Liganded androgen receptor interaction with beta-catenin: nuclear co-localization and modulation of transcriptional activity in neuronal cells

J Biol Chem. 2002 Jun 7;277(23):20702-10. doi: 10.1074/jbc.M200545200. Epub 2002 Mar 26.


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.

Publication types

  • Research Support, U.S. Gov't, Non-P.H.S.

MeSH terms

  • Androgen Antagonists / pharmacology
  • Animals
  • Blotting, Western
  • COS Cells
  • Cell Line
  • Cell Nucleus / metabolism*
  • Cytoskeletal Proteins / metabolism*
  • Estrogen Receptor alpha
  • Immunohistochemistry
  • Ligands
  • Mice
  • Neurons / metabolism*
  • Precipitin Tests
  • Promoter Regions, Genetic
  • Protein Transport
  • Receptors, Androgen / metabolism*
  • Receptors, Estrogen / metabolism
  • Receptors, Glucocorticoid / metabolism
  • Receptors, Progesterone / metabolism
  • Trans-Activators*
  • Transcription, Genetic*
  • Two-Hybrid System Techniques
  • beta Catenin


  • Androgen Antagonists
  • CTNNB1 protein, mouse
  • Cytoskeletal Proteins
  • Estrogen Receptor alpha
  • Ligands
  • Receptors, Androgen
  • Receptors, Estrogen
  • Receptors, Glucocorticoid
  • Receptors, Progesterone
  • Trans-Activators
  • beta Catenin