| First Author | Kaasik K | Year | 2013 |
| Journal | Cell Metab | Volume | 17 |
| Issue | 2 | Pages | 291-302 |
| PubMed ID | 23395175 | Mgi Jnum | J:198048 |
| Mgi Id | MGI:5495337 | Doi | 10.1016/j.cmet.2012.12.017 |
| Citation | Kaasik K, et al. (2013) Glucose sensor O-GlcNAcylation coordinates with phosphorylation to regulate circadian clock. Cell Metab 17(2):291-302 |
| abstractText | Posttranslational modifications play central roles in myriad biological pathways including circadian regulation. We employed a circadian proteomic approach to demonstrate that circadian timing of phosphorylation is a critical factor in regulating complex GSK3beta-dependent pathways and identified O-GlcNAc transferase (OGT) as a substrate of GSK3beta. Interestingly, OGT activity is regulated by GSK3beta; hence, OGT and GSK3beta exhibit reciprocal regulation. Modulating O-GlcNAcylation levels alter circadian period length in both mice and Drosophila; conversely, protein O-GlcNAcylation is circadianly regulated. Central clock proteins, Clock and Period, are reversibly modified by O-GlcNAcylation to regulate their transcriptional activities. In addition, O-GlcNAcylation of a region in PER2 known to regulate human sleep phase (S662-S674) competes with phosphorylation of this region, and this interplay is at least partly mediated by glucose levels. Together, these results indicate that O-GlcNAcylation serves as a metabolic sensor for clock regulation and works coordinately with phosphorylation to fine-tune circadian clock. |
