DEC1 negatively regulates AMPK activity via LKB1.
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.
Department of Radiation Oncology and Lineberger Comprehensive Cancer Center, School of Medicine, University of North Carolina at Chapel Hill, Chapel Hill, NC 27514, USA; Department of Pathology, Wakayama Medical University School of Medicine, Wakayama 641-8509, Japan. Electronic address: fsatoDEC1DEC2@yahoo.co.jp.
Fuyuki
F
Sato
Department of Pathology, Wakayama Medical University School of Medicine, Wakayama 641-8509, Japan.
Yasuteru
Y
Muragaki
Department of Radiation Oncology and Lineberger Comprehensive Cancer Center, School of Medicine, University of North Carolina at Chapel Hill, Chapel Hill, NC 27514, USA; Jiangsu Center for the Collaboration and Innovation of Cancer Biotherapy, Cancer Institute, Xuzhou Medical College, Xuzhou, Jiangsu 221002, China. Electronic address: ypzhang@med.unc.edu.
Yanping
Y
Zhang
D055372:AMP-Activated Protein Kinases; D000263:Adenylate Kinase / Q000378:metabolism*; D000818:Animals; D051792:Basic Helix-Loop-Helix Proteins / Q000502:physiology*; D002460:Cell Line; D002940:Circadian Rhythm; D018398:Homeodomain Proteins / Q000502:physiology*; D006801:Humans; D008099:Liver / Q000201:enzymology / Q000378:metabolism / Q000502:physiology; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D011401:Promoter Regions, Genetic; D017346:Protein Serine-Threonine Kinases / Q000235:genetics / Q000378:metabolism*
D055372:AMP-Activated Protein Kinases; D000263:Adenylate Kinase; D051792:Basic Helix-Loop-Helix Proteins; D018398:Homeodomain Proteins; D017346:Protein Serine-Threonine Kinases; C491539:Bhlhe40 protein, mouse; C491654:Stk11 protein, mouse
AMPK; Clock gene; DEC1; LKB1