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首页> 外文期刊>Molecular and Cellular Biology >Role of the Ada adaptor complex in gene activation by the glucocorticoid receptor.
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Role of the Ada adaptor complex in gene activation by the glucocorticoid receptor.

机译：Ada接头复合物在糖皮质激素受体基因激活中的作用。

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We have shown that the Ada adaptor complex is important for the gene activation capacity of the glucocorticoid receptor in yeast. The recently isolated human Ada2 protein also increases the potency of the receptor protein in mammalian cells. The Ada pathway is of key significance for the tau1 core transactivation domain (tau1c) of the receptor, which requires Ada for activity in vivo and in vitro. Ada2 can be precipitated from nuclear extracts by a glutathione S-transferase-tau1 fusion protein coupled to agarose beads, and a direct interaction between Ada2 and tau1c can be shown by using purified proteins. This interaction is strongly reduced by a mutation in tau1c that reduces transactivation activity. Mutations affecting the Ada complex do not reverse transcriptional squelching by the tau1 domain, as they do for the VP16 transactivation domain, and thus these powerful acidic activators differ in at least some important aspects of gene activation. Mutations that reduce the activity of the tau1c domain in wild-type yeast strains cause similar reductions in ada mutants that contain little or no Ada activity. Thus, gene activation mechanisms, in addition to the Ada pathway, are involved in the activity of the tau1c domain.
机译：我们已经表明，Ada衔接子复合物对于酵母中糖皮质激素受体的基因激活能力很重要。最近分离的人Ada2蛋白还增加了哺乳动物细胞中受体蛋白的效力。 Ada途径对于受体的tau1核心反式激活结构域（tau1c）至关重要，该结构需要Ada在体内和体外具有活性。 Ada2可以通过与琼脂糖珠偶联的谷胱甘肽S-转移酶-tau1融合蛋白从核提取物中沉淀出来，并且可以使用纯化的蛋白显示Ada2和tau1c之间的直接相互作用。 tau1c中的一种突变会大大降低这种相互作用，而该突变会降低反式激活活性。影响Ada复合体的突变不会像tVP16反式激活结构域那样逆转tau1结构域的转录抑制，因此，这些强大的酸性激活剂至少在基因激活的某些重要方面有所不同。降低野生型酵母菌株中tau1c域活性的突变会导致ada突变体的相似降低，而ada突变体几乎没有或没有Ada活性。因此，除Ada途径外，基因激活机制也参与了tau1c域的活性。

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