Tumor suppressor REIC/DKK-3 and co-chaperone SGTA: Their interaction and roles in the androgen sensitivity
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Kazuhiko Ochiai1,*, Masami Morimatsu2,*, Yuiko Kato1, Toshina Ishiguro-Oonuma3, Chihiro Udagawa1, Oumaporn Rungsuriyawiboon4, Daigo Azakami1, Masaki Michishita5, Yuichi Ariyoshi6, Hideo Ueki6, Yasutomo Nasu6, Hiromi Kumon6, Masami Watanabe6, Toshinori Omi1
1Department of Veterinary Nursing and Technology, School of Veterinary Science, Nippon Veterinary and Life Science University, Tokyo 180-8602, Japan
2Laboratory of Laboratory Animal Science and Medicine, Department of Disease Control, Graduate School of Veterinary Medicine, Hokkaido University, Sapporo 060-0818, Japan
3Department of Biological Resources, Integrated Center for Science, Ehime University, Ehime 791-0295, Japan
4Department of Veterinary Technology Faculty of Veterinary Technology, Kasetsart University, Bangkok 10900, Thailand
5Department of Veterinary Pathology, School of Veterinary Science, Nippon Veterinary and Life Science University, Tokyo 180-8602, Japan
6Department of Urology, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University, Okayama 700-8558, Japan
*These authors have contributed equally to this work
Masami Watanabe, e-mail: email@example.com
Keywords: REIC/DKK-3, SGTA, androgen, TCTEX-1, prostate cancer.
Received: July 13, 2015 Accepted: November 21, 2015 Published: December 02, 2015
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.
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