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Ribosomal protein S3: A multi-functional protein that interacts with both p53 and MDM2 through its KH domain

Sridevi Yadavilli1, Lindsey D Mayo, Maureen Higgins

  • 1Pennington Biomedical Research Center, Louisiana State University System, Baton Rouge, 70808, USA.

DNA Repair
|August 7, 2009
PubMed

Insights

Researchers discovered ribosomal protein S3 (RPS3) interacts with MDM2 and p53, proteins crucial for cellular stress response and DNA repair. RPS3 may play a key role in regulating p53 stability and maintaining genomic integrity.

Area of Science:

  • Molecular Biology
  • Cellular Biology
  • Genomics

Background:

  • The p53 protein is a critical regulator of cellular responses to stress, controlling cell cycle, apoptosis, and DNA repair.
  • MDM2 protein targets p53 for degradation, maintaining low p53 levels under normal conditions.
  • Identifying novel proteins in the p53-MDM2 regulatory loop is essential for understanding cellular stress responses.

Purpose of the Study:

  • To identify novel proteins interacting with MDM2 in the p53 regulatory pathway.
  • To investigate the role of identified proteins in modulating p53 and MDM2 interactions and cellular stress responses.

Main Methods:

  • MDM2 peptide pull-down assay and mass spectrometry to identify interacting partners.
  • His and GST pull-down assays, FRET, and in situ proximity ligation assays to confirm interactions.
  • siRNA-mediated knockdown and DNA pull-down assays to assess functional roles.

Main Results:

  • Ribosomal protein S3 (RPS3) was identified as a novel interacting partner of MDM2 and p53.
  • RPS3 knockdown under oxidative stress led to decreased p53 levels and impaired MDM2 E3 ubiquitin ligase activity.
  • RPS3 functions as a scaffold, facilitating the binding of MDM2 and p53 to DNA, suggesting a role in genomic integrity maintenance.

Conclusions:

  • RPS3 is a novel component of the p53-MDM2 regulatory network.
  • RPS3 influences p53 stability and MDM2 ligase activity, particularly under oxidative stress.
  • RPS3 may serve as a scaffold protein crucial for DNA repair mechanisms involving p53 and MDM2.

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