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ΔN-p53, a natural isoform of p53 lacking the first transactivation domain, counteracts growth suppression by wild-type p53

Oncogene volume 21, pages 6722–6728 (2002)Cite this article

Abstract

The tumor suppressor protein p53 is ubiquitously expressed as a major isoform of 53 kD, but several forms of lower molecular weight have been observed. Here, we describe a new isoform, ΔN-p53, produced by internal initiation of translation at codon 40 and lacking the N-terminal first transactivation domain. This isoform has impaired transcriptional activation capacity, and does not complex with the p53 regulatory protein Mdm2. Furthermore, ΔN-p53 oligomerizes with full-length p53 (FL-p53) and negatively regulates its transcriptional and growth-suppressive activities. Consistent with the lack of Mdm2 binding, ΔN-p53 does not accumulate in response to DNA-damage, suggesting that this isoform is not involved in the response to genotoxic stress. However, in serum-starved cells expressing wild-type p53, ΔN-p53 becomes the predominant p53 form during the synchronous progression into S phase after serum stimulation. These results suggest that ΔN-p53 may play a role as a transient, negative regulator of p53 during cell cycle progression.

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Acknowledgements

The authors thank the following colleagues who provided materials for the study (Dr V Band: 21PT cells; Dr B Vogelstein: HCT116 cells, PIG3 and P21WAF1-Luciferase plasmids; Dr T Frebourg: pRGCΔFosLacZ plasmid; Dr C Prives: CYCLIN-G and GADD45-Luciferase plasmids; Dr S Daujat: Mdm2-Luciferase plasmid. The help of Mr G Mollon in the preparation of the figures is acknowledged. S Courtois, G Verhaegh and S North were supported by Special Training Awards of the IARC. This work is supported in part by a research contract from the French Association against Cancer (ARC) and by European Community Grant QLG1-1999-00273.

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Author notes

  1. Gerald Verhaegh

    Present address: Department of Experimental Urology, Nijmegen Center for Molecular Life Sciences (190-RT), University Medical Center Nijmegen, PO Box 9101, HB Nijmegen, 6500, The Netherlands

  2. Sophie North

    Present address: INSERM EPI 0113, Laboratoire des Facteurs de Croissance, Avenue des Facultés, Université de Bordeaux I, Talence, 33405, France

  3. Maria-Gloria Luciani

    Present address: Department of Molecular and Cellular Pathology, University of Dundee, Ninewells Hospital & Medical School, Dundee, DD1 9SY, UK

Authors and Affiliations

  1. Group of Molecular Carcinogenesis, International Agency for Research on Cancer, 150 cours Albert Thomas, Lyon, 69372, Cedex 08, France

    Stéphanie Courtois, Gerald Verhaegh, Sophie North, Maria-Gloria Luciani & Pierre Hainaut

  2. Institut de Génétique Moléculaire, CNRS UMR5535, Montpellier, 34293, Cedex 5, France

    Patrice Lassus & Ula Hibner

  3. Department of Molecular Cell Biology, The Weizmann Institute of Science, POB 26, Rehovot, 76100, Israel

    Moshe Oren

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  1. Stéphanie Courtois
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Correspondence to Pierre Hainaut.

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Courtois, S., Verhaegh, G., North, S. et al. ΔN-p53, a natural isoform of p53 lacking the first transactivation domain, counteracts growth suppression by wild-type p53. Oncogene 21, 6722–6728 (2002). https://doi.org/10.1038/sj.onc.1205874

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