Negative cyclic AMP response elements in the promoter of the L‐type pyruvate kinase gene

FEBS Letters

Vasseur-Cognet, Mireille¹  Lou, Dan Qing¹  Gourdon, Laurence¹  Raymondjean, Michel¹  Kahn, Axel¹ 

[1] Unité de Recherches en Physiologie et Pathologie Génétiques et Moléculaires, Institut Cochin de Génétique Moléculaire, INSERM Unité 129, 24 rue du Faubourg Saint Jacques, 75014 Paris, France

关键词: L-type pyruvate kinase gene;    Cyclic AMP-dependent inhibition;    Hepatocyte nuclear factor 4;   

DOI  :  10.1016/S0014-5793(99)01203-X

学科分类：生物化学/生物物理

来源: John Wiley & Sons Ltd.

【 摘 要 】

L-type pyruvate kinase gene expression is modulated by hormonal and nutritional conditions. Here, we show by transient transfections in hepatocytes in primary culture that both the glucose response element and the contiguous hepatocyte nuclear factor 4 (HNF4) binding site (L3) of the promoter were negative cyclic AMP (cAMP) response elements and that cAMP-dependent inhibition through L3 requires HNF4 binding. Another HNF4 binding site-dependent construct was also inhibited by cAMP. However, HNF4 mutants whose putative PKA-dependent phosphorylation sites have been mutated still conferred cAMP-sensitive transactivation of a L3-dependent reporter gene. Overexpression of the CREB binding protein (CBP) increased the HNF4-dependent transactivation but this effect remained sensitive to cAMP inhibition.

【 授权许可】

Unknown