2024-03-29T07:15:22Zhttp://digital.csic.es/dspace-oai/requestoai:digital.csic.es:10261/491662022-12-20T10:04:20Zcom_10261_11773com_10261_1col_10261_11774
http://hdl.handle.net/10261/49166
10.1074/jbc.M111.299180
50897
Prolyl hydroxylase-dependent modulation of eukaryotic elongation factor 2 activity and protein translation in acute hypoxia
American Society for Biochemistry and Molecular Biology
2012
artículo
Romero-Ruiz, Antonio
Bautista, Lucía
Navarro, Virginia
Heras-Garvin, Antonio
March Díaz, Rosana
Castellano, Antonio
Gómez-Díaz, Raquel
Castro-Pérez, M. J.
Berra, Edurne
López-Barneo, José
Pascual Bravo, Alberto
rp04001
AMP Kinase
Hydroxylase
Hypoxia
Phosphatase
Phosphorylation
Translation Elongation Factors
2012-02-03
24 páginas, 8 figuras, 2 tablas.
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.
Journal of Biological Chemistry
2012
287
9651
9658