AMPK regulates the circadian clock by cryptochrome phosphorylation and degradation. Science (New York, N.Y.) [Science] Journal article

Title	AMPK regulates the circadian clock by cryptochrome phosphorylation and degradation.
Author(s)	Lamia KA, Sachdeva UM, DiTacchio L, Williams EC, Alvarez JG, Egan DF, Vasquez DS, Juguilon H, Panda S, Shaw RJ, Thompson CB, Evans RM
Institution	Gene Expression Laboratory, the Salk Institute, La Jolla, CA 92037, USA.
Source	Science 2009 Oct 16; 326(5951):437-40.
MeSH	AMP-Activated Protein Kinases Amino Acid Substitution Aminoimidazole Carboxamide Animals Basic Helix-Loop-Helix Transcription Factors Cell Line Cell Nucleus Cells, Cultured Circadian Rhythm Culture Media Flavoproteins Food Glucose Humans Liver Mice Mutagenesis, Site-Directed Mutant Proteins Phosphorylation Promoter Regions, Genetic Protein Stability Recombinant Fusion Proteins Ribonucleotides Signal Transduction
Abstract	Circadian clocks coordinate behavioral and physiological processes with daily light-dark cycles by driving rhythmic transcription of thousands of genes. Whereas the master clock in the brain is set by light, pacemakers in peripheral organs, such as the liver, are reset by food availability, although the setting, or "entrainment," mechanisms remain mysterious. Studying mouse fibroblasts, we demonstrated that the nutrient-responsive adenosine monophosphate-activated protein kinase (AMPK) phosphorylates and destabilizes the clock component cryptochrome 1 (CRY1). In mouse livers, AMPK activity and nuclear localization were rhythmic and inversely correlated with CRY1 nuclear protein abundance. Stimulation of AMPK destabilized cryptochromes and altered circadian rhythms, and mice in which the AMPK pathway was genetically disrupted showed alterations in peripheral clocks. Thus, phosphorylation by AMPK enables cryptochrome to transduce nutrient signals to circadian clocks in mammalian peripheral organs.
Language	eng
Pub Type(s)	Journal Article Research Support, N.I.H., Extramural Research Support, Non-U.S. Gov't
PubMed ID	19833968

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