ArticleJournal of medical genetics2002
Genetic and functional analysis of the von Hippel-Lindau (VHL) tumour suppressor gene promoter.
Article in Journal of medical genetics, 2002. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 13 papers.
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Who cites it
13 citing papers in PubMed, 37 citations in OpenAlex.
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- Molecular Insights into the Oxygen-Sensing Pathway and Erythropoietin Expression Regulation in Erythropoiesis.International journal of molecular sciences · 2021Review
- Dysregulation at multiple points of the kynurenine pathway is a ubiquitous feature of renal cancer: implications for tumour immune evasion.British journal of cancer · 2020Article
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- Regulation of cell proliferation and migration by TAK1 via transcriptional control of von Hippel-Lindau tumor suppressor.The Journal of biological chemistry · 2009Article
- Hypoxia-Inducible Factor (HIF)-1 regulatory pathway and its potential for therapeutic intervention in malignancy and ischemia.The Yale journal of biology and medicine · 2007Review
- A distance difference matrix approach to identifying transcription factors that regulate differential gene expression.Genome biology · 2007Article
- An 11-bp duplication in the promoter region of the VHL gene in a patient with cerebellar hemangioblastoma and renal oncocytoma.Journal of human genetics · 2007Article
- Detection of germline deletions using real-time quantitative polymerase chain reaction in Japanese patients with von Hippel-Lindau disease.Cancer science · 2006Article
- Molecular analysis of two uncharacterized sequence variants of the VHL gene.Journal of human genetics · 2006Article
- Microsatellite analysis of chromosome 3p region in sporadic renal cell carcinomas.Pathology oncology research : POR · 2002Article
Corrections and comments
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Authors and funding
7 authors at 2 institutions in 2 countries.
Funding
Abstract
The VHL gatekeeper tumour suppressor gene is inactivated in the familial cancer syndrome von Hippel-Lindau disease and in most sporadic clear cell renal cell carcinomas. Recently the VHL gene product has been identified as a specific component of a SCF-like complex, which regulates proteolytic degradation of the hypoxia inducible transcription factors HIF-1 and HIF-2. pVHL is critical for normal development and mRNA expression studies suggest a role in nephrogenesis. Despite the importance of VHL in oncogenesis and development, little is known about the regulation of VHL expression. To investigate VHL promoter activity, we performed comparative sequence analysis of human, primate, and rodent 5' VHL sequences. We then proceeded to deletion analysis of regions showing significant evolutionary conservation between human and rat promoter sequences, and defined two positive and one negative regulatory regions. Analysis of specific putative transcription factor binding sites identified a functional Sp1 site, which was shown to be a regulatory element. Overlapping Sp1/AP2 sites were also identified and candidate E2F1 binding sites evaluated. Three binding sites for as yet unidentified transcription factors were mapped also. These investigations provide a basis for elucidating the regulation of VHL expression in development, the molecular pathology of epigenetic silencing of VHL in tumourigenesis, and suggest a possible link between Sp1, VHL, and nephrogenesis.
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