Skip to main content

Thank you for visiting nature.com. You are using a browser version with limited support for CSS. To obtain the best experience, we recommend you use a more up to date browser (or turn off compatibility mode in Internet Explorer). In the meantime, to ensure continued support, we are displaying the site without styles and JavaScript.

  • Original Paper
  • Published:

p73α expression induces both accumulation and activation of wt-p53 independent of the p73α transcriptional activity

Oncogene volume 22, pages 5451–5456 (2003)Cite this article

Abstract

The p53 tumor suppressor gene belongs to a multigene family that includes two paralogues, p63 and p73. p73α has common activities with p53, such as DNA binding and transactivation, and can thus activate the transcription of p53-responsive genes. Using the adenoviral system, we report that an overexpression of either wt-p73α or one of the two transcriptional inactive mutants, ΔNp73α or p73αR292H, induces an accumulation of the endogenous wt-p53 expressed in the three transformed cell lines, SK-N-SH, MCF-7 and U-2OS, without stimulating the p53 gene transcription. p73-mediated accumulation of p53 protein coincides with an increase of p53-target gene expression in cells expressing either wt-p73α or the transcriptional inactive mutant p73αR292H, but not ΔNp73α that encodes a dominant-negative mutant of both p73 and p53. The fact that an ectopic expression of p73αR292H leads to both accumulation of p53 and stimulation of p53 target gene expression strongly suggests that p73α is able to induce activation of p53. This was confirmed by showing that p73αR292H no longer stimulated Waf1/p21 expression in MCF7/R-A1 cells that expressed a transcriptional inactive mutant of p53. We thus conclude that p73α protein was able to both stabilize and activate wt-p53 protein, independent of the p73α transcriptional activity.

This is a preview of subscription content, access via your institution

Access options

Buy this article

  • Purchase on Springer Link
  • Instant access to full article PDF
Buy now

Prices may be subject to local taxes which are calculated during checkout

Figure 1
Figure 2
Figure 3
Figure 4

Similar content being viewed by others

References

  • Balint E, Bates S and Vousden KH . (1999). Oncogene, 18, 3923–3929.

    Article  Google Scholar 

  • Cai Z, Korner M, Tarantino N and Chouaib S . (1997). J. Biol. Chem., 272, 96–101.

    Article  CAS  Google Scholar 

  • Chen J, Marechal V and Levine AJ . (1993). Mol. Cell. Biol., 13, 4107–4114.

    Article  CAS  Google Scholar 

  • Drané P, Bravard A, Bouvard V and May E . (2001). Oncogene, 20, 430–439.

    Article  CAS  Google Scholar 

  • Drané P, Leblanc V, Miro-Mur F, Saffroy R, Debuire B and May E . (2002). Cell Death Differ., 9, 527–537.

    Article  Google Scholar 

  • Fillippovich I, Sorokina N, Gatei M, Haupt Y, Hobson K, Moallem E, Spring K, Mould M, McGuckin MA, Lavin MF and Khanna KK . (2001). Oncogene, 20, 514–522.

    Article  CAS  Google Scholar 

  • Flores ER, Tsai KY, Crowley D, Sengupta S, Yang A, McKeon F and Jacks T . (2002). Nature, 416, 560–564.

    Article  CAS  Google Scholar 

  • Grob TJ, Novak U, Maisse C, Barcaroli D, Luthi AU, Pirnia F, Hugli B, Graber HU, De L, V, Fey MF, Melino G and Tobler A . (2001). Cell Death Differ., 8, 1213–1223.

    Article  CAS  Google Scholar 

  • Irwin MS and Kaelin WG . (2001). Cell Growth Differ., 12, 337–349.

  • Jost CA, Marin MC and Kaelin Jr WG . (1997). Nature, 389, 191–194.

    Article  CAS  Google Scholar 

  • Kaghad M, Bonnet H, Yang A, Creancier L, Biscan JC, Valent A, Minty A, Chalon P, Lelias JM, Dumont X, Ferrara P, McKeon F and Caput D . (1997). Cell, 90, 809–819.

    Article  CAS  Google Scholar 

  • Kartasheva NN, Contente A, Lenz-Stoppler C, Roth J and Dobbelstein M . (2002). Oncogene, 21, 4715–4727.

