Modification of p53 with O-linked N-acetylglucosamine regulates p53 activity and stability

Nat Cell Biol. 2006 Oct;8(10):1074-83. doi: 10.1038/ncb1470. Epub 2006 Sep 10.

Abstract

Post-translational addition of O-linked N-acetylglucosamine (O-GlcNAc) to p53 is known to occur, but the site of O-GlcNAcylation and its effects on p53 are not understood. Here, we show that Ser 149 of p53 is O-GlcNAcylated and that this modification is associated with decreased phosphorylation of p53 at Thr 155, which is a site that is targeted by the COP9 signalosome, resulting in decreased p53 ubiquitination. Accordingly, O-GlcNAcylation at Ser 149 stabilizes p53 by blocking ubiquitin-dependent proteolysis. Our results indicate that the dynamic interplay between O-GlcNAc and O-phosphate modifications coordinately regulate p53 stability and activity.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Acetylglucosamine / metabolism*
  • Breast Neoplasms / metabolism*
  • Cell Survival
  • Electrophoresis, Gel, Two-Dimensional
  • Humans
  • Immunoprecipitation
  • Lung Neoplasms / metabolism*
  • Phosphates / metabolism
  • Phosphorylation
  • Protein Processing, Post-Translational / drug effects
  • Proto-Oncogene Proteins c-mdm2 / metabolism
  • Spectrometry, Mass, Matrix-Assisted Laser Desorption-Ionization
  • Tumor Cells, Cultured
  • Tumor Suppressor Protein p53 / metabolism*
  • Ubiquitin / metabolism*

Substances

  • Phosphates
  • Tumor Suppressor Protein p53
  • Ubiquitin
  • MDM2 protein, human
  • Proto-Oncogene Proteins c-mdm2
  • Acetylglucosamine