The HIF pathway as a therapeutic target.
Hypoxia-inducible factor (HIF) is an alpha,beta-heterodimeric transcription factor that mediates cellular responses to low oxygen concentration via the transcriptional activation of specific genes involved in both tumorogenesis and angiogenesis. Manipulation of the HIF pathway has potential use for the treatment of ischemic disease and cancer. Unlike HIF-beta, which is constitutively expressed, the levels and activity of the HIF-alpha subunit are regulated by processes involving posttranslational hydroxylation, catalyzed by Fe(II)- and 2-oxoglutarate-dependent oxygenases. This review focuses on the HIF pathway as a therapeutic target.
Hewitson
Kirsty S
KS
Oxford Centre for Molecular Sciences and the Department of Chemistry, Chemistry Research Laboratory, Mansfield Road, Oxford, OX1 3TA, UK. kirsty.hewitson@chem.ox.ac.uk
Schofield
Christopher J
CJ
D000818:Animals; D051792:Basic Helix-Loop-Helix Proteins; D015536:Down-Regulation; D018257:Helix-Loop-Helix Motifs; D006801:Humans; D006900:Hydroxylation; D051795:Hypoxia-Inducible Factor 1, alpha Subunit; D007511:Ischemia / Q000378:metabolism / Q000628:therapy; D009369:Neoplasms / Q000098:blood supply / Q000378:metabolism / Q000628:therapy; D021122:Protein Subunits; D015534:Trans-Activators / Q000037:antagonists & inhibitors / Q000378:metabolism*; D014157:Transcription Factors / Q000037:antagonists & inhibitors / Q000378:metabolism*; D015854:Up-Regulation; D000099162:Endothelial PAS Domain-Containing Protein 1
D051792:Basic Helix-Loop-Helix Proteins; D051795:Hypoxia-Inducible Factor 1, alpha Subunit; D021122:Protein Subunits; D015534:Trans-Activators; D014157:Transcription Factors; D000099162:Endothelial PAS Domain-Containing Protein 1; C497442:HIF1A protein, human