PMID: 23395175

 

    Legend: Gene, Sites

Title : Glucose sensor O-GlcNAcylation coordinates with phosphorylation to regulate circadian clock

Abstract :

1. Posttranslational modifications play central roles in myriad biological pathways including circadian regulation
2. We employed a circadian proteomic approach to demonstrate that circadian timing of phosphorylation is a critical factor in regulating complex GSK3β-d ependent pathways and identified O-GlcNAc transferase ( OGT ) as a substrate of GSK3β.
3. Interestingly, OGT activity is regulated by GSK3β; hence, OGT and GSK3β exhibit reciprocal regulation
4. Modulating O-GlcNAcylation levels alter circadian period length in both mice and Drosophila; conversely, protein O-GlcNAcylation is circadianly regulated
5. Central clock proteins , Clock and Period, are reversibly modified by O-GlcNAcylation to regulate their transcriptional activities
6. 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
7. 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

Output (sent_index, trigger, protein, sugar, site):

• 5. modified, , Central clock proteins, O-GlcNAcylation, -
• 5. modified, , Clock, O-GlcNAcylation, -
• 6. O-GlcNAcylation, , PER2, O-GlcNAcylation, -
• 6. region, , -, O-GlcNAcylation, -

Output(Part-Of) (sent_index, protein, site):

*Output_Site_Fusion* (sent_index, protein, sugar, site):

 

Protein	NCBI ID	SENTENCE INDEX
GSK3β.	56637	2
clock	12753	7
GSK3β	56637	3
OGT	108155	2,3
GSK3β-d	56637	2
Clock	12753	5
Central clock proteins	12753	5
PER2	8864	6
GSK3β;	56637	3