Function

VHL is part of an SCF related E3-ubiquitin ligase complex with 'gatekeeper' function in renal carcinoma.

The von Hippel-Lindau (pVHL) protein plays an important role in hypoxia sensing. It binds to the hydroxylated hypoxia-inducible factor 1 alpha (HIF-1 alpha) and serves as a recognition component of an E3-ubiquitin ligase complex.

In hypoxia or secondary to a mutated VHL gene, the nondegraded HIF-1 alpha forms a heterodimer with HIF-beta and leads to increased transcription of hypoxia-inducible genes, including erythropoietin (EPO).

Pathology

 The autosomal dominant cancer-predisposition von Hippel-Lindau syndrome is due to inheritance of a single mutated allele of VHL.
 Somatic mutations in renal cell carcinoma
 homozygous VHL germline mutation in congenital polycythemia (#12844285#)

Features

 VHL interacting proteins

References

 Maher ER. Von Hippel-Lindau disease. Curr Mol Med. 2004 Dec;4(8):833-42. PMID: #15579030#

 Barry RE, Krek W. The von Hippel-Lindau tumour suppressor: a multi-faceted inhibitor of tumourigenesis. Trends Mol Med. 2004 Sep;10(9):466-72. PMID: #15350900#

 George DJ, Kaelin WG Jr. The von Hippel-Lindau protein, vascular endothelial growth factor, and kidney cancer. N Engl J Med. 2003 Jul 31;349(5):419-21. PMID: #12890838#

 Kaelin WG Jr. Molecular basis of the VHL hereditary cancer syndrome. Nat Rev Cancer. 2002 Sep;2(9):673-82. PMID: #12209156#

 Kaelin WG Jr, Maher ER. The VHL tumour-suppressor gene paradigm. Trends Genet. 1998 Oct;14(10):423-6. PMID: #9820032#