期刊
MOLECULAR AND CELLULAR ENDOCRINOLOGY
卷 366, 期 2, 页码 163-169出版社
ELSEVIER IRELAND LTD
DOI: 10.1016/j.mce.2012.06.017
关键词
Circadian; Metabolism; AMPK
资金
- NIDDK NIH HHS [K01 DK090188] Funding Source: Medline
Circadian clocks coordinate behavior and physiology with daily environmental cycles and thereby optimize the timing of metabolic processes such as glucose production and insulin secretion. Such circadian regulation of metabolism provides an adaptive advantage in diverse organisms. Mammalian clocks are primarily based on a transcription and translation feedback loop in which a heterodimeric complex of the transcription factors CLOCK (circadian locomotor output cycles kaput) and BMAL1 (brain and muscle Arnt-like protein 1) activates the expression of its own repressors, the period (PER1-3) and cryptochrome (CRY1 and CRY2) proteins. Posttranslational modification of these core clock components is critical for setting clock time or adjusting the speed of the clock. AMP-activated protein kinase (AMPK) is one of several metabolic sensors that have been reported to transmit energy-dependent signals to the mammalian clock. AMPK does so by driving the phosphorylation and destabilization of CRY and PER proteins. In addition, AMPK subunit composition, sub-cellular localization, and substrate phosphorylation are dependent on clock time. Given the well-established role of AMPK in diverse aspects of metabolic physiology, the reciprocal regulation of AMPK and circadian clocks likely plays an important role in circadian metabolic regulation. (C) 2012 Elsevier Ireland Ltd. All rights reserved.
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