Yao T P, Forman B M, Jiang Z, Cherbas L, Chen J D, McKeown M, Cherbas P, Evans R M
Howard Hughes Medical Institute, Salk Institute for Biological Studies, La Jolla, California 92037.
Nature. 1993 Dec 2;366(6454):476-9. doi: 10.1038/366476a0.
Although the biological activity of the insect moulting hormone ecdysone, is manifested through a hormonally regulated transcriptional cascade associated with chromosomal puffing, a direct association of the receptor with the puff has yet to be established. The cloned ecdysone receptor (EcR) is by itself incapable of high-affinity DNA binding or transcriptional activation. Rather, these activities are dependent on heterodimer formation with Ultraspiracle (USP) the insect homologue of vertebrate retinoid X receptor. Here we report that native EcR and USP are co-localized on ecdysone-responsive loci of polytene chromosomes. Moreover, we show that natural ecdysones selectively promote physical association between EcR and USP, and conversely, that high-affinity hormone binding requires both EcR and USP. Replacement of USP with retinoid X receptor produces heterodimers with distinct pharmacological and functional properties. These results redefine the ecdysone receptor as a dynamic complex whose activity may be altered by combinatorial interactions among subunits and ligand.
尽管昆虫蜕皮激素蜕皮甾酮的生物活性是通过与染色体疏松相关的激素调节转录级联反应来体现的，但受体与疏松区之间的直接关联尚未确立。克隆的蜕皮甾酮受体（EcR）自身无法进行高亲和力的DNA结合或转录激活。相反，这些活性依赖于与脊椎动物类视黄醇X受体的昆虫同源物超气门蛋白（USP）形成异二聚体。我们在此报告，天然的EcR和USP共定位于多线染色体的蜕皮甾酮反应位点上。此外，我们表明天然蜕皮甾酮选择性地促进EcR和USP之间的物理结合，反之，高亲和力的激素结合需要EcR和USP两者。用类视黄醇X受体替代USP会产生具有不同药理学和功能特性的异二聚体。这些结果将蜕皮甾酮受体重新定义为一种动态复合物，其活性可能会因亚基和配体之间的组合相互作用而改变。
