Figure 2: Regulation of gene expression by HIF-1a. In normoxic conditions, FIH and PHDs hydroxylate residues in the CTAD and ODD domains of HIF-1a, which in turn activates VHL binding and ubiquitination of HIF-1a, ultimately leading to its proteasomal degradation. Under hypoxic conditions, however, the lack of oxygen inhibits the action of FIH and PHDs, so HIF-1a is able to stabilise and dimerize with HIF-1ß, ultimately activating target gene transcription through recruitment of coactivators. Adapted from Kenneth and Rocha (2008).