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.

Cancer

Three birds with one stone

Nature volume 460, pages 466–467 (2009)Cite this article

The core domain of the p53 protein has been found to affect microRNA processing — its third known antitumour activity. Most cancerous p53 mutations affect this domain and may abolish all tumour-suppressor functions.

The p53 protein is a major tumour suppressor. The gene that encodes it (TP53) is mutated in about half of human cancers, and most remaining tumours find other ways to inactivate the p53 pathway1. p53 functions mainly as a transcription factor, and responds to stresses such as DNA damage by binding to specific DNA sequences and activating target genes that promote programmed cell death (apoptosis) or permanent cell-cycle arrest (senescence). Most TP53 mutations in cancers affect the protein's core DNA-binding domain and abrogate p53's transcriptional activity1. Several regulators of apoptosis also interact with p53 through the DNA-binding domain, leading to the proposal2 that mutations in this domain act as 'dual hits', affecting both p53's transcriptional capacity and its ability to promote apoptosis in a transcription-independent manner. Suzuki et al.3 (page 529) now identify a third function for p53's DNA-binding domain — modulation of the processing of small RNAs called microRNAs (miRNAs).

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

Relevant articles

Open Access articles citing this article.

Access options

Rent or buy this article

Get just this article for as long as you need it

$39.95

Learn more

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

Figure 1: Three antitumour functions.

References

  1. Toledo, F. & Wahl, G. M. Nature Rev. Cancer 6, 909–923 (2006).

    Article  CAS  Google Scholar 

  2. Green, D. R. & Kroemer, G. Nature 458, 1127–1130 (2009).

    Article  ADS  CAS  Google Scholar 

  3. Suzuki, H. I. et al. Nature 460, 529–533 (2009).

    Article  ADS  CAS  Google Scholar 

  4. Ventura, A. & Jacks, T. Cell 136, 586–591 (2009).

    Article  CAS  Google Scholar 

  5. He, L., He, X., Lowe, S. W. & Hannon, G. J. Nature Rev. Cancer 7, 819–822 (2007).

    Article  CAS  Google Scholar 

  6. Lozano, G. Curr. Opin. Genet. Dev. 17, 66–70 (2007).

    Article  CAS  Google Scholar 

  7. Suh, E.-K. et al. Nature 444, 624–628 (2006).

    Article  ADS  CAS  Google Scholar 

  8. Bourdon, J.-C. et al. Genes Dev. 19, 2122–2137 (2005).

    Article  CAS  Google Scholar 

  9. Whibley, C., Pharoah, P. D. P. & Hollstein, M. Nature Rev. Cancer 9, 95–107 (2009).

    Article  CAS  Google Scholar 

  10. Vazquez, A., Bond, E. E., Levine, A. J. & Bond, G. L. Nature Rev. Drug Discov. 7, 979–987 (2008).

    Article  CAS  Google Scholar 

  11. Vousden, K. H. & Lane, D. P. Nature Rev. Mol. Cell Biol. 8, 275–283 (2007).

    Article  CAS  Google Scholar 

  12. Fuller-Pace, F. V. Nucleic Acids Res. 34, 4206–4215 (2006).

    Article  CAS  Google Scholar 

Download references

Author information

Authors and Affiliations

  1. Franck Toledo and Boris Bardot are in the Genetics of Tumor Suppression Group, Institut Curie, 75248 Paris Cedex 05, France, and at the Université Pierre et Marie Curie Paris 06, Paris, France. franck.toledo@curie.fr ,

    Franck Toledo & Boris Bardot

Authors
  1. Franck Toledo
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Boris Bardot
    View author publications

    You can also search for this author in PubMed Google Scholar

Rights and permissions

Reprints and Permissions

About this article

Cite this article

Toledo, F., Bardot, B. Three birds with one stone. Nature 460, 466–467 (2009). https://doi.org/10.1038/460466a

Download citation

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1038/460466a

This article is cited by

Search

Advanced search

Quick links

Nature Briefing

Sign up for the Nature Briefing newsletter — what matters in science, free to your inbox daily.

Get the most important science stories of the day, free in your inbox. Sign up for Nature Briefing