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A functional link between the tumour suppressors ARF and p33ING1

Oncogene volume 25, pages 5173–5179 (2006)Cite this article

Abstract

The ARF tumour suppressor protein plays a critical role in the activation of p53 in response to oncogenic stress. ARF can activate p53 through nucleolar sequestration of Mdm2. However, several lines of evidence indicate that this is not the only way of action of ARF, and alternative mechanisms must exist. p33ING1 is a putative tumour suppresor, which induces cell-cycle arrest and apoptosis in a p53-dependent manner. Here, we describe that ARF and p33ING1 can interact in vivo. We also show that the subcellular localization of ING1 can be modulated by ARF protein levels, causing a displacement from nuclear to nucleolar localization. Finally, the ability of p33ING1 to cause cell-cycle arrest and induction of p21CIP1, or Mdm2, is impaired in ARF-deficient primary mouse fibroblasts. Based on these observations, we propose that the interaction with p33ING1 represents a novel mechanism for the tumour suppression function of ARF.

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Acknowledgements

We are grateful to Charles Sherr for p19ARF-null mice, to Gigi Lozano for p53/Mdm2-null MEFs, to Gordon Peters for GFP-p14ARF constructs and to Aria Baniahmad for p33ING1 deletion constructs. This work was supported by Grants INTACT (to MS) from the EU, and by Grants SAF2005-03018 (to MS), SAF03-0244 (to CLO) and SAF2003-00801 (to IP) from the Spanish Ministry of Science and Technology.

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Authors and Affiliations

  1. Institute of Biomedical Research, CSIC-UAM, Arturo Duperier 4, Madrid, Spain

    L González & I Palmero

  2. Department of Biochemistry and Molecular Biology, Institute of Oncology, University of Oviedo, Oviedo, Spain

    J M P Freije, S Cal & C López-Otín

  3. Spanish National Cancer Center (CN10), Melchor Fernandez Almagro 3, Madrid, Spain

    M Serrano

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  1. L González
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  2. J M P Freije
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  3. S Cal
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Correspondence to I Palmero.

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Supplementary Information accompanies the paper on the Oncogene website (http://www.nature.com/onc)

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González, L., Freije, J., Cal, S. et al. A functional link between the tumour suppressors ARF and p33ING1. Oncogene 25, 5173–5179 (2006). https://doi.org/10.1038/sj.onc.1209526

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