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

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

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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Crossref · 10.1074/jbc.m200545200

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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
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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