Systemic VHL gene functions and the VHL disease

FEBS Lett. 2012 Jun 4;586(11):1562-9. doi: 10.1016/j.febslet.2012.04.032. Epub 2012 Apr 25.


The von Hippel-Lindau tumor suppressor gene (VHL) is best known as an E3 ubiquitin ligase that negatively regulates the hypoxia inducible factor (HIF). VHL mutations are the genetic defects underlying several human diseases including polycythemia, familial VHL tumor syndrome and sporadic renal cell carcinoma. VHL mutations can lead to cell-autonomous phenotypes in the tumor cells. However, non-tumor cell-autonomous functions of VHL have also been noted. VHL tumor-derived cytokines can promote inflammation and induce mobilization of endothelial progenitor cells. Up-regulation of HIF caused by VHL loss-of-function mutants, including heterozygotes, has been shown to increase the activities of hematopoietic stem cells, endothelial cells and myeloid cells. As such, systemic functions of VHL likely play important roles in the development of VHL disease.

Publication types

  • Research Support, N.I.H., Extramural
  • Review

MeSH terms

  • Animals
  • Hematopoiesis / genetics
  • Humans
  • Neoplasms / genetics
  • Neoplasms / metabolism
  • Neoplasms / pathology
  • Neovascularization, Pathologic / genetics
  • Polycythemia / genetics
  • Von Hippel-Lindau Tumor Suppressor Protein / genetics*
  • Von Hippel-Lindau Tumor Suppressor Protein / metabolism*
  • von Hippel-Lindau Disease / genetics*
  • von Hippel-Lindau Disease / metabolism
  • von Hippel-Lindau Disease / pathology
  • von Hippel-Lindau Disease / physiopathology


  • Von Hippel-Lindau Tumor Suppressor Protein