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Quantitative assessment of the p53-Mdm2 feedback loop using protein lysate microarrays

  1. Author:
    Ramalingam, S.
    Honkanen, P.
    Young, L.
    Shimura, T.
    Austin, J.
    Steeg, P. S.
    Nishizuka, S.

  2. Author Address

    NCI, Mol Therapeut Program, NIH, Bethesda, MD 20892 USA. NCI, Lab Mol Pharmacol, NIH, Bethesda, MD 20892 USA. NIH, Ctr Informat Technol, Bethesda, MD 20892 USA. Aushon BioSyst, Burlington, MA USA. Sci Applicat Int Corp Frederick Inc, Lab Proteom & Analyt Technol, Res Technol Program, Natl Canc Inst, Frederick, MD USA.;Nishizuka, S, Iwate Med Univ, Sch Med, Dept Surg, 19-1 Uchimaru, Morioka, Iwate 0208505, Japan.;nishizus@mail.nih.gov
    1. Year: 2007
    2. Date: Jul
  2. Journal: Cancer Research
    1. 67
    2. 13
    3. Pages: 6247-6252
  4. Type of Article: Article
  5. ISSN: 0008-5472
  1. Abstract:

    Mathematical simulations of the p53-Mdm2 feedback loop suggest that both proteins will exhibit impulsive expression characteristics in response to high cellular stress levels. However, little quantitative experimental evaluation has been done, particularly of the phosphorylated forms. To evaluate the mathematical models experimentally, we used lysate microarrays from an isogenic pair of gamma-ray-irradiated cell lysates from HCT116 (p53(+/+), and p53(-/-)). Both p53 and Mdm2 proteins showed expected pulses in the wild type, whereas no pulses were seen in the knockout. Based on experimental observations, we determined model parameters and generated an in silico "knockout," reflecting the experimental data, including phosphorylated proteins.

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External Sources

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  2. DOI: 10.1158/0008-5472.can-07-0342
  3. View record in Web of Science®
  4. WOS: 000247772000032

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