AMPK Regulates the Circadian Clock by Cryptochrome Phosphorylation and Degradation Export

@article{citeulike:5961163, 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. 10.1126/science.1172156}, author = {Lamia, Katja A. and Sachdeva, Uma M. and DiTacchio, Luciano and Williams, Elliot C. and Alvarez, Jacqueline G. and Egan, Daniel F. and Vasquez, Debbie S. and Juguilon, Henry and Panda, Satchidananda and Shaw, Reuben J. and Thompson, Craig B. and Evans, Ronald M.}, citeulike-article-id = {5961163}, citeulike-linkout-0 = {http://dx.doi.org/10.1126/science.1172156}, citeulike-linkout-1 = {http://www.sciencemag.org/content/326/5951/437.abstract}, citeulike-linkout-2 = {http://www.sciencemag.org/content/326/5951/437.full.pdf}, citeulike-linkout-3 = {http://view.ncbi.nlm.nih.gov/pubmed/19833968}, citeulike-linkout-4 = {http://www.hubmed.org/display.cgi?uids=19833968}, day = {16}, doi = {10.1126/science.1172156}, journal = {Science}, keywords = {ampk, circadian, circadian\_clock, clock, cry1, food\_nutrition, metabolism}, month = {October}, number = {5951}, pages = {437--440}, posted-at = {2009-11-04 18:05:35}, priority = {2}, title = {AMPK Regulates the Circadian Clock by Cryptochrome Phosphorylation and Degradation}, url = {http://dx.doi.org/10.1126/science.1172156}, volume = {326}, year = {2009} }

TY - JOUR ID - citeulike:5961163 L3 - citeulike-article-id:5961163 N2 - 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. 10.1126/science.1172156 IS - 5951 JF - Science EP - 440 TI - AMPK Regulates the Circadian Clock by Cryptochrome Phosphorylation and Degradation VL - 326 SP - 437 KW - ampk KW - circadian KW - circadian_clock KW - clock KW - cry1 KW - food_nutrition KW - metabolism AU - Lamia, Katja AU - Sachdeva, Uma AU - DiTacchio, Luciano AU - Williams, Elliot AU - Alvarez, Jacqueline AU - Egan, Daniel AU - Vasquez, Debbie AU - Juguilon, Henry AU - Panda, Satchidananda AU - Shaw, Reuben AU - Thompson, Craig AU - Evans, Ronald PY - 2009/10/16/ UR - http://dx.doi.org/10.1126/science.1172156 ER -