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Purification of Ubiquitinated p53 Proteins from Mammalian Cells
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Purification of Ubiquitinated p53 Proteins from Mammalian Cells

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Aurora B kinase phosphorylates and instigates degradation of p53

Chris P Gully1, Guermarie Velazquez-Torres, Ji-Hyun Shin

  • 1Graduate School of Biomedical Sciences, University of Texas, Houston, TX 77030, USA.

Proceedings of the National Academy of Sciences of the United States of America
|May 22, 2012
PubMed

Insights

Aurora B kinase phosphorylates tumor suppressor p53, accelerating its degradation and suppressing its cell cycle inhibition. Inhibiting Aurora B restores p53 function, offering a potential cancer therapy strategy.

Area of Science:

  • Cell Biology
  • Molecular Oncology
  • Biochemistry

Background:

  • Aurora B kinase is crucial for cell division and frequently overexpressed in cancers.
  • Tumor suppressor p53 regulates the cell cycle and apoptosis.
  • The relationship between Aurora B and p53 during the cell cycle was previously unknown.

Purpose of the Study:

  • To investigate the interaction and regulation between Aurora B kinase and p53.
  • To elucidate the mechanism by which Aurora B affects p53 function.
  • To explore the therapeutic potential of targeting Aurora B in cancer cells with wild-type p53.

Main Methods:

  • Co-immunoprecipitation to detect protein interactions.
  • Western blotting to assess protein levels and phosphorylation.
  • Ubiquitination assays to study protein degradation pathways.
  • Cell-based assays to evaluate gene expression and cell proliferation.

Main Results:

  • Aurora B directly interacts with p53 in the nucleus and at centromeres.
  • Aurora B phosphorylates p53 at specific sites (S183, T211, S215), promoting its degradation via the ubiquitin-proteasome system.
  • This phosphorylation suppresses the expression of p53 target genes involved in cell cycle arrest and apoptosis (e.g., p21, PUMA).
  • Inhibition of Aurora B in cancer cells with wild-type p53 increased p53 levels and its target gene expression, leading to tumor growth inhibition.

Conclusions:

  • Aurora B directly regulates p53 stability and function by promoting its degradation.
  • Overexpression of Aurora B can inactivate the tumor suppressor function of p53.
  • Targeting Aurora B kinase is a promising therapeutic strategy for cancers with wild-type p53.

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