Liganded Androgen Receptor Interaction with β-Catenin
Open accessAbstract
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.
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Ligand-bound AR decreases the transcriptional activity of TCF4 in prostate cancer, colon cancer, and neurons.
“Indeed, ligand-bound AR decreases the transcriptional activity of TCF4 in prostate cancer, colon cancer [21], and neurons [16].”
From The FKBP52 Cochaperone Acts in Synergy with β-Catenin to Potentiate Androgen Receptor Signaling (2015) · cites this paper as [16]
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- Authors
- Pawlowski, J. E., Ertel, J. R., Allen, M. P., Xu, M., Butler, C., Wilson, E. M., & Wierman, M. E.
- Affiliations
- Veterans Health Administration (US)
- University of Colorado Health (US)
- University of North Carolina at Chapel Hill (US)
- Corresponding author
- Wierman, Margaret E.
- Venue
- Journal of Biological Chemistry
- Publisher
- Elsevier BV
- Published
- 2002-06
- Volume
- 277
- Issue
- 23
- Pages
- 20702-20710
- ISSN
- 0021-9258 (ISSN-L)
- OpenAlex
- W2033728702
- Cited by
- 166
- References
- 66
- Citations by year
- 2025: 1 · 2024: 1 · 2023: 2 · 2022: 4 · 2021: 4 · 2020: 1 · 2019: 3 · 2018: 5 · 2017: 3 · 2016: 2 · 2015: 5 · 2014: 6 · 2013: 10 · 2012: 4
- FWCI
- 6.26
- Type
- journal article
- Language
- en
- Open access
- hybrid
- doi.org
- Licence
- Locations
- Journal of Biological Chemistry (publishedVersion, cc-by)
- PubMed (publishedVersion)
- Topics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Wnt/β-catenin signaling in development and cancer
- Health Sciences › Medicine › Pulmonary and Respiratory Medicine › Prostate Cancer Treatment and Research
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Genetics › Estrogen and related hormone effects
- Keywords
- androgen receptor, β-catenin, protein-protein interaction, nuclear translocation, dihydrotestosterone, GnRH neurons, transcriptional repression, T-cell factor, bicalutamide, hydroxyflutamide, androgen receptor antagonists, transcriptional regulation
- MeSH terms
- Androgen Antagonists, Animals, Cell Line, Cell Nucleus, Cytoskeletal Proteins, Immunohistochemistry, Ligands, Neurons, Precipitin Tests, Promoter Regions, Genetic, Receptors, Androgen, Receptors, Estrogen, Receptors, Glucocorticoid, Receptors, Progesterone, Transcription, Genetic, Blotting, Western, Trans-Activators, COS Cells, Two-Hybrid System Techniques, Protein Transport, Estrogen Receptor alpha, beta Catenin, Mice
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