Hahm Johnnie B, Privalsky Martin L
Department of Microbiology, University of California at Davis, Davis, CA 95616, USA.
Mol Endocrinol. 2013 May;27(5):840-59. doi: 10.1210/me.2012-1117. Epub 2013 Apr 4.
Thyroid hormone receptors (TRs) are expressed as a series of interrelated isoforms that perform distinct biological roles. The TRβ2 isoform is found predominantly in the hypothalamus, pituitary, retina, and cochlea and displays unique transcriptional properties relative to the other TR isoforms. To more fully understand the isoform-specific biological and molecular properties of TRβ2, we have identified a series of previously unrecognized proteins that selectively interact with TRβ2 compared with the more widely expressed TRβ1. Several of these proteins preferentially enhance the transcriptional activity of TRβ2 when coexpressed in cells and are likely to represent novel, isoform-specific coactivators. Additional proteins were also identified in our screen that bind equally to TRβ1 and TRβ2 and may function as isoform-independent auxiliary proteins for these and/or other nuclear receptors. We propose that a combination of isoform-specific recruitment and tissue-specific expression of these newly identified coregulator candidates serves to customize TR function for different biological purposes in different cell types.
甲状腺激素受体（TRs）以一系列相互关联的异构体形式表达，这些异构体发挥着不同的生物学作用。TRβ2异构体主要存在于下丘脑、垂体、视网膜和耳蜗中，相对于其他TR异构体，它表现出独特的转录特性。为了更全面地了解TRβ2异构体特异性的生物学和分子特性，我们已经鉴定出一系列先前未被识别的蛋白质，与广泛表达的TRβ1相比，这些蛋白质能与TRβ2选择性相互作用。当在细胞中共表达时，其中几种蛋白质优先增强TRβ2的转录活性，并且可能代表新的、异构体特异性的共激活因子。在我们的筛选中还鉴定出了其他蛋白质，它们与TRβ1和TRβ2的结合能力相同，可能作为这些和/或其他核受体的异构体非依赖性辅助蛋白发挥作用。我们认为，这些新鉴定的共调节因子候选物的异构体特异性募集和组织特异性表达相结合，有助于为不同细胞类型中的不同生物学目的定制TR功能。
