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Reciprocal down-regulation of p53 and SOD2 gene expression–implication in p53 mediated apoptosis

Oncogene volume 20, pages 430–439 (2001)Cite this article

Abstract

p53 regulates the transcription of a number of genes among which are different redox-related genes. It has been proposed that these genes can induce a cellular oxidative stress leading to p53-dependent apoptosis (Polyak et al., 1997). MnSOD, the product of superoxide dismutase 2 (SOD2) gene, is one of the major cellular defences against oxidative stress. We demonstrate here that p53 is able to repress SOD2 gene expression and that this repression takes place at promoter level. We show the importance of this regulation for the p53 function, by demonstrating that an overexpression of MnSOD decreases p53-mediated induction of apoptosis. Moreover, we demonstrate that MnSOD overexpression decreases p53-gene expression at the promoter level. These findings raise the hypothesis that p53 and SOD2 genes are mutually regulated leading to the modulation of various cellular processes including apoptosis.

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Acknowledgements

We are grateful to A Atfi, J Jenkins, M Oren and V Rotter, for providing some of the plasmids used in this study, to YS Ho for providing the rat SOD2 cDNA, to S Chouaib for the MCF-7/R-A1 cell line and to D Lane for providing DO-7 hybridoma cells. We wish to thank JC Lelouf for kindly providing his help in EMSA experiments and P May for critical reading of the manuscript. This work was supported by a grant from the ‘Association pour la Recherche sur le Cancer' (ARC), and by a grant from ‘Electricité de France’ (EDF). VB was supported by EDF.

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  1. Commissariat à l'Energie Atomique (CEA), Laboratoire de Cancérogenèse Moléculaire, UMR217 CEA-CNRS, DRR, DSV, BP6 92265, Fontenay-aux-Roses, Cedex, France

    Pascal Drane, Véronique Bouvard & Evelyne May

  2. Commissariat à l'Energie Atomique (CEA), Laboratoire de Radiobiologie Cellulaire, DRR, DSV, BP6 92265, Fontenay-aux-Roses, Cedex, France

    Anne Bravard

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Drane, P., Bravard, A., Bouvard, V. et al. Reciprocal down-regulation of p53 and SOD2 gene expression–implication in p53 mediated apoptosis. Oncogene 20, 430–439 (2001). https://doi.org/10.1038/sj.onc.1204101

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