Molecular basis of the VHL hereditary cancer syndrome

Nat Rev Cancer. 2002 Sep;2(9):673-82. doi: 10.1038/nrc885.


The von Hippel-Lindau hereditary cancer syndrome was first described about 100 years ago. The unusual clinical features of this disorder predicted a role for the von Hippel-Lindau gene (VHL) in the oxygen-sensing pathway. Indeed, recent studies of this gene have helped to decipher how cells sense changes in oxygen availability, and have revealed a previously unappreciated role of prolyl hydroxylation in intracellular signalling. These studies, in turn, are laying the foundation for the treatment of a diverse set of disorders, including cancer, myocardial infarction and stroke.

Publication types

  • Review

MeSH terms

  • Animals
  • Gene Expression Regulation, Neoplastic
  • Genetic Predisposition to Disease*
  • Humans
  • Ligases / genetics*
  • Neoplasms / complications*
  • Neoplasms / genetics*
  • Neoplasms / metabolism
  • Neoplasms / pathology
  • Tumor Suppressor Proteins*
  • Ubiquitin-Protein Ligases*
  • Von Hippel-Lindau Tumor Suppressor Protein
  • von Hippel-Lindau Disease / complications*
  • von Hippel-Lindau Disease / genetics*
  • von Hippel-Lindau Disease / metabolism
  • von Hippel-Lindau Disease / pathology


  • Tumor Suppressor Proteins
  • Ubiquitin-Protein Ligases
  • Von Hippel-Lindau Tumor Suppressor Protein
  • Ligases
  • VHL protein, human