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p14ARF is a component of the p53 response following ionizing irradiation of normal human fibroblasts

Oncogene volume 23, pages 6040–6046 (2004)Cite this article

Abstract

Ionizing radiation leads to rapid stabilization and activation of the p53 tumor suppressor. Previous reports demonstrate that murine p19ARF cooperates with p53 in the cellular response to gamma irradiation. Here, we show that endogenous ARF sequentially interacts with p53 and MDM2 following irradiation of primary human and mouse embryonic fibroblasts. Shortly after irradiation, p14ARF binds p53 independently of MDM2. As nuclear pools of p53 decline, endogenous p14ARF co-immunoprecipitates with MDM2 and is localized within the nucleolus. Interestingly, p14ARF nucleolar localization during this response is abrogated in cells lacking functional p53. Taken together, our data suggest that human and murine ARF contribute to the mammalian DNA damage response.

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Acknowledgements

We thank Dr Geoffrey Wahl and Dr Gordon Peters for reagents and helpful discussion. We are grateful to Dr Karen Vousden for providing HDM2 expression vectors, Dr Jamil Momand for the 2A10 reagent, Dr Pui Chan for anti-B23 antibodies and Dr Gigi Lozano for providing p53−/−mdm2−/− MEFs. We also thank Drs Emma Lees and Bruno Amati for critical review of this manuscript. DNAX Research Incorporated is a subsidiary of Schering Plough Corporation.

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  1. Department of Discovery Research, DNAX Research Incorporated, Palo Alto, 94304, CA, USA

    Shireen Khan, Claudia Guevara, Greg Fujii & David Parry

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  1. Shireen Khan
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Correspondence to David Parry.

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Khan, S., Guevara, C., Fujii, G. et al. p14ARF is a component of the p53 response following ionizing irradiation of normal human fibroblasts. Oncogene 23, 6040–6046 (2004). https://doi.org/10.1038/sj.onc.1207824

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