    Article  CAS  Google Scholar 

  • Levrero M, De Laurenzi V, Costanzo A, Gong J, Wang JY and Melino G . (2000). J. Cell Sci., 113, 1661–1670.

  • May P and May E . (1999). Oncogene, 18, 7621–7636.

    Article  CAS  Google Scholar 

  • Mills AA, Zheng BH, Wang XJ, Vogel H, Roop DR and Bradley A . (1999). Nature, 398, 708–713.

    Article  CAS  Google Scholar 

  • Nakagawa T, Takahashi M, Ozaki T, Watanabe K, Todo S, Mizuguchi H, Hayakawa T and Nakagawara A . (2002). Mol. Cell. Biol., 22, 2575–2585.

  • Stiewe T, Theseling CC and Putzer BM . (2002a). J. Biol. Chem., 277, 14177–14185.

    Article  CAS  Google Scholar 

  • Stiewe T, Zimmermann S, Frilling A, Esche H and Putzer BM . (2002b). Cancer Res., 62, 3598–3602.

  • Vossio S, Palescandolo E, Pediconi N, Moretti F, Balsano C, Levrero M and Costanzo A . (2002). Oncogene, 21, 3796–3803.

    Article  CAS  Google Scholar 

  • Yang A, Kaghad M, Caput D and McKeon F . (2002). Trends Genet., 18, 90–95.

  • Yang A, Kaghad M, Wang Y, Gillett E, Fleming MD, Dotsch V, Andrews NC, Caput D and McKeon F . (1998). Mol. Cell, 2, 305–316.

  • Yang A, Walker N, Bronson R, Kaghad M, Oosterwegel M, Bonnin J, Vagner C, Bonnet H, Dikkes P, Sharpe A, McKeon F and Caput D . (2000). Nature, 404, 99–103.

    Article  CAS  Google Scholar 

  • Zeng X, Chen L, Jost CA, Maya R, Keller D, Wang X, Kaelin Jr WG, Oren M, Chen J and Lu H . (1999). Mol. Cell. Biol., 19, 3257–3266.

    Article  CAS  Google Scholar 

  • Zhu JH, Nozell S, Wang J, Jiang JY, Zhou WJ and Chen XB . (2001). Oncogene, 20, 4050–4057.

    Article  CAS  Google Scholar 

Download references

Acknowledgements

We are grateful to Drs Jean Bénard and Sétha Douc-Rasy for communicating their data before publication. We thank Dr Daniel Caput (Sanofi Recherche) for p73α constructs, Dr Salem Chouaib for providing MCF7/R-A1 cells, Dr David Lane for providing DO-7 hybridoma, and Drs Henry Neel, Jacques Piette and Vincent Maréchal for their gift of antibodies directed against hMDM2. This work was supported by a grant from ARC (Association pour la Recherche sur le Cancer). Anne Meiller was supported by a fellowship from ‘Electricité de France’ and Francesc Miro-Mur by a fellowship from ‘Fondation pour la Recherche Médicale’.

Author information

Author notes

  1. Francesc Miro-Mur and Anne Meiller: These authors contributed equally to the work

Authors and Affiliations

  1. Commissariat à l'énergie atomique (CEA), CNRS, Laboratoire de Cancérogenèse Moléculaire, UMR217, DRR, DSV, route du Panorama, Fontenay-aux-Roses Cedex, 92265, France

    Francesc Miro-Mur, Anne Meiller & Evelyne May

  2. Departament de Bioquimica i Biologia Molecular, Facultat de Ciencies, Universitat Autonoma de Barcelona, Barcelona, 08193, Spain

    Francesc Miro-Mur

  3. U362 INSERM Institut Gustave-Roussy, 39 rue Camille Desmoulins, Villejuif, 94805, France

    Hedi Haddada

Authors
  1. Francesc Miro-Mur
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Anne Meiller
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Hedi Haddada
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. Evelyne May
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to Evelyne May.

Rights and permissions

Reprints and permissions

About this article

Cite this article

Miro-Mur, F., Meiller, A., Haddada, H. et al. p73α expression induces both accumulation and activation of wt-p53 independent of the p73α transcriptional activity. Oncogene 22, 5451–5456 (2003). https://doi.org/10.1038/sj.onc.1206538

Download citation

  • Received:

  • Revised:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1038/sj.onc.1206538

Keywords

This article is cited by

Search

Advanced search

Quick links