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The role of ubiquitin-proteasome system in hepatitis B virus replication

Research Project

Project/Area Number 18K07961
Research Category

Grant-in-Aid for Scientific Research (C)

Allocation TypeMulti-year Fund
Section一般
Review Section Basic Section 53010:Gastroenterology-related
Research InstitutionThe University of Tokyo

Principal Investigator

TANAKA YASUO  東京大学, 医学部附属病院, 助教 (40422290)

Co-Investigator(Kenkyū-buntansha) 建石 良介  東京大学, 医学部附属病院, 講師 (50444089)
Project Period (FY) 2018-04-01 – 2021-03-31
Project Status Completed (Fiscal Year 2020)
Budget Amount *help
¥4,420,000 (Direct Cost: ¥3,400,000、Indirect Cost: ¥1,020,000)
Fiscal Year 2020: ¥1,300,000 (Direct Cost: ¥1,000,000、Indirect Cost: ¥300,000)
Fiscal Year 2019: ¥1,300,000 (Direct Cost: ¥1,000,000、Indirect Cost: ¥300,000)
Fiscal Year 2018: ¥1,820,000 (Direct Cost: ¥1,400,000、Indirect Cost: ¥420,000)
KeywordsHBV / HBV Xタンパク / ユビキチン・プロテアソーム系 / ユビキチンリガーゼ / CUL4-DDB1 / Xタンパク
Outline of Final Research Achievements

In this study, we investigated the role of ubiquitin-proteasome system in HBV replication. We identified DDX1(ATP-dependent RNA helicase DDX1) as a novel HBx-interacting protein using a tandem affinity purification method and demonstrated that DDX1 enhanced HBV RNA transcription. Furthermore, the ATPase domain of DDX1 was responsible for the enhancement of HBV replication. These results suggest that DDX1 could be an attractive therapeutic target for inhibiting HBV pathogenesis.

Academic Significance and Societal Importance of the Research Achievements

B型肝炎ウイルスは既存の内服薬により増殖を抑えることが可能だが、長期投与による薬剤耐性株の出現と薬剤中止による肝炎再燃が大きな問題となっており、新規抗ウイルス薬の開発が求められている。本研究ではタンパク分解系であるユビキチン・プロテアソーム系のB型肝炎ウイルス複製における役割を検討することにより、ウイルスの増殖に関与する宿主タンパクを同定し得た。本研究の新規治療法の開発への寄与が期待される。

Report

(4 results)
  • 2020 Annual Research Report   Final Research Report ( PDF )
  • 2019 Research-status Report
  • 2018 Research-status Report
  • Research Products

    (16 results)

All 2021 2020 2019 2018

All Journal Article (12 results) (of which Int'l Joint Research: 3 results,  Peer Reviewed: 12 results,  Open Access: 8 results) Presentation (4 results)

  • [Journal Article] Inhibition of histone methyltransferase G9a attenuates liver cancer initiation by sensitizing DNA-damaged hepatocytes to p53-induced apoptosis2021

    • Author(s)
      Takuma Nakatsuka, Keisuke Tateishi*, Hiroyuki Kato, Hiroaki Fujiwara, Keisuke Yamamoto, Yotaro Kudo, Hayato Nakagawa, Yasuo Tanaka, Hideaki Ijichi, Tsuneo Ikenoue, Takeaki Ishizawa, Kiyoshi Hasegawa, Makoto Tachibana, Yoichi Shinkai, Kazuhiko Koike
    • Journal Title

      Cell Death and Disease

      Volume: 12 Issue: 1 Pages: 99111-99111

    • DOI

      10.1038/s41419-020-03381-1

    • Related Report
      2020 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] Soluble VCAM-1 promotes gemcitabine resistance via macrophage infiltration and predicts therapeutic response in pancreatic cancer2020

    • Author(s)
      Takahashi Ryota、Ijichi Hideaki、Sano Makoto、Miyabayashi Koji、Mohri Dai、Kim Jinsuk、Kimura Gen、Nakatsuka Takuma、Fujiwara Hiroaki、Yamamoto Keisuke、Kudo Yotaro、Tanaka Yasuo、Tateishi Keisuke、Nakai Yousuke、Morishita Yasuyuki、Soma Katsura、Takeda Norihiko、Moses Harold L.、Isayama Hiroyuki、Koike Kazuhiko
    • Journal Title

      Scientific Reports

      Volume: 10 Issue: 1 Pages: 1-13

    • DOI

      10.1038/s41598-020-78320-3

    • Related Report
      2020 Annual Research Report
    • Peer Reviewed / Open Access / Int'l Joint Research
  • [Journal Article] Deletion of Histone Methyltransferase G9a Suppresses Mutant Kras-driven Pancreatic Carcinogenesis Carcinogenesis2020

