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Updated: Aug 23, 2026

Yeast As a Chassis for Developing Functional Assays to Study Human P53
14:57

Yeast As a Chassis for Developing Functional Assays to Study Human P53

Published on: August 4, 2019

The p53 paddy wagon: COP1, Pirh2 and MDM2 are found resisting apoptosis and growth arrest

Chad A Corcoran1, Ying Huang, M Saeed Sheikh

  • 1Department of Pharmacology, State University of New York, Upstate Medical University, Syracuse, New York 13210, USA.

Cancer Biology & Therapy
|July 29, 2004
PubMed

Insights

The tumor suppressor p53

Area of Science:

  • Molecular Biology
  • Cancer Research
  • Cellular Regulation

Background:

  • The tumor suppressor p53's growth inhibitory effects were primarily attributed to the ubiquitin ligase MDM2.
  • MDM2 targets p53 for proteasomal degradation, a well-established mechanism.
  • Recent findings suggest MDM2 may not be the sole regulator of p53 function.

Purpose of the Study:

  • To investigate potential alternative ubiquitin ligases that negatively regulate p53.
  • To explore the roles of Pirh2 and COP1 in p53 degradation.
  • To understand the broader regulatory network controlling p53 activity.

Main Methods:

  • Investigating the interaction between p53 and newly identified proteins.
  • Assessing the ubiquitination and degradation of p53 mediated by Pirh2 and COP1.
  • Analyzing the upregulation of Pirh2 and COP1 in response to p53 and genotoxic stress.

Main Results:

  • Pirh2 and COP1, alongside MDM2, are implicated in p53 degradation via the ubiquitin-proteasome pathway.
  • Both Pirh2 and COP1 directly promote p53 ubiquitination and degradation.
  • Pirh2 and COP1 expression is upregulated by p53 and genotoxic stress.

Conclusions:

  • MDM2 is not the only ubiquitin ligase controlling p53 function.
  • Pirh2 and COP1 are novel negative regulators of p53 activity.
  • Further research is needed to clarify the physiological roles of these three p53-degrading molecules.

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