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Differential modulation of transcriptional activity of oestrogen receptors by direct protein–protein interactions with retinoid receptors
- Source :
- Biochemical Journal. 336:711-717
- Publication Year :
- 1998
- Publisher :
- Portland Press Ltd., 1998.
-
Abstract
- Control of oestradiol-responsive gene regulation by oestrogen receptors (ERs) may involve complex cross-talk with retinoic acid receptors (RARs) and retinoid X receptors (RXRs). Recently, we have shown that ERalpha directly interacts with RARalpha and RXRalpha through their ligand binding domains (LBDs). In the present work, we extend these results by showing that ERbeta binds similarly to RARalpha and RXRalpha but not to the glucocorticoid receptor, as demonstrated by the yeast two-hybrid tests and glutathione S-transferase pull-down assays. These direct interactions were also demonstrated in gel-shift assays, in which the oestrogen response element (ERE) binding by ERalpha was enhanced by the RXRalpha LBD but was abolished by the RARalpha LBD. In addition, we showed that RARalpha and RXRalpha bound the ERE as efficiently as ERalpha, suggesting that competition for DNA binding may affect the transactivation function of the ER. In transient transfection experiments, co-expression of RARalpha or RXRalpha, along with ERalpha or ERbeta, revealed differential modulation of the ERE-dependent transactivation, which was distinct from the results when each receptor alone was co-transfected. Importantly, when the LBD of RARalpha was co-expressed with ERalpha, transactivation of ERalpha on the ERE was repressed as efficiently as when wild-type RARalpha was co-expressed. Furthermore, liganded RARalpha or unliganded RXRalpha enhanced the ERalpha transactivation, suggesting the formation of transcriptionally active heterodimer complexes between the ER and retinoid receptors. Taken together, these results suggest that direct protein-protein interactions may play major roles in the determination of the biological consequences of cross-talk between ERs and RARalpha or RXRalpha.
- Subjects :
- Transcriptional Activation
Receptors, Retinoic Acid
medicine.drug_class
Response element
Retinoic acid
Biology
Transfection
Biochemistry
Cell Line
Protein–protein interaction
Transactivation
chemistry.chemical_compound
Glucocorticoid receptor
Culture Techniques
Tumor Cells, Cultured
medicine
Animals
Humans
Retinoid
Receptor
Molecular Biology
Regulation of gene expression
Cell Biology
Molecular biology
Retinoid X Receptors
Receptors, Estrogen
chemistry
Electrophoresis, Polyacrylamide Gel
hormones, hormone substitutes, and hormone antagonists
Protein Binding
Transcription Factors
Research Article
Subjects
Details
- ISSN :
- 14708728 and 02646021
- Volume :
- 336
- Database :
- OpenAIRE
- Journal :
- Biochemical Journal
- Accession number :
- edsair.doi.dedup.....f9e1acd56cf3f176bdf875145527c134