Oxygen-dependent regulation of the hypoxia-inducible factor alpha (HIFA) and von Hippel-Lindau (VHL) proteins

A schematic representation of the oxygen-dependent regulation of HIFA. During normoxia, HIFA is hydroxylated by PHDs on proline residues. These proline residues are recognized by pVHL, which results in proteasomal degradation. Upon hypoxia, HIFA is not hydroxylated and is subsequently translocated to the nucleus. In the nucleus, HIFA heterodimerizes with HIFB; this allows the cofactors p300 and CBP to bind to the heterodimer. The complex binds to HRE and thereby induces gene expression.