Cited by 166Wnt/β-catenin signaling in development and cancerProstate Cancer Treatment and ResearchEstrogen and related hormone effects

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Liganded Androgen Receptor Interaction with β-Catenin

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Pawlowski, John E., Ertel, Jessica R., Allen, Melissa P., Xu, Mei, Butler, Cheryl, Wilson, Elizabeth M., Wierman, Margaret E.·2002·Journal of Biological Chemistry

DOI 10.1074/jbc.m200545200

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Abstract

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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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.
ORCID: Pawlowski, John E.
Xu, Mei
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)
DOI: 10.1074/jbc.m200545200
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: cc-by
www.elsevier.com/tdm/userlicense/1.0/ (tdm)
creativecommons.org/licenses/by/4.0/ (vor, 6697 d)
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
Life Sciences › Biochemistry, Genetics and Molecular Biology › Cancer Research › Prostate Cancer Treatment and Research
Life Sciences › Biochemistry, Genetics and Molecular Biology › Endocrinology › 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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Liganded Androgen Receptor Interaction with β-Catenin

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