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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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Ribosomal protein L4 is a novel regulator of the MDM2-p53 loop

Xia He1,2, Yuhuang Li1, Mu-Shui Dai1

  • 1Department of Molecular and Medical Genetics, School of Medicine and The OHSU Knight Cancer Institute, Oregon Health & Science University, Portland, OR, USA.

Oncotarget
|February 25, 2016
PubMed

Insights

Ribosomal protein L4 (RPL4) regulates cell growth by stabilizing p53 through interaction with MDM2. RPL4

Area of Science:

  • Molecular Biology
  • Cell Biology
  • Cancer Research

Background:

  • Ribosomal proteins (RPs) coordinate ribosome biogenesis with cell growth.
  • RPs can suppress MDM2 to activate p53, but the regulation mechanism is unclear.
  • Identifying RPs that regulate the MDM2-p53 pathway is crucial.

Purpose of the Study:

  • To investigate the role of ribosomal protein L4 (RPL4) in regulating the MDM2-p53 pathway.
  • To identify additional RPs involved in this regulatory loop.

Main Methods:

  • Co-immunoprecipitation assays to study protein interactions.
  • Western blotting to assess protein levels and ubiquitination.
  • Cell cycle analysis to determine proliferation effects.
  • Gene knockdown and overexpression studies.

Main Results:

  • RPL4 directly interacts with MDM2, suppressing p53 ubiquitination and degradation.
  • RPL4 overexpression enhances MDM2 binding to RPL5 and RPL11.
  • RPL4 knockdown increases p53 levels and induces p53-dependent cell cycle arrest.
  • The p53-dependent effects of RPL4 depletion require RPL5 and RPL11, indicating ribosomal stress.

Conclusions:

  • Balanced RPL4 levels are critical for normal cell growth and proliferation.
  • RPL4 regulates the MDM2-p53 axis, impacting cell cycle control.
  • RPL4 acts in concert with RPL5 and RPL11 to mediate ribosomal stress responses.
Keywords:
MDM2RPL4p53ribosome proteinsubiquitination

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