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O-GlcNAc Signaling Entrains the Circadian Clock by Inhibiting BMAL1/CLOCK Ubiquitination
O-GlcNAc signaling helps set the body’s daily clock by preventing breakdown of key timing proteins
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Abstract
O-GlcNAc transferase (OGT) is shown to influence circadian clock oscillations.
- The hexosamine/O-GlcNAc pathway is linked to the regulation of peripheral clock oscillation.
- OGT enhances the expression of BMAL1/CLOCK target genes, impacting circadian rhythms.
- Both BMAL1 and CLOCK undergo rhythmic O-GlcNAcylation, which stabilizes these proteins.
- O-GlcNAcylation inhibits the ubiquitination of BMAL1 and CLOCK, affecting their stability.
- Genetically modified mice with altered hepatic OGT expression exhibit disrupted glucose homeostasis rhythms.
- These findings suggest that O-GlcNAc signaling may transmit nutritional information to the circadian clock.
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