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The c-Rel transcription factor can both induce and inhibit apoptosis in the same cells via the upregulation of MnSOD

Oncogene volume 21, pages 4392–4402 (2002)Cite this article

Abstract

Rel/NF-κB transcription factors are involved in several physiological processes, including the regulation of apoptosis. These factors were shown to exhibit pro- or anti-apoptotic activities in different cellular models, but at present, the mechanisms underlying these opposite effects are poorly understood. In this study, we show that the constitutive expression of a transcriptionally active member of the Rel/NF-κB family, c-Rel, first induces a resistance against TNFα-induced apoptosis and later increases the level of spontaneous apoptosis of HeLa cells. Both the anti- and pro-apoptotic effects increase with the level of c-Rel overexpression. The up-regulation by c-Rel of the manganese superoxide dismutase (MnSOD) could explain both the rapid anti-apoptotic effect and the delayed pro-apoptotic one. Indeed, the enzymatic activity of MnSOD is to transform the toxic O2.− in H2O2. Hence, on one hand, its induction helps cells to resist against the apoptogenic burst of O2.− produced upon TNFα stimulation, but on the other hand, it leads to a progressive H2O2 accumulation that ultimately results in apoptosis. These results indicate that the anti- and pro-apoptotic effects of Rel/NF-κB factors are not necessarily alternative but can occur successively in the same cell, via the up-regulation of the same target gene.

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Acknowledgements

We thank N Rice for the human c-rel plasmid. This work was supported by grants from the Centre National de la Recherche Scientifique, the Université Lille 2, the Association pour la Recherche sue le Cancer, the Ligue Contre le Cancer, Comité du Nord, the Institut Pasteur de Lille, the Conseil Régional Nord/Pas-de-Calais and the European Regional Development Fund. C Abbadie is Maître de Conférences at the Université Lille 1.

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  1. David Bernard

    Present address: The Department of Molecular Biology 2, The Wolfson Institute for Biomedical Research, University College London, Gower Street, London, WC1E 6BT, UK

Authors and Affiliations

  1. FRE 2353 CNRS/Institut Pasteur de Lille/Université Lille 2, Institut de Biologie de Lille, 1 rue Calmette, Lille Cedex, 59021, France

    David Bernard, Bernard Vandenbunder & Corinne Abbadie

  2. UMR 8526 CNRS/Institut Pasteur de Lille/Université Lille 2, Institut de Biologie de Lille, 1 rue Calmette, Lille Cedex, 59021, France

    Didier Monte

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Correspondence to Corinne Abbadie.

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Bernard, D., Monte, D., Vandenbunder, B. et al. The c-Rel transcription factor can both induce and inhibit apoptosis in the same cells via the upregulation of MnSOD. Oncogene 21, 4392–4402 (2002). https://doi.org/10.1038/sj.onc.1205536

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