When hypoxic cells return to normoxia, HIF-alpha is ubiquitinated in the nucleus and exported to the cytosol (Groulx and Lee 2002). The shuttling of VHL between the nucleus and cytosol is required (Groulx and Lee 2002, Lee et al. 1999). Different cell types have different nucleocytoplasmic compartmentalization of HIF degradation (Zheng et al. 2006).