TRRAP as a hepatic coactivator of LXR and FXR function.
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.
Unno
Atsushi
A
Institute of Molecular and Cellular Biosciences, University of Tokyo, Yayoi, Bunkyo-ku, Tokyo 113-0032, Japan.
Takada
Ichiro
I
Takezawa
Shinichiro
S
Oishi
Hajime
H
Baba
Atsushi
A
Shimizu
Takafumi
T
Tokita
Akifumi
A
Yanagisawa
Junn
J
Kato
Shigeaki
S
D048868:Adaptor Proteins, Signal Transducing; D001647:Bile Acids and Salts / Q000378:metabolism; D004268:DNA-Binding Proteins / Q000235:genetics / Q000378:metabolism*; D005786:Gene Expression Regulation; D008024:Ligands; D050356:Lipid Metabolism; D008099:Liver / Q000378:metabolism*; D000071518:Liver X Receptors; D009687:Nuclear Proteins / Q000235:genetics / Q000378:metabolism / Q000502:physiology*; D057093:Orphan Nuclear Receptors; D047495:PPAR gamma / Q000378:metabolism; D018160:Receptors, Cytoplasmic and Nuclear / Q000235:genetics / Q000378:metabolism*; D014157:Transcription Factors / Q000235:genetics / Q000378:metabolism*; D015533:Transcriptional Activation; D000099150:Receptor, Farnesoid X-Activated
D048868:Adaptor Proteins, Signal Transducing; D001647:Bile Acids and Salts; D004268:DNA-Binding Proteins; D008024:Ligands; D000071518:Liver X Receptors; D009687:Nuclear Proteins; D057093:Orphan Nuclear Receptors; D047495:PPAR gamma; D018160:Receptors, Cytoplasmic and Nuclear; D014157:Transcription Factors; D000099150:Receptor, Farnesoid X-Activated; C113829:transformation-transcription domain-associated protein