[PDF][PDF] Oxygen sensing by metazoans: the central role of the HIF hydroxylase pathway

WG Kaelin, PJ Ratcliffe - Molecular cell, 2008 - cell.com
WG Kaelin, PJ Ratcliffe
Molecular cell, 2008cell.com
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 …
Summary
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.
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