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TRRAP as a hepatic coactivator of LXR and FXR function
- Source :
- Biochemical and Biophysical Research Communications. 327:933-938
- Publication Year :
- 2005
- Publisher :
- Elsevier BV, 2005.
-
Abstract
- TBP-free TAF II-containing-type HAT complex subclasses, which contain hGCN5 HAT and TRRAP, appear to act as common coactivator complexes for nuclear receptors. However, their physiological significance with respect to each nuclear receptor remains to be established. To address this issue, we used hepatic cell lines (HepG2) with reduced endogenous TRRAP expression through antisense RNA expression or with overexpressed TRRAP or other major coactivators. The ligand-induced transactivation function of liver X receptor alpha (LXRalpha) and farnesoid X receptor/bile acid receptor reflected TRRAP expression levels, while that of PPARgamma did not. A GST pull-down assay indicated that TRRAP contains two potential LXRalpha-interacting domains in the C-terminal and central domains. Expression of antisense TRRAP RNA in HepG2 cells abolished the ligand-induced expression of LXRalpha target genes. These results suggested that TRRAP plays an important role as a coactivator, presumably part of a complex, in lipid metabolism through regulation of the LXRalpha-mediated gene cascade in hepatic cells.
- Subjects :
- Transcriptional Activation
Biophysics
Receptors, Cytoplasmic and Nuclear
Biology
Ligands
Biochemistry
Bile Acids and Salts
Transactivation
Coactivator
Liver X receptor
Molecular Biology
Adaptor Proteins, Signal Transducing
Liver X Receptors
Regulation of gene expression
Nuclear Proteins
Liver X receptor alpha
Cell Biology
Lipid Metabolism
Orphan Nuclear Receptors
G protein-coupled bile acid receptor
DNA-Binding Proteins
PPAR gamma
Gene Expression Regulation
Liver
Nuclear receptor
Cancer research
lipids (amino acids, peptides, and proteins)
Farnesoid X receptor
Transcription Factors
Subjects
Details
- ISSN :
- 0006291X
- Volume :
- 327
- Database :
- OpenAIRE
- Journal :
- Biochemical and Biophysical Research Communications
- Accession number :
- edsair.doi.dedup.....148d6892f979850c79a676dd78b03d6b