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.

  • Correspondence
  • Published:

NMR indicates that the small molecule RITA does not block p53-MDM2 binding in vitro

Nature Medicine volume 11, pages 1135–1136 (2005)Cite this article

To the editor:

Issaeva et al. recently reported the discovery of a small molecule, RITA, that restores apoptosis-inducing function of p53 in tumor cells1. The authors reported that the mechanism of action of this compound involved the binding of RITA to the N-terminal domain of p53, inhibition of the p53-MDM2 complex and activation of p53 function. Our results show that RITA does not block the formation of the complex in vitro between p53 (residues 1–312) and the N-terminal p53-binding domain of MDM2 (residues 1–118).

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

Relevant articles

Open Access articles citing this article.

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: HSQC spectra of the 15N-labeled MDM2 (residues 1–118) with or without RITA.
Figure 2: HSQC spectra of the flexible N-terminal residues (1–93) of the 15N-labeled p53 (the residues of the p53 DNA core domain are mostly not seen because of their broad linewidths).

References

  1. Issaeva, N. et al. Nat. Med. 10, 1321–1328 (2004).

    Article  CAS  Google Scholar 

  2. Stockman, B.J. & Dalvit, C. Prog. NMR Spectrosc. 41, 187–231 (2002).

    Article  CAS  Google Scholar 

  3. Lepre, C.A., Moore, J.M. & Peng, J.W. Chem. Rev. 104, 3641–3675 (2004).

    Article  CAS  Google Scholar 

  4. Bell, S., Klein, C., Müller, L., Hansen, S. & Buchner, J. J. Mol. Biol. 322, 917–927 (2002).

    Article  CAS  Google Scholar 

  5. Ayed, A. et al. Nat. Struct. Biol. 8, 756–760 (2001).

    Article  CAS  Google Scholar 

  6. Lee, H. et al. J. Biol. Chem. 275, 29426–29432 (2000).

    Article  CAS  Google Scholar 

  7. Kussie, P.H. et al. Science 274, 948–953 (1996).

    Article  CAS  Google Scholar 

  8. Picksley, S.M., Vojtesek, B., Sparks, A. & Lane, D.P. Oncogene 9, 2523–2529 (1994).

    CAS  PubMed  Google Scholar 

  9. D'Silva, L. et al. J. am. Chem. Soc. 127, 13220–13226 (2005)

    Article  CAS  Google Scholar 

  10. Vassilev, L.T. et al. Science 303, 844–848 (2004).

    Article  CAS  Google Scholar 

Download references

Author information

Authors and Affiliations

  1. Max Planck Institute for Biochemistry, Martinsried, D-82152, Germany

    Marcin Krajewski, Przemyslaw Ozdowy, Loyola D'Silva, Ulli Rothweiler & Tad A Holak

Authors
  1. Marcin Krajewski
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Przemyslaw Ozdowy
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Loyola D'Silva
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. Ulli Rothweiler
    View author publications

    You can also search for this author in PubMed Google Scholar

  5. Tad A Holak
    View author publications

    You can also search for this author in PubMed Google Scholar

Supplementary information

Supplementary Fig. 1

HSQC spectra of the 15N labeled MDM2 (residues 1-118). (PDF 87 kb)

Supplementary Fig. 2

HSQC spectra of the 15N labeled MDM2 (residues 1-118). (PDF 104 kb)

Supplementary Fig. 3

Superposition of HSQC spectra of 15N labeled p53 in 5% DMSO (red) and after addition of RITA (blue). (PDF 135 kb)

Supplementary Methods (PDF 146 kb)

Supplementary Note (PDF 336 kb)

Rights and permissions

Reprints and permissions

About this article

Cite this article

Krajewski, M., Ozdowy, P., D'Silva, L. et al. NMR indicates that the small molecule RITA does not block p53-MDM2 binding in vitro. Nat Med 11, 1135–1136 (2005). https://doi.org/10.1038/nm1105-1135

Download citation

  • Issue Date:

  • DOI: https://doi.org/10.1038/nm1105-1135

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