ID | 64376 |
フルテキストURL | |
著者 |
Huang, Rongsheng
Department of Cellular Physiology Okayama University Graduate School of Medicine, Dentistry, and Pharmaceutical Sciences
Yamamoto, Takahiro
Department of Molecular Physiology Kumamoto University Faculty of Life Sciences Kumamoto
Nakata, Eiji
Department of Orthopedic Surgery Okayama University Graduate School of Medicine, Dentistry, and Pharmaceutical Sciences
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Ozaki, Toshifumi
Department of Orthopedic Surgery Okayama University Graduate School of Medicine, Dentistry, and Pharmaceutical Sciences
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Kurozumi, Kazuhiko
Department of Neurosurgery Hamamatsu University School of Medicine Hamamatsu
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Wei, Fanyan
Department of Modomics Biology and Medicine Institute of Development, Aging and Cancer Tohoku University
Tomizawa, Kazuhito
Department of Molecular Physiology Kumamoto University Faculty of Life Sciences Kumamoto
Fujimura, Atsushi
Department of Cellular Physiology Okayama University Graduate School of Medicine, Dentistry, and Pharmaceutical Sciences
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抄録 | Cancer stem-like cells (CSCs) have a unique translation mode, but little is understood about the process of elongation, especially the contribution of tRNA modifications to the maintenance of CSCs properties. Here, it is reported that, contrary to the initial aim, a tRNA-modifying methylthiotransferase CDKAL1 promotes CSC-factor SALL2 synthesis by assembling the eIF4F translation initiation complex. CDKAL1 expression is upregulated in patients with worse prognoses and is essential for maintaining CSCs in rhabdomyosarcoma (RMS) and common cancers. Translatome analysis reveals that a group of mRNAs whose translation is CDKAL1-dependent contains cytosine-rich sequences in the 5' untranslated region (5'UTR). Mechanistically, CDKAL1 promotes the translation of such mRNAs by organizing the eIF4F translation initiation complex. This complex formation does not require the enzyme activity of CDKAL1 but requires only the NH2-terminus domain of CDKAL1. Furthermore, sites in CDKAL1 essential for forming the eIF4F complex are identified and discovered candidate inhibitors of CDKAL1-dependent translation.
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キーワード | cancer stem-like cells
CG-rich 5'UTR
eIF4F complex
CDKAL1
SALL2
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発行日 | 2023-02-14
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出版物タイトル |
Advanced Science
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出版者 | Wiley
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開始ページ | 2206542
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ISSN | 2198-3844
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資料タイプ |
学術雑誌論文
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言語 |
英語
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OAI-PMH Set |
岡山大学
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著作権者 | © 2023 The Authors.
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論文のバージョン | publisher
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DOI | |
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関連URL | isVersionOf https://doi.org/10.1002/advs.202206542
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ライセンス | https://creativecommons.org/licenses/by/4.0/
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助成機関名 |
Japan Society for the Promotion of Science
Japan Agency for Medical Research and Development
Naito Memorial Foundation
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助成番号 | JP20K07618
JP18cm0106143
JP20cm0106179
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