Hj. Kim et al., MOLECULAR-CLONING OF XSRC-3, A NOVEL TRANSCRIPTION COACTIVATOR FROM XENOPUS, THAT IS RELATED TO AIB1, P CIP, AND TIF2/, Molecular endocrinology, 12(7), 1998, pp. 1038-1047
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.