title: The multifaceted von Hippel-Lindau tumour suppressor protein.
abstract: Loss of von Hippel-Lindau protein (pVHL) is known to contribute to the initiation and progression of tumours associated with VHL disease as well as certain sporadic tumours including clear cell renal cell carcinoma (ccRCC). The VHL gene was first identified and cloned over 20 years ago and our understanding of its functions and effects has significantly increased since then. The best-known function of pVHL is its role in promoting the degradation of hypoxia-inducible factor α subunit (HIFα) as part of an E3 ubiquitin ligase complex. HIF stabilisation and transcriptional activation are also associated with various epigenetic alterations, indicating a potential role for VHL loss with changes in the epigenome. This review will highlight current knowledge regarding pVHL as well as discuss potentially novel roles of pVHL and how these may impact on cancer progression.
authors.affiliation: Department of Laboratory Medicine and Pathobiology, Faculty of Medicine, University of Toronto, Toronto, Ontario, Canada.
authors.forename: Claire M
authors.initials: CM
authors.lastname: Robinson
authors.affiliation: Department of Laboratory Medicine and Pathobiology, Faculty of Medicine, University of Toronto, Toronto, Ontario, Canada; Department of Biochemistry, Faculty of Medicine, University of Toronto, Toronto, Ontario, Canada. Electronic address: michael.ohh@utoronto.ca.
authors.forename: Michael
authors.initials: M
authors.lastname: Ohh
mesh_terms: D000818:Animals; D051792:Basic Helix-Loop-Helix Proteins / Q000378:metabolism; D042002:Chromatin Assembly and Disassembly; D018450:Disease Progression; D044127:Epigenesis, Genetic; D006801:Humans; D009369:Neoplasms / Q000235:genetics / Q000378:metabolism; D051794:Von Hippel-Lindau Tumor Suppressor Protein / Q000378:metabolism*
chemical_list: D051792:Basic Helix-Loop-Helix Proteins; D051794:Von Hippel-Lindau Tumor Suppressor Protein; C497446:VHL protein, human
keywords: Clear-cell renal cell carcinoma (ccRCC); Epigenetics; Hypoxia-inducible factor (HIF); von Hippel–Lindau protein (pVHL)