A distal region involving hepatocyte nuclear factor 4alpha and CAAT/enhancer binding protein markedly potentiates the protein kinase A stimulation of the glucose-6-phosphatase promoter

Molecular Endocrinology
Amandine Gautier-SteinF Rajas

Abstract

Glucose-6-phosphatase (Glc6Pase) is the last enzyme of gluconeogenesis and is only expressed in the liver, kidney, and small intestine. In these tissues, the mRNA and its activity are increased when cAMP levels increased (e.g. in fasting or diabetes). We first report that a proximal region (within -200 bp relative to the transcription start site) and a distal region (-694/-500 bp) are both required for a potent cAMP and a protein kinase A (PKA) responsiveness of the Glc6Pase promoter. Using different molecular approaches, we demonstrate that hepatocyte nuclear factor (HNF4alpha), CAAT/enhancer-binding protein-alpha (C/EBPalpha), C/EBPbeta, and cAMP response element-binding protein (CREB) are involved in the potentiated PKA responsiveness: in the distal region, via one HNF4alpha- and one C/EBP-binding sites, and in the proximal region, via two HNF4alpha and two CREB-binding sites. We also show that HNF4alpha, C/EBPalpha, and C/EBPbeta are constitutively bound to the endogenous Glc6Pase gene, whereas CREB and CREB-binding protein (CBP) will be bound to the gene upon stimulation by cAMP. These data strongly suggest that the cAMP responsiveness of the Glc6Pase promoter requires a tight cooperation between a proximal and a distal re...Continue Reading

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Citations

Apr 9, 2008·World Journal of Gastroenterology : WJG·Yoshiyuki TakaharaShuhei Nishiguchi
Dec 4, 2014·Comparative Biochemistry and Physiology. Part A, Molecular & Integrative Physiology·Feng GuoRuqian Zhao
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Jan 15, 2015·Neurogastroenterology and Motility : the Official Journal of the European Gastrointestinal Motility Society·F De VadderG Mithieux
Oct 19, 2011·The International Journal of Biochemistry & Cell Biology·Sarawut Jitrapakdee
Sep 10, 2010·Journal of Biosciences·Nirmala Yabaluri, Murali D Bashyam
Apr 8, 2006·Physiological Reviews·Béatrice DesvergneWalter Wahli
Nov 16, 2006·American Journal of Physiology. Endocrinology and Metabolism·Kim B PedersenDonald K Scott
Mar 7, 2009·Molecular Endocrinology·Preeti RamadossAnthony N Hollenberg
Dec 7, 2005·The Journal of Biological Chemistry·Anja Krones-HerzigStephan Herzig
Jul 20, 2021·IScience·Sara FukushimaShin-Ichiro Takahashi

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