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In Vitro Analysis of E3 Ubiquitin Ligase Function
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In Vitro Analysis of E3 Ubiquitin Ligase Function

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MDM2-C Functions as an E3 Ubiquitin Ligase

Jun Yeob Kim1, Rusia Lee1,2, Gu Xiao1

  • 1The Department of Biological Sciences, Hunter College, City University of New York, New York, NY, USA.

Cancer Management and Research
|September 9, 2020
PubMed
Abstract

Insights

The MDM2-C protein isoform exhibits E3 ubiquitin ligase activity, promoting ubiquitination of both wild-type and mutant p53. This finding clarifies MDM2-C

Area of Science:

  • Oncology
  • Molecular Biology
  • Biochemistry

Background:

  • Mouse double minute 2 (MDM2) is an over-expressed E3 ubiquitin ligase in many cancers.
  • While full-length MDM2 (MDM2-FL) targets wild-type p53 for degradation, functions of MDM2 splice variants are underexplored.
  • MDM2-C is over-expressed in breast cancer and linked to poorer survival with mutant p53.

Purpose of the Study:

  • To investigate the biochemical function of the MDM2-C isoform.
  • To determine if MDM2-C possesses E3 ubiquitin ligase activity, similar to MDM2-FL.

Main Methods:

  • In vitro ubiquitination assay.
  • Glutaraldehyde cross-linking assay.

Main Results:

  • MDM2-C demonstrates E3 auto-ubiquitin ligase activity.
  • MDM2-C promotes ubiquitination of wild-type p53 and mutant p53 R273H.
  • MDM2-C forms protein-protein interactions with p53.

Conclusions:

  • MDM2-C exhibits biochemical activities, including p53 ubiquitination.
  • These activities may explain varied patient outcomes based on MDM2-C and p53 status (wild-type vs. mutant).
Keywords:
MDM2 splice variantsbreast cancermutant p53wild-type p53

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