Tumor suppressor REIC/DKK-3 and co-chaperone SGTA: Their interaction and roles in the androgen sensitivity

Autor: Hiromi Kumon, Masami Watanabe, Masaki Michishita, Oumaporn Rungsuriyawiboon, Toshinori Omi, Yasutomo Nasu, Yuiko Kato, Hideo Ueki, Kazuhiko Ochiai, Masami Morimatsu, Yuichi Ariyoshi, Toshina Ishiguro-Oonuma, Chihiro Udagawa, Daigo Azakami
Rok vydání: 2015
Předmět:
Male
TCTEX-1
040301 veterinary sciences
Blotting
Western
Apoptosis
androgen
Adenocarcinoma
Real-Time Polymerase Chain Reaction
Human prostate
law.invention
0403 veterinary science
REIC/DKK-3
03 medical and health sciences
Prostate cancer
0302 clinical medicine
law
Two-Hybrid System Techniques
Veterinary nursing
Tumor Cells
Cultured
Humans
Medicine
Protein Interaction Maps
RNA
Messenger
prostate cancer
Adaptor Proteins
Signal Transducing
Cell Proliferation
Reverse Transcriptase Polymerase Chain Reaction
business.industry
Prostatic Neoplasms
Androgen sensitivity
04 agricultural and veterinary sciences
medicine.disease
Disease control
Androgen receptor
Co-chaperone
SGTA
Oncology
Receptors
Androgen
030220 oncology & carcinogenesis
Immunology
Cancer research
Intercellular Signaling Peptides and Proteins
Suppressor
Chemokines
Protein Multimerization
Carrier Proteins
business
Molecular Chaperones
Research Paper
Zdroj: Oncotarget
ResearcherID
ISSN: 1949-2553
Popis: // Kazuhiko Ochiai 1,* , Masami Morimatsu 2,* , Yuiko Kato 1 , Toshina Ishiguro-Oonuma 3 , Chihiro Udagawa 1 , Oumaporn Rungsuriyawiboon 4 , Daigo Azakami 1 , Masaki Michishita 5 , Yuichi Ariyoshi 6 , Hideo Ueki 6 , Yasutomo Nasu 6 , Hiromi Kumon 6 , Masami Watanabe 6 , Toshinori Omi 1 1 Department of Veterinary Nursing and Technology, School of Veterinary Science, Nippon Veterinary and Life Science University, Tokyo 180-8602, Japan 2 Laboratory of Laboratory Animal Science and Medicine, Department of Disease Control, Graduate School of Veterinary Medicine, Hokkaido University, Sapporo 060-0818, Japan 3 Department of Biological Resources, Integrated Center for Science, Ehime University, Ehime 791-0295, Japan 4 Department of Veterinary Technology Faculty of Veterinary Technology, Kasetsart University, Bangkok 10900, Thailand 5 Department of Veterinary Pathology, School of Veterinary Science, Nippon Veterinary and Life Science University, Tokyo 180-8602, Japan 6 Department of Urology, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University, Okayama 700-8558, Japan * These authors have contributed equally to this work Correspondence to: Masami Watanabe , e-mail: mwcorrespondence@gmail.com Keywords: REIC/DKK-3, SGTA, androgen, TCTEX-1, prostate cancer. Received: July 13, 2015 Accepted: November 21, 2015 Published: December 02, 2015 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.
Databáze: OpenAIRE
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