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目的:研究COBRA1(cofactor for BRCA1)在雌激素受体α(ERα)信号途径中的潜在作用。方法:用GSTpu ll-down实验检测COBRA1与ERα的相互作用、定位相互作用的区域,探讨不同配体对相互作用的影响。用免疫共沉淀方法检测COBRA1与ERα在细胞内的相互作用。利用含有雌激素应答元件(estrogen responsive elem ent,ERE)的荧光素酶(luc iferase,LUC)报告基因(C3-LUC)检测COBRA1对ERα转录活性的影响。结果:在体内外,COBRA1与ERα存在相互作用,COBRA1和ERα的中间区域是它们相互作用的区域。抗雌激素可增强COBRA1与ERα的结合。COBRA1以激素依赖方式抑制ERα的转录活性。结论:COBRA1是一新型ERα共抑制因子,可能在ERα信号途径中起重要作用。
AIM: To investigate the potential role of COBRA1 (cofactor for BRCA1) in the estrogen receptor α (ERα) signaling pathway. METHODS: The interaction between COBRA1 and ERα was detected by GSTpu ll-down assay, and the interaction between COBRA1 and ERα was investigated. The interaction between different ligands was also investigated. Co-immunoprecipitation was used to detect the intracellular interaction of COBRA1 and ERα. The effect of COBRA1 on ERα transcriptional activity was examined using the luciferase (LUC) reporter gene (C3-LUC) containing estrogen responsive elem ent (ERE). Results: In vitro and in vivo, COBRA1 interacts with ERα, and the middle region between COBRA1 and ERα is the region where they interact. Antiestrogen enhances the binding of COBRA1 to ERα. COBRA1 inhibits ERα transcriptional activity in a hormone-dependent manner. Conclusion: COBRA1 is a novel ERα costimulatory factor that may play an important role in the ERα signaling pathway.