• 主题
高级搜索  >
历史搜索 清空历史
首页> 外文期刊>Journal of Molecular Biology >Dissection of androgen receptor-promoter interactions: Steroid receptors partition their interaction energetics in parallel with their phylogenetic divergence
【24h】

Dissection of androgen receptor-promoter interactions: Steroid receptors partition their interaction energetics in parallel with their phylogenetic divergence

机译：雄激素受体-启动子相互作用的解剖：类固醇受体分配其相互作用的能量与它们的系统发育分歧并行。

获取原文
获取原文并翻译 | 示例
           
页面导航
  • 摘要
  • 著录项
  • 相似文献
  • 相关主题

摘要

Steroid receptors comprise a homologous family of ligand-activated transcription factors. The members include androgen receptor (AR), estrogen receptor (ER), glucocorticoid receptor (GR), mineralocorticoid receptor (MR), and progesterone receptor (PR). Phylogenetic studies demonstrate that AR, GR, MR, and PR are most closely related, falling into subgroup 3C. ER is more distantly related, falling into subgroup 3A. To determine the quantitative basis by which receptors generate their unique transcriptional responses, we are systematically dissecting the promoter-binding energetics of all receptors under a single "standard state" condition. Here, we examine the self-assembly and promoter-binding energetics of full-length AR and a mutant associated with prostate cancer, T877A. We first demonstrate that both proteins exist only as monomers, showing no evidence of dimerization. Although this result contradicts the traditional understanding that steroid receptors dimerize in the absence of DNA, it is fully consistent with our previous work demonstrating that GR and two PR isoforms either do not dimerize or dimerize only weakly. Moreover, both AR proteins exhibit substantial cooperativity between binding sites, again as seen for GR and PR. In sharp contrast, the more distantly related ER-α dimerizes so strongly that energetics can only be measured indirectly, yet cooperativity is negligible. Thus, homologous receptors partition their promoter-binding energetics quite differently. Moreover, since receptors most closely related by phylogeny partition their energetics similarly, such partitioning appears to be evolutionarily conserved. We speculate that such differences in energetics, coupled with different promoter architectures, serve as the basis for generating receptor-specific promoter occupancy and thus function.
机译：类固醇受体包含配体激活的转录因子的同源家族。成员包括雄激素受体（AR），雌激素受体（ER），糖皮质激素受体（GR），盐皮质激素受体（MR）和孕激素受体（PR）。系统发育研究表明，AR，GR，MR和PR关系最密切，属于3C亚组。 ER更远地相关，属于3A子组。为了确定受体产生其独特转录反应的定量基础，我们正在系统地剖析单个“标准状态”条件下所有受体的启动子结合能。在这里，我们检查了全长AR和与前列腺癌T877A相关的突变体的自组装和启动子结合能。我们首先证明两种蛋白质仅以单体形式存在，没有显示二聚化的迹象。尽管该结果与传统的理解（即在不存在DNA的情况下类固醇受体会二聚化）相矛盾，但这与我们先前的研究完全一致，表明GR和两个PR亚型不会二聚化或仅微弱地二聚化。而且，两种AR蛋白在结合位点之间均显示出实质性的协同作用，再次对于GR和PR可见。与之形成鲜明对比的是，距离更远的ER-α如此强烈地二聚化，以至于只能间接地测量能量，而协同作用却可以忽略不计。因此，同源受体以不同的方式分配其启动子结合能。此外，由于与系统发育关系最密切的受体相似地分配其能量，因此这种分配似乎在进化上是保守的。我们推测这种能量学上的差异，加上不同的启动子体系结构，是产生受体特异性启动子占有率并因此起作用的基础。

著录项

相似文献

  • 外文文献
  • 中文文献
  • 专利
获取原文

客服邮箱：kefu@zhangqiaokeyan.com

京公网安备：11010802029741号 ICP备案号：京ICP备15016152号-6 六维联合信息科技 (北京) 有限公司©版权所有

  • 客服微信

  • 服务号