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 language | English |
|---|---|
| Pages (from-to) | 1074-1083 |
| Number of pages | 10 |
| Journal | Nature Cell Biology |
| Volume | 8 |
| Issue number | 10 |
| DOIs | |
| Publication status | Published - 2006 Oct |
Bibliographical note
Funding Information:This work was supported by grants from the Korea Science and Engineering Foundation through the center for Protein Network Research Center at Yonsei University (R112000078020010); the Glycomics Research Program of Ministry of Science and Technology (2004-02130 to J.W.C.); a Korea Research Foundation Grant (KRF-2004-005-C00112), through the Yonsei Biomedical Science and Technology Initiative Program; and, in part, by a grant from the Korea Health 21 R&D Project, via the Ministry of Health & Welfare, Republic of Korea (03-PJ10-PG6-GP01-0002). This work was also supported, in part, by Brain Korea 21 project. This work was made possible through the use of research facilities in the Yonsei Center for Biotechnology.
All Science Journal Classification (ASJC) codes
- Cell Biology