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Dynamically regulated sumoylation of HDAC2 controls p53 deacetylation and restricts apoptosis following genotoxic

André Brandl1, Tobias Wagner, Katharina M Uhlig

  • 1Center for Molecular Biomedicine, Institute for Biochemistry and Biophysics, Department of Biochemistry, Friedrich Schiller University of Jena, Hans-Knöll-Straße 2, 07745 Jena, Germany.

Journal of Molecular Cell Biology
|April 12, 2012
PubMed

Insights

Small ubiquitin-related modifier 1 (SUMO1) modification of histone deacetylase 2 (HDAC2) regulates the tumor suppressor p53. This SUMO1-HDAC2 interaction impacts cell fate decisions following genotoxic stress.

Area of Science:

  • Molecular Biology
  • Cancer Biology
  • Biochemistry

Background:

  • Histone deacetylase 2 (HDAC2) is crucial for homeostasis and gastrointestinal cancer.
  • Post-translational modifications regulate protein function and cellular processes.

Purpose of the Study:

  • To investigate the role of HDAC2 sumoylation in regulating the tumor suppressor p53.
  • To elucidate the molecular mechanism by which sumoylated HDAC2 affects p53 activity and downstream gene expression.

Main Methods:

  • Western blotting and immunoprecipitation to detect and analyze protein modifications.
  • Chromatin immunoprecipitation assays to assess protein-DNA interactions.
  • Reporter gene assays to measure gene expression levels.

Main Results:

  • Endogenous HDAC2 is modified by small ubiquitin-related modifier 1 (SUMO1) at lysine 462.
  • Sumoylated HDAC2 binds to and deacetylates p53 at lysine 320.
  • Deacetylation of p53 by sumoylated HDAC2 inhibits p53-dependent gene expression and apoptosis.
  • Genotoxic stress induces desumoylation of HDAC2, restoring p53 function.

Conclusions:

  • A novel regulatory switch involving HDAC2 sumoylation/p53 acetylation controls cell fate decisions after genotoxic stress.
  • Sumoylated HDAC2 acts as a site-specific deacetylase for p53, restricting its tumor suppressor functions.
  • Targeting the HDAC2-sumoylation pathway may offer new therapeutic strategies for gastrointestinal cancers.

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