Title |
O-GlcNAc Signaling Entrains the Circadian Clock by Inhibiting BMAL1/CLOCK Ubiquitination
|
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Published in |
Cell Metabolism (Science Direct), February 2013
|
DOI | 10.1016/j.cmet.2012.12.015 |
Pubmed ID | |
Authors |
Min-Dian Li, Hai-Bin Ruan, Michael E. Hughes, Jeong-Sang Lee, Jay P. Singh, Steven P. Jones, Michael N. Nitabach, Xiaoyong Yang |
Abstract |
Circadian clocks are coupled to metabolic oscillations through nutrient-sensing pathways. Nutrient flux into the hexosamine biosynthesis pathway triggers covalent protein modification by O-linked β-D-N-acetylglucosamine (O-GlcNAc). Here we show that the hexosamine/O-GlcNAc pathway modulates peripheral clock oscillation. O-GlcNAc transferase (OGT) promotes expression of BMAL1/CLOCK target genes and affects circadian oscillation of clock genes in vitro and in vivo. Both BMAL1 and CLOCK are rhythmically O-GlcNAcylated, and this protein modification stabilizes BMAL1 and CLOCK by inhibiting their ubiquitination. In vivo analysis of genetically modified mice with perturbed hepatic OGT expression shows aberrant circadian rhythms of glucose homeostasis. These results establish the counteraction between O-GlcNAcylation and ubiquitination as a key mechanism that regulates the circadian clock and suggest a crucial role for O-GlcNAc signaling in transducing nutritional signals to the core circadian timing machinery. |
X Demographics
Geographical breakdown
Country | Count | As % |
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Japan | 1 | 33% |
United Kingdom | 1 | 33% |
Unknown | 1 | 33% |
Demographic breakdown
Type | Count | As % |
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Members of the public | 2 | 67% |
Science communicators (journalists, bloggers, editors) | 1 | 33% |
Mendeley readers
Geographical breakdown
Country | Count | As % |
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France | 2 | 1% |
United States | 2 | 1% |
Sweden | 1 | <1% |
Portugal | 1 | <1% |
United Kingdom | 1 | <1% |
Czechia | 1 | <1% |
Unknown | 181 | 96% |
Demographic breakdown
Readers by professional status | Count | As % |
---|---|---|
Student > Ph. D. Student | 51 | 27% |
Researcher | 43 | 23% |
Student > Master | 24 | 13% |
Professor > Associate Professor | 12 | 6% |
Student > Bachelor | 9 | 5% |
Other | 25 | 13% |
Unknown | 25 | 13% |
Readers by discipline | Count | As % |
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Biochemistry, Genetics and Molecular Biology | 48 | 25% |
Medicine and Dentistry | 14 | 7% |
Chemistry | 5 | 3% |
Neuroscience | 4 | 2% |
Other | 12 | 6% |
Unknown | 30 | 16% |