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Functional Conservation of the Glutamine-Rich Domains of Yeast Gal11 and Human SRC-1 in the Transactivation of Glucocorticoid Receptor Tau 1 in Saccharomyces cerevisiae

机译:酵母Gal11和人类SRC-1中富含谷氨酰胺的域在酿酒酵母中糖皮质激素受体Tau 1的反式激活中的功能保守性。

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The yeast Gal11 protein, a component of the Mediator complex, is required for the transcriptional activation of many class II genes as a physiological target of various activator proteins in vivo. In this study, we identified the yeast (Saccharomyces cerevisiae) Mediator complex as a novel coactivator of the transcriptional activity of the glucocorticoid receptor (GR) tau 1 (τ1), the major transcriptional activation domain of the GR. GR τ1 directly interacted with the Mediator complex in vivo and in vitro in a Gal11 module-dependent manner, and the Gal11p subunit interacted directly with GR τ1. Specific amino acid residues within the glutamine-rich (Qr) domain of Gal11p (residues 116 to 277) were essential for its interaction with GR τ1 and GR τ1 transactivity in yeast, as demonstrated by mutational analysis of the Gal11 Qr domain, which is highly conserved among human steroid receptor coactivator (SRC) proteins. A Gal11p variant, mini-Gal11p, comprised of the Mediator association and Qr domains of Gal11p or chimeric mini-Gal11p containing the Qr domain of SRC-1 could potentiate the GR τ1 transactivity in a gal11Δ yeast strain. These results suggest that there is functional conservation between Qr domains of yeast Gal11p and mammalian SRC proteins as direct targets of activator proteins in yeast.
机译:酵母Gal11蛋白是介体复合物的组成部分,它是许多II类基因在体内作为多种激活蛋白的生理靶点进行转录激活所必需的。在这项研究中,我们确定了酵母(Saccharomyces cerevisiae )介体复合物是糖皮质激素受体(GR)tau 1(τ1)(GR的主要转录激活域)的转录活性的新型共激活因子。 。 GRτ1在体内和体外以Gal11模块依赖性方式直接与介体复合物相互作用,而Gal11p亚基与GRτ1直接相互作用。 Gal11p富含谷氨酰胺(Qr)结构域中的特定氨基酸残基(残基116至277)对于其与酵母中GRτ1和GRτ1活性的相互作用至关重要,如Gal11 Qr结构域的突变分析所证明的那样在人类类固醇受体共激活蛋白(SRC)蛋白中保守。由Gal11p介体关联和Qr结构域组成的Gal11p变体mini-Gal11p或含有SRC-1 Qr结构域的嵌合mini-Gal11p可以增强 gal11 Δ酵母菌株的GRτ1活性。 。这些结果表明,在酵母Gal11p的Qr结构域和哺乳动物SRC蛋白之间存在功能保守性,作为酵母中激活蛋白的直接靶标。

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