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:

δEF1 repressor controls selectively p53 family members during differentiation

Oncogene volume 24, pages 7273–7280 (2005)Cite this article

Abstract

The discovery of two new p53 homologs, p73 and p63, has defined a family of transcription factors heavily involved in the control of growth suppression, apoptosis, differentiation and development. While p53-deficient mice undergo spontaneous tumors, p73 and p63 knockout mice exhibit severe developmental defects. We demonstrate here that p73 gene is an in vivo transcriptional target of the muscle regulatory factors MyoD, myogenin, Myf5 and Myf6. Ectopic expression of the transcriptional repressor δEF1/ZEB/zfhx1a counteracts MyoD/Myf5- or MyoD/Myf6-mediated transcriptional activation of p73. A distinct pattern of in vivo recruitment of muscle regulatory factors and δEF1 on p73 regulatory regions was found between proliferating and differentiating muscle cells. We also found that δEF1 plays a role in the transcriptional regulation of p53 family members during keratinocytic differentiation. Mouse embryo fibroblasts derived from δEF1-deficient mice exhibit unbalanced expression of ΔNp63, TAp73 and ΔNp73 but not of TAp63 and p53. The analysis of tissues derived from δEF1+/− mice exhibit a selective enrichment of ΔNp63 in skin.

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

  • Bamberger C, Pollet D and Schmale H . (2002). J. Invest. Dermatol., 118, 133–138.

  • Blandino G and Dobbelstein M . (2004). Cell Cycle, 3, 886–894.

  • De Laurenzi V, Costanzo A, Barcaroli D, Terrinoni A, Falco M, Annichiarico-Petruzzelli M, Levrero M and Melino G . (1998). J. Exp. Med., 188, 1763–1768.

  • De Laurenzi V, Rossi A, Terrinoni A, Barcaroli D, Levrero M, Costanzo A, Knight RA, Guerrieri P and Melino G . (2000). Biochem. Biophys. Res. Commun., 273, 342–346.

  • Fontemaggi G, Gurtner A, Strano S, Higashi Y, Sacchi A, Piaggio G and Blandino G . (2001). Mol. Cell. Biol., 21, 8461–8470.

  • Fortini ME, Lai Z and Rubin GM . (1991). Mech. Dev., 34, 113–122.

  • Genetta T, Ruezinsky D and Kadesh T . (1994). Mol. Cell. Biol., 14, 6153–6163.

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

  • Higashi Y, Moribe H, Takagi T, Sekido R, Kawakami K, Kikutani H and Kondoh H . (1997). J. Exp. Med., 185, 1467–1480.

  • 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.

  • Lai Z, Rushton E, Bate M and Rubin GM . (1993). Proc. Natl. Acad. Sci. USA, 90, 4122–4126.

  • Lundell MJ and Hirsh J . (1992). Dev. Biol., 154, 84–94.

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

  • Morena A, Riccioni S, Marchetti A, Polcini AT, Mercurio AM, Blandino G, Sacchi A and Falcioni R. . (2002). Blood, 100, 96–106.

  • Postigo AA and Dean DC . (1997). EMBO J., 16, 3935–3943.

  • Takagi T, Moribe H, Kondoh H and Higashi Y . (1998). Development, 125, 21–31.

  • Yang A, Schweitzer R, Sun D, Kaghad M, Walker N, Bronson RT, Tabin C, Sharpe A, Caput D, Crum C and McKeon F . (1999). Nature, 398, 714–718.

  • 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.

  • Yang A and McKeon F . (2002). Nat. Rev. Mol. Cell. Biol., 1, 199–207.

Download references

Acknowledgements

We are grateful to M Oren, D Lane, D Dean and M Crescenzi for plasmids and antibodies. This work was supported by Telethon (n.GGP030358), Italian Association for Cancer Research (AIRC), by Ministero della Salute, by MIUR-FIRB Italy, by Italia-USA and by EC FP6 funding (Contract 503576). This publication reflects the authors' views and not necessarily those of the European Community. The EC is not liable for any use that may be made of the information contained herein. AD is recipient of EMBO long-term fellowship.

Author information

Authors and Affiliations

  1. Department of Experimental Oncology, Regina Elena Cancer Institute, Rome, Italy, 00158

    Giulia Fontemaggi, Aymone Gurtner, Alexander Damalas, Ada Sacchi, Sabrina Strano, Giulia Piaggio & Giovanni Blandino

  2. Rome Oncogenomic Center, Rome, 00158, Italy

    Giulia Fontemaggi, Giulia Piaggio & Giovanni Blandino

  3. Department of Dermatology, University of Rome ‘Tor Vergata’, Rome, 00133, Italy

    Antonio Costanzo

  4. Institute for Molecular and Cellular Biology, Osaka University, Osaka, 565-0871, Japan

    Yujiro Higashi

Authors
  1. Giulia Fontemaggi
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Aymone Gurtner
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Alexander Damalas
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. Antonio Costanzo
    View author publications

    You can also search for this author in PubMed Google Scholar

  5. Yujiro Higashi
    View author publications

    You can also search for this author in PubMed Google Scholar

  6. Ada Sacchi
    View author publications

    You can also search for this author in PubMed Google Scholar

  7. Sabrina Strano
    View author publications

    You can also search for this author in PubMed Google Scholar

  8. Giulia Piaggio
    View author publications

    You can also search for this author in PubMed Google Scholar

  9. Giovanni Blandino
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to Giovanni Blandino.

Rights and permissions

Reprints and permissions

About this article

Cite this article

Fontemaggi, G., Gurtner, A., Damalas, A. et al. δEF1 repressor controls selectively p53 family members during differentiation. Oncogene 24, 7273–7280 (2005). https://doi.org/10.1038/sj.onc.1208891

Download citation

  • Received:

  • Revised:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1038/sj.onc.1208891

Keywords

This article is cited by

Search

Advanced search

Quick links