Wei L N, Hu X, Chinpaisal C
Department of Pharmacology, University of Minnesota, Minneapolis, Minnesota 55455, USA.
J Biol Chem. 2000 Apr 21;275(16):11907-14. doi: 10.1074/jbc.275.16.11907.
The orphan nuclear receptor TR2 functions as a constitutive activator for the endogenous retinoic acid receptor beta2 (RAR(beta2)) gene expression in P19 embryonal carcinoma cells and for reporters driven by the RAR(beta2) promoter in COS-1 cells. The activation of RAR(beta2) by TR2 is mediated by the direct repeat-5 (DR5) element located in the RAR(beta2) promoter. Furthermore, cAMP exerts an enhancing effect on the activation of RAR(beta2) by TR2, which is mediated by the cAMP response element located in the 5'-flanking region of the DR5. The constitutive activation function-1 (AF-1) of TR2 is mapped to amino acid residues 10-30 in its N-terminal A segment. A direct molecular interaction occurs between CREMtau and TR2, detected by co-immunoprecipitation, which is mediated by the N-terminal AB segment of TR2. In gel mobility shift assays, TR2 competes with P19 nuclear factor binding to the RAR(beta2) promoter, and TR2 and CREMtau bind simultaneously to this DNA fragment. The role of TR2 in the early events of RA signaling process is discussed.
孤儿核受体TR2在P19胚胎癌细胞中作为内源性视黄酸受体β2（RAR(β2)）基因表达的组成型激活剂，并在COS-1细胞中作为由RAR(β2)启动子驱动的报告基因的激活剂。TR2对RAR(β2)的激活由位于RAR(β2)启动子中的直接重复序列5（DR5）元件介导。此外，cAMP对TR2介导的RAR(β2)激活具有增强作用，这由位于DR5 5'侧翼区域的cAMP反应元件介导。TR2的组成型激活功能-1（AF-1）定位于其N端A段的第10至30个氨基酸残基。通过共免疫沉淀检测到CREMtau与TR2之间存在直接分子相互作用，这由TR2的N端AB段介导。在凝胶迁移率变动分析中，TR2与P19核因子竞争结合RAR(β2)启动子，并且TR2和CREMtau同时结合到该DNA片段上。文中讨论了TR2在RA信号传导过程早期事件中的作用。