    • Author(s)
      Hiroyuki Kato, Keisuke Tateishi*, Hiroaki Fujiwara, Hideaki Ijichi, Keisuke Yamamoto, Takuma Nakatsuka, Miwako Kakiuchi, Makoto Sano, Yotaro Kudo, Yoku Hayakawa, Hayato Nakagawa, Yasuo Tanaka, Motoyuki Otsuka, Yoshihiro Hirata, Makoto Tachibana, Yoichi Shinkai, Kazuhiko Koike
    • Journal Title

      Cancer Genomics Proteomics

      Volume: 17 Issue: 6 Pages: 695705-695705

    • DOI

      10.21873/cgp.20224

    • Related Report
      2020 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] Improved liver function in patients with cirrhosis due to chronic hepatitis C virus who achieve sustained virologic response is not accompanied by increased liver volume2020

    • Author(s)
      Wake Taijiro、Tateishi Ryosuke、Fukumoto Tsuyoshi、Nakagomi Ryo、Kinoshita Mizuki Nishibatake、Nakatsuka Takuma、Sato Masaya、Minami Tatsuya、Uchino Koji、Enooku Kenichiro、Nakagawa Hayato、Fujinaga Hidetaka、Asaoka Yoshinari、Tanaka Yasuo、Otsuka Motoyuki、Koike Kazuhiko
    • Journal Title

      PLOS ONE

      Volume: 15 Issue: 4 Pages: e0231836-e0231836

    • DOI

      10.1371/journal.pone.0231836

    • URL

      https://pure.teikyo.jp/en/publications/fc54350e-ae3f-49ea-8e39-98b85bff7a2e

    • Related Report
      2020 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] Mutant IDH1 confers resistance to energy stress in normal biliary cells through PFKP-induced aerobic glycolysis and AMPK activation2019

    • Author(s)
      Fujiwara H、Tateishi K、Misumi K、Hayashi A、Igarashi K、Kato H、Nakatsuka T、Suzuki N、Yamamoto K、Kudo Y、Hayakawa Y、Nakagawa 、Tanaka Y、Ijichi H、Kogure H、Nakai Y、Isayama H、Hasegawa K、Fukayama M、Soga T、Koike K
    • Journal Title

      Scientific Reports

      Volume: 9 Issue: 1 Pages: 18859-18859

    • DOI

      10.1038/s41598-019-55211-w

    • Related Report
      2019 Research-status Report
    • Peer Reviewed / Open Access
  • [Journal Article] A Novel Non-invasive Method for Predicting Liver Fibrosis by Quantifying the Hepatic Vein Waveform2019

    • Author(s)
      Soroida Y, Nakatsuka T, Sato M, Nakagawa H, Tanaka M, Yamauchi N, Wake T, Nakagomi R, Kinoshita MN, Minami T, Uchino K, Enooku K, Asaoka Y, Tanaka Y, Endo M, Nakamura A, Kobayashi T, Kurihara M, Hikita H, Sato M, Gotoh H, Iwai T, Fukayama M, Ikeda H, Tateishi R, Yatomi Y, Koike K.
    • Journal Title

      Ultrasound Med Biol.

      Volume: 45 Issue: 9 Pages: 2363

    • DOI

      10.1016/j.ultrasmedbio.2019.05.028

    • Related Report
      2019 Research-status Report
    • Peer Reviewed
  • [Journal Article] Successful treatment of chronic hepatitis C virus infection with crushed glecaprevir/pibrentasvir administered via a percutaneous endoscopic gastrostomy tube: case report and review of the literature.2019

    • Author(s)
      Tanaka Y、Tateishi R、Koike K
    • Journal Title

      Clinical Journal of Gastroenterology

      Volume: 12 Issue: 6 Pages: 588-591

    • DOI

      10.1007/s12328-019-00997-5

    • Related Report
      2019 Research-status Report
    • Peer Reviewed
  • [Journal Article] Ischemic complications after percutaneous radiofrequency ablation of liver tumors: Liver volume loss and recovery2019

    • Author(s)
      Wake T、Tateishi R、Nakagomi R、Fujiwara N、Kinoshita MN、Nakatsuka T、Sato M、Minami T、Uchino K、Enooku K、Nakagawa H、Asaoka Y、Tanaka Y、Shiina S、Koike K
    • Journal Title

