Understanding the VHL Tumor Suppressor Complex

During the 1990s, several labs in the United States and United Kingdom investigated the von Hippel-Lindau tumor suppressor (pVHL).

Jennifer Fisher Wilson
Apr 29, 2001
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uring the 1990s, several labs in the United States and United Kingdom investigated the von Hippel-Lindau tumor suppressor (pVHL). Many important findings developed, including the belief that HIF (hypoxia-inducible factor) pathway activation could be central to renal cancer development. Interfering with this pathway could help in treating renal cancer and central nervous system hemangioblastoma. Despite the gains, many questions remain. 

VHL is a cancer syndrome characterized by highly vascularized tumors, such as hemangioblastomas and clear cell carcinomas. Those with von Hippel-Lindau disease inherit one mutated copy of the VHL gene in the germ line. Their cells still behave normally, but every so often the gene's second copy mutates in somatic cells, leading to disease.

In 1993, National Institutes of Health researchers successfully identified and cloned the VHL tumor-suppressor gene.1 Subsequent work at the Oklahoma Medical Research Foundation and the Baylor College of Medicine in Houston, Texas, discovered Rbx1,...