Gene/Protein
Disease
Symptom
Drug
Enzyme
Compound
Pivot Concepts:
Gene/Protein
Disease
Symptom
Drug
Enzyme
Compound
Target Concepts:
Gene/Protein
Disease
Symptom
Drug
Enzyme
Compound
Query: EC:4.1.1.32 (
phosphoenolpyruvate carboxykinase
)
4,204
document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)
DAX-1
(dosage-sensitive sex reversal adrenal hypoplasia congenital critical region on X chromosome, gene 1) is an atypical member of the nuclear receptor family and acts as a corepressor of a number of nuclear receptors. HNF4alpha (hepatocyte nuclear factor 4alpha) is a liver-enriched transcription factor that controls the expression of a variety of genes involved in cholesterol, fatty acid, and glucose metabolism. Here we show that
DAX-1
inhibits transcriptional activity of HNF4alpha and modulates hepatic gluconeogenic gene expression. Hepatic
DAX-1
expression is increased by insulin and SIK1 (salt-inducible kinase 1), whereas it is decreased in high fat diet-fed and diabetic mice. Coimmunoprecipitation assay from mouse liver samples depicts that endogenous
DAX-1
interacts with HNF4alpha in vivo. In vivo chromatin immunoprecipitation assay affirms that the recruitment of
DAX-1
on the
phosphoenolpyruvate carboxykinase
(
PEPCK
) gene promoter is inversely correlated with the recruitment of PGC-1alpha and HNF4alpha under fasting and refeeding, showing that
DAX-1
could compete with the coactivator PGC-1alpha for binding to HNF4alpha. Adenovirus-mediated expression of
DAX-1
decreased both HNF4alpha- and forskolin-mediated gluconeogenic gene expressions. In addition, knockdown of
DAX-1
partially reverses the insulin-mediated inhibition of gluconeogenic gene expression in primary hepatocytes. Finally,
DAX-1
inhibits
PEPCK
and glucose-6-phosphatase gene expression and significantly lowers fasting blood glucose level in high fat diet-fed mice, suggesting that
DAX-1
can modulate hepatic gluconeogenesis in vivo. Overall, this study demonstrates that
DAX-1
acts as a corepressor of HNF4alpha to negatively regulate hepatic gluconeogenic gene expression in liver.
...
PMID:DAX-1 acts as a novel corepressor of orphan nuclear receptor HNF4alpha and negatively regulates gluconeogenic enzyme gene expression. 1965 76