      Hepatology Research

      Volume: 49 Issue: 4 Pages: 453

    • DOI

      10.1111/hepr.13302

    • Related Report
      2019 Research-status Report
    • Peer Reviewed
  • [Journal Article] Blocking CXCLs?CXCR2 axis in tumor?stromal interactions contributes to survival in a mouse model of pancreatic ductal adenocarcinoma through reduced cell invasion/migration and a shift of immune-inflammatory microenvironment2019

    • Author(s)
      Sano Makoto、Ijichi Hideaki、Takahashi Ryota、Miyabayashi Koji、Fujiwara Hiroaki、Yamada Tomoharu、Kato Hiroyuki、Nakatsuka Takuma、Tanaka Yasuo、Tateishi Keisuke、Morishita Yasuyuki、Moses Harold L.、Isayama Hiroyuki、Koike Kazuhiko
    • Journal Title

      Oncogenesis

      Volume: 8 Issue: 2 Pages: 8-8

    • DOI

      10.1038/s41389-018-0117-8

    • Related Report
      2019 Research-status Report
    • Peer Reviewed / Open Access / Int'l Joint Research
  • [Journal Article] Proteoglycans Are Attractive Biomarkers and Therapeutic Targets in Hepatocellular Carcinoma.2018

    • Author(s)
      Tanaka Y, Tateishi R, Koike K.
    • Journal Title

      Int J Mol Sci.

      Volume: 19 Issue: 10 Pages: 3070-3070

    • DOI

      10.3390/ijms19103070

    • Related Report
      2018 Research-status Report
    • Peer Reviewed / Open Access
  • [Journal Article] Isocitrate dehydrogenase 1 mutation sensitizes intrahepatic cholangiocarcinoma to the BET inhibitor JQ12018

    • Author(s)
      Fujiwara Hiroaki、Tateishi Keisuke、Kato Hiroyuki、Nakatsuka Takuma、Yamamoto Keisuke、Tanaka Yasuo、Ijichi Hideaki、Takahara Naminatsu、Mizuno Suguru、Kogure Hirofumi、Matsubara Saburo、Nakai Yousuke、Koike Kazuhiko
    • Journal Title

      Cancer Science

      Volume: 109 Issue: 11 Pages: 3602-3610

    • DOI

      10.1111/cas.13784

    • Related Report
      2018 Research-status Report
    • Peer Reviewed
  • [Journal Article] CPT2 downregulation adapts HCC to lipid-rich environment and promotes carcinogenesis via acylcarnitine accumulation in obesity2018

    • Author(s)
      Fujiwara Naoto、Nakagawa Hayato、Enooku Kenichiro、Otsuka Motoyuki、Tateishi Keisuke、Koike Kazuhiko
    • Journal Title

      Gut

      Volume: 67 Issue: 8 Pages: 1493-1504

    • DOI

      10.1136/gutjnl-2017-315193

    • Related Report
      2018 Research-status Report
    • Peer Reviewed / Open Access / Int'l Joint Research
  • [Presentation] 治療後 cell-free DNA 解析による分子標的薬の治療効果予測2020

    • Author(s)
      中塚拓馬、中川勇人、早田有希、和気泰次郎、山田友春、木下瑞希、中込良、 佐藤雅哉、南達也、榎奥健一郎、工藤洋太郎、田中康雄、 大塚基之、建石良介、小池和彦
    • Organizer
      第23回日本肝がん分子標的治療研究会
    • Related Report
      2020 Annual Research Report
  • [Presentation] 肝癌前駆細胞を制御するヒストンメチル化修飾機構2018

    • Author(s)
      中塚拓馬,立石敬介,工藤洋太郎,山本恵介,中川勇人,藤原弘明,田中康雄,酒井寿郎,油谷浩幸,眞貝洋一,小池和彦.
    • Organizer
      第25 回肝細胞研究会
    • Related Report
      2018 Research-status Report
  • [Presentation] 肝癌前駆細胞を制御するヒストンメチル化修飾機構2018

    • Author(s)
      中塚拓馬,立石敬介,工藤洋太郎,山本恵介,中川勇人,藤原弘明,田中康雄,酒井寿郎,油谷浩幸,眞貝洋一,小池和彦.
    • Organizer
      第55 回日本臨床分子医学会学術集会
    • Related Report
      2018 Research-status Report
  • [Presentation] ATP 依存性RNA ヘリカーゼDDX1 のHBV 複製における役割の検討2018

    • Author(s)
      田中康雄,立石敬介,小池和彦.
    • Organizer
      第104 回日本消化器病学会総会
    • Related Report
      2018 Research-status Report

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Published: 2018-04-23   Modified: 2022-01-27  

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