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Purification of Ubiquitinated p53 Proteins from Mammalian Cells
10:55

Purification of Ubiquitinated p53 Proteins from Mammalian Cells

Published on: March 21, 2022

Ribosomal protein L11 negatively regulates oncoprotein MDM2 and mediates a p53-dependent ribosomal-stress checkpoint

Yanping Zhang1, Gabrielle White Wolf, Krishna Bhat

  • 1Department of Molecular and Cellular Oncology, The University of Texas M. D. Anderson Cancer Center, Houston, Texas 77030, USA. ypzhang@mdanderson.org

Molecular and Cellular Biology
|November 13, 2003
PubMed

Insights

Ribosomal protein L11 negatively regulates HDM2, a key protein in cancer. This interaction stabilizes p53, preventing degradation and promoting cell cycle arrest, suggesting a new pathway for tumor suppression.

Area of Science:

  • Molecular Biology
  • Oncology
  • Cell Biology

Background:

  • The p53 tumor suppressor pathway is crucial for preventing cancer and is frequently disrupted in human malignancies.
  • MDM2 (Mouse double minute 2 homolog) is a key negative regulator of p53, controlling its activity and stability.
  • p53 activation, typically in response to cellular stress like DNA damage, is essential for tumor suppression.

Purpose of the Study:

  • To investigate the interaction between HDM2 (human homolog of MDM2) and ribosomal protein L11.
  • To elucidate the functional consequences of the L11-HDM2 interaction on p53 regulation.
  • To explore a potential L11-HDM2-p53 pathway involved in monitoring ribosomal integrity.

Main Methods:

  • Co-immunoprecipitation assays to detect L11-HDM2 binding.
  • Western blotting to assess p53 and p21 protein levels.
  • Cell cycle analysis to evaluate cell cycle arrest.
  • Treatment with actinomycin D to interfere with ribosomal biogenesis.

Main Results:

  • Ribosomal protein L11 directly binds to HDM2 at a site distinct from the ARF binding region.
  • L11 binding to HDM2 inhibits HDM2-mediated p53 ubiquitination and degradation.
  • This interaction leads to p53 stabilization, increased p21 protein levels, and p53-dependent cell cycle arrest.
  • Interference with ribosomal biogenesis increases L11-HDM2 interaction and p53 stabilization.

Conclusions:

  • Ribosomal protein L11 acts as a negative regulator of HDM2.
  • A novel L11-HDM2-p53 pathway may exist in vivo to monitor ribosomal integrity.
  • This pathway represents a potential new target for cancer therapy by restoring p53 function.

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