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Updated: Oct 13, 2026

Purification of Ubiquitinated p53 Proteins from Mammalian Cells
10:55

Purification of Ubiquitinated p53 Proteins from Mammalian Cells

Published on: March 21, 2022

The MDM2 RING-finger domain is required to promote p53 nuclear export

R K Geyer1, Z K Yu, C G Maki

  • 1Harvard School of Public Health, Department of Cancer Cell Biology, 665 Huntington Avenue, Boston, Massachusetts 02115, USA.

Nature Cell Biology
|September 12, 2000
PubMed

Insights

MDM2 protein targets p53 for degradation by promoting its nuclear export and ubiquitination. This study reveals MDM2

Area of Science:

  • Molecular Biology
  • Cell Biology
  • Cancer Research

Background:

  • MDM2 (mouse double minute 2 homolog) is a key negative regulator of the tumor suppressor p53.
  • MDM2 facilitates p53 ubiquitination and proteasomal degradation.
  • Nuclear export of p53 is considered essential for MDM2-mediated degradation, but MDM2's role in this process is unclear.

Purpose of the Study:

  • To elucidate the mechanism by which MDM2 promotes the nuclear export of p53.
  • To investigate the role of MDM2's functional domains and p53's nuclear export signal (NES) in this process.

Main Methods:

  • Transient transfection assays in cells.
  • Site-directed mutagenesis of MDM2 and p53.
  • Analysis of p53 ubiquitination and localization.
  • Assessment of p53 nuclear export and protein stability.

Main Results:

  • MDM2 directly promotes the nuclear export of p53, dependent on p53's NES.
  • MDM2's RING-finger domain is crucial for both p53 ubiquitination and MDM2-mediated p53 nuclear export.
  • Inhibiting p53 nuclear export leads to p53 stabilization and nuclear accumulation of ubiquitinated p53.

Conclusions:

  • MDM2-mediated ubiquitination or associated RING-finger domain activities stimulate p53 nuclear export via p53's NES.
  • This finding clarifies a critical step in the regulation of p53 stability and function by MDM2.

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