Abstract
The von Hippel-Lindau tumor suppressor gene product, pVHL, functions as the substrate recognition component of an E3-ubiquitin ligase, which targets the oxygen-sensitive α-subunit of hypoxia-inducible factor (HIF) for rapid proteasomal degradation under normoxic conditions and as such plays a central role in molecular oxygen sensing. Mutations in pVHL can be found in familial and sporadic clear cell carcinomas of the kidney, hemangioblastomas of the retina and central nervous system, and pheochromocytomas, underscoring its gatekeeper function in the pathogenesis of these tumors. Tissue-specific gene targeting of VHL in mice has demonstrated that efficient execution of pVHL-mediated HIF proteolysis under normoxia is fundamentally important for survival, proliferation, differentiation and normal physiology of many cell types, and has provided novel insights into the biological function of individual HIF transcription factors. In this review, we discuss the role of HIF in the development of the VHL phenotype.
| Original language | English (US) |
|---|---|
| Pages (from-to) | 650-659 |
| Number of pages | 10 |
| Journal | Cell Death and Differentiation |
| Volume | 15 |
| Issue number | 4 |
| DOIs | |
| State | Published - Apr 2008 |
Funding
Acknowledgements. VHH is supported by grants from the National Cancer Institute (NCI), the National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK) and the American Heart Association (AHA). Because of space limitations, the authors were unable to accommodate all relevant references and apologize to our colleagues whose work was not cited.
ASJC Scopus subject areas
- Molecular Biology
- Cell Biology
