A conserved family of prolyl-4-hydroxylases that modify HIF.

Article Details


Bruick RK, McKnight SL

A conserved family of prolyl-4-hydroxylases that modify HIF.

Science. 2001 Nov 9;294(5545):1337-40. Epub 2001 Oct 11.

PubMed ID
11598268 [ View in PubMed

Mammalian cells respond to changes in oxygen availability through a conserved pathway that is regulated by the hypoxia-inducible factor (HIF). The alpha subunit of HIF is targeted for degradation under normoxic conditions by a ubiquitin-ligase complex that recognizes a hydroxylated proline residue in HIF. We identified a conserved family of HIF prolyl hydoxylase (HPH) enzymes that appear to be responsible for this posttranslational modification. In cultured mammalian cells, inappropriate accumulation of HIF caused by forced expression of the HIF-1alpha subunit under normoxic conditions was attenuated by coexpression of HPH. Suppression of HPH in cultured Drosophila melanogaster cells by RNA interference resulted in elevated expression of a hypoxia-inducible gene (LDH, encoding lactate dehydrogenase) under normoxic conditions. These findings indicate that HPH is an essential component of the pathway through which cells sense oxygen.

DrugBank Data that Cites this Article

NameUniProt ID
Egl nine homolog 3Q9H6Z9Details