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

R. K. Bruick, S. L. McKnight

Research output: Contribution to journalArticle

1902 Scopus citations

Abstract

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-1α 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.

Original languageEnglish (US)
Pages (from-to)1337-1340
Number of pages4
JournalScience
Volume294
Issue number5545
DOIs
StatePublished - Nov 9 2001

ASJC Scopus subject areas

  • General

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