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 re sponse elements of target genes. Herein, we report the molecular cloni ng and characterization of a novel Xenopus cDNA encoding a transcripti on coactivator xSRC-3 by using retinoid X receptor (RXR) as a bait in the yeast two-hybrid screening. It belongs to a growing coactivator fa mily 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 intera cts with a series of nuclear receptors including retinoic acid recepto r (RAR), thyroid hormone receptor (TR), and orphan nuclear receptors [ hepatocyte nuclear receptor 4 (HNF4) and constitutive androstane recep tor (CAR)]. However, it does not interact with small heterodimer partn er (SHP), an orphan nuclear receptor known to antagonize ligand-depend ent transactivation of other nuclear receptors. In CV-1 cells, cotrans fection of xSRC-3 differentially stimulates ligand-induced transactiva tion of RXR, TR, and RAR in a dose-dependent manner. Interestingly, xS RC-3 is highly expressed in adult liver and early stages of oocyte dev elopment, suggesting that studies of xSRC-3 may lead to better underst anding of the roles nuclear receptors play in oocyte development as we ll as liver-specific gene expression.