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The FIH hydroxylase is a cellular peroxide sensor that modulates HIF transcriptional activity
Author(s) -
Masson Norma,
Singleton Rachelle S,
Sekirnik Rok,
Trudgian David C,
Ambrose Lucy J,
Miranda Melroy X,
Tian YaMin,
Kessler Benedikt M,
Schofield Christopher J,
Ratcliffe Peter J
Publication year - 2012
Publication title -
embo reports
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 4.584
H-Index - 184
eISSN - 1469-3178
pISSN - 1469-221X
DOI - 10.1038/embor.2012.9
Subject(s) - hypoxia (environmental) , hypoxia inducible factor 1 , peroxide , hypoxia inducible factors , transcriptional activity , microbiology and biotechnology , biochemistry , chemistry , enzyme , transcription factor , biology , oxygen , gene , organic chemistry
Hypoxic and oxidant stresses can coexist in biological systems, and oxidant stress has been proposed to activate hypoxia pathways through the inactivation of the ‘oxygen‐sensing’ hypoxia‐inducible factor (HIF) prolyl and asparaginyl hydroxylases. Here, we show that despite reduced sensitivity to cellular hypoxia, the HIF asparaginyl hydroxylase—known as FIH, factor inhibiting HIF—is strikingly more sensitive to peroxide than the HIF prolyl hydroxylases. These contrasting sensitivities indicate that oxidant stress is unlikely to signal hypoxia directly to the HIF system, but that hypoxia and oxidant stress can interact functionally as distinct regulators of HIF transcriptional output.