Role of nuclear and cytoplasmic localization in the tumour-suppressor activity of the von Hippel-Lindau protein.
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/DeltaNES-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.
Lewis
Martin D
MD
School of Pharmaceutical, Molecular and Biomedical Sciences, Reid Building, Frome Rd., University of South Australia, Adelaide 5000, Australia.
Roberts
Ben J
BJ
D000595:Amino Acid Sequence; D001426:Bacterial Proteins / Q000378:metabolism; D002292:Carcinoma, Renal Cell / Q000378:metabolism; D002467:Cell Nucleus / Q000378:metabolism*; D003094:Collagen / Q000494:pharmacology; D003593:Cytoplasm / Q000378:metabolism*; D015536:Down-Regulation; D004338:Drug Combinations; D004591:Electrophoresis, Polyacrylamide Gel; D005353:Fibronectins / Q000378:metabolism; D015972:Gene Expression Regulation, Neoplastic; D005822:Genetic Vectors; D051272:Glucose Transporter Type 1; D006801:Humans; D051795:Hypoxia-Inducible Factor 1, alpha Subunit; D039482:Integrin alpha5 / Q000378:metabolism; D007680:Kidney Neoplasms / Q000378:metabolism; D007797:Laminin / Q000494:pharmacology; D008025:Ligases / Q000378:metabolism*; D008164:Luminescent Proteins / Q000378:metabolism; D008856:Microscopy, Fluorescence; D008969:Molecular Sequence Data; D009004:Monosaccharide Transport Proteins / Q000378:metabolism; D017434:Protein Structure, Tertiary; D011509:Proteoglycans / Q000494:pharmacology; D011994:Recombinant Proteins / Q000378:metabolism; D014157:Transcription Factors / Q000378:metabolism; D014407:Tumor Cells, Cultured; D025521:Tumor Suppressor Proteins; D044767:Ubiquitin-Protein Ligases; D051794:Von Hippel-Lindau Tumor Suppressor Protein
D001426:Bacterial Proteins; D004338:Drug Combinations; D005353:Fibronectins; D051272:Glucose Transporter Type 1; C497442:HIF1A protein, human; D051795:Hypoxia-Inducible Factor 1, alpha Subunit; D039482:Integrin alpha5; D007797:Laminin; D008164:Luminescent Proteins; D009004:Monosaccharide Transport Proteins; D011509:Proteoglycans; D011994:Recombinant Proteins; C495677:SLC2A1 protein, human; D014157:Transcription Factors; D025521:Tumor Suppressor Proteins; C054562:yellow fluorescent protein, Bacteria; C059485:matrigel; D003094:Collagen; D044767:Ubiquitin-Protein Ligases; D051794:Von Hippel-Lindau Tumor Suppressor Protein; D008025:Ligases; C497446:VHL protein, human