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:

The N-terminus of a novel isoform of human iASPP is required for its cytoplasmic localization

Oncogene volume 23, pages 9007–9016 (2004)Cite this article

Abstract

ASPP1 and ASPP2 are both proteins that interact with p53 and enhance its ability to induce apoptosis by selectively elevating the expression of proapoptotic p53-responsive genes. iASPP(RAI) is a third member of the family that is the most conserved inhibitor of p53-mediated apoptosis. Here, we have described iASPP, a longer form of iASPP(RAI), which at 828 amino acids is more than twice the size of iASPP(RAI). Using two antibodies that recognize both iASPP and iASPP(RAI), we report that this longer form of iASPP is the predominant form of the molecule expressed in cells. Like iASPP(RAI), iASPP also binds to p53 and inhibits apoptosis induced by p53 overexpression. However, whereas iASPP(RAI) is predominantly nuclear, the N-terminus of iASPP is entirely cytoplasmic, and the longer iASPP is located in both the cytoplasm and the nucleus. The effect upon subcellular localization of the longer N-terminus of iASPP means that this new, longer form of the molecule may be subject to greater regulation and provides another layer in the control of p53-induced apoptosis.

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
Figure 6

Similar content being viewed by others

References

  • Bergamaschi D, Samuels Y, Jin B, Duraisingham S, Crook T and Lu X . (2004). Mol. Cell. Biol., 24, 1341–1350.

  • Bergamaschi D, Samuels Y, O'Neil NJ, Trigiante G, Crook T, Hsieh J-K, O'Connor DJ, Zhong S, Campargue I, Tomlinson ML, Kuwabara PE and Lu X . (2003). Nat. Genet., 33, 162–167.

  • Brummelkamp TR, Bernards R and Agami R . (2002). Science, 296, 550–553.

  • Derry WB, Putzke AP and Rothman JH . (2001). Science, 294, 591–595.

  • Gorina S and Pavletich NP . (1996). Science, 274, 1001–1005.

  • Hsieh J-K, Fredersdorf S, Kouzarides T, Martin K and Lu X . (1997). Genes Dev., 11, 1840–1852.

  • Iwabuchi K, Bartel PL, Li B, Marraccino R and Fields S . (1994). Proc. Natl. Acad. Sci. USA, 91, 6098–6102.

  • Mihara M, Erster S, Zaika A, Petrenko O, Chittenden T, Pancoska P and Moll UM . (2003). Mol. Cell, 11, 577–590.

  • Naumovski L and Cleary ML . (1996). Mol. Cell. Biol., 16, 3884–3892.

  • Sachdev S, Hoffmann A and Hannink M . (1998). Mol. Cell. Biol., 18, 2524–2534.

  • Samuels-Lev Y, O'Connor DJ, Bergamaschi D, Trigiante G, Hsieh JK, Zhong S, Campargue I, Naumovski L, Crook T and Lu X . (2001). Mol. Cell, 8, 781–794.

  • Schumacher B, Hofmann K, Boulton S and Gartner A . (2001). Curr. Biol., 11, 1722–1727.

  • Slee EA and Lu X . (2003). Tox. Lett., 139, 81–87.

  • Slee EA, O'Connor DJ and Lu X . (2004). Oncogene, 23, 2809–2818.

  • Vogelstein B, Lane D and Levine AJ . (2000). Nature, 408, 307–310.

  • Vousden KH and Lu X . (2002). Nat. Rev. Cancer, 2, 594–604.

  • Yang J-P, Hori M, Sanda T and Okamoto T . (1999). J. Biol. Chem., 274, 15662–15670.

  • Yap DB, Hsieh JK and Lu X . (2000). J. Biol. Chem., 275, 37296–37302.

Download references

Acknowledgements

This work was funded by the Ludwig Institute for Cancer Research. DB was supported by a grant from the Association of International Cancer Research.

Author information

Author notes

  1. Elizabeth A Slee, Sébastien Gillotin, Daniele Bergamaschi, Christophe Royer & Xin Lu

    Present address: Ludwig Institute for Cancer Research, University College London, 91 Riding House Street, London, W1W 7BS, UK

Authors and Affiliations

  1. Ludwig Institute for Cancer Research, Imperial College School of Medicine, Norfolk Place, London, W2 1PG, UK

    Elizabeth A Slee, Sébastien Gillotin, Daniele Bergamaschi, Christophe Royer, Susana Llanos, Safia Ali, Giuseppe Trigiante & Xin Lu

  2. Department of Immunology, Fourth Military Medical University, Xian, 710032, People's Republic of China

    Boquan Jin

Authors
  1. Elizabeth A Slee
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Sébastien Gillotin
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Daniele Bergamaschi
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. Christophe Royer
    View author publications

    You can also search for this author in PubMed Google Scholar

  5. Susana Llanos
    View author publications

    You can also search for this author in PubMed Google Scholar

  6. Safia Ali
    View author publications

    You can also search for this author in PubMed Google Scholar

  7. Boquan Jin
    View author publications

    You can also search for this author in PubMed Google Scholar

  8. Giuseppe Trigiante
    View author publications

    You can also search for this author in PubMed Google Scholar

  9. Xin Lu
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to Xin Lu.

Rights and permissions

Reprints and permissions

About this article

Cite this article

Slee, E., Gillotin, S., Bergamaschi, D. et al. The N-terminus of a novel isoform of human iASPP is required for its cytoplasmic localization. Oncogene 23, 9007–9016 (2004). https://doi.org/10.1038/sj.onc.1208088

Download citation

  • Received:

  • Revised:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1038/sj.onc.1208088

Keywords

This article is cited by

Search

Advanced search

Quick links