O-GlcNAcylation of BMAL1 regulates circadian rhythms in NIH3T3 fibroblasts

► Circadian core protein BMAL1 is modified with an O-linked β-N-acetylglucosamine (O-GlcNAc). ► O-GlcNAcylation of BMAL1 stabilizes the protein. ► O-GlcNAcylation of BMAL1 enhances its transcriptional activity. ► Inhibition of O-GlcNAcylation results in dampened circadian rhythms of clock gene expre...

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Bibliographic Details
Published in:Biochemical and biophysical research communications 2013-02, Vol.431 (3), p.382-387
Main Authors: Ma, Yan-Tao, Luo, Hunjin, Guan, Wen-Juan, Zhang, Hua, Chen, Chongfen, Wang, Ziyao, Li, Jia-Da
Format: Article
Language:English
Subjects:
Acetylglucosamine - metabolism
Acylation - drug effects
Animals
ARNTL Transcription Factors - genetics
ARNTL Transcription Factors - metabolism
BMAL1
Circadian Rhythm - drug effects
Circadian Rhythm - genetics
Circadian Rhythm - physiology
Circadian rhythms
Fibroblasts - physiology
Genes, Reporter
HEK293 Cells
Humans
Luciferases - genetics
Mice
NIH 3T3 Cells
O-GlcNAcylation
Protein Stability
Stability
Transcription, Genetic
Transcriptional activity
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Summary:► Circadian core protein BMAL1 is modified with an O-linked β-N-acetylglucosamine (O-GlcNAc). ► O-GlcNAcylation of BMAL1 stabilizes the protein. ► O-GlcNAcylation of BMAL1 enhances its transcriptional activity. ► Inhibition of O-GlcNAcylation results in dampened circadian rhythms of clock gene expression. Various physiological processes and behaviors show a circadian rhythm of approximately 24h, which is crucial in coordinating internal metabolic processes and environmental signals. Post-translational modifications play an important role in regulating circadian core proteins. In this study, we demonstrated that BMAL1 was modified with an O-linked β-N-acetylglucosamine (O-GlcNAc), which stabilized BMAL1 and enhanced its transcriptional activity. Conversely, inhibition of O-GlcNAcylation resulted in inhibition of circadian rhythms of clock gene expression. Because O-GlcNAcylation is sensitive to the glucose level, such a modification may provide a new mechanism connecting metabolism with circadian rhythms.
ISSN:0006-291X
1090-2104
DOI:10.1016/j.bbrc.2013.01.043