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Updated: Aug 10, 2026

Biochemical Reconstitution of Steroid Receptor•Hsp90 Protein Complexes and Reactivation of Ligand Binding
Published on: September 21, 2011
Steroid receptor coactivator-1 coactivates activating protein-1-mediated transactivations through interaction with
Abstract:
Steroid receptor coactivator-1 (SRC-1) specifically bound to the transcription factor AP-1 subunits c-Jun and c-Fos, as demonstrated by the yeast two-hybrid tests and glutathione S-transferase pull down assays. The c-Jun and c-Fos binding sites were localized to the C-terminal subregion of SRC-1 (amino acids 1101-1441) that encompasses the previously described histone acetyltransferase and receptor-binding domains. In mammalian cells, SRC-1, similar to the previous results with CBP-p300 (Arias, J., Alberts, A. S., Brindle, P., Claret, F. X., Smeal, T., Karin, M., Feramisco, J., and Montminy, M. (1994) Nature 370, 226-229; Bannister, A. J., and Kouzarides, T. (1995) EMBO J. 14, 4758-4762), potentiated the AP-1-mediated transactivations in a dose-dependent manner and derepressed the mutual inhibitions between nuclear receptors and AP-1. Furthermore, coexpression of p300 further enhanced this SRC-1-potentiated level of transactivations. Thus, we concluded that at least two distinct coactivator molecules may cooperate to regulate AP-1-dependent transactivations and mediate transrepression between AP-1 and nuclear receptors in vivo.
Insights
Steroid receptor coactivator-1 (SRC-1) binds transcription factor AP-1. SRC-1 and p300 cooperate to regulate AP-1 activity and gene repression involving nuclear receptors.
Area of Science:
- Molecular Biology
- Gene Regulation
- Protein-Protein Interactions
Background:
- Steroid receptor coactivator-1 (SRC-1) is a key transcriptional coactivator.
- The transcription factor AP-1, composed of c-Jun and c-Fos, regulates gene expression.
- Cross-talk between AP-1 and nuclear receptors influences cellular responses.
Purpose of the Study:
- To investigate the interaction between SRC-1 and AP-1 subunits.
- To determine the functional consequences of SRC-1 binding to AP-1.
- To elucidate the role of coactivators in mediating cross-talk between AP-1 and nuclear receptors.
Main Methods:
- Yeast two-hybrid assays to detect protein-protein interactions.
- Glutathione S-transferase (GST) pull-down assays to confirm binding.
- Mammalian cell transfections to assess transcriptional activity.
Main Results:
- SRC-1 directly binds to c-Jun and c-Fos subunits of AP-1.
- The binding site for c-Jun and c-Fos on SRC-1 is located in its C-terminal region (amino acids 1101-1441).
- SRC-1 potentiates AP-1-mediated transactivation and derepresses mutual inhibition between AP-1 and nuclear receptors.
- Coexpression of p300 enhances SRC-1-mediated potentiation of AP-1 transactivation.
Conclusions:
- SRC-1 interacts with AP-1, modulating its transcriptional activity.
- Cooperation between SRC-1 and p300 is crucial for regulating AP-1-dependent transcription.
- These coactivators mediate transrepression between AP-1 and nuclear receptors in vivo.
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