Liganded Androgen Receptor Interaction with β-Catenin

• Published in: The Journal of biological chemistry 2002-06, Vol.277 (23), p.20702
• Main Authors: John E. Pawlowski, Jessica R. Ertel, Melissa P. Allen, Mei Xu, Cheryl Butler, Elizabeth M. Wilson, Margaret E. Wierman
• Format: Article
• Language: English
• ISSN: 0021-9258; 1083-351X
• DOI: 10.1074/jbc.M200545200

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-(Δ371–485)) as a bait, β-catenin was identified as an AR-interacting protein from a gonadotropin-releasing hormone neuronal cell library. Immunolocalization of co-transfected AR and FLAG-β-catenin demonstrated that FLAG-β-catenin was predominantly cytoplasmic in the absence of androgen. In the presence of 5α-dihydrotestosterone, FLAG-β-catenin completely co-localized to the nucleus with AR. This effect was specific to AR because liganded progesterone, glucocorticoid, or estrogen α receptors did not translocate FLAG-β-catenin to the nucleus. Agonist-bound AR was required because the AR antagonists casodex and hydroxyflutamide failed to translocate β-catenin. Time course experiments demonstrated that co-translocation occurred with similar kinetics. Nuclear co-localization was independent of the glycogen synthase kinase-3β, 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 β-catenin/T cell factor-responsive reporter gene activity. Conversely, co-expression of β-catenin/T cell factor repressed AR stimulation of AR-responsive reporter gene activity. Our data suggest that liganded AR shuttles β-catenin to the nucleus and that nuclear interaction of AR with β-catenin may modulate transcriptional activity in androgen target tissues.