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MDM2 promotes SUMO-2/3 modification of p53 to modulate transcriptional activity

Maren H Stindt1, Stephanie Carter, Arnaud M Vigneron

  • 1The Beatson Institute for Cancer Research; Glasgow, UK.

Cell Cycle (Georgetown, Tex.)
|September 9, 2011
PubMed

Insights

The tumor suppressor p53 undergoes SUMO-2/3 modification, enhanced by MDM2, ARF, and L11. This modification impacts p53-target gene activity.

Area of Science:

  • Molecular Biology
  • Cellular Biology
  • Biochemistry

Background:

  • The tumor suppressor p53 is a critical regulator of cellular responses to stress.
  • Post-translational modifications, including SUMOylation, play a significant role in p53 regulation.
  • MDM2 is a known regulator of p53, primarily involved in its ubiquitylation.

Purpose of the Study:

  • To investigate the role of MDM2 in SUMO-2/3 conjugation of p53.
  • To determine the factors that promote SUMO-2/3 modification of p53.
  • To elucidate the functional consequences of SUMO-2/3 conjugation on p53 activity.

Main Methods:

  • Western blotting to detect SUMO-2/3 conjugation to p53.
  • Co-immunoprecipitation assays to study protein interactions.
  • Analysis of p53-target gene expression.

Main Results:

  • MDM2 enhances the conjugation of endogenous SUMO-2/3 to p53.
  • p53-MDM2 binding is required for SUMO-2/3 conjugation, independent of the RING finger domain.
  • ARF and L11 also promote SUMO-2/3 conjugation of p53.
  • SUMO-2/3 conjugation of p53 does not require MDM2 relocalization to the nucleolus.
  • Mouse p53, lacking the SUMO consensus, is not modified by SUMO-2/3.
  • SUMO-2/3 conjugation of p53 correlates with reduced activation and repression of target genes.

Conclusions:

  • MDM2, ARF, and L11 are key regulators of p53 SUMO-2/3 modification.
  • SUMO-2/3 conjugation of p53 influences the transcriptional activity of a subset of its target genes.
  • This study reveals a novel regulatory mechanism for p53 involving SUMO-2/3 conjugation.

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