Sterol Regulatory Element-binding Protein-1c Mimics the Negative Effect of Insulin on Phosphoenolpyruvate Carboxykinase (GTP) Gene Transcription - Université Pierre et Marie Curie Accéder directement au contenu
Article Dans Une Revue Journal of Biological Chemistry Année : 2001

Sterol Regulatory Element-binding Protein-1c Mimics the Negative Effect of Insulin on Phosphoenolpyruvate Carboxykinase (GTP) Gene Transcription

Kaushik Chakravarty
  • Fonction : Auteur
Patrick Leahy
  • Fonction : Auteur
Dominique Becard
  • Fonction : Auteur
Parvin Hakimi
  • Fonction : Auteur
Marc Foretz
Richard Hanson
  • Fonction : Auteur

Résumé

We have assessed the potential role of sterol regulatory element-binding protein-1c (SREBP-1c) on the transcription of the gene for the cytosolic form of phosphoenolpyruvate carboxykinase (GTP) (EC ) (PEPCK-C). SREBP-1c introduced into primary hepatocytes with an adenovirus vector caused a total loss of PEPCK-C mRNA and a marked induction of fatty acid synthase mRNA that directly coincided with the appearance of SREBP-1c in the hepatocytes. It also blocked the induction of PEPCK-C mRNA by cAMP and dexamethasone in these cells. In contrast, a dominant negative form of SREBP-1c (dnSREBP-1c) stimulated the accumulation of PEPCK-C mRNA in these cells. SREBP-1c completely blocked the induction of PEPCK-C gene transcription by the catalytic subunit of protein kinase A (PKA), and increasing concentrations of dnSREBP-1c reversed the negative effect of insulin on transcription from the PEPCK-C gene promoter in WT-IR cells. The more than 10-fold induction of PKA-stimulated PEPCK-C gene transcription caused by the co-activator CBP, was also blocked by SREBP-1c. In addition, dnSREBP-1c reversed the strong negative effect of E1A and NF1 on PKA-stimulated transcription from the PEPCK-C gene promoter. An analysis of the possible site of action of SREBP-1c using stepwise truncations of the PEPCK-C gene promoter indicated that the negative effect of SREBP-1c on transcription is exerted at a site between -355 and -277. We conclude that SREBP-1c is an intermediate in the action of insulin on PEPCK-C gene transcription in the liver and acts by blocking the stimulatory effect cAMP that is mediated via an interaction with cAMP-binding protein.

Dates et versions

hal-02546621 , version 1 (18-04-2020)

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Citer

Kaushik Chakravarty, Patrick Leahy, Dominique Becard, Parvin Hakimi, Marc Foretz, et al.. Sterol Regulatory Element-binding Protein-1c Mimics the Negative Effect of Insulin on Phosphoenolpyruvate Carboxykinase (GTP) Gene Transcription. Journal of Biological Chemistry, 2001, 276 (37), pp.34816-34823. ⟨10.1074/jbc.M103310200⟩. ⟨hal-02546621⟩
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