The HIF and other quandaries in VHL disease.

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.

journal_name

Oncogene

journal_title

Oncogene

authors

Tarade D,Ohh M

doi

10.1038/onc.2017.338

subject

Has Abstract

pub_date

2018-01-11 00:00:00

pages

139-147

issue

2

eissn

0950-9232

issn

1476-5594

pii

onc2017338

journal_volume

37

pub_type

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