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

Won Ho Yang, Ji Eun Kim, Hyung Wook Nam, Jung Won Ju, Hoe Suk Kim, Yu Sam Kim, Jin Won Cho

Research output: Contribution to journalArticle

267 Citations (Scopus)

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.

Original languageEnglish
Pages (from-to)1074-1083
Number of pages10
JournalNature Cell Biology
Volume8
Issue number10
DOIs
Publication statusPublished - 2006 Oct 1

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Acetylglucosamine
Ubiquitination
Ubiquitin
Proteolysis
Phosphates
Phosphorylation
COP9 signalosome complex

All Science Journal Classification (ASJC) codes

  • Cell Biology

Cite this

Yang, Won Ho ; Kim, Ji Eun ; Nam, Hyung Wook ; Ju, Jung Won ; Kim, Hoe Suk ; Kim, Yu Sam ; Cho, Jin Won. / Modification of p53 with O-linked N-acetylglucosamine regulates p53 activity and stability. In: Nature Cell Biology. 2006 ; Vol. 8, No. 10. pp. 1074-1083.
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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.",
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Modification of p53 with O-linked N-acetylglucosamine regulates p53 activity and stability. / Yang, Won Ho; Kim, Ji Eun; Nam, Hyung Wook; Ju, Jung Won; Kim, Hoe Suk; Kim, Yu Sam; Cho, Jin Won.

In: Nature Cell Biology, Vol. 8, No. 10, 01.10.2006, p. 1074-1083.

Research output: Contribution to journalArticle

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