title: Androgen receptor nuclear translocation is facilitated by the f-actin cross-linking protein filamin.
abstract: The human androgen receptor (hAR) is a ligand-dependent transcription factor responsible for the development of the male phenotype. The mechanism whereby nuclear translocation of the hAR is induced by its natural ligand 5alpha-dihydrotestosterone is a phenomenon not fully understood. The two-hybrid interaction trap assay has been used to isolate proteins that interact with the hAR in an attempt to identify molecules involved in hAR transactivation and movement. We have identified the actin-binding protein filamin, a 280-kDa component of the cytoskeleton, as an hAR interacting protein. This interaction is ligand independent but is enhanced in its presence. The functional significance of this interaction was analyzed using a cell line deficient in filamin via transient expression of a green fluorescent protein-hAR chimera. In filamin-deficient cells this revealed that hAR remained cytoplasmic even after prolonged exposure to synthetic ligand. Nuclear shuttling was restored when this cell line regained wild-type expression of filamin. These data suggest a novel role for filamin, implicating it as an important molecule in AR movement from the cytoplasm to the nucleus.
authors.affiliation: Prostate Research Group, School of Surgical and Reproductive Sciences, Medical School, University of Newcastle upon Tyne, England.
authors.forename: D M
authors.initials: DM
authors.lastname: Ozanne
authors.forename: M E
authors.initials: ME
authors.lastname: Brady
authors.forename: S
authors.initials: S
authors.lastname: Cook
authors.forename: L
authors.initials: L
authors.lastname: Gaughan
authors.forename: D E
authors.initials: DE
authors.lastname: Neal
authors.forename: C N
authors.initials: CN
authors.lastname: Robson
mesh_terms: D000199:Actins / Q000378:metabolism*; D000818:Animals; D000911:Antibodies, Monoclonal; D001665:Binding Sites; D001692:Biological Transport / Q000187:drug effects; D002467:Cell Nucleus / Q000378:metabolism*; D003285:Contractile Proteins / Q000172:deficiency / Q000494:pharmacology / Q000502:physiology*; D003432:Cross-Linking Reagents; D004247:DNA / Q000378:metabolism; D013196:Dihydrotestosterone / Q000494:pharmacology; D004742:Enhancer Elements, Genetic; D064448:Filamins; D049452:Green Fluorescent Proteins; D006801:Humans; D007163:Immunosorbent Techniques; D008164:Luminescent Proteins / Q000235:genetics; D051379:Mice; D008840:Microfilament Proteins / Q000172:deficiency / Q000494:pharmacology / Q000502:physiology*; D010446:Peptide Fragments / Q000737:chemistry / Q000378:metabolism; D011944:Receptors, Androgen / Q000235:genetics / Q000378:metabolism*; D011993:Recombinant Fusion Proteins; D020218:Response Elements / Q000235:genetics; D013256:Steroids / Q000378:metabolism; D014158:Transcription, Genetic / Q000187:drug effects; D015533:Transcriptional Activation; D014162:Transfection
chemical_list: D000199:Actins; D000911:Antibodies, Monoclonal; D003285:Contractile Proteins; D003432:Cross-Linking Reagents; D064448:Filamins; D008164:Luminescent Proteins; D008840:Microfilament Proteins; D010446:Peptide Fragments; D011944:Receptors, Androgen; D011993:Recombinant Fusion Proteins; D013256:Steroids; D013196:Dihydrotestosterone; D049452:Green Fluorescent Proteins; D004247:DNA