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Negative cyclic AMP response elements in the promoter of the L‐type pyruvate kinase gene
Author(s) -
Gourdon Laurence,
Lou Dan Qing,
Raymondjean Michel,
Vasseur-Cognet Mireille,
Kahn Axel
Publication year - 1999
Publication title -
febs letters
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.593
H-Index - 257
eISSN - 1873-3468
pISSN - 0014-5793
DOI - 10.1016/s0014-5793(99)01203-x
Subject(s) - transactivation , creb , hepatocyte nuclear factor 4 , creb1 , creb binding protein , protein kinase a , cyclic amp response element binding protein , microbiology and biotechnology , reporter gene , binding site , response element , chemistry , biology , pyruvate kinase , kinase , promoter , gene , gene expression , transcription factor , biochemistry , enzyme , glycolysis , nuclear receptor
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.