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

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.
Mesh Terms:
Acetylglucosamine, Breast Neoplasms, Cell Survival, Electrophoresis, Gel, Two-Dimensional, Humans, Immunoprecipitation, Lung Neoplasms, Phosphates, Phosphorylation, Protein Processing, Post-Translational, Proto-Oncogene Proteins c-mdm2, Spectrometry, Mass, Matrix-Assisted Laser Desorption-Ionization, Tumor Cells, Cultured, Tumor Suppressor Protein p53, Ubiquitin
Nat. Cell Biol.
Date: Oct. 01, 2006
Download 1 Interactions For This Publication
Switch View:
  • Interactions 1