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The HIF and other quandaries in VHL disease

Oncogene volume 37, pages 139–147 (2018)Cite this article

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Abstract

Mutations in VHL underlie von Hippel–Lindau (VHL) disease, a hereditary cancer syndrome with several subtypes depending on the risk of developing certain combination of classic features, such as clear cell renal cell carcinoma (ccRCC), hemangioblastoma and pheochromocytoma. Although numerous potential substrates and functions of pVHL have been described over the past decade, the best-defined role of pVHL has remained as the negative regulator of the heterodimeric hypoxia-inducible factor (HIF) transcription factor via the oxygen-dependent ubiquitin-mediated degradation of HIF-α subunit. Despite the seminal discoveries that led to the molecular elucidation of the mammalian oxygen-sensing VHL–HIF axis, which have provided several rational therapies, the mechanisms underlying the complex genotype–phenotype correlation in VHL disease are unclear. This review will discuss and highlight the studies that have provided interesting insights as well as uncertainties to the underlying mechanisms governing VHL disease.

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Acknowledgements

We thank Dr Claire Robinson, Shelley He and Aline Zara for helpful discussions and comments. This work was supported by funds from the Canadian Institutes of Health Research (CIHR, MOP 77718 and 136978). DT is a recipient of the CIHR Scholarship.

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  1. Department of Laboratory Medicine & Pathobiology, University of Toronto, Toronto, Ontario, Canada

    D Tarade & M Ohh

  2. Department of Biochemistry, University of Toronto, MaRS Centre West Tower, Toronto, Ontario, Canada

    M Ohh

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  1. D Tarade
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Tarade, D., Ohh, M. The HIF and other quandaries in VHL disease. Oncogene 37, 139–147 (2018). https://doi.org/10.1038/onc.2017.338

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