肌钙蛋白I2辅助活化多种核受体的反式作用

Troponin I2 Co-activating Transactivation of Multiple Nuclear Receptors

为深入研究乳腺癌中孤儿受体ERRα1参与基因表达调控的详细机理,特别是核受体辅激活蛋白在其中的作用,以ERRα1的LBD为诱饵,用酵母双杂交系统筛选人乳腺组织cDNA文库得到了与其有明显相互作用的快速骨骼肌型肌钙蛋白I(TNNI2).应用酵母双杂交技术研究表明,TNNI2与多种核受体存在相互作用,且这种作用依赖于功能性的核受体AF2结构域.在哺乳细胞瞬时共转染实验中,TNNI2显示了对多种核受体反式激活功能的辅助活化作用.研究证明,TNNI2与许多辅激活蛋白类似,以配体依赖(对类固醇激素受体而言)或非依赖(对孤儿受体而言)的方式与核受体功能性AF2结构域相互作用,并增强多种核受体介导的反式作用.

To further understand the detailed molecular mechanism of transcription regulation controlled by estrogen receptor related receptor al （ERRα1） in breast cancer and to identify coactivators interacting with ERRα1, human mammary gland tissue cDNA library was screened with ligand binding domain （LBD） of ERRal as the bait by yeast two-hybrid system. TNNI2 （troponin I2） was found to interact with several nuclear receptors in yeast two-hybrid assay. Functional AF-2 domain is required for nuclear receptors to interact with TNNI2. In transient co-transfection experiments, relative luciferase activity assay showed TNNI2 had the ability of enhancing the transcription mediated by multiple nuclear receptors. Like most of the nuclear receptor coactivators, TNNI2 interacts with the functional AF-2 domain of the nuclear receptors in either a liganddependent manner or ligand-independent manner （for orphan receptors）. TNNI2 enhances the transcription mediated by multiole nuclear receptors.