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HIF plays a central role in the transcriptional response to changes in oxygen availability. The PHD family of oxygen-dependent prolyl hydroxylases plays a pivotal role in regulating HIF stability. The biochemical properties of these enzymes make them well suited to act as oxygen sensors. They also respond to other intracellular signals, including reactive oxygen species, nitric oxide, and certain metabolites, that can modulate the hypoxic response. HIF transcriptional activity is further tuned by FIH1-mediated asparagine hydroxylation. HIF affects signaling pathways that influence development, metabolism, inflammation, and integrative physiology. Accordingly, HIF-modulatory drugs are now being developed for diverse diseases.

Original publication




Journal article


Mol Cell

Publication Date





393 - 402


Animals, Ascorbic Acid, Asparagine, Citric Acid Cycle, Enzyme Stability, Gene Expression Regulation, Humans, Hypoxia-Inducible Factor 1, Iron, Isoenzymes, Mixed Function Oxygenases, Nitric Oxide, Oxygen, Procollagen-Proline Dioxygenase, Reactive Oxygen Species, Repressor Proteins, Signal Transduction, Transcription Factors, Transcription, Genetic