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In Vitro Ubiquitination and Deubiquitination Assays of Nucleosomal Histones
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In Vitro Ubiquitination and Deubiquitination Assays of Nucleosomal Histones

Published on: July 25, 2019

E6AP promotes the degradation of the PML tumor suppressor

I Louria-Hayon1, O Alsheich-Bartok, Y Levav-Cohen

  • 1Lautenberg Center for General and Tumour Immunology, The Hebrew University, Hadassah Medical School, Jerusalem, Israel.

Cell Death and Differentiation
|March 28, 2009
PubMed

Insights

The E3 ligase E6AP targets the PML tumor suppressor for proteasomal degradation, regulating its stability and the formation of PML nuclear bodies (NBs). This discovery sheds light on PML regulation in cancer and response to DNA damage.

Area of Science:

  • Molecular Biology
  • Cancer Biology
  • Cellular Regulation

Background:

  • The promyelocytic leukemia (PML) tumor suppressor is crucial for PML nuclear bodies (NBs) formation.
  • PML and PML-NBs are involved in regulating cell growth, senescence, and apoptosis.
  • PML is activated by stress but downregulated in cancers, with factors affecting its stability being unclear.

Purpose of the Study:

  • To identify factors that regulate the stability of the PML protein.
  • To investigate the role of E3 ligase E6AP in PML protein degradation.

Main Methods:

  • In vitro ubiquitination assays to assess E6AP's effect on PML.
  • Co-immunoprecipitation to study E6AP and PML interaction.
  • Analysis of PML protein expression in E6AP null mice.

Main Results:

  • Catalytically active E6AP promotes PML degradation via the proteasome, reducing its half-life.
  • E6AP and PML interact and colocalize within PML-NBs.
  • PML protein levels and PML-NBs are elevated in E6AP null mice, particularly after DNA damage.

Conclusions:

  • E6AP is identified as a key regulator of PML protein stability and PML-NB formation.
  • Understanding E6AP-mediated PML regulation offers insights into cancer mechanisms and DNA damage response.

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