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RETRACTED ARTICLE: p14ARF promotes RB accumulation through inhibition of its Tip60-dependent acetylation

Oncogene volume 25, pages 4147–4154 (2006)Cite this article

This article was retracted on 31 July 2023

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Abstract

p14ARF is a tumour suppressor which plays a critical role in p53-dependent or -independent cell growth control. Several studies have recently provided evidence that p14ARF can also interfere either directly or indirectly with some components of the RB signalling pathway to mediate its antiproliferative activity. The aim of this study was to explore the existence of direct relationships between p14ARF and RB proteins. We show that p14ARF promotes the accumulation of a hypoacetylated RB protein, when it is upregulated in a model of stable-inducible clones or physiologically induced following cell exposure to cytotoxic agents. Looking for the mechanisms involved in this process, we demonstrate that the histone acetyl transferase Tip60 directly interacts with RB and stimulates its degradation by the proteasome through acetylation of its C-terminus. Furthermore, and consistent with p14ARF-induced RB accumulation, we provide evidence that p14ARF prevents Tip60-mediated RB acetylation, therefore precluding its proteasomal degradation. Overall, our results identify a novel mechanism by which p14ARF controls the RB pathway to trigger its antiproliferative function.

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Acknowledgements

We thank Dr Bruno Amati (Milan, Italy) for the generous gift of anti-Tip60 antibody and Dr Didier trouche (Toulouse, France), Pr Lars-Gunnar Larsson (Upsala, Sweden) and Dr McCance for the gift of various plasmids used in this work. We are also grateful to Celine Lampreia and Pascal Perron for technical assistance. This work was supported by a grant to EB from La Ligue Nationale Contre le Cancer as an ‘équipe labellisée’ and by the Region Rhône Alpes (Thématique prioritaire cancer and Canceropole 2003, 2005: Oncocell, Epimed, INACancer) (EPIPRO). SK laboratory is supported by a sidaction grant and EC is supported by sidaction from 2004 as well as by ANRS (2002-2004).

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Authors and Affiliations

  1. INSERM U578, Groupe de Recherche sur le Cancer du Poumon, Université Joseph Fourier, Faculté de Medecine, Institut Albert Bonniot, La Tronche Cedex, France

    C Leduc, P Claverie, B Eymin, E Brambilla & S Gazzeri

  2. INSERM U309, Institut Albert Bonniot, Laboratoire de Biologie Moléculaire et cellulaire de la Differenciation, Universite Joseph Fourier, La Tronche Cedex, France

    E Col & S Khochbin

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  1. C Leduc
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Correspondence to S Gazzeri.

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

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Leduc, C., Claverie, P., Eymin, B. et al. RETRACTED ARTICLE: p14ARF promotes RB accumulation through inhibition of its Tip60-dependent acetylation. Oncogene 25, 4147–4154 (2006). https://doi.org/10.1038/sj.onc.1209446

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