Prolyl Hydroxylase Domain Enzyme (PHD)

Prolyl hydroxylase domain enzymes (PHDs) are a family of intracellular oxygen-sensing enzymes that play a central role in the regulation of cellular responses to oxygen availability. They regulate the stability of hypoxia-inducible factor alpha (HIF-α) subunits through post-translational hydroxylation, targeting HIF-α for proteasomal degradation under normoxic conditions. There are four main PHD isoforms: PHD1 (EGLN2), PHD2 (EGLN1), PHD3 (EGLN3), and PHD4 (P4H-TM, EGLN4). PHDs require molecular oxygen, ferrous iron, 2-oxoglutarate, and ascorbic acid for their activity. Dysregulation or altered expression/activity of PHDs is implicated in various diseases, including cancer and erythrocytosis. Inhibitors targeting these enzymes have been explored as potential cancer therapeutics.

Other names

EGLN1EGLN2EGLN3EGLN4PHD1PHD2PHD3P4H-TM

Inhibition of PHD leads to increased HIF-alpha stability and activity, impacting angiogenesis, metabolism, and cell survival.