The PHD1 oxygen sensor in health and disease

Abstract

The hypoxia-inducible factor (HIF) co-ordinates the adaptive transcriptional response to hypoxia in metazoan cells. The hypoxic sensitivity of HIF is conferred by a family of oxygen-sensing enzymes termed HIF hydroxylases. This family consists of three prolyl hydroxylases (PHD1-3) and a single asparagine hydroxylase termed factor inhibitor HIF (FIH). It has recently become clear that HIF hydroxylases are functionally non-redundant and have discreet but overlapping physiologic roles. Furthermore, altered abundance or activity of these enzymes is associated with a number of pathologies. Pharmacologic HIF-hydroxylase inhibitors have recently proven to be both tolerated and therapeutically effective in patients. In this review, we focus on the physiology, pathophysiology and therapeutic potential of the PHD1 isoform which has recently been implicated in diseases including inflammatory bowel disease, ischemia and cancer.

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