In:
Science, American Association for the Advancement of Science (AAAS), Vol. 326, No. 5951 ( 2009-10-16), p. 437-440
Kurzfassung:
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.
Materialart:
Online-Ressource
ISSN:
0036-8075
,
1095-9203
DOI:
10.1126/science.1172156
Sprache:
Englisch
Verlag:
American Association for the Advancement of Science (AAAS)
Publikationsdatum:
2009
ZDB Id:
128410-1
ZDB Id:
2066996-3
ZDB Id:
2060783-0
SSG:
11
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