Gene/Protein
Disease
Symptom
Drug
Enzyme
Compound
Pivot Concepts:
Gene/Protein
Disease
Symptom
Drug
Enzyme
Compound
Target Concepts:
Gene/Protein
Disease
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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)
SHP (small heterodimer partner; NR0B2) is an atypical orphan NR (nuclear receptor) that functions as a transcriptional co-repressor by interacting with a diverse set of NRs and transcriptional factors.
HNF-6
(hepatocyte nuclear factor-6) is a key regulatory factor in pancreatic development, endocrine differentiation and the formation of the biliary tract, as well as glucose metabolism. In this study, we have investigated the function of SHP as a putative repressor of
HNF-6
. Using transient transfection assays, we have shown that SHP represses the transcriptional activity of
HNF-6
. Confocal microscopy revealed that both SHP and
HNF-6
co-localize in the nuclei of cells. SHP physically interacted with
HNF-6
in protein-protein association assays in vitro. EMSAs (electrophoretic mobility-shift assays) and ChIP (chromatin immunoprecipitation) assays demonstrated that SHP inhibits the DNA-binding activity of
HNF-6
to an
HNF-6
-response element consensus sequence, and the
HNF-6
target region of the endogenous G6Pase (glucose 6-phosphatase) promoter respectively. Northern blot analysis of
HNF-6
target genes in cells infected with adenoviral vectors for SHP and SHP siRNAs (small inhibitory RNAs) indicated that SHP represses the expression of endogenous G6Pase and PEPCK (
phosphoenolpyruvate carboxykinase
). Our results suggest that
HNF-6
is a novel target of SHP in the regulation of gluconeogenesis.
...
PMID:Orphan nuclear receptor SHP interacts with and represses hepatocyte nuclear factor-6 (HNF-6) transactivation. 1845 45
