AMP-activated protein kinase regulates PEPCK gene expression by direct phosphorylation of a novel zinc finger transcription factor

作     者：Inoue, Erina Yamauchi, Jun 

作者机构：Natl Inst Hlth & Nutr Bio Index Project Nutrit Epidemiol Program Bioindex ProjectShinjyuku Tokyo 1628636 Japan 

出 版 物：《BIOCHEMICAL AND BIOPHYSICAL RESEARCH COMMUNICATIONS》 (生物化学与生物物理学研究通讯)

年 卷 期：2006年第351卷第4期

页      面：793-799页

核心收录：

学科分类：0710[理学-生物学] 071010[理学-生物化学与分子生物学] 07[理学] 

基　　金：Ministry of Education  Culture  Sports  Science and Technology  MEXT  (17680106) 

主　　题：AMPK PEPCK gluconeogenesis zinc finger transcription RNAi 

摘      要：AMP-activated protein kinase (AMPK) acts as an intracellular sensor for maintaining the energy balance. Activation of AMPK switches on ATP-generating process while switches off ATP-consuming process. It achieves these effects by phosphorylation of downstream metabolic enzymes. It has been proposed that AMPK also regulates gene expression through phosphorylation of certain transcription factors;however its molecular mechanism is not fully understood. Here we show the cloning and characterization of a novel zinc finger transcription factor referred to as AREBP. AREBP is phosphorylated at Ser(470) by AMPK. Phosphorylation reduces he DNA-binding activity of AREBP. Transient transfection experiments indicate that wild-type AREBP, but not Ser(470) to Ala(470) substituted non-phosphorylating mutant, represses gene expression of the phosphoenolpyruvate carboxykinase (PEPCK), a key enzyme of gluconeogenesis. RNA interference-mediated reduction of endogenous AREBP expression attenuates AMPK-induced PEPCK down-regulation. These results implicate AREBP as a novel key modulator of PEPCK gene expression regulated by AMPK. (c) 2006 Elsevier Inc. All rights reserved.