A Conserved Family of Prolyl-4-Hydroxylases That Modify HIF
Copyright policy )A Conserved Family of Prolyl-4-Hydroxylases That Modify HIF
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.
- The University of Texas Southwestern Medical Center United States
L-Lactate Dehydrogenase, Molecular Sequence Data, Genes, Insect, Hydroxylation, Hypoxia-Inducible Factor 1, alpha Subunit, Cell Hypoxia, Gene Expression Regulation, Enzymologic, Cell Line, DNA-Binding Proteins, Hydroxyproline, Drosophila melanogaster, Amino Acid Substitution, Genes, Reporter, Mutation, Animals, Humans, Amino Acid Sequence, Hypoxia-Inducible Factor 1, Cloning, Molecular, Conserved Sequence
L-Lactate Dehydrogenase, Molecular Sequence Data, Genes, Insect, Hydroxylation, Hypoxia-Inducible Factor 1, alpha Subunit, Cell Hypoxia, Gene Expression Regulation, Enzymologic, Cell Line, DNA-Binding Proteins, Hydroxyproline, Drosophila melanogaster, Amino Acid Substitution, Genes, Reporter, Mutation, Animals, Humans, Amino Acid Sequence, Hypoxia-Inducible Factor 1, Cloning, Molecular, Conserved Sequence
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