PMID:19833968

Citation	Lamia, KA, Sachdeva, UM, DiTacchio, L, Williams, EC, Alvarez, JG, Egan, DF, Vasquez, DS, Juguilon, H, Panda, S, Shaw, RJ, Thompson, CB and Evans, RM (2009) AMPK regulates the circadian clock by cryptochrome phosphorylation and degradation. Science 326:437-40
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.
Links	PubMed PMC2819106 Online version:10.1126/science.1172156
Keywords	AMP-Activated Protein Kinases/metabolism; ARNTL Transcription Factors; Amino Acid Substitution; Aminoimidazole Carboxamide/analogs & derivatives; Aminoimidazole Carboxamide/pharmacology; Animals; Basic Helix-Loop-Helix Transcription Factors/genetics; Cell Line; Cell Nucleus/metabolism; Cells, Cultured; Circadian Rhythm/physiology; Cryptochromes; Culture Media; Flavoproteins/genetics; Flavoproteins/metabolism; Food; Glucose/metabolism; Glucose/pharmacology; Humans; Liver/metabolism; Mice; Mutagenesis, Site-Directed; Mutant Proteins/metabolism; Phosphorylation; Promoter Regions, Genetic; Protein Stability; Recombinant Fusion Proteins/metabolism; Ribonucleotides/pharmacology; Signal Transduction
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Annotations

Gene product	Qualifier	GO Term	Evidence Code	with/from	Aspect	Extension	Notes	Status
MOUSE:CRY1	enables	GO:0019901: protein kinase binding	ECO:0000353: physical interaction evidence used in manual assertion	UniProtKB:Q8BRK8	F		Seeded From UniProt	complete
MOUSE:CRY1	enables	GO:0019901: protein kinase binding	ECO:0000353: physical interaction evidence used in manual assertion	UniProtKB:Q5EG47	F		Seeded From UniProt	complete
MOUSE:CRY1	involved_in	GO:0042752: regulation of circadian rhythm	ECO:0000315: mutant phenotype evidence used in manual assertion		P		Seeded From UniProt	complete
MOUSE:AAPK1	enables	GO:0005515: protein binding	ECO:0000353: physical interaction evidence used in manual assertion	UniProtKB:P97784	F		Seeded From UniProt	complete
MOUSE:AAPK2	enables	GO:0005515: protein binding	ECO:0000353: physical interaction evidence used in manual assertion	UniProtKB:P97784	F		Seeded From UniProt	complete
MOUSE:AAPK2	enables	GO:0004679: AMP-activated protein kinase activity	ECO:0000314: direct assay evidence used in manual assertion		F		Seeded From UniProt	complete
MOUSE:AAPK2	involved_in	GO:0042752: regulation of circadian rhythm	ECO:0000315: mutant phenotype evidence used in manual assertion		P		Seeded From UniProt	complete
MOUSE:AAPK1	part_of	GO:0005634: nucleus	ECO:0000314: direct assay evidence used in manual assertion		C		Seeded From UniProt	complete
MOUSE:AAPK1	enables	GO:0004679: AMP-activated protein kinase activity	ECO:0000314: direct assay evidence used in manual assertion		F		Seeded From UniProt	complete
MOUSE:AAPK1	involved_in	GO:0042752: regulation of circadian rhythm	ECO:0000315: mutant phenotype evidence used in manual assertion		P		Seeded From UniProt	complete

References

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