FIGURE 2.

Regulation of HIF under normoxic and hypoxic conditions. When oxygen is abundant, HIF is hydroxylated by prolyl hydroxylase domain protein (PHD) enzymes at two specific proline residues, enabling it to bind VHL. VHL targets hydroxylated HIF subunits for ubiquitin-mediated proteasomal degradation. Under hypoxic conditions, inactivation of PHD and FIH-1 results in HIF stabilization and translocation into the nucleus where it stabilizes and dimerizes with HIF-1β, which together with the co-transcription factors p300 and CBP, drives hypoxia Transcription of target genes of response elements (HREs).