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The multifaceted von Hippel–Lindau tumour suppressor protein
Author(s) -
Robinson Claire M.,
Ohh Michael
Publication year - 2014
Publication title -
febs letters
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.593
H-Index - 257
eISSN - 1873-3468
pISSN - 0014-5793
DOI - 10.1016/j.febslet.2014.02.026
Subject(s) - ubiquitin ligase , epigenome , cancer research , hypoxia inducible factors , ubiquitin , biology , epigenetics , suppressor , tumor suppressor gene , loss function , clear cell renal cell carcinoma , renal cell carcinoma , cancer , carcinogenesis , gene , genetics , dna methylation , medicine , gene expression , phenotype
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.