VHL

Von Hippel-Lindau (VHL) protein, also recognized as pVHL, functions as the substrate recognition component of the E3 ubiquitin ligase complex. It principally mediates oxygen-dependent ubiquitination and proteasomal degradation of HIF-α, governing the hypoxia-inducible signaling cascade and modulating cell cycle, angiogenesis and metabolic reprogramming.
Germline or somatic VHL inactivation predisposes individuals to von Hippel-Lindau syndrome, clear cell renal cell carcinoma and hemangioblastoma. Pharmacological strategies including HIF inhibitors, molecular chaperones and proteolysis-targeting chimeras are actively explored in preclinical and clinical trials to restore downstream homeostasis for VHL-deficient malignancies.