Kim H J, Lee S K, Na S Y, Choi H S, Lee J W
College of Pharmacy, Chonnam National University, Kwangju, South Korea.
Mol Endocrinol. 1998 Jul;12(7):1038-47. doi: 10.1210/mend.12.7.0139.
Nuclear receptors regulate transcription by binding to specific DNA response elements of target genes. Herein, we report the molecular cloning and characterization of a novel Xenopus cDNA encoding a transcription coactivator xSRC-3 by using retinoid X receptor (RXR) as a bait in the yeast two-hybrid screening. It belongs to a growing coactivator family that includes a steroid receptor coactivator amplified in breast cancer (AIB1), p300/ CREB-binding protein (CBP)-interacting protein (p/ CIP), and transcriptional intermediate factor 2 (TIF2). It also interacts with a series of nuclear receptors including retinoic acid receptor (RAR), thyroid hormone receptor (TR), and orphan nuclear receptors [hepatocyte nuclear receptor 4 (HNF4) and constitutive androstane receptor (CAR)]. However, it does not interact with small heterodimer partner (SHP), an orphan nuclear receptor known to antagonize ligand-dependent transactivation of other nuclear receptors. In CV-1 cells, cotransfection of xSRC-3 differentially stimulates ligand-induced transactivation of RXR, TR, and RAR in a dose-dependent manner. Interestingly, xSRC-3 is highly expressed in adult liver and early stages of oocyte development, suggesting that studies of xSRC-3 may lead to better understanding of the roles nuclear receptors play in oocyte development as well as liver-specific gene expression.
核受体通过与靶基因的特定DNA反应元件结合来调节转录。在此，我们报告了通过在酵母双杂交筛选中使用视黄酸X受体（RXR）作为诱饵，对一种编码转录共激活因子xSRC-3的非洲爪蟾新cDNA进行分子克隆和特性分析。它属于一个不断扩大的共激活因子家族，该家族包括在乳腺癌中扩增的类固醇受体共激活因子（AIB1）、p300/CREB结合蛋白（CBP）相互作用蛋白（p/CIP）和转录中间因子2（TIF2）。它还与一系列核受体相互作用，包括视黄酸受体（RAR）、甲状腺激素受体（TR）和孤儿核受体[肝细胞核受体4（HNF4）和组成型雄甾烷受体（CAR）]。然而，它不与小异二聚体伴侣（SHP）相互作用，SHP是一种已知可拮抗其他核受体配体依赖性反式激活的孤儿核受体。在CV-1细胞中，xSRC-3的共转染以剂量依赖的方式差异性地刺激RXR、TR和RAR的配体诱导的反式激活。有趣的是，xSRC-3在成年肝脏和卵母细胞发育早期高度表达，这表明对xSRC-3的研究可能有助于更好地理解核受体在卵母细胞发育以及肝脏特异性基因表达中所起的作用。
