HIF is a heterodimer consisting of a α and a β subunits, also known as aryl hydrocarbon nuclear translocator . While HIF-1β protein levels remain largely unchanged in hypoxia, HIF-α levels are extremely sensitive to change in oxygen availability. Oxygen sensitivity is conferred to the HIF system, via the action of a class of dioxygenases called prolyl hydroxylases (PHDs). PHDs require molecular oxygen, 2-oxoglutarate, and iron as cofactors to perform proline hydroxylation of their targets . Proline hydroxylation of two conserved residues within HIF-α creates a high-affinity binding site for a ubiquitin E3 ligase complex containing the tumour suppressor, von Hippel Lindau (VHL). VHL thus promotes the ubiquitination and proteasome-dependent degradation of HIF-α under normal oxygen conditions .