Transcription coactivator TRAP220 is required for PPARγ2-stimulated adipogenesis
Transcription coactivator TRAP220 is required for PPARγ2-stimulated adipogenesis
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DOI：
10.1038/417563a
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发表时间：
2002-05-30
期刊：
影响因子：
64.8
通讯作者：
Roeder, RG
中科院分区：
文献类型：
--
作者：
Ge, K;Guermah, M;Roeder, RG
TRAP（甲状腺激素受体相关蛋白）转录辅激活因子复合物（也称为介体）首先被分离为一组促进甲状腺激素受体功能的蛋白质（1）。该复合物通过TRAP 220亚基与几种核受体物理相互作用，并通过其他亚基与不同的激活剂相互作用（2）。据报道，TRAP 220显示出配体增强的与过氧化物酶体增殖物激活受体γ（2）（PPARgamma 2）（3，4）的相互作用，该受体是脂肪形成所必需的核受体（5-8）。在这里，我们发现Trap 220（-/-）成纤维细胞对PPARgamma（2-）刺激的脂肪生成不敏感，但对MyoD刺激的肌生成不敏感，并且不表达脂肪生成标志物或PPARgamma 2靶基因。这些缺陷可以通过表达外源性TRAP 220来恢复。进一步表明TRAP 220通过TRAP复合物在PPARgamma 2功能中的直接作用，TRAP在纯化的体外系统中直接作为PPARgamma 2的转录共激活因子发挥作用，并以配体和TRAP 220依赖性方式与PPARgamma 2相互作用。这些数据表明，TRAP 220通过TRAP复合物作为PPARgamma 2选择性共激活剂起作用，因此，相对于另一种成纤维细胞分化途径（肌生成），它对一种成纤维细胞分化途径（脂肪生成）具有特异性。
The TRAP (thyroid hormone receptor-associated proteins) transcription coactivator complex (also known as Mediator) was first isolated as a group of proteins that facilitate the function of the thyroid hormone receptor(1). This complex interacts physically with several nuclear receptors through the TRAP220 subunit, and with diverse activators through other subunits(2). TRAP220 has been reported to show ligand-enhanced interaction with peroxisome proliferator-activated receptor gamma(2) (PPARgamma2)(3,4),a nuclear receptor essential for adipogenesis(5-8). Here we show that Trap220(-/-) fibroblasts are refractory to PPARgamma(2-)stimulated adipogenesis, but not to MyoD-stimulated myogenesis, and do not express adipogenesis markers or PPARgamma2 target genes. These defects can be restored by expression of exogenous TRAP220. Further indicative of a direct role for TRAP220 in PPARgamma2 function via the TRAP complex, TRAP functions directly as a transcriptional coactivator for PPARgamma2 in a purified in vitro system and interacts with PPARgamma2 in a ligand- and TRAP220-dependent manner. These data indicate that TRAP220 acts, via the TRAP complex, as a PPARgamma2-selective coactivator and, accordingly, that it is specific for one fibroblast differentiation pathway (adipogenesis) relative to another (myogenesis).