Liganded androgen receptor interaction with beta-catenin: nuclear co-localization and modulation of transcriptional activity in neuronal cells.
A yeast two-hybrid assay was employed to identify androgen receptor (AR) protein partners in gonadotropin-releasing hormone neuronal cells. By using an AR deletion construct (AR-(Delta371-485)) as a bait, beta-catenin was identified as an AR-interacting protein from a gonadotropin-releasing hormone neuronal cell library. Immunolocalization of co-transfected AR and FLAG-beta-catenin demonstrated that ... FLAG-beta-catenin was predominantly cytoplasmic in the absence of androgen. In the presence of 5alpha-dihydrotestosterone, FLAG-beta-catenin completely co-localized to the nucleus with AR. This effect was specific to AR because liganded progesterone, glucocorticoid, or estrogen alpha receptors did not translocate FLAG-beta-catenin to the nucleus. Agonist-bound AR was required because the AR antagonists casodex and hydroxyflutamide failed to translocate beta-catenin. Time course experiments demonstrated that co-translocation occurred with similar kinetics. Nuclear co-localization was independent of the glycogen synthase kinase-3beta, p42/44 ERK mitogen-activated protein kinase, and phosphatidylinositol 3-kinase pathways because inhibitors of these pathways had no effect. Transcription assays demonstrated that liganded AR repressed beta-catenin/T cell factor-responsive reporter gene activity. Conversely, co-expression of beta-catenin/T cell factor repressed AR stimulation of AR-responsive reporter gene activity. Our data suggest that liganded AR shuttles beta-catenin to the nucleus and that nuclear interaction of AR with beta-catenin may modulate transcriptional activity in androgen target tissues.
Mesh Terms:
Androgen Antagonists, Animals, Blotting, Western, COS Cells, Cell Line, Cell Nucleus, Cytoskeletal Proteins, Estrogen Receptor alpha, Immunohistochemistry, Ligands, Mice, Neurons, Precipitin Tests, Promoter Regions, Genetic, Protein Transport, Receptors, Androgen, Receptors, Estrogen, Receptors, Glucocorticoid, Receptors, Progesterone, Trans-Activators, Transcription, Genetic, Two-Hybrid System Techniques, beta Catenin
Androgen Antagonists, Animals, Blotting, Western, COS Cells, Cell Line, Cell Nucleus, Cytoskeletal Proteins, Estrogen Receptor alpha, Immunohistochemistry, Ligands, Mice, Neurons, Precipitin Tests, Promoter Regions, Genetic, Protein Transport, Receptors, Androgen, Receptors, Estrogen, Receptors, Glucocorticoid, Receptors, Progesterone, Trans-Activators, Transcription, Genetic, Two-Hybrid System Techniques, beta Catenin
J. Biol. Chem.
Date: Jun. 07, 2002
PubMed ID: 11916967
View in: Pubmed Google Scholar
Download Curated Data For This Publication
1634
Switch View:
- Interactions 2