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mdm2 expression is induced by wild type p53 activity

Y Barak1, T Juven, R Haffner

  • 1Department of Chemical Immunology, Weizmann Institute of Science, Rehovot, Israel.

The EMBO Journal
|February 1, 1993
PubMed
Summary
This summary is machine-generated.

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We identified a protein, mdm2, that binds to p53. Its levels increase with wild-type p53 activity, suggesting mdm2 autoregulates p53 function.

Area of Science:

  • Molecular Biology
  • Oncology
  • Cell Biology

Background:

  • A 95 kDa protein (p95) shows increased binding to temperature-sensitive p53 (ts-p53) at 32.5°C.
  • At 32.5°C, ts-p53 exhibits wild-type (wt)-like activities.

Purpose of the Study:

  • To identify the protein p95.
  • To investigate the interaction between p95 and ts-p53.
  • To elucidate the regulatory mechanism of p53 activity.

Main Methods:

  • Protein characterization
  • Temperature shift experiments
  • Western blotting
  • mRNA analysis

Main Results:

  • p95 was identified as a product of the mdm2 gene.

Related Experiment Videos

  • Elevated mdm2 protein levels at 32.5°C enhance mdm2-ts-p53 complex formation.
  • p53 directly induces mdm2 expression at the mRNA level with rapid kinetics.
  • This induction does not require new protein synthesis.

    • Conclusions:

    • The mdm2 gene is a transcriptional target of wild-type p53.
    • mdm2 acts as a specific antagonist of p53 activity.
    • This interaction suggests a negative feedback loop for p53 autoregulation in cells.