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  • Original Paper
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Stability of nucleolar versus non-nucleolar forms of human p14ARF

Oncogene volume 23, pages 6186–6192 (2004)Cite this article

Abstract

Fusion proteins containing the amino-terminal domain of human p14ARF linked to green fluorescent protein are able to bind MDM2 and stabilize p53 without localization in the nucleolus. However, these fusion proteins are inherently unstable, with half-lives considerably shorter than either authentic ARF or chimaeras containing the entire coding domain, both of which are predominantly nucleolar. We present evidence that the unstable fusion proteins are significantly stabilized if redirected to the nucleolus by addition of a basic motif based on the nuclear localization signal of SV40 T-antigen. Moreover, the stability of these proteins can be enhanced by modulating the functions of MDM2 and p53. These data are consistent with a model in which ARF interacts with MDM2 in the nucleoplasm but is consequently subject to proteasomal degradation. Nucleolar localization may serve to store or stabilize ARF.

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Acknowledgements

We are grateful to Domenico Migliorini for providing MDMX plasmids and to Takashi Toda and Giampietro Schiavo for comments on the manuscript.

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Author notes

  1. Susana Llanos

    Present address: CNIO, Madrid, Spain

  2. Contributed equally to this work

Authors and Affiliations

  1. Cancer Research UK, London Research Institute, Lincoln's Inn Fields, London, WC2A 3PX, UK

    Helen Rodway, Susana Llanos, Janice Rowe & Gordon Peters

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  1. Helen Rodway
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  2. Susana Llanos
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  4. Gordon Peters
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Correspondence to Gordon Peters.

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Rodway, H., Llanos, S., Rowe, J. et al. Stability of nucleolar versus non-nucleolar forms of human p14ARF. Oncogene 23, 6186–6192 (2004). https://doi.org/10.1038/sj.onc.1207854

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