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The ATM protein is required for sustained activation of NF-κB following DNA damage

Oncogene volume 18, pages 2261–2271 (1999)Cite this article

Abstract

Cells lacking an intact ATM gene are hypersensitive to ionizing radiation and show multiple defects in the cell cycle-coupled checkpoints. DNA damage usually triggers cell cycle arrest through, among other things, the activation of p53. Another DNA-damage responsive factor is NF-κB. It is activated by various stress situations, including oxidative stress, and by DNA-damaging compounds such as topoisomerase poisons. We found that cells from Ataxia Telangiectasia patients exhibit a defect in NF-κB activation in response to treatment with camptothecin, a topoisomerase I poison. In AT cells, this activation is shortened or suppressed, compared to that observed in normal cells. Ectopic expression of the ATM protein in AT cells increases the activation of NF-κB in response to camptothecin. MO59J glioblastoma cells that do not express the DNA-PK catalytic subunit respond normally to camptothecin. These results support the hypothesis that NF-κB is a DNA damage-responsive transcription factor and that its activation pathway by DNA damage shares some components with the one leading to p53 activation.

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Acknowledgements

We thank Dr J Turner for the generous gift of MO59J and MO59K cells lines, Dr Y Shiloh for the plasmids pEBS7 and pEBS7-YZ5 and C Dargemont (Curie Institute, Paris) for the MAD10B antibody. BP is supported by the Belgian Fonds pour la Formation à la Recherche dans l'Industrie et l'Agriculture. SS is supported by a Concerted Research Program from the Communauté Française de Belgique. JP is Research Director at the Belgian National Fund for Scientific Research (NFSR). Financial support for this study was provided by the Belgian NFSR, Télévie (Brussels, Belgium) and the Sidaction (Paris, France).

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  1. Laboratory of Fundamental Virology and Immunology, University of Liège, CHU, B23, Sart Tilman, Liège, B-4000, Belgium

    Bernard Piret, Sonia Schoonbroodt & Jacques Piette

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Piret, B., Schoonbroodt, S. & Piette, J. The ATM protein is required for sustained activation of NF-κB following DNA damage. Oncogene 18, 2261–2271 (1999). https://doi.org/10.1038/sj.onc.1202541

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