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Exp Cell Res. 2017 Jul 15;356(2):116-121. doi: 10.1016/j.yexcr.2017.03.008. Epub 2017 Mar 15.

New horizons in hypoxia signaling pathways.

Author information

1
Target Discovery Institute, University of Oxford, OX3 7FZ, UK. Electronic address: chris.pugh@ndm.ox.ac.uk.
2
Target Discovery Institute, University of Oxford, OX3 7FZ, UK; Francis Crick Institute, Midland Road, London NW1 1AT, UK. Electronic address: peter.ratcliffe@ndm.ox.ac.uk.

Abstract

Investigation into the regulation of the erythropoietin gene by oxygen led to the discovery of a process of direct oxygen sensing that transduces many cellular and systemic responses to hypoxia. The oxygen-sensitive signal is generated through the catalytic action of a series of 2-oxoglutarate-dependent oxygenases that regulate the transcription factor hypoxia-inducible factor (HIF) by the post-translational hydroxylation of specific amino acid residues. Here we review the implications of the unforeseen complexity of the HIF transcriptional cascade for the physiology and pathophysiology of hypoxia, and consider the origins of post-translational hydroxylation as a signaling process.

KEYWORDS:

Cancer; Hypoxia; Hypoxia-inducible factor; Prolyl hydroxylase; Protein hydroxylation; Transcription

PMID:
28315322
PMCID:
PMC5653532
DOI:
10.1016/j.yexcr.2017.03.008
[Indexed for MEDLINE]
Free PMC Article

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