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.

  • Brief Communication
  • Published:

Nucleophosmin regulates the stability and transcriptional activity of p53

Nature Cell Biology volume 4, pages 529–533 (2002)Cite this article

Abstract

Nucleophosmin (NPM) is a ubiquitously expressed nucleolar phosphoprotein that continuously shuttles between the nucleus and cytoplasm1. It has been proposed to function in ribosomal protein assembly and transport2, and also as a molecular chaperone that prevents proteins from aggregating in the crowded environment of the nucleolus3. The NPM gene is involved in several tumour-associated chromosome translocations, which have resulted in the formation of fusion proteins that retain the amino terminus of NPM, including NPM–ALK4, NPM–RAR5 and NPM–MLF1 (ref. 6). It is generally thought that the NPM component is not involved in the transforming potential of these fusion proteins7, but instead provides a dimerization interface for the oligomerization and the oncogenic conversion of the various NPM partners (ALK, RAR, MLF1). Here we show that NPM interacts directly with the tumour suppressor p53, regulates the increase in stability and transcriptional activation of p53 after different types of stress, and induces p53-dependent premature senescence on overexpression in diploid fibroblasts. These findings indicate that NPM is a crucial regulator of p53 and suggest that alterations of the NPM function by NPM fusion proteins might lead to deregulation of p53 in tumours.

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: NPM induces replicative senescence.
Figure 2: NPM interacts with p53.
Figure 3: NPM influences p53 stability and activity.
Figure 4: Effects of NPM–siRNA on p53 stability and activation.

Similar content being viewed by others

References

  1. Borer, R. A., Lehner, C. F., Eppenberger, H. M. & Nigg, E. A. Cell 56, 379–390 (1989).

    Article  CAS  Google Scholar 

  2. Olson, M. O., Wallace, M. O., Herrera, A. H., Marshall-Carlson, L. & Hunt, R. C. Biochemistry 25, 484–491 (1986).

    Article  CAS  Google Scholar 

  3. Szebeni, A. & Olson, M. O. Protein Sci. 8, 905–912 (1999).

    Article  CAS  Google Scholar 

  4. Morris, S. W. et al. Science 263, 1281–1284 (1994).

    Article  CAS  Google Scholar 

  5. Redner, R. L., Rush, E. A., Faas, S., Rudert, W. A. & Corey, S. J. Blood 87, 882–886 (1996).

    CAS  PubMed  Google Scholar 

  6. Yoneda-Kato, N. et al. Oncogene 12, 265–275 (1996).

    CAS  PubMed  Google Scholar 

  7. Bischof, D., Pulford, K., Mason, D. Y. & Morris, S. W. Mol. Cell. Biol. 17, 2312–2325 (1997).

    Article  CAS  Google Scholar 

  8. Dimri, G. P. et al. Proc. Natl Acad. Sci. USA 92, 9363–9367 (1995).

    Article  CAS  Google Scholar 

  9. Harvey, M. et al. Oncogene 8, 2457–2467 (1993).

    CAS  PubMed  Google Scholar 

  10. Valdez, B. C. et al. J. Biol. Chem. 269, 23776–23783 (1994).

    CAS  PubMed  Google Scholar 

  11. Li, Y. P. J. Virol. 71, 4098–4102 (1997).

    CAS  PubMed  PubMed Central  Google Scholar 

  12. Llanos, S., Clark, P. A., Rowe, J. & Peters, G. Nature Cell Biol. 3, 445–452 (2001).

    Article  CAS  Google Scholar 

  13. Serrano, M., Lin, A. W., McCurrach, M. E., Beach, D. & Lowe, S. W. Cell 88, 593–602 (1997).

    Article  CAS  Google Scholar 

  14. Lin, A. W. & Lowe, S. W. Proc. Natl Acad. Sci. USA 98, 5025–5030 (2001).

    Article  CAS  Google Scholar 

  15. Wu, X., Bayle, J. H., Olson, D. & Levine, A. J. Genes Dev. 7, 1126–1132 (1993).

    Article  CAS  Google Scholar 

  16. el-Deiry, W. S. et al. Cell 75, 817–825 (1993).

    Article  CAS  Google Scholar 

  17. Elbashir, S. M. et al. Nature 411, 494–498 (2001).

    Article  CAS  Google Scholar 

  18. Allan, L. A. & Fried, M. Oncogene 18, 5403–5412 (1999).

    Article  CAS  Google Scholar 

  19. Kastan, M. B. et al. Cell 71, 587–597 (1992).

    Article  CAS  Google Scholar 

  20. Mattern, K. A., Humbel, B. M., Muijsers, A. O., de Jong, L. & van Driel, R. J. Cell. Biochem. 62, 275–289. (1996).

    Article  CAS  Google Scholar 

  21. Jiang, M. et al. Oncogene 20, 5449–5458 (2001).

    Article  CAS  Google Scholar 

  22. He, L. Z., Merghoub, T. & Pandolfi, P. P. Oncogene 18, 5278–5292 (1999).

    Article  CAS  Google Scholar 

  23. Grignani, F. et al. Cell 74, 423–431 (1993).

    Article  CAS  Google Scholar 

  24. Pearson, M. et al. Nature 406, 207–210 (2000).

    Article  CAS  Google Scholar 

  25. Fogal, V. et al. EMBO J. 19, 6185–6195 (2000).

    Article  CAS  Google Scholar 

  26. Deveraux, Q., Ustrell, V., Pickart, C. & Rechsteiner, M. J. Biol. Chem. 269, 7059–7061 (1994).

    CAS  PubMed  Google Scholar 

  27. Cordell, J. L. et al. Blood 93, 632–642 (1999).

    CAS  PubMed  Google Scholar 

  28. Thullberg, M. et al. Hybridoma 19, 63–72 (2000).

    Article  CAS  Google Scholar 

Download references

Acknowledgements

We thank K. Helin, M. Pearson and A. Ventura for discussions; S. Polo for the GST–S5a construct; and E. Canidio for technical support. J.-C.M. and E.C. are recipients of fellowships from the European Community (Marie Curie Fellowship) and the Association for International Cancer Research (AICR), respectively. This work was supported by grants from the AIRC and the European Community.

Author information

Authors and Affiliations

  1. Department of Experimental Oncology, European Institute of Oncology, Via Ripamonti 435, Milan, 20141, Italy

    Emanuela Colombo, Jean-Christophe Marine, Davide Danovi & Pier Giuseppe Pelicci

  2. Institutes of Haematology and Internal Medicine, University of Perugia, Perugia, 06100, Italy

    Brunangelo Falini

  3. FIRC Institute of Molecular Oncology (IFOM), Via Adamello 16, Milan, 20141, Italy

    Pier Giuseppe Pelicci

Authors
  1. Emanuela Colombo
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Jean-Christophe Marine
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Davide Danovi
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. Brunangelo Falini
    View author publications

    You can also search for this author in PubMed Google Scholar

  5. Pier Giuseppe Pelicci
    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

Colombo, E., Marine, JC., Danovi, D. et al. Nucleophosmin regulates the stability and transcriptional activity of p53. Nat Cell Biol 4, 529–533 (2002). https://doi.org/10.1038/ncb814

Download citation

  • Received:

  • Revised:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1038/ncb814

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