Hypoxia-inducible factor prolyl-4-hydroxylase 1 (HIF-PH1)

Hypoxia-inducible factor prolyl-4-hydroxylase 1 (HIF-PH1), also known as PHD1 or EGLN2, is a critical oxygen-sensing enzyme that regulates the stability of hypoxia-inducible factors (HIFs) (UniProt Q96KS0). Under normoxic conditions, HIF-PH1 catalyzes the hydroxylation of specific proline residues on HIF-alpha subunits, marking them for recognition by the von Hippel-Lindau (VHL) E3 ubiquitin ligase and subsequent proteasomal degradation (PubMed: 11595184). When oxygen levels drop, the enzyme's activity is inhibited, allowing HIF-alpha to stabilize and activate the transcription of genes involved in erythropoiesis, angiogenesis, and anaerobic metabolism (PubMed: 11595183). Beyond its role in oxygen sensing, HIF-PH1 is uniquely involved in regulating the cell cycle by stabilizing cyclin D1 and modulating mitochondrial metabolism in skeletal muscle (PubMed: 16774888, PubMed: 18463627). Pharmacological inhibition of HIF-PH1, primarily through pan-PHD inhibitors like Roxadustat, is a clinically validated strategy for treating anemia in chronic kidney disease by stimulating endogenous erythropoietin production (PubMed: 31340088). Additionally, HIF-PH1 is a target of interest in oncology and cardiovascular research due to its influence on cell proliferation and its protective role in ischemic tissues (PubMed: 21169515).

Other names

EGLN2PHD1HPH-1Prolyl hydroxylase domain-containing protein 1Egl nine homolog 2HIF-prolyl hydroxylase 1

HIF prolyl hydroxylase inhibitor