Biochemical purification and pharmacological inhibition of a mammalian prolyl hydroxylase acting on hypoxia-inducible factor

摘要: The product of the von Hippel–Lindau gene, pVHL, targets α subunits heterodimeric transcription factor hypoxia-inducible (HIF) for polyubiquitination in presence oxygen. binding pVHL to HIF is governed by enzymatic hydroxylation conserved prolyl residues within peptidic motifs present HIFα family members. By using a biochemical purification strategy, we have identified human homolog Caenorhabditis elegans Egl9 as hydroxylase. In addition, studied activity structurally diverse collection low molecular weight inhibitors procollagen 4-hydroxylase potential A model compound this series stabilized variety cells, leading increased production its downstream target, vascular endothelial growth factor.