SIGNAL TRANSDUCTION AND TRANSCRIPTIONAL REGULATION BY GLUCOCORTICOID RECEPTOR-LEXA FUSION PROTEINS
SIGNAL TRANSDUCTION AND TRANSCRIPTIONAL REGULATION BY GLUCOCORTICOID RECEPTOR-LEXA FUSION PROTEINS
复制标题
DOI：
10.1126/science.3043662
复制
发表时间：
1988-08-12
期刊：
影响因子：
56.9
通讯作者：
YAMAMOTO, KR
中科院分区：
文献类型：
--
作者：
GODOWSKI, PJ;PICARD, D;YAMAMOTO, KR
糖皮质激素受体在与其同源激素结合后调节转录起始。构建了一系列融合基因来研究激素调节转录增强的机制。将细菌莱克萨阻遏物的DNA结合结构域融合到受体衍生物上，所述受体衍生物缺乏在糖皮质激素反应元件（GRE）处特异性DNA结合和转录增强所必需和足够的区域。所得到的杂合蛋白激活从连接到lex操纵子的启动子的转录。增强仍然需要激素结合的杂交受体，无论确切定位的莱克萨结合结构域内的蛋白质。因此，受体的未配体激素结合结构域以独立于受体识别DNA的方式作为受体活性的强但可逆的抑制剂。结果还直接表明，该受体含有至少一个“增强域”以外的重叠的GRE结合区;第二个域，enh 2，占据了受体氨基末端附近的区域。
The glucocorticoid receptor regulates transcriptional initiation upon binding to its cognate hormone. A series of fusion genes was constructed to examine the mechanism of hormone-regulated transcriptional enhancement. The DNA binding domain of the bacterial LexA repressor was fused to receptor derivatives lacking the region that is necessary and sufficient for specific DNA binding and transcriptional enhancement at glucocorticoid response elements (GRE's). The resultant hybrid proteins activated transcription from promoters linked to the lex operator. Enhancement still required hormone binding by the hybrid receptor regardless of the exact positioning of the LexA binding domain within the protein. Thus, the unliganded hormone binding domain of the receptor acts as a strong but reversible inhibitor of receptor activity in a manner that is independent of the means by which the receptor recognizes DNA. The results also show directly that the receptor contains at least one "enhancement domain" other than that overlapping the GRE binding region; the second domain, enh2, occupies a region near the receptor amino terminus.