Von Hippel–Lindau tumor suppressor

HIF_and_pVHL.png

Protein-coding gene in the species Homo sapiens

Von Hippel–Lindau tumor suppressor

Symbol	VHL
HGNC ID	12687
Alternative symbols	–
Entrez Gene	7428
OMIM	608537
RefSeq	NM_000551
UniProt	–
Chromosome	–
Locus supplementary data	–

The Von Hippel–Lindau tumor suppressor (VHL) is a protein that in humans is encoded by the VHL gene. This gene is a tumor suppressor gene and is associated with Von Hippel–Lindau disease, a hereditary condition that predisposes individuals to develop a variety of benign and malignant tumors.

Function

The VHL protein is part of a complex involved in the degradation of hypoxia-inducible factor (HIF), a transcription factor that responds to changes in oxygen levels in the cellular environment. Under normal oxygen conditions, VHL targets HIF for ubiquitination and subsequent degradation by the proteasome. This process is crucial for the regulation of genes involved in angiogenesis, metabolism, and cell proliferation.

Clinical Significance

Mutations in the VHL gene can lead to the development of Von Hippel–Lindau disease, which is characterized by the formation of hemangioblastomas, renal cell carcinoma, pheochromocytoma, and other types of tumors. The disease is inherited in an autosomal dominant manner, meaning that a single copy of the mutated gene can cause the disorder.

Pathophysiology

The loss of VHL function results in the stabilization and accumulation of HIF, even under normal oxygen conditions. This leads to the overexpression of HIF target genes, promoting tumorigenesis through increased angiogenesis and altered cellular metabolism. The VHL protein also interacts with other cellular pathways, including those involved in extracellular matrix formation and cell cycle regulation.

Diagnosis and Treatment

Diagnosis of Von Hippel–Lindau disease typically involves genetic testing to identify mutations in the VHL gene. Imaging studies such as MRI and CT scan are used to detect tumors associated with the condition. Treatment options vary depending on the type and location of the tumors and may include surgery, radiation therapy, and targeted therapy.

Research Directions

Ongoing research aims to better understand the molecular mechanisms of VHL function and its role in tumor suppression. There is also significant interest in developing targeted therapies that can mimic VHL function or inhibit the pathways activated by HIF.

See also

• Von Hippel–Lindau disease
• Hypoxia-inducible factor
• Tumor suppressor gene
• Renal cell carcinoma

References

   This article is a medical stub. You can help WikiMD by expanding it!