title: Androgen-receptor coregulators mediate the suppressive effect of androgen signals on vitamin D receptor activity.
abstract: Overexpression of androgen receptors (AR) in PC-3 cell, and treatment of 5alpha-dihydrotestosterone in LNCaP cells lead to the suppression of VDR transactivation. Competition for shared coregulators between AR and VDR is one possible mechanism to explain the suppressive effect of androgen-AR signals on VDR activity. Among the AR coregulators we tested, ARA54, ARA70, supervillin, and gelsolin were found to enhance VDR transactivation. Further characterization of the interaction between ARA54 or ARA70 and VDR demonstrated a direct interaction between VDR and ARA70, but no association between ARA54 and VDR. The LXXLL motif of ARA70 is essential for interaction with VDR and partially responsible for its function as a coactivator of VDR. The suppression of VDR transactivation by AR signal was restored by overexpression of ARA70, but not ARA54. Together, ARA70 and ARA54 modulate VDR transactivation, and the competition for ARA70 mediates the suppressive effect of androgen-AR on VDR transactivation.
authors.affiliation: Department of Urology, University of Rochester, 601 Elmwood Ave., Rochester, NY 14642, USA.
authors.forename: Huei-Ju
authors.initials: HJ
authors.lastname: Ting
authors.forename: Bo-Ying
authors.initials: BY
authors.lastname: Bao
authors.forename: Cheng-Lung
authors.initials: CL
authors.lastname: Hsu
authors.forename: Yi-Fen
authors.initials: YF
authors.lastname: Lee
mesh_terms: D020816:Amino Acid Motifs; D000818:Animals; D019556:COS Cells; D002117:Calcitriol / Q000037:antagonists & inhibitors / Q000378:metabolism / Q000494:pharmacology*; D045744:Cell Line, Tumor; D002522:Chlorocebus aethiops; D004268:DNA-Binding Proteins / Q000494:pharmacology; D018260:Gelsolin / Q000494:pharmacology; D005982:Glutathione Transferase / Q000378:metabolism; D051548:Histone Acetyltransferases; D006727:Hormone Antagonists / Q000494:pharmacology; D006801:Humans; D047908:Intracellular Signaling Peptides and Proteins / Q000494:pharmacology; D008297:Male; D008565:Membrane Proteins / Q000494:pharmacology; D008840:Microfilament Proteins / Q000494:pharmacology; D056985:Nuclear Receptor Co-Repressor 2; D056920:Nuclear Receptor Coactivator 1; D056918:Nuclear Receptor Coactivators; D015513:Oncogene Proteins / Q000494:pharmacology; D011471:Prostatic Neoplasms / Q000188:drug therapy / Q000378:metabolism*; D011944:Receptors, Androgen / Q000378:metabolism; D018167:Receptors, Calcitriol / Q000378:metabolism*; D012097:Repressor Proteins / Q000494:pharmacology; D014157:Transcription Factors / Q000494:pharmacology; D015533:Transcriptional Activation / Q000187:drug effects; D014162:Transfection; D020798:Two-Hybrid System Techniques
chemical_list: D004268:DNA-Binding Proteins; D018260:Gelsolin; D006727:Hormone Antagonists; D047908:Intracellular Signaling Peptides and Proteins; D008565:Membrane Proteins; D008840:Microfilament Proteins; C111382:NCOA4 protein, human; C539130:NCOR2 protein, human; D056985:Nuclear Receptor Co-Repressor 2; D056918:Nuclear Receptor Coactivators; D015513:Oncogene Proteins; C118499:RNF14 protein, human; D011944:Receptors, Androgen; D018167:Receptors, Calcitriol; D012097:Repressor Proteins; C109413:SVIL protein, human; D014157:Transcription Factors; D051548:Histone Acetyltransferases; C538859:NCOA1 protein, human; D056920:Nuclear Receptor Coactivator 1; D005982:Glutathione Transferase; D002117:Calcitriol