Von Hippel–Lindau tumor suppressor protein (pVHL)

The **Von Hippel–Lindau tumor suppressor protein (pVHL)** is a cellular protein encoded by the *VHL* gene and acts as the substrate recognition subunit of a multi-protein E3 ubiquitin ligase complex. pVHL is essential for the regulated degradation of hypoxia-inducible factors (HIF-1α and HIF-2α), transcription factors that control gene expression under low oxygen conditions and are central to angiogenesis, erythropoiesis, and cell metabolism. Loss or mutation of pVHL leads to constitutive HIF activation, driving increased blood vessel formation, uncontrolled cellular proliferation, and predisposition to various tumors, most notably **clear cell renal cell carcinoma, hemangioblastoma of the CNS and retina, and pheochromocytoma**, as seen in **Von Hippel–Lindau disease**—an autosomal dominant hereditary cancer syndrome. The protein also plays roles in cell cycle control and extracellular matrix assembly. Targeting the pVHL/HIF/VEGF axis is the basis for several approved therapies in VHL-related and sporadic cancers, though resistance and broad toxicity remain challenges[1][2][3][4][6][7][8].

Other names

VHL proteinpVHLVHL1VHL_HUMAN

Inhibition of vascular endothelial growth factor (VEGF) pathway Inhibition of mTOR pathway Restoration of HIF inactivation (vitamin C, theorized)