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14:57

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Published on: August 4, 2019

Mdm2 and MdmX partner to regulate p53

Xinjiang Wang1, Xuejun Jiang

  • 1Department of Pharmacology & Therapeutics, Roswell Park Cancer Institute, Buffalo, NY 14263, USA. xinjiang.wang@roswellpark.org

FEBS Letters
|June 8, 2012
PubMed

Insights

MdmX enhances Mdm2

Area of Science:

  • Molecular Biology
  • Cellular Biology
  • Biochemistry

Background:

  • Mdm2 protein regulates p53 stability, translation, localization, and activity.
  • Mdm2-dependent p53 inhibition is crucial for development and adult tissues.
  • MdmX, an Mdm2 homolog, is also vital for p53 inhibition in vivo.

Purpose of the Study:

  • To elucidate the role of the MdmX RING domain in Mdm2-dependent p53 polyubiquitination and degradation.
  • To understand how MdmX modulates Mdm2's E3 ligase activity towards p53.

Main Methods:

  • Biochemical studies
  • Genetic studies

Main Results:

  • MdmX's RING domain is essential for Mdm2-mediated p53 polyubiquitination and degradation.
  • MdmX converts Mdm2 from a monoubiquitin E3 ligase to a polyubiquitin E3 ligase for p53 via RING-RING domain interactions.
  • MdmX functions as both an activator and substrate within the Mdm2/MdmX E3 complex.

Conclusions:

  • MdmX plays a critical role in regulating p53 stability by enhancing Mdm2's E3 ligase activity.
  • The Mdm2/MdmX complex is a key regulator of p53 polyubiquitination and degradation.
  • Stress signals targeting MdmX can disrupt the p53/Mdm2 feedback loop, influencing p53 responses.

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