title: Modification of p53 with O-linked N-acetylglucosamine regulates p53 activity and stability.
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.
authors.affiliation: Department of Biology, Yonsei University, 134 Shinchon-dong, Seodaemun-gu, Seoul 120-749, Korea.
authors.forename: Won Ho
authors.initials: WH
authors.lastname: Yang
authors.forename: Ji Eun
authors.initials: JE
authors.lastname: Kim
authors.forename: Hyung Wook
authors.initials: HW
authors.lastname: Nam
authors.forename: Jung Won
authors.initials: JW
authors.lastname: Ju
authors.forename: Hoe Suk
authors.initials: HS
authors.lastname: Kim
authors.forename: Yu Sam
authors.initials: YS
authors.lastname: Kim
authors.forename: Jin Won
authors.initials: JW
authors.lastname: Cho
mesh_terms: D000117:Acetylglucosamine / Q000378:metabolism*; D001943:Breast Neoplasms / Q000378:metabolism*; D002470:Cell Survival; D015180:Electrophoresis, Gel, Two-Dimensional; D006801:Humans; D047468:Immunoprecipitation; D008175:Lung Neoplasms / Q000378:metabolism*; D010710:Phosphates / Q000378:metabolism; D010766:Phosphorylation; D011499:Protein Processing, Post-Translational / Q000187:drug effects; D051736:Proto-Oncogene Proteins c-mdm2 / Q000378:metabolism; D019032:Spectrometry, Mass, Matrix-Assisted Laser Desorption-Ionization; D014407:Tumor Cells, Cultured; D016159:Tumor Suppressor Protein p53 / Q000378:metabolism*; D025801:Ubiquitin / Q000378:metabolism*
chemical_list: D010710:Phosphates; D016159:Tumor Suppressor Protein p53; D025801:Ubiquitin; C497206:MDM2 protein, human; D051736:Proto-Oncogene Proteins c-mdm2; D000117:Acetylglucosamine