Molecular cloning of xSRC-3, a novel transcription coactivator from Xenopus, that is related to AIB1, p/CIP, and TIF2

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.