Title |
Estrogen receptor-dependent activation of AP-1 via non-genomic signalling
|
---|---|
Published in |
Nuclear Receptor, June 2004
|
DOI | 10.1186/1478-1336-2-3 |
Pubmed ID | |
Authors |
Linda Björnström, Maria Sjöberg |
Abstract |
BACKGROUND: Ligand-bound estrogen receptor alpha (ERalpha) and estrogen receptor beta (ERbeta) modulate AP-1-dependent transcription via protein-protein interactions on DNA, in a manner that depends on the type of cells and the subtype of ER. We present here evidence for an additional mechanism by which ERs modulate the transcriptional activity of AP-1. RESULTS: We show that ERs located in the cytoplasm efficiently activate transcription at AP-1 sites in response to 17beta-estradiol, while ERs present in the nucleus repress transcription under the same conditions. 17beta-estradiol-induced activation of the coll-73-luc reporter correlated with cytoplasmic localization of various ERalpha and ERbeta mutant receptors, and was inhibited in the presence of the full estrogen antagonist ICI 182,780 and the MAP-kinase inhibitor UO126. We also show that the selective estrogen receptor modulator (SERM) tamoxifen is as potent as 17beta-estradiol in inducing activation of AP-1 when ERalpha is present in the cytoplasm. CONCLUSIONS: These results suggest that non-genomic signalling is involved in the mechanism by which ERalpha and ERbeta influence AP-1-dependent transcription. We have previously shown that Stat3 and Stat5 are targeted by non-genomic actions of ERs, and the results presented here allow us to conclude that ERs bound to 17beta-estradiol mediate the transcriptional activation of promoters regulated by AP-1 and by Stat proteins via different combinations of signal transduction pathways. Our observations thereby provide new insights into the mechanisms by which ERs act at alternate response elements, and suggest a mechanism by which tamoxifen exerts its action as a tissue-selective agonist. |
Mendeley readers
Geographical breakdown
Country | Count | As % |
---|---|---|
South Africa | 1 | 2% |
Unknown | 48 | 98% |
Demographic breakdown
Readers by professional status | Count | As % |
---|---|---|
Student > Ph. D. Student | 13 | 27% |
Researcher | 7 | 14% |
Student > Master | 7 | 14% |
Student > Bachelor | 5 | 10% |
Lecturer | 2 | 4% |
Other | 8 | 16% |
Unknown | 7 | 14% |
Readers by discipline | Count | As % |
---|---|---|
Agricultural and Biological Sciences | 20 | 41% |
Biochemistry, Genetics and Molecular Biology | 7 | 14% |
Medicine and Dentistry | 6 | 12% |
Pharmacology, Toxicology and Pharmaceutical Science | 3 | 6% |
Environmental Science | 1 | 2% |
Other | 4 | 8% |
Unknown | 8 | 16% |