| http://purl.uniprot.org/citations/20670916 | http://www.w3.org/1999/02/22-rdf-syntax-ns#type | http://purl.uniprot.org/core/Journal_Citation |
| http://purl.uniprot.org/citations/20670916 | http://www.w3.org/2000/01/rdf-schema#comment | "Hepatocyte nuclear factor-4 alpha (HNF-4alpha) is a member of the nuclear receptor superfamily with important roles in hepatic metabolism. Fasting induces the cAMP/protein kinase A (PKA)-signaling pathway. The mechanisms whereby cAMP regulates HNF-4alpha transcriptional activity are incompletely understood. We have therefore investigated the role of cAMP/PKA in regulation of HNF-4alpha in COS-1 cells and the hepatoma HepG2 cell line. cAMP/PKA inhibited the transcriptional activity of HNF-4alpha in COS-1 cells, whereas a stimulatory effect was observed in HepG2 cells. The cAMP-induced inhibition of HNF-4alpha in COS-1 cells was counteracted by overexpression of the nuclear receptor coactivator PGC-1alpha, and cAMP/PKA-dependent induction of the PGC1A gene in HepG2 cells seems to explain the cell specific differences. This was further supported by knock-down of PGC-1alpha in HepG2 cells, which abolished the stimulatory effect of PKA on HNF-4alpha transcriptional activity. Similar to the cAMP/PKA-mediated regulation of HNF-4alpha, overexpression of the cAMP-response element binding protein (CREB) inhibited the transcriptional activity of HNF-4alpha in COS-1 cells, regardless of cAMP/PKA activation and CREB phosphorylation. Moreover, activation of CREB by cAMP/PKA further stimulated HNF-4alpha transactivation in HepG2 cells. cAMP induced the expression of the HNF-4alpha target genes PCK1 and G6Pase in these cells. In conclusion, our results suggest that the level of PGC-1alpha determines whether the cAMP/PKA-pathway overall stimulates or inhibits HNF-4alpha transcriptional activation."xsd:string |
| http://purl.uniprot.org/citations/20670916 | http://purl.org/dc/terms/identifier | "doi:10.1016/j.bbamcr.2010.05.008"xsd:string |
| http://purl.uniprot.org/citations/20670916 | http://purl.uniprot.org/core/author | "Hoang T."xsd:string |
| http://purl.uniprot.org/citations/20670916 | http://purl.uniprot.org/core/author | "Sagen J.V."xsd:string |
| http://purl.uniprot.org/citations/20670916 | http://purl.uniprot.org/core/author | "Dankel S.N."xsd:string |
| http://purl.uniprot.org/citations/20670916 | http://purl.uniprot.org/core/author | "Mellgren G."xsd:string |
| http://purl.uniprot.org/citations/20670916 | http://purl.uniprot.org/core/author | "Flageng M.H."xsd:string |
| http://purl.uniprot.org/citations/20670916 | http://purl.uniprot.org/core/date | "2010"xsd:gYear |
| http://purl.uniprot.org/citations/20670916 | http://purl.uniprot.org/core/name | "Biochim Biophys Acta"xsd:string |
| http://purl.uniprot.org/citations/20670916 | http://purl.uniprot.org/core/pages | "1013-1019"xsd:string |
| http://purl.uniprot.org/citations/20670916 | http://purl.uniprot.org/core/title | "cAMP-mediated regulation of HNF-4alpha depends on the level of coactivator PGC-1alpha."xsd:string |
| http://purl.uniprot.org/citations/20670916 | http://purl.uniprot.org/core/volume | "1803"xsd:string |
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