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  • Title: Circadian modification network of a core clock driver BMAL1 to harmonize physiology from brain to peripheral tissues.
    Author: Tamaru T, Takamatsu K.
    Journal: Neurochem Int; 2018 Oct; 119():11-16. PubMed ID: 29305918.
    Abstract:
    Circadian clocks dictate various physiological functions by brain SCN (a central clock) -orchestrating the temporal harmony of peripheral clocks of tissues/organs in the whole body, with adaptability to environments by resetting their timings. Dysfunction of this circadian adaptation system (CAS) occasionally causes/exacerbates diseases. CAS is based on cell-autonomous molecular clocks, which oscillate via a core transcriptional/translational feedback loop with clock genes/proteins, e.g., BMAL1: CLOCK circadian transcription driver and CRY1/2 and PER1/2 suppressors, and is modulated by various regulatory loops including clock protein modifications. Among mutants with a single clock gene, BMAL1-deficient mice exhibit the most drastic loss of circadian functions. Here, we highlight on numerous circadian protein modifications of mammalian BMAL1, e.g., multiple phosphorylations, SUMOylation, ubiquitination, acetylation, O-GlcNAcylation and S-nitrosylation, which mutually interplay to control molecular clocks and coordinate physiological functions from the brain to peripheral tissues through the input and output of the clocks.
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