DEC1 negatively regulates AMPK activity via LKB1.
DEC1 negatively regulates AMPK activity via LKB1.
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DOI：
10.1016/j.bbrc.2015.10.077
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发表时间：
2015-11-27
影响因子：
3.1
通讯作者：
Zhang Y
中科院分区：
文献类型：
--
作者：
Sato F;Muragaki Y;Zhang Y
碱性螺旋-环-螺旋转录因子DEC1(bHLHE40/Stra13/Sharp2)是生物钟基因之一，在多种组织中具有昼夜节律。AMP激活的蛋白激酶(AMPK)活性在糖耗竭引起的代谢过程和细胞死亡中起重要作用。最近的报道表明，AMPK的活性表现出昼夜节律。然而，关于AMPK活动的昼夜节律所涉及的调控机制却知之甚少。本研究的目的是探讨DEC1的表达与AMPK活性之间是否存在直接的相关性。DEC1蛋白和AMPK活性在小鼠肝脏中呈现不同峰值的昼夜节律。下调DEC1表达可增加AMPK活性，而过表达DEC1则降低AMPK活性。过量表达DEC1碱性突变体对AMPK活性影响不大。DEC1与LKB1启动子的E-box结合，降低了LKB1的活性和总蛋白水平。DEC1表达与AMPK活性呈负相关。我们的结果表明，DEC1通过LKB1负性调节AMPK活性。
Basic helix-loop-helix (bHLH) transcription factor DEC1 (bHLHE40/Stra13/Sharp2) is one of the clock genes that show a circadian rhythm in various tissues. AMP-activated protein kinase (AMPK) activity plays important roles in the metabolic process and in cell death induced by glucose depletion. Recent reports have shown that AMPK activity exhibited a circadian rhythm. However, little is known regarding the regulatory mechanisms involved in the circadian rhythm of AMPK activity. The aim of this study is to investigate whether there is a direct correlation between DEC1 expression and AMPK activity. DEC1 protein and AMPK activity showed a circadian rhythm in the mouse liver with different peak levels. Knocking down DEC1 expression increased AMPK activity, whereas overexpression of DEC1 decreased it. Overexpressing the DEC1 basic mutants had little effect on the AMPK activity. DEC1 bound to the E-box of the LKB1 promoter, decreased LKB1 activity and total protein levels. There was an inverse relationship between DEC1 expression and AMPK activity. Our results suggest that DEC1 negatively regulates AMPK activity via LKB1.