cProline hydroxylation (post translationally) in the oxygen dependent degradation (ODD) domain of HIF is necessary for the correct interaction between HIF and VHL. The mechanism by which cobalt mimics hypoxia, causing accumulation of HIF-1 and HIF-2 is still not well understood. The authors then show initial evidence that cobalt inhibits pVHL binding to HIF,even when HIF, is hydroxylated. Removing 17 amino acids within the ODD domain of HIF-2 ( normally required for pVHL binding) inhibited cobalt binding and stabilized HIF-2, during normoxia. The authors conclude that cobalt mimics hypoxia by accessing the VHL-binding domain of HIF,and in so doing prevents HIF degradation.