title: Tumor suppressor REIC/DKK-3 and co-chaperone SGTA: Their interaction and roles in the androgen sensitivity.
abstract: REIC/DKK-3 is a tumor suppressor, however, its intracellular physiological functions and interacting molecules have not been fully clarified. Using yeast two-hybrid screening, we found that small glutamine-rich tetratricopeptide repeat-containing protein α (SGTA), known as a negative modulator of cytoplasmic androgen receptor (AR) signaling, is a novel interacting partner of REIC/DKK-3. Mammalian two-hybrid and pull-down assay results indicated that the SGTA-REIC/DKK-3 interaction involved the N-terminal regions of both REIC/DKK-3 and SGTA and that REIC/DKK-3 interfered with the dimerization of SGTA, which is a component of the AR complex and a suppressor of dynein motor-dependent AR transport and signaling. A reporter assay in human prostate cancer cells that displayed suppressed AR signaling by SGTA showed recovery of AR signaling by REIC/DKK-3 expression. Considering these results and our previous data that REIC/DKK-3 interacts with the dynein light chain TCTEX-1, we propose that the REIC/DKK-3 protein interferes with SGTA dimerization, promotes dynein-dependent AR transport and then upregulates AR signaling.
authors.affiliation: Department of Veterinary Nursing and Technology, School of Veterinary Science, Nippon Veterinary and Life Science University, Tokyo 180-8602, Japan.
authors.forename: Kazuhiko
authors.initials: K
authors.lastname: Ochiai
authors.affiliation: Laboratory of Laboratory Animal Science and Medicine, Department of Disease Control, Graduate School of Veterinary Medicine, Hokkaido University, Sapporo 060-0818, Japan.
authors.forename: Masami
authors.initials: M
authors.lastname: Morimatsu
authors.affiliation: Department of Veterinary Nursing and Technology, School of Veterinary Science, Nippon Veterinary and Life Science University, Tokyo 180-8602, Japan.
authors.forename: Yuiko
authors.initials: Y
authors.lastname: Kato
authors.affiliation: Department of Biological Resources, Integrated Center for Science, Ehime University, Ehime 791-0295, Japan.
authors.forename: Toshina
authors.initials: T
authors.lastname: Ishiguro-Oonuma
authors.affiliation: Department of Veterinary Nursing and Technology, School of Veterinary Science, Nippon Veterinary and Life Science University, Tokyo 180-8602, Japan.
authors.forename: Chihiro
authors.initials: C
authors.lastname: Udagawa
authors.affiliation: Department of Veterinary Technology Faculty of Veterinary Technology, Kasetsart University, Bangkok 10900, Thailand.
authors.forename: Oumaporn
authors.initials: O
authors.lastname: Rungsuriyawiboon
authors.affiliation: Department of Veterinary Nursing and Technology, School of Veterinary Science, Nippon Veterinary and Life Science University, Tokyo 180-8602, Japan.
authors.forename: Daigo
authors.initials: D
authors.lastname: Azakami
authors.affiliation: Department of Veterinary Pathology, School of Veterinary Science, Nippon Veterinary and Life Science University, Tokyo 180-8602, Japan.
authors.forename: Masaki
authors.initials: M
authors.lastname: Michishita
authors.affiliation: Department of Urology, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University, Okayama 700-8558, Japan.
authors.forename: Yuichi
authors.initials: Y
authors.lastname: Ariyoshi
authors.affiliation: Department of Urology, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University, Okayama 700-8558, Japan.
authors.forename: Hideo
authors.initials: H
authors.lastname: Ueki
authors.affiliation: Department of Urology, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University, Okayama 700-8558, Japan.
authors.forename: Yasutomo
authors.initials: Y
authors.lastname: Nasu
authors.affiliation: Department of Urology, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University, Okayama 700-8558, Japan.
authors.forename: Hiromi
authors.initials: H
authors.lastname: Kumon
authors.affiliation: Department of Urology, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University, Okayama 700-8558, Japan.
authors.forename: Masami
authors.initials: M
authors.lastname: Watanabe
authors.affiliation: Department of Veterinary Nursing and Technology, School of Veterinary Science, Nippon Veterinary and Life Science University, Tokyo 180-8602, Japan.
authors.forename: Toshinori
authors.initials: T
authors.lastname: Omi
mesh_terms: D048868:Adaptor Proteins, Signal Transducing; D000230:Adenocarcinoma / Q000235:genetics / Q000378:metabolism* / Q000473:pathology; D017209:Apoptosis; D015153:Blotting, Western; D002352:Carrier Proteins / Q000235:genetics / Q000378:metabolism*; D049109:Cell Proliferation; D018925:Chemokines; D006801:Humans; D036341:Intercellular Signaling Peptides and Proteins / Q000235:genetics / Q000378:metabolism*; D008297:Male; D018832:Molecular Chaperones; D011471:Prostatic Neoplasms / Q000235:genetics / Q000378:metabolism* / Q000473:pathology; D060066:Protein Interaction Maps; D055503:Protein Multimerization; D012333:RNA, Messenger / Q000235:genetics; D060888:Real-Time Polymerase Chain Reaction; D011944:Receptors, Androgen / Q000235:genetics / Q000378:metabolism*; D020133:Reverse Transcriptase Polymerase Chain Reaction; D014407:Tumor Cells, Cultured; D020798:Two-Hybrid System Techniques
chemical_list: C410798:AR protein, human; D048868:Adaptor Proteins, Signal Transducing; D002352:Carrier Proteins; D018925:Chemokines; C498624:DKK3 protein, human; D036341:Intercellular Signaling Peptides and Proteins; D018832:Molecular Chaperones; D012333:RNA, Messenger; D011944:Receptors, Androgen; C114575:SGTA protein, human
keywords: REIC/DKK-3; SGTA; TCTEX-1; androgen; prostate cancer.