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A possible role of p73 on the modulation of p53 level through MDM2

X Q Wang1, W M Ongkeko, A W Lau

  • 1Department of Biochemistry Hong Kong University of Science and Technology, Clear Water Bay, Hong Kong.

Cancer Research
|March 14, 2001
PubMed

Insights

The protein p73 increases MDM2 levels and stability, unlike p53. This suggests p73 influences p53 responses to DNA damage and may contribute to tumorigenesis.

Area of Science:

  • Molecular Biology
  • Cell Biology
  • Cancer Research

Background:

  • MDM2 negatively regulates p53 through degradation, forming a feedback loop.
  • p53-related protein p73 binds MDM2 but is not degraded.
  • The role of p73 in regulating MDM2 and p53 stability is not fully understood.

Purpose of the Study:

  • To investigate the interaction between p73 and MDM2.
  • To determine how p73 affects MDM2 transcription and stability.
  • To elucidate the impact of p73 on p53 levels and responses to DNA damage.

Main Methods:

  • Transfection assays in p53-null cell lines.
  • Analysis of MDM2 promoter activity.
  • Assessment of MDM2 and p53 protein levels.
  • Investigation of MDM2-mediated proteolysis.

Main Results:

  • p73 transactivates the MDM2 promoter in p53-null cells, increasing MDM2 transcription and protein stability.
  • Higher MDM2 concentrations are needed to inhibit p73 transcriptional activity compared to p53.
  • p73 expression reduces both ectopic and endogenous p53 levels, likely via enhanced MDM2-mediated proteolysis.
  • Transcriptional activity of p73 is required for modulating p53 levels.

Conclusions:

  • p73 enhances MDM2 expression and stability, distinct from p53's regulation.
  • p73 influences p53 degradation pathways, modulating cellular responses to DNA damage.
  • Differential p73 levels may regulate p53 activity after stress, with potential implications for tumorigenesis.

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