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

Martin D. Lewis; Ben J. Roberts

doi:10.1038/sj.onc.1206683

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

Martin D. Lewis, Ben J. Roberts

Lifelong Health

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25 Citations (Scopus)

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.

Original language	English
Pages (from-to)	3992-3997
Number of pages	6
Journal	Oncogene
Volume	22
Issue number	26
DOIs	https://doi.org/10.1038/sj.onc.1206683
Publication status	Published or Issued - 26 Jun 2003

Keywords

HIF-1α
RCC
VHL

ASJC Scopus subject areas

Molecular Biology
Genetics
Cancer Research

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10.1038/sj.onc.1206683

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

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.",

keywords = "HIF-1α, RCC, VHL",

author = "Lewis, {Martin D.} and Roberts, {Ben J.}",

note = "Funding Information: 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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doi = "10.1038/sj.onc.1206683",

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journal = "Oncogene",

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AU - Lewis, Martin D.

AU - Roberts, Ben J.

N1 - Funding Information: 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.

PY - 2003/6/26

Y1 - 2003/6/26

N2 - 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.

AB - 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.

KW - HIF-1α

KW - RCC

KW - VHL

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JO - Oncogene

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ER -

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

Abstract

Keywords

ASJC Scopus subject areas

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