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J-GLOBAL ID：202002249133908836   整理番号：20A1172916

IMPデヒドロゲナーゼ-2は膠芽腫において異常な核小体活性を駆動し,腫瘍形成を促進する【JST・京大機械翻訳】

IMP dehydrogenase-2 drives aberrant nucleolar activity and promotes tumorigenesis in glioblastoma

著者 (69件)： Kofuji Satoshi (Division of Hematology and Oncology, Department of Internal Medicine, University of Cincinnati College of Medicine, Cincinnati, OH, USA) ,  Kofuji Satoshi (Graduate School of Biomedical & Health Sciences, Hiroshima University, Hiroshima, Japan) ,  Hirayama Akiyoshi (Institute for Advanced Biosciences, Keio University, Tsuruoka, Japan) ,  Eberhardt Alexander Otto (Institute of Biochemistry and Biophysics, Center for Molecular Biomedicine, Friedrich Schiller University Jena, Jena, Germany) ,  Eberhardt Alexander Otto (Leibniz-Institute on Aging-Fritz Lipmann Institute, Jena, Germany) ,  Kawaguchi Risa (Division of Hematology and Oncology, Department of Internal Medicine, University of Cincinnati College of Medicine, Cincinnati, OH, USA) ,  Kawaguchi Risa (Artificial Intelligence Research Center, National Institute of Advanced Industrial Science and Technology, Tokyo, Japan) ,  Sugiura Yuki (Department of Biochemistry, Keio University School of Medicine, Tokyo, Japan) ,  Sampetrean Oltea (Division of Gene Regulation, Institute for Advanced Medical Research, Keio University School of Medicine, Tokyo, Japan) ,  Ikeda Yoshiki (Division of Hematology and Oncology, Department of Internal Medicine, University of Cincinnati College of Medicine, Cincinnati, OH, USA) ,  Warren Mikako (Division of Pathology, Cincinnati Children’s Hospital Medical Center, Cincinnati, OH, USA) ,  Warren Mikako (Department of Pathology and Laboratory Medicine, Children’s Hospital Los Angeles and Keck School of Medicine, University of Southern California, Los Angeles, CA, USA) ,  Sakamoto Naoya (Graduate School of Biomedical & Health Sciences, Hiroshima University, Hiroshima, Japan) ,  Kitahara Shuji (Department of Anatomy and Developmental Biology, Tokyo Women’s Medical University School of Medicine, Tokyo, Japan) ,  Yoshino Hirofumi (Division of Hematology and Oncology, Department of Internal Medicine, University of Cincinnati College of Medicine, Cincinnati, OH, USA) ,  Yamashita Daisuke (Department of Neurosurgery, University of Alabama at Birmingham, Birmingham, AL, USA) ,  Sumita Kazutaka (Division of Hematology and Oncology, Department of Internal Medicine, University of Cincinnati College of Medicine, Cincinnati, OH, USA) ,  Wolfe Kara (Division of Hematology and Oncology, Department of Internal Medicine, University of Cincinnati College of Medicine, Cincinnati, OH, USA) ,  Lange Lisa (Institute of Biochemistry and Biophysics, Center for Molecular Biomedicine, Friedrich Schiller University Jena, Jena, Germany) ,  Lange Lisa (Leibniz-Institute on Aging-Fritz Lipmann Institute, Jena, Germany) ,  Ikeda Satsuki (Institute for Advanced Biosciences, Keio University, Tsuruoka, Japan) ,  Shimada Hiroko (Division of Hematology and Oncology, Department of Internal Medicine, University of Cincinnati College of Medicine, Cincinnati, OH, USA) ,  Minami Noriaki (Division of Gene Regulation, Institute for Advanced Medical Research, Keio University School of Medicine, Tokyo, Japan) ,  Malhotra Akshiv (Division of Hematology and Oncology, Department of Internal Medicine, University of Cincinnati College of Medicine, Cincinnati, OH, USA) ,  Morioka Shin (Graduate School of Biomedical & Health Sciences, Hiroshima University, Hiroshima, Japan) ,  Ban Yuki (Graduate School of Biomedical & Health Sciences, Hiroshima University, Hiroshima, Japan) ,  Asano Maya (Graduate School of Biomedical & Health Sciences, Hiroshima University, Hiroshima, Japan) ,  Flanary Victoria L. (Department of Neurosurgery, University of Alabama at Birmingham, Birmingham, AL, USA) ,  Ramkissoon Annmarie (Cancer and Blood Diseases Institute, Cincinnati Children’s Hospital Medical Center, Cincinnati, OH, USA) ,  Chow Lionel M. L. (Cancer and Blood Diseases Institute, Cincinnati Children’s Hospital Medical Center, Cincinnati, OH, USA) ,  Kiyokawa Juri (Department of Neurosurgery, Massachusetts General Hospital and Harvard Medical School, Boston, MA, USA) ,  Mashimo Tomoyuki (Department of Internal Medicine; Harold C. Simmons Comprehensive Cancer Center; Annette G. Strauss Center for Neuro-Oncology, University of Texas Southwestern Medical Center, Dallas, TX, USA) ,  Lucey Greg (Division of Neuropathology, Department of Pathology and Laboratory Medicine, David Geffen School of Medicine at UCLA, Los Angeles, CA, USA) ,  Mareninov Sergey (Division of Neuropathology, Department of Pathology and Laboratory Medicine, David Geffen School of Medicine at UCLA, Los Angeles, CA, USA) ,  Ozawa Tatsuya (Division of Human Biology, Solid Tumor and Translational Research, Fred Hutchinson Cancer Research Center, Seattle, WA, USA) ,  Onishi Nobuyuki (Division of Gene Regulation, Institute for Advanced Medical Research, Keio University School of Medicine, Tokyo, Japan) ,  Okumura Koichi (Division of Hematology and Oncology, Department of Internal Medicine, University of Cincinnati College of Medicine, Cincinnati, OH, USA) ,  Terakawa Jumpei (Division of Transgenic Animal Science, Advanced Science Research Center, Kanazawa University, Kanazawa, Japan) ,  Daikoku Takiko (Division of Transgenic Animal Science, Advanced Science Research Center, Kanazawa University, Kanazawa, Japan) ,  Wise-Draper Trisha (Division of Hematology and Oncology, Department of Internal Medicine, University of Cincinnati College of Medicine, Cincinnati, OH, USA) ,  Majd Nazanin (Department of Neurology, University of Cincinnati College of Medicine, Cincinnati, OH, USA) ,  Kofuji Kaori (Division of Hematology and Oncology, Department of Internal Medicine, University of Cincinnati College of Medicine, Cincinnati, OH, USA) ,  Sasaki Mika (Division of Hematology and Oncology, Department of Internal Medicine, University of Cincinnati College of Medicine, Cincinnati, OH, USA) ,  Mori Masaru (Institute for Advanced Biosciences, Keio University, Tsuruoka, Japan) ,  Kanemura Yonehiro (Department of Biomedical Research and Innovation, Institute for Clinical Research, National Hospital Organization Osaka National Hospital, Osaka, Japan) ,  Smith Eric P. (Department of Internal Medicine, University of Cincinnati College of Medicine, Cincinnati, OH, USA) ,  Anastasiou Dimitrios (Cancer Metabolism Laboratory, The Francis Crick Institute, London, UK) ,  Wakimoto Hiroaki (Department of Neurosurgery, Massachusetts General Hospital and Harvard Medical School, Boston, MA, USA) ,  Holland Eric C. (Division of Human Biology, Solid Tumor and Translational Research, Fred Hutchinson Cancer Research Center, Seattle, WA, USA) ,  Yong William H. (Division of Neuropathology, Department of Pathology and Laboratory Medicine, David Geffen School of Medicine at UCLA, Los Angeles, CA, USA) ,  Horbinski Craig (Department of Pathology, University of Kentucky College of Medicine, Lexington, KY, USA) ,  Horbinski Craig (Departments of Pathology and Neurosurgery, Northwestern University, Chicago, IL, USA) ,  Nakano Ichiro (Department of Neurosurgery, University of Alabama at Birmingham, Birmingham, AL, USA) ,  DeBerardinis Ralph J. (Howard Hughes Medical Institute; Children’s Medical Center Research Institute; Department of Pediatrics and Eugene McDermott Center for Human Growth and Development, University of Texas Southwestern Medical Center, Dallas, TX, USA) ,  Bachoo Robert M. (Department of Internal Medicine; Harold C. Simmons Comprehensive Cancer Center; Annette G. Strauss Center for Neuro-Oncology, University of Texas Southwestern Medical Center, Dallas, TX, USA) ,  Bachoo Robert M. (Department of Neurology and Neurotherapeutics, University of Texas Southwestern Medical Center, Dallas, TX, USA) ,  Mischel Paul S. (Ludwig Institute for Cancer Research; Department of Pathology; Moores Cancer Center, University of California San Diego School of Medicine, La Jolla, CA, USA) ,  Yasui Wataru (Graduate School of Biomedical & Health Sciences, Hiroshima University, Hiroshima, Japan) ,  Suematsu Makoto (Department of Biochemistry, Keio University School of Medicine, Tokyo, Japan) ,  Saya Hideyuki (Division of Gene Regulation, Institute for Advanced Medical Research, Keio University School of Medicine, Tokyo, Japan) ,  Soga Tomoyoshi (Institute for Advanced Biosciences, Keio University, Tsuruoka, Japan) ,  Soga Tomoyoshi (AMED-CREST, AMED, Tokyo, Japan) ,  Grummt Ingrid (Division of Molecular Biology of the Cell II, German Cancer Research Center, DKFZ-ZMBH Alliance, Heidelberg, Germany) ,  Bierhoff Holger (Institute of Biochemistry and Biophysics, Center for Molecular Biomedicine, Friedrich Schiller University Jena, Jena, Germany) ,  Bierhoff Holger (Leibniz-Institute on Aging-Fritz Lipmann Institute, Jena, Germany) ,  Sasaki Atsuo T. (Division of Hematology and Oncology, Department of Internal Medicine, University of Cincinnati College of Medicine, Cincinnati, OH, USA) ,  Sasaki Atsuo T. (Institute for Advanced Biosciences, Keio University, Tsuruoka, Japan) ,  Sasaki Atsuo T. (Department of Cancer Biology, University of Cincinnati College of Medicine, Cincinnati, OH, USA) ,  Sasaki Atsuo T. (Department of Neurosurgery, Brain Tumor Center at UC Gardner Neuroscience Institute, Cincinnati, OH, USA)
資料名： Nature Cell Biology  (Nature Cell Biology)
巻： 21  号： 8  ページ： 1003-1014  発行年： 2019年 
JST資料番号： W1369A  ISSN： 1465-7392  資料種別： 逐次刊行物 (A)
記事区分： 原著論文  発行国： ドイツ (DEU)  言語： 英語 (EN)

