Avram D, Ishmael J E, Nevrivy D J, Peterson V J, Lee S H, Dowell P, Leid M
Laboratory of Molecular Pharmacology, College of Pharmacy, Oregon State University, Corvallis, Oregon 97331-3507, USA.
J Biol Chem. 1999 May 14;274(20):14331-6. doi: 10.1074/jbc.274.20.14331.
Members of the chicken ovalbumin upstream promoter-transcription factor (COUP-TF) subfamily of orphan nuclear receptors, which minimally includes COUP-TFI and ARP1, are highly expressed in brain and are generally considered to be constitutive repressors of transcription. We have used a yeast two-hybrid system to isolate proteins expressed in brain that interact with ARP1. One of the proteins isolated in this screen was Ear2, another orphan receptor that has been suggested to be a member of the COUP-TF subfamily. Here we demonstrate that ARP1 and Ear2 form heterodimers in solution and on directly repeated response elements with high efficiency and a specificity differing from that of homodimeric complexes composed of either receptor. ARP1 and Ear2 were observed to interact in mammalian cells, and the tissue distribution of Ear2 transcripts was found to overlap precisely with the expression pattern of ARP1 in several mouse tissues and embryonal carcinoma cell lines. Heterodimeric interactions between ARP1 and Ear2 may define a distinct pathway of orphan receptor signaling.
鸡卵清蛋白上游启动子转录因子(COUP-TF)孤儿核受体亚家族的成员,至少包括COUP-TFI和ARP1,在大脑中高度表达,通常被认为是转录的组成型抑制因子。我们利用酵母双杂交系统分离在大脑中表达且与ARP1相互作用的蛋白质。在此筛选中分离出的一种蛋白质是Ear2,另一种孤儿受体,有人认为它是COUP-TF亚家族的成员。在这里我们证明,ARP1和Ear2在溶液中以及在直接重复反应元件上高效形成异二聚体,其特异性不同于由任一受体组成的同二聚体复合物。观察到ARP1和Ear2在哺乳动物细胞中相互作用,并且发现Ear2转录本的组织分布与ARP1在几种小鼠组织和胚胎癌细胞系中的表达模式精确重叠。ARP1和Ear2之间的异二聚体相互作用可能定义了孤儿受体信号传导的一条独特途径。