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:

p53 directs conformational change and translation initiation blockade of human fibroblast growth factor 2 mRNA

Oncogene volume 20, pages 4613–4620 (2001)Cite this article

Abstract

Tumour suppressor p53 has been shown to inhibit fibroblast growth factor 2 expression post-transcriptionally in cultured cells. Here we have investigated the mechanism responsible for this post-transcriptional blockade. Deletion mutagenesis of the FGF-2 mRNA leader revealed the requirement of at least four RNA cis-acting elements to mediate the inhibitory effect of p53 in SK-Hep-1 transfected cells, suggesting the involvement of RNA secondary or tertiary structures. Recombinant wild-type, but not Ala143 mutant p53, was able to specifically repress FGF-2 mRNA translation in rabbit reticulocyte lysate, in a dose dependent manner. Sucrose gradient experiments showed that p53 blocks translation initiation by preventing 80S ribosome formation on an mRNA bearing the FGF-2 mRNA leader sequence. Interaction of wild-type and mutant p53 with different RNAs showed no significant correlation between p53 RNA binding activity and its translational inhibiting effect. However, by checking the accessibility of the FGF-2 mRNA leader to complementary oligonucleotide probes, we showed that the binding to RNA of wild-type, but not mutant p53, induced RNA conformational changes that might be responsible for the translational blockade. This strongly suggests that p53 represses FGF-2 mRNA translation by a direct mechanism involving its nucleic acid unwinding–annealing 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
Figure 5

Similar content being viewed by others

References

  • Baker SJ, Markowitz S, Fearon ER, Willson JK, Vogelstein B . 1990 Science 249: 912–915

  • Creancier L, Morello D, Mercier P, Prats AC . 2000 J. Cell. Biol. 150: 275–281

  • Delphin C, Cahen P, Lawrence JJ, Baudier J . 1994 Eur. J. Biochem. 223: 683–692

  • Fontoura BM, Atienza CA, Sorokina EA, Morimoto T, Carroll RB . 1997 Mol. Cell. Biol. 17: 3146–3154

  • Galy B, Créancier L, Zanibellato C, Prats A-C, Prats H . 2001 Oncogene 20: 1669–1677

  • Galy B, Maret A, Prats AC, Prats H . 1999 Cancer Res. 59: 165–171

  • Marechal V, Elenbaas B, Piette J, Nicolas JC, Levine AJ . 1994 Mol. Cell. Biol. 14: 7414–7420

  • Miller SJ, Suthiphongchai T, Zambetti GP, Ewen ME . 2000 Mol. Cell. Biol. 20: 8420–8431

  • Moll UM, LaQuaglia M, Benard J, Riou G . 1995 Proc. Natl. Acad. Sci. USA 92: 4407–4411

  • Mosner J, Mummenbrauer T, Bauer C, Sczakiel G, Grosse F, Deppert W . 1995 EMBO J. 14: 4442–4449

  • Oberosler P, Hloch P, Ramsperger U, Stahl H . 1993 EMBO J. 12: 2389–2396

  • Prats AC, Sarih L, Gabus C, Litvak S, Keith G, Darlix JL . 1988 EMBO J. 7: 1777–1783

  • Prats AC, Vagner S, Prats H, Amalric F . 1992 Mol. Cell. Biol. 12: 4796–4805

  • Shaulsky G, Ben-Ze'ev A, Rotter V . 1990 Oncogene 5: 1707–1711

  • Stommel JM, Marchenko ND, Jimenez GS, Moll UM, Hope TJ, Wahl GM . 1999 EMBO J. 18: 1660–1672

  • Vagner S, Gensac MC, Maret A, Bayard F, Amalric F, Prats H, Prats AC . 1995 Mol. Cell. Biol. 15: 35–44

  • Vagner S, Touriol C, Galy B, Audigier S, Gensac MC, Amalric F, Bayard F, Prats H, Prats AC . 1996 J. Cell. Biol. 135: 1391–1402

  • Wu L, Bayle JH, Elenbaas B, Pavletich NP, Levine AJ . 1995 Mol. Cell. Biol. 15: 497–504

Download references

Acknowledgements

We thank Stephan Vagner and F Bayard for helpful discussions, and D Warwick for English proofreading. We are grateful to W Deppert and J Mosner (University of Hamburg, Germany) for the murine p53 exon 1. This work was supported by grants from the Association pour la Recherche sur le Cancer, the Ligue Nationale contre le Cancer, the Conseil Régional Midi-Pyrénées, the European Commission Biotechnology program (subprogram Cell Factory, Actions de Recherches Concertées, contract 94/99-181) and Aventis. B Galy had a fellowship from the Ligue Nationale contre le Cancer and then from Retina France. L Creancier was financed by the EC BIOTECH Program and then by Retina France.

Author information

Author notes

  1. Bruno Galy

    Present address: Gene Expression Programme, European Molecular Biology Laboratory, Meyerhofstrasse 1, Heidelberg, D-69117, Germany

Authors and Affiliations

  1. Institut National de la Santé et de la Recherche Médicale U397, Endocrinologie et Communication Cellulaire, Institut Fédératif de Recherche Louis Bugnard, C.H.U. Rangueil, 31403 Toulouse Cedex 04, France

    Bruno Galy, Laurent Créancier, Leonel Prado-Lourenço, Anne-Catherine Prats & Hervé Prats

Authors
  1. Bruno Galy
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Laurent Créancier
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Leonel Prado-Lourenço
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. Anne-Catherine Prats
    View author publications

    You can also search for this author in PubMed Google Scholar

  5. Hervé Prats
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to Hervé Prats.

Rights and permissions

Reprints and permissions

About this article

Cite this article

Galy, B., Créancier, L., Prado-Lourenço, L. et al. p53 directs conformational change and translation initiation blockade of human fibroblast growth factor 2 mRNA. Oncogene 20, 4613–4620 (2001). https://doi.org/10.1038/sj.onc.1204630

Download citation

  • Received:

  • Revised:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1038/sj.onc.1204630

Keywords

This article is cited by

Search

Advanced search

Quick links