抄録/ポイント： 多くの癌において,高い増殖率はrRNAおよびtRNAレベルの上昇および核小体肥大と相関する。しかしながら,増加した核小体転写と腫瘍形成を結びつける基礎となる機構は,わずかにしか理解されていない。ここでは,de novoグアニンヌクレオチド生合成に対する律速酵素,IMPデヒドロゲナーゼ-2(IMPDH2)が,高致死性脳ガングリア芽細胞腫で過剰発現することを示した。これにより,rRNAおよびtRNA合成の増加,核小体GTP結合蛋白質ヌクレオステミンの安定化,および拡大し,形成された核小体が誘導された。グリア芽細胞腫におけるIMPDH2の薬理学的または遺伝的不活性化はこれらの効果を逆転させ,細胞増殖を阻害するが,非形質転換グリア細胞は類似のIMPDH2摂動により影響を受けない。IMPDH2活性の障害は,機能的p53の不在下でさえ,グリア芽細胞腫細胞の核小体ストレスと成長停止を誘発する。著者らの結果は,IMPDH2のアップレギュレーションが異常な核小体機能の発生のための必要条件であり,グリア芽細胞腫における同化過程を増加させることを明らかにし,それは神経膠腫形成における一次イベントを構成する。Kofujiらは,IMPDH2のアップレギュレーションがヌクレオステミン安定化と核小体奇形を促進し,その不活性化がグリア芽細胞腫における成長停止を誘導することを示す。Copyright The Author(s), under exclusive licence to Springer Nature Limited 2019 Translated from English into Japanese by JST.【JST・京大機械翻訳】

シソーラス用語： 酵素 ,  生合成 ,  rRNA ,  tRNA ,  遺伝 ,  細胞増殖 ,  グリア細胞 ,  神経膠腫 ,  薬理学 ,  摂動 ,  アップレギュレーション ,  *腫瘤形成 ,  p53タンパク質 ,  *膠芽腫 ,  過剰発現

分類 (2件)： 腫ようの化学・生化学・病理学  (GE02030N) ,  生物学的機能  (EB03040U)

タイトルに関連する用語 (6件)： IMPデヒドロゲナーゼ ,  膠芽腫 ,  核小体 ,  活性 ,  腫瘍形成 ,  促進