Von Hippel-Lindau tumor suppressor

Overview
The Von Hippel-Lindau tumor suppressor protein is a protein whose inactivation is associated with Von Hippel-Lindau disease.

The disease is caused by mutations of the VHL gene on the short arm of the third chromosome (3p26-p25).

Function
The resultant protein is produced in two forms, an 18 kDa and a 30 kDa protein that functions as a tumor suppressor gene. The main action of the VHL protein is thought to be its E3 ubiquitin ligase activity that results in specific target proteins being 'marked' for degradation.

The most researched of these targets is hypoxia inducible factor 1a (HIF1a), a transcription factor that induces the expression of a number of angiogenesis related factors. (However, VHL does play other roles in tumor regulation.)

Pathology
It stands to reason that the loss of VHL protein activity results in an increased amount of HIF1a, and thus increased levels of angiogenic factors, including VEGF and PDGF. In turn, this leads to unregulated blood vessel growth, one of the prerequisites of a tumour.