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|Title:||Role of nuclear and cytoplasmic localization in the tumour-suppressor activity of the von Hippel-Lindau protein|
|Citation:||Oncogene, 2003; 22(26):3992-3997|
|Publisher:||Nature Publishing Group|
|Martin D Lewis and Ben J Roberts|
|Abstract:||Mutations in the von Hippel-Lindau (VHL) tumour-suppressor gene result in several forms of cancer. In the present study, we investigated the role of VHL subcellular localization in its antitumour properties. We generated renal cell carcinoma (RCC) lines stably expressing either exclusively nuclear (RCC/NLS-VHL), cytoplasmic (RCC/NES-VHL) or nucleo-cytoplasmic shuttling (RCC/NES-VHL or RCC/VHL) forms of VHL and investigated several parameters linked to tumorigenesis and known to be dysregulated in VHL disease. Remarkably, although the expression of wild-type VHL is largely cytoplasmic, all of the antitumour properties of VHL tested could be reconstituted by expressing exclusively nuclear VHL.|
|Keywords:||Tumor Cells, Cultured; Cell Nucleus; Cytoplasm; Humans; Carcinoma, Renal Cell; Kidney Neoplasms; Collagen; Ligases; Ubiquitin-Protein Ligases; Proteoglycans; Bacterial Proteins; Monosaccharide Transport Proteins; Fibronectins; Laminin; Luminescent Proteins; Integrin alpha5; Tumor Suppressor Proteins; Recombinant Proteins; Transcription Factors; Drug Combinations; Microscopy, Fluorescence; Electrophoresis, Polyacrylamide Gel; Down-Regulation; Gene Expression Regulation, Neoplastic; Amino Acid Sequence; Protein Structure, Tertiary; Genetic Vectors; Molecular Sequence Data; Glucose Transporter Type 1; Von Hippel-Lindau Tumor Suppressor Protein; Hypoxia-Inducible Factor 1, alpha Subunit|
|Rights:||© 2003 Nature Publishing Group. All rights reserved.|
|Appears in Collections:||Molecular and Biomedical Science publications|
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