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Jun dimerization protein 2 functions as a progesterone receptor N-terminal domain coactivator
Suzanne E Wardell1, Viroj Boonyaratanakornkit, James S Adelman
1Program in Molecular Biology, Department of Pathology, University of Colorado Health Sciences Center, Denver, CO 80262, USA.
Molecular and Cellular Biology
|July 9, 2002
Summary
Jun dimerization protein 2 (JDP-2) acts as a novel coactivator for the progesterone receptor (PR). JDP-2 enhances PR activity by interacting with the PR DNA binding domain and recruiting other coactivators, suggesting a key role in PR function.
Area of Science:
- Molecular Biology
- Endocrinology
- Gene Regulation
Background:
- The progesterone receptor (PR) regulates gene expression via two activation functions (AF-1 and AF-2).
- AF-2 activity is well-characterized, but AF-1 mechanisms remain unclear.
- Steroid receptor coactivators (SRCs) modulate PR activity.
Purpose of the Study:
- To identify novel proteins interacting with the progesterone receptor (PR).
- To elucidate the mechanism by which Jun dimerization protein 2 (JDP-2) modulates PR activity.
- To investigate the role of JDP-2 in progesterone-mediated gene transcription.
Main Methods:
- Interaction cloning to identify PR-binding proteins.
- In vitro binding assays and coimmunoprecipitation to confirm protein interactions.
- Chromatin immunoprecipitation (ChIP) assays to assess in vivo promoter recruitment.
- Cell transfection assays to evaluate transactivation activity.
Main Results:
- Jun dimerization protein 2 (JDP-2) was identified as a novel PR-interacting protein.
- JDP-2 directly binds the PR DNA binding domain (DBD) and enhances PR-mediated transactivation.
- JDP-2 primarily stimulates AF-1 activity, acting as a potent coactivator independent of SRC-1.
- JDP-2 functions by docking to the PR DBD and recruiting general coactivators like CBP and pCAF.
Conclusions:
- JDP-2 is a novel coactivator that enhances progesterone receptor (PR) activity through a unique mechanism involving the PR DNA binding domain.
- JDP-2's ability to stimulate AF-1 activity suggests a significant role in progesterone-regulated gene expression.
- The preferential activity of JDP-2 on PR and its expression in target tissues indicate a physiological role in PR function.