Shanshan Liang1,2,3, Hidehisa Takahashi4,5, Tetsuro Hirose6, Yasuhiro Kuramitsu7, Shigetsugu Hatakeyama4, Hironori Yoshiyama2, Ruoyu Wang1, Jun-Ichi Hamada8,7, Hisashi Iizasa9,3. 1. The Key Laboratory of Biomarker High-throughput Screening and Target Translation of Breast and Gastrointestinal Tumor, Oncology Department, Affiliated Zhongshan Hospital of Dalian University, Dalian, P.R. China. 2. Department of Microbiology, Faculty of Medicine, Shimane University, Shimane, Japan. 3. Division of Stem Cell Biology, Institute for Genetic Medicine, Hokkaido University, Hokkaido, Japan. 4. Department of Biochemistry, Hokkaido University Graduate School of Medicine, Sapporo, Japan. 5. Department of Molecular Biology, Yokohama City University School of Medicine, Yokohama City University Graduate School of Medical Science, Yokohama, Japan. 6. Division of RNA Bio-function, Institute for Genetic Medicine, Hokkaido University, Sapporo, Japan. 7. Health Science University of Hokkaido School of Nursing & Social Services, Hokkaido, Japan. 8. Division of Stem Cell Biology, Institute for Genetic Medicine, Hokkaido University, Hokkaido, Japan jun1hamada@hoku-iryo-u.ac.jp iizasah@med.shimane-u.ac.jp. 9. Department of Microbiology, Faculty of Medicine, Shimane University, Shimane, Japan jun1hamada@hoku-iryo-u.ac.jp iizasah@med.shimane-u.ac.jp.
Abstract
BACKGROUND/AIM: Sex determining region Y (SRY)-box 2 (SOX2) is a transcription factor essential for the maintenance of proliferation and self-renewal of cancer stem cells and is associated with breast cancer initiation. Regulation of cancer stem cell plasticity by SOX2 requires both positive and negative SOX2 transcription factors, but the negative regulator is still largely unknown. MATERIALS AND METHODS: SOX2 promoter-binding proteins were identified by liquid chromatography-mass spectrometry/mass spectrometry, luciferase assay, and chromatin immunoprecipitation. The effects of one such transcription factor on SOX2 expression was investigated by knockdown and overexpression experiments. RESULTS: Non-POU domain-containing octamer-binding protein (NONO) (also known as 54-kDa nuclear RNA-binding protein, P54NRB) was identified as a SOX2 promoter-binding protein and a negative regulator of SOX2 expression. Its activity was controlled by its coiled-coil domain and the C-terminal domain. CONCLUSION: These results suggest that NONO acts as a key regulator of SOX2 transcription through the repression of SOX2 promoter activity in breast cancer cells. Copyright
BACKGROUND/AIM: Sex determining region Y (SRY)-box 2 (SOX2) is a transcription factor essential for the maintenance of proliferation and self-renewal of cancer stem cells and is associated with breast cancer initiation. Regulation of cancer stem cell plasticity by SOX2 requires both positive and negative SOX2 transcription factors, but the negative regulator is still largely unknown. MATERIALS AND METHODS:SOX2 promoter-binding proteins were identified by liquid chromatography-mass spectrometry/mass spectrometry, luciferase assay, and chromatin immunoprecipitation. The effects of one such transcription factor on SOX2 expression was investigated by knockdown and overexpression experiments. RESULTS:Non-POU domain-containing octamer-binding protein (NONO) (also known as 54-kDa nuclear RNA-binding protein, P54NRB) was identified as a SOX2 promoter-binding protein and a negative regulator of SOX2 expression. Its activity was controlled by its coiled-coil domain and the C-terminal domain. CONCLUSION: These results suggest that NONO acts as a key regulator of SOX2 transcription through the repression of SOX2 promoter activity in breast cancer cells. Copyright
Authors: Daniel M Passon; Mihwa Lee; Oliver Rackham; Will A Stanley; Agata Sadowska; Aleksandra Filipovska; Archa H Fox; Charles S Bond Journal: Proc Natl Acad Sci U S A Date: 2012-03-13 Impact factor: 11.205
Authors: Daniela Grimm; Johann Bauer; Petra Wise; Marcus Krüger; Ulf Simonsen; Markus Wehland; Manfred Infanger; Thomas J Corydon Journal: Semin Cancer Biol Date: 2019-03-23 Impact factor: 15.707