Figure 1.

Expression of hypoxia-inducible factors (HIF)1α and HIF2α in Von Hippel–Lindau (VHL)-deficient clear cell renal cell carcinoma (ccRCC). The expression of VHL/E3 ubiquitin ligase complex leads to the proteasomal degradation of HIFα subunits, which assure that HIF1α and HIF2α inactivation in healthy renal epithelial cells. Upon VHL gene inactivation in ccRCC, HIF1α and HIF2α cannot be degraded and, therefore, are constitutively expressed in a large number of ccRCC. However, HIF1α acts as a ccRCC tumor suppressor and in this line, HIF1α locus is inactivated in some ccRCC while the expression of HIF2α—acting as a ccRCC oncoprotein—persists in some other ccRCC subtypes.