Modulation of estrogen receptor-alpha transcriptional activity by the coactivator PGC-1.
A transcriptional coactivator of the peroxisome proliferator-activated receptor-gamma (PPARgamma), PPARgamma-coactivator-1(PGC-1) interacts in a constitutive manner with the hinge domain of PPARgamma and enhances its transcriptional activity. In this study we demonstrate that PGC-1 is a coactivator of estrogen receptor-alpha (ERalpha)-dependent transcriptional activity. However the mechanism by which PGC-1 interacts with ERalpha is different from that of PPARgamma. Specifically, it was determined that the carboxyl terminus of PGC-1 interacts in a ligand-independent manner with the ERalpha hinge domain. In addition, an LXXLL motif within the amino terminus of PGC-1 was shown to interact in an agonist-dependent manner with the AF2 domain within the carboxyl terminus of ERalpha. The ability of PGC-1 to associate with and potentiate the transcriptional activity of an ERalpha-AF2 mutant that is unable to interact with the p160 class of coactivators suggests that this coactivator may have a unique role in estrogen signaling. It is concluded from these studies that PGC-1 is a bona fide ERalpha coactivator, which may serve as a convergence point between PPARgamma and ERalpha signaling.
Duke Scholars
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- Tumor Cells, Cultured
- Transcription, Genetic
- Transcription Factors
- Trans-Activators
- Signal Transduction
- Receptors, Estrogen
- Receptors, Cytoplasmic and Nuclear
- Mutation
- Humans
- Estrogen Receptor alpha
Citation
Published In
DOI
ISSN
Publication Date
Volume
Issue
Start / End Page
Location
Related Subject Headings
- Tumor Cells, Cultured
- Transcription, Genetic
- Transcription Factors
- Trans-Activators
- Signal Transduction
- Receptors, Estrogen
- Receptors, Cytoplasmic and Nuclear
- Mutation
- Humans
- Estrogen Receptor alpha