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Papillomavirus E2 induces p53-independent apoptosis in HeLa cells

Oncogene volume 18, pages 4538–4545 (1999)Cite this article

Abstract

We have previously shown that expression of the papillomavirus E2 protein in HeLa cells induces p53 accumulation and causes both cell cycle arrest and apoptosis. In contrast to growth arrest, onset of apoptosis was not correlated with an increase of p53 transcriptional activity. In the present study, we conducted biochemical and genetic experiments in order to determine whether E2-induced apoptosis was independent of p53 induction. We showed that E2 did not alter the transcription of Bax, a known p53-activated cell death inducer. The time course of apoptotic cell death preceded p53 induction by several hours. Overexpression of the HPV18 E6 oncogene prevented E2-mediated p53 accumulation, but did not alter the rate of cell death. Finally, point mutants of the HPV18 E2 transactivation domain induced apoptosis, although they were unable to induce high p53 accumulation or cell cycle arrest. In addition, the results obtained with these mutants indicated that both transcriptional activation and replication functions of E2 were dispensable for the induction of cell death. These observations show that E2-induced apoptosis is an early event, independent of p53 accumulation and unrelated to downstream p53-dependent transcriptional events.

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Acknowledgements

This work was supported by the ‘Association pour la Recherche contre le Cancer (ARC)’ and the ‘Ligue Française contre le Cancer’. We are very grateful to Jonathan Weitzman and Caroline Demeret for critical reading of the manuscript. We thank Martin Scheffner for the gift of HPV18 E6 expression plasmid and Moshe Oren for MDM2-CAT.

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  1. Christian Desaintes

    Present address: Radiobiology Unit, SCK-CEN 200, Boeretang, B-2400, Mol, Belgium

Authors and Affiliations

  1. département des biotechnologies, Unité des virus oncogènes, URA 1644 du CNRS, Institut Pasteur, 25 rue du Dr Roux, Paris, cedex 15, 75724, Paris, France

    Christian Desaintes, Sylvain Goyat, Serge Garbay, Moshe Yaniv & Françoise Thierry

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Desaintes, C., Goyat, S., Garbay, S. et al. Papillomavirus E2 induces p53-independent apoptosis in HeLa cells. Oncogene 18, 4538–4545 (1999). https://doi.org/10.1038/sj.onc.1202818

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