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Role of nuclear and cytoplasmic localization in the tumour-suppressor activity of the von Hippel-Lindau protein

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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/ΔNES-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.

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Acknowledgements

This work was supported in part by the National Health and Medical Research Council of Australia, Project Grant No. 10365, awarded to BJ Roberts. We also acknowledge the assistance of the Whitelaw laboratory (School of Molecular Life Sciences, University of Adelaide) in providing several plasmids used in this study.

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  1. School of Pharmaceutical, Molecular and Biomedical Sciences, Reid Building, Frome Rd. University of South Australia, Adelaide, 5000, Australia

    Martin D Lewis & Ben J Roberts

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  1. Martin D Lewis
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  2. Ben J Roberts
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Correspondence to Ben J Roberts.

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Lewis, M., Roberts, B. Role of nuclear and cytoplasmic localization in the tumour-suppressor activity of the von Hippel-Lindau protein. Oncogene 22, 3992–3997 (2003). https://doi.org/10.1038/sj.onc.1206683

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  • DOI: https://doi.org/10.1038/sj.onc.1206683

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