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首页> 外文期刊>Molecular and Cellular Biology >Alien, a Highly Conserved Protein with Characteristics of a Corepressor for Members of the Nuclear Hormone Receptor Superfamily
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Alien, a Highly Conserved Protein with Characteristics of a Corepressor for Members of the Nuclear Hormone Receptor Superfamily

机译:外星人,一种高度保守的蛋白质,具有核激素受体超家族成员的corepressor特征

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Some members of nuclear hormone receptors, such as the thyroid hormone receptor (TR), silence gene expression in the absence of the hormone. Corepressors, which bind to the receptor’s silencing domain, are involved in this repression. Hormone binding leads to dissociation of corepressors and binding of coactivators, which in turn mediate gene activation. Here, we describe the characteristics of Alien, a novel corepressor. Alien interacts with TR only in the absence of hormone. Addition of thyroid hormone leads to dissociation of Alien from the receptor, as shown by the yeast two-hybrid system, glutathioneS-transferase pull-down, and coimmunoprecipitation experiments. Reporter assays indicate that Alien increases receptor-mediated silencing and that it harbors an autonomous silencing function. Immune staining shows that Alien is localized in the cell nucleus. Alien is a highly conserved protein showing 90% identity between human and Drosophila. Drosophila Alien shows similar activities in that it interacts in a hormone-sensitive manner with TR and harbors an autonomous silencing function. Specific interaction of Alien is seen with Drosophila nuclear hormone receptors, such as the ecdysone receptor and Seven-up, the Drosophila homologue of COUP-TF1, but not with retinoic acid receptor, RXR/USP, DHR 3, DHR 38, DHR 78, or DHR 96. These properties, taken together, show that Alien has the characteristics of a corepressor. Thus, Alien represents a member of a novel class of corepressors specific for selected members of the nuclear hormone receptor superfamily.
机译:核激素受体的某些成员,例如甲状腺激素受体(TR),在没有激素的情况下沉默基因表达。与受体的沉默结构域结合的共抑制因子参与了这种抑制。激素的结合导致了corepressor的解离和coactivator的结合,进而介导了基因激活。在这里,我们描述了新型压纸机Alien的特征。外星人只有在没有激素的情况下才与TR相互作用。酵母双杂交系统,谷胱甘肽 S -转移酶下拉和共免疫沉淀实验表明,添加甲状腺激素会导致外星人与受体解离。记者分析表明,外星人会增加受体介导的沉默,并具有自主沉默功能。免疫染色显示外星人位于细胞核中。外星人是一种高度保守的蛋白质,在人和果蝇之间显示出90%的同一性。果蝇外星人也表现出类似的活动,因为它以激素敏感的方式与TR相互作用,并具有自主的沉默功能。外星人与果蝇核苷受体,如蜕皮激素受体和COUP-TF1的果蝇同源物Seven-up和Seven-up有特异性相互作用,但与视黄酸受体,RXR / USP,DHR 3没有相互作用,DHR 38,DHR 78或DHR96。这些属性加在一起,表明Alien具有镇压器的特性。因此,外星人代表新的一类针对核心激素受体超家族的选定成员的共生抑制剂的成员。

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