright, with all rights reserved, unless otherwise indicated.