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首页> 外文期刊>Proceedings of the National Academy of Sciences of the United States of America >Ligand-dependent interactions of coactivators steroid receptor coactivator-1 and peroxisome proliferator- activated receptor binding protein with nuclear hormone receptors can be imaged in live cells and are required for transcription
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Ligand-dependent interactions of coactivators steroid receptor coactivator-1 and peroxisome proliferator- activated receptor binding protein with nuclear hormone receptors can be imaged in live cells and are required for transcription

机译：共激活因子类固醇受体共激活因子1和过氧化物酶体增殖物激活的受体结合蛋白与核激素受体的配体依赖性相互作用可以在活细胞中成像，并且是转录所必需的

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摘要

Members of the nuclear receptor superfamily are thought to activate transcription by recruitment of one or more recently identified coactivator complexes. Here we demonstrate that both peroxisome proliferator-activated receptor binding protein (PBP) and steroid receptor coactivator-1 (SRC-1) are required for ligand- dependent transcription of transiently transfected and chromo- somally integrated reporter genes by the estrogen receptor (ER) and retinoic acid receptor (RAR). To examine ligand-dependent interactions between nuclear receptors and specific coactivators in living cells, these proteins were tagged with cyan (CFP) and yellow (YFP) mutants of the green fluorescent protein. Fluorescence res- onance energy transfer (FRET) from the CFP to the YFP indicated interaction between the receptor and coactivator. CFP fusions to RAR or its ligand-binding domain exhibited rapid ligand-depen- dent FRET to YFP-tagged nuclear receptor interaction domains of the coactivators SRC-1 and PBP. The ER-ligand-binding domain, unlike RAR, also exhibited some basal interaction with coactivators in unstimulated cells that was aboIished by the receptor antago- nists tamoxifen or ICI182.780. Inhibition of FRET by tamoxifen but not lCl182,780 could be reversed by estradiol. whereas estradiol- enhanced FRET could not be inhibited by either antagonist, indi- cating that ligand effects can show varying degrees of hysteresis. These findings suggest that ligand-dependent transcriptional ac- tivities of the RAR and ER require concurrent or sequential recruit- ment of SRC-1 and PBP-containing coactivator complexes.
机译：核受体超家族成员被认为通过募集一种或多种最近鉴定的共激活复合物来激活转录。在这里，我们证明过氧化物酶体增殖物激活受体结合蛋白（PBP）和类固醇受体共激活因子1（SRC-1）都是雌激素受体（ER）瞬时转染和染色体整合的报告基因配体依赖性转录所必需的和视黄酸受体（RAR）。为了检查活细胞中核受体与特定共激活因子之间的配体依赖性相互作用，将这些蛋白标记为绿色荧光蛋白的青色（CFP）和黄色（YFP）突变体。从CFP到YFP的荧光共振能量转移（FRET）表明受体与共激活剂之间存在相互作用。 CFP与RAR或其配体结合结构域的融合表现出快速的配体依赖性FRET与共激活剂SRC-1和PBP的YFP标记的核受体相互作用结构域。与RAR不同，ER-配体结合域在未刺激的细胞中也表现出与共激活因子的基础相互作用，这被受体拮抗剂他莫昔芬或ICI182.780所废除。他莫昔芬对FRET的抑制作用可被雌二醇逆转，而对lCl182,780则不能。而雌二醇增强的FRET不能被任何一种拮抗剂抑制，这表明配体的作用可以表现出不同程度的滞后作用。这些发现表明，RAR和ER的依赖配体的转录活性需要同时或相继募集SRC-1和含PBP的共激活复合物。

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