Signal-dependent control of gluconeogenic key enzyme genes through 
coactivator-associated arginine methyltransferase 1

Krones-Herzig, A.; Mesaros, A.; Metzger, D.; Ziegler, A.; Lemke, U.; Bruning, J. C.; Herzig, S.

doi:10.1074/jbc.M509770200

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Signal-dependent control of gluconeogenic key enzyme genes through coactivator-associated arginine methyltransferase 1

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Mesaros, A.
Phenotyping, Core Facilities, Max Planck Institute for Biology of Ageing, Max Planck Society;

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https://www.ncbi.nlm.nih.gov/pubmed/16330542
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引用

Krones-Herzig, A., Mesaros, A., Metzger, D., Ziegler, A., Lemke, U., Bruning, J. C., & Herzig, S. (2006). Signal-dependent control of gluconeogenic key enzyme genes through coactivator-associated arginine methyltransferase 1. J Biol Chem, 281(6), 3025-9. doi:10.1074/jbc.M509770200.

引用: https://hdl.handle.net/21.11116/0000-000B-7492-D

要旨

Together with impaired glucose uptake in skeletal muscle, elevated hepatic gluconeogenesis is largely responsible for the hyperglycemic phenotype in type II diabetic patients. Intracellular glucocorticoid and cyclic adenosine monophosphate (cAMP)/protein kinase A-dependent signaling pathways contribute to aberrant hepatic glucose production through the induction of gluconeogenic enzyme gene expression. Here we show that the coactivator-associated arginine methyltransferase 1 (CARM1) is required for cAMP-mediated activation of rate-limiting gluconeogenic phosphoenolpyruvate carboxykinase (PEPCK; EC 4.1.1.32) and glucose-6-phosphatase genes. Mutational analysis showed that CARM1 mediates its effect via the cAMP-responsive element within the PEPCK promoter, which is identified here as a CARM1 target in vivo. In hepatocytes, endogenous CARM1 physically interacts with cAMP-responsive element binding factor CREB and is recruited to the PEPCK and glucose-6-phosphatase promoters in a cAMP-dependent manner associated with increased promoter methylation. CARM1 might, therefore, represent a critical component of cAMP-dependent glucose metabolism in the liver.