A transcriptional coactivator, steroid receptor coactivator-3, selectively augments steroid receptor transcriptional activity.

Estrogen receptors ERalpha and ERbeta are members of the family of nuclear hormone receptors and act as ligand-inducible transcriptional factors, which regulate the expression of target genes on binding to cognate response elements. We report here the characterization of steroid receptor coactivator-3 (SRC-3), a coactivator of nuclear receptor transcription that ...
is a member of a family of steroid receptor coactivators that includes SRC-1 and transcription intermediate factor-2. SRC-3 enhanced ERalpha and progesterone receptor-stimulated gene transcription in a ligand-dependent manner, but stimulation of ERbeta-mediated transcription was not observed. Protein-protein interaction assays, including real-time interaction analyses with BIAcore, demonstrated that the affinity of the ERalpha interaction with SRC-3 was much higher than that observed for the ERbeta interaction with SRC-3. Mutational analysis suggests a potential interplay between the transactivation function-1 and -2 domains of ERalpha and SRC-3. Furthermore, an intrinsic transactivation function was observed in the C-terminal half of SRC-3. Finally, SRC-3 was differentially expressed in various tissues and, among several tumor cells examined, was most abundant in the nuclear fraction of MCF-7 breast cancer cells. Therefore, SRC-3, a third member of a family of steroid receptor coactivators, has a distinct tissue distribution and intriguing selectivity between ERalpha and ERbeta.
Mesh Terms:
Acetyltransferases, Biosensing Techniques, Cloning, Molecular, DNA, Complementary, Estrogen Receptor alpha, Gene Expression Regulation, Histone Acetyltransferases, Humans, Nuclear Receptor Coactivator 3, Oncogene Proteins, Protein Binding, Receptors, Estrogen, Receptors, Progesterone, Saccharomyces cerevisiae, Tissue Distribution, Trans-Activators, Transcription, Genetic
J. Biol. Chem.
Date: Oct. 16, 1998
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