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
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Research Support, Non-U.S. Gov't
MeSH terms
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Acetylglucosamine / metabolism*
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Breast Neoplasms / metabolism*
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Cell Survival
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Electrophoresis, Gel, Two-Dimensional
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Humans
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Immunoprecipitation
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Lung Neoplasms / metabolism*
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Phosphates / metabolism
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Phosphorylation
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Protein Processing, Post-Translational / drug effects
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Proto-Oncogene Proteins c-mdm2 / metabolism
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Spectrometry, Mass, Matrix-Assisted Laser Desorption-Ionization
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Tumor Cells, Cultured
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Tumor Suppressor Protein p53 / metabolism*
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Ubiquitin / metabolism*
Substances
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Phosphates
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Tumor Suppressor Protein p53
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Ubiquitin
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MDM2 protein, human
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Proto-Oncogene Proteins c-mdm2
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Acetylglucosamine