Mutual trans activational repression of Runx2 and the androgen receptor by an impairment of their normal compartmentalization
Mutual trans activational repression of Runx2 and the androgen receptor by an impairment of their normal compartmentalization
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DOI：
10.1016/j.jsbmb.2006.11.020
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发表时间：
2007-06-01
影响因子：
4.1
通讯作者：
Takayanagi, Ryoichi
中科院分区：
文献类型：
--
作者：
Kawate, Hisaya;Wu, Yin;Takayanagi, Ryoichi
类固醇激素不仅在生殖系统中起重要作用，而且在骨代谢中也起重要作用。我们研究了类固醇激素受体和Runx2转录因子之间的功能关系，Runx2转录因子对成骨细胞的分化和增殖至关重要。一个功能性的报告基因检测使用的启动子携带类固醇激素反应元件显示，Runx2抑制受体介导的配体依赖性转录激活。为了研究这些蛋白质的细胞内定位，通过激光扫描共聚焦显微镜对绿色荧光蛋白（GFP）融合蛋白进行三维成像研究。如前所述，配体结合的人雄激素受体（AR）从细胞质易位到细胞核，形成核下的细灶。人Runx2的共表达破坏了AR亚核细灶的形成，AR的核内荧光模式变得与Runx2相似。另一方面，配体结合的AR抑制Runx2介导的反式激活功能。Runx2也通过配体结合的AR从其原始隔室中提取。这些结果表明，Runx2和AR抑制反式激活功能的其他蛋白质从其原来的隔室提取。AR和Runx2可能在成骨细胞的转录激活中发挥相互作用。(c)2007爱思唯尔有限公司版权所有。
Steroid hormones play important roles not only in the reproductive system but also in bone metabolism. We examined the functional relationship between steroid hormone receptors and the Runx2 transcription factor that is essential for osteoblast differentiation and proliferation. A functional reporter assay using promoters carrying steroid hormone-responsive elements revealed that Runx2 suppressed ligand-dependent transcriptional activation mediated by receptors. To examine intracellular localization of these proteins, a three-dimensional imaging study was performed by laser scanning confocal microscopy of green fluorescent protein (GFP)-fused proteins. As previously reported, ligand-bound human androgen receptor (AR) was translocated from the cytoplasm to the nucleus and formed subnuclear fine foci. Coexpression of human Runx2 disrupted the AR subnuclear fine foci formation, and the intranuclear fluorescent pattern of AR became similar to that of Runx2. On the other hand, ligand-bound ARs repressed the Runx2-mediated transactivation function. Runx2 was also extracted from its original compartment by ligand-bound ARs. These results suggest that both Runx2 and ARs repress the transactivation function of the other protein by extracting it from its original compartment. The AR and Runx2 may play a mutual role in transcriptional activation in osteoblasts. (c) 2007 Elsevier Ltd. All rights reserved.