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. Author manuscript; available in PMC: 2019 Jun 12.
Published in final edited form as: Biochim Biophys Acta Rev Cancer. 2018 Jun 28;1870(1):23–31. doi: 10.1016/j.bbcan.2018.06.003

Figure 1. Regulation of hypoxia-inducible factor (HIF) signaling by the von Hippel-Lindau (VHL) tumor suppressor.

Figure 1.

Under oxygen-replete conditions, HIF-α subunits are hydroxylated by prolyl hydroxylases (PHDs) and then ubiquitinated by an E3-ubiquitin ligase complex containing pVHL, tagging them for proteasomal degradation. In hypoxia, or when VHL is inactivated (such as in ccRCC), HIF-α subunits escape degradation, translocate to the nucleus, and |heterodimerize with HIF-1β (ARNT). HIFs generally promote a transcriptional program favoring increased angiogenesis, glycolysis, and metastatic capabilities of ccRCC tumors. HRE = hypoxia response element.