TRRAP as a hepatic coactivator of LXR and FXR function.
TRRAP as a hepatic coactivator of LXR and FXR function.
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DOI：
10.1016/j.bbrc.2004.12.095
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发表时间：
2005-02
影响因子：
3.1
通讯作者：
A. Unno;I. Takada;Shin‐ichiro Takezawa;H. Oishi;A. Baba;Takafumi Shimizu;A. Tokita;J. Yanagisawa;S. Kato
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文献类型：
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作者：
A. Unno;I. Takada;Shin‐ichiro Takezawa;H. Oishi;A. Baba;Takafumi Shimizu;A. Tokita;J. Yanagisawa;S. Kato
不含TBP的TAFⅡ类含hGCN5 HAT和TRRAP的HAT复合体是常见的核受体共激活复合体。然而，它们对每个核受体的生理意义仍有待确定。为了解决这个问题，我们使用了通过反义RNA表达或TRRAP过表达或其他主要辅助激活因子降低内源性TRRAP表达的肝细胞株(HepG2)。配体诱导的肝X受体α(LXRα)和法尼醇X受体/胆汁酸受体的反式激活功能反映了TRRAP的表达水平，而PPARγ不能反映TRRAP的表达水平。GST下拉分析表明，TRRAP在C-末端和中央区域含有两个潜在的LXRα相互作用结构域。反义TRRAP RNA在细胞中的表达可阻断配体诱导的LXRα靶基因表达。这些结果表明，TRRAP作为辅助激活剂，可能是复合体的一部分，通过调节肝细胞中LXRα介导的基因级联，在脂质代谢中发挥重要作用。
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 α (LXRα) and farnesoid X receptor/bile acid receptor reflected TRRAP expression levels, while that of PPARγ did not. A GST pull-down assay indicated that TRRAP contains two potential LXRα-interacting domains in the C-terminal and central domains. Expression of antisense TRRAP RNA in HepG2 cells abolished the ligand-induced expression of LXRα 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 LXRα-mediated gene cascade in hepatic cells.