The hypoxia‐inducible‐factor hydroxylases bring fresh air into hypoxia signalling

Abstract
Metazoans rapidly respond to changes in oxygen availability by regulating gene expression. The transcription factor hypoxia‐inducible‐factor (HIF), which controls the expression of several genes, ‘senses’ the oxygen concentration indirectly through the hydroxylation of two proline residues that earmarks the HIF‐α subunits for proteasomal degradation. We review the expression, regulation and function of the HIF prolyl hydroxylases or prolyl hydroxylases domain proteins, which are genuine oxygen sensors.