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Publication : Phosphorylation Is a Central Mechanism for Circadian Control of Metabolism and Physiology.

First Author  Robles MS Year  2017
Journal  Cell Metab Volume  25
Issue  1 Pages  118-127
PubMed ID  27818261 Mgi Jnum  J:256620
Mgi Id  MGI:6107127 Doi  10.1016/j.cmet.2016.10.004
Citation  Robles MS, et al. (2017) Phosphorylation Is a Central Mechanism for Circadian Control of Metabolism and Physiology. Cell Metab 25(1):118-127
abstractText  Circadian clocks are self-sustainable endogenous oscillators, present in virtually every cell, driving daily cycles of metabolism and physiology. The molecular mechanism of the circadian clock is based on interconnected transcriptional and translational feedback loops. While many studies have addressed circadian rhythms of the transcriptome and, to a lesser extent, the proteome, none have investigated the phosphoproteome. We apply mass spectrometry-based phosphoproteomics to obtain the first global in vivo quantification of circadian phosphorylation in mammals. Of more than 20,000 phosphosites, 25% significantly oscillate in the mouse liver, including novel sites on core clock proteins. The extent and amplitude of phosphorylation cycles far exceeds those observed in RNA and protein abundance. Our data indicate a dominant regulatory role for phosphorylation-dependent circadian tuning of signaling pathways. This allows the organism to integrate different signals and rapidly and economically respond to daily changes in nutrient availability and physiological states.
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