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RB18A regulates p53-dependent apoptosis

Oncogene volume 21, pages 861–866 (2002)Cite this article

Abstract

We previously demonstrated that RB18A, a member of TRAP220/DRIP205/PBP family, in vivo acted as a cofactor of transcription by differently regulating p53wt transactivating activity on physiological promoters. Using p53-negative cells transfected with different constructs, we herein demonstrated that RB18A down-regulated p53wt-dependent apoptosis. This biological regulation was due to a specific diminution of p53wt protein level, as level of p53mut and GAPDH proteins was not modified. This p53wt diminution was dependent on proteasome activity, as inhibited by MG-132 inhibitor. This specific p53wt degradation was correlated with an increase in expression of MDM2, which promoted p53wt degradation into proteasome. RB18A up-regulated MDM2 expression by activating MDM2 promoter, even in absence of p53wt. Altogether, these data emphasized that RB18A could regulate p53wt function not only by direct interaction between both proteins, but also by up-regulating promoter activity of MDM2, a p53-regulating partner.

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Acknowledgements

The authors would like to thank Gérard Drevet for technical assistance. This work was supported by INSERM, Ministère de l'Education Nationale et de la Recherche, Fondation de France, Association de Recherches contre le Cancer (ARC, Villejuif), and Ligue National Contre le Cancer (Comité de Paris).

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  1. Raymond Frade and Monique Barel: R Frade and M Barel contributed equally to this publication

Authors and Affiliations

  1. Immunochimie des Régulations Cellulaires et des Interactions Virales, INSERM U.354, Centre INSERM, Hôpital Saint-Antoine, Paris, 75012, France

    Raymond Frade, Michelle Balbo & Monique Barel

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  1. Raymond Frade
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  2. Michelle Balbo
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  3. Monique Barel
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Correspondence to Raymond Frade.

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Frade, R., Balbo, M. & Barel, M. RB18A regulates p53-dependent apoptosis. Oncogene 21, 861–866 (2002). https://doi.org/10.1038/sj.onc.1205177

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