Figure 2
From: von Hippel–Lindau disease: A clinical and scientific review
Top panel: in normoxic cells without VHL inactivation a pVHL containing complex ubiquitylates the α-subunits of the HIF transcription factors targeting them for proteasomal degradation. Lower panel: in VHL disease tumour cells the absence of wild type pVHL causes stabilization of the HIF α-subunits and the HIF transcription factors then activate downstream targets including VEGF (vascular endothelial growth factor), PDGF (platelet derived growth factor) and TGFα (transforming growth factor α). Tyrosine kinase inhibitors such as sorafenib and sunitinib inhibit the VEGF and PDGF receptors and so block some of the effects of VHL inactivation (modified from Woodward and Maher50).
