C-terminal ubiquitination of p53 contributes to nuclear export

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Updated: Oct 3, 2026

Purification of Ubiquitinated p53 Proteins from Mammalian Cells
10:55

Purification of Ubiquitinated p53 Proteins from Mammalian Cells

Published on: March 21, 2022

M A Lohrum1, D B Woods, R L Ludwig

  • 1Regulation of Cell Growth Laboratory, National Cancer Institute at Frederick, Building 5460, Rm. 22-96, 1050 Boyles St., Frederick, MD 21702-1201, USA.

Molecular and Cellular Biology
|November 20, 2001
PubMed

Insights

MDM2-mediated ubiquitination of p53 protein drives its nuclear export and degradation. However, these processes are not strictly dependent on each other for controlling cell growth.

Area of Science:

  • Molecular Biology
  • Cell Biology
  • Cancer Research

Background:

  • The tumor suppressor protein p53's growth inhibitory functions are regulated by its degradation in unstressed cells.
  • MDM2, an E3 ligase, is a key regulator of p53 stability, ubiquinating p53 and promoting its degradation.
  • MDM2 also facilitates p53 nuclear export, a critical step in regulating p53 activity.

Purpose of the Study:

  • To investigate the role of MDM2-mediated ubiquitination in p53 nuclear export.
  • To determine the relationship between p53 nuclear export and degradation.
  • To compare the effect of MDM2 on p53 and the related protein p73.

Main Methods:

  • Studied the ubiquitination of p53 by MDM2.
  • Investigated the impact of MDM2 on p53 localization between the nucleus and cytoplasm.
  • Examined the role of the export receptor CRM1 in p53 nuclear export.
  • Assessed the effect of nuclear export on p53 degradation.

Main Results:

  • MDM2-mediated ubiquitination of p53's C-terminus promotes its efficient export from the nucleus to the cytoplasm.
  • MDM2 did not induce nuclear export of the p53-related protein p73.
  • Overexpression of CRM1 enhanced p53 nuclear export but did not lead to p53 degradation.
  • Nuclear export was not essential for p53 degradation, and degradation could occur independently of export.

Conclusions:

  • MDM2-mediated ubiquitination of p53 contributes to both its nuclear export and degradation.
  • These two processes, nuclear export and degradation, are linked but not absolutely dependent on each other.
  • Understanding this regulatory mechanism is crucial for cancer research and therapeutic development.

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