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Crosstalk between stress granules and autophagy in protein degradation

Research Project

Project/Area Number 15H04704
Research Category

Grant-in-Aid for Scientific Research (B)

Allocation TypeSingle-year Grants
Section一般
Research Field Pathological medical chemistry
Research InstitutionNiigata University

Principal Investigator

Fujii Masahiro  新潟大学, 医歯学系, 教授 (30183099)

Co-Investigator(Kenkyū-buntansha) 小野寺 理  新潟大学, 脳研究所, 教授 (20303167)
Co-Investigator(Renkei-kenkyūsha) Komatsu Masaaki  新潟大学, 医歯学系, 教授 (90356254)
Research Collaborator Takahashi Masahiko  
Kageyama Shun  
Hara Toshifumi  
Higuchi Masaya  
Saito Kousuke  
Koyama Akihide  
Katsuragi Yoshinori  
Kakihana Taichi  
Project Period (FY) 2015-04-01 – 2018-03-31
Project Status Completed (Fiscal Year 2017)
Budget Amount *help
¥16,900,000 (Direct Cost: ¥13,000,000、Indirect Cost: ¥3,900,000)
Fiscal Year 2017: ¥5,200,000 (Direct Cost: ¥4,000,000、Indirect Cost: ¥1,200,000)
Fiscal Year 2016: ¥5,200,000 (Direct Cost: ¥4,000,000、Indirect Cost: ¥1,200,000)
Fiscal Year 2015: ¥6,500,000 (Direct Cost: ¥5,000,000、Indirect Cost: ¥1,500,000)
Keywordsストレス顆粒 / USP10 / 造血幹細胞 / アポトーシス / SCF / G3BP1 / G3BP2 / ストレス / 神経科学 / 癌 / 脳・神経 / 老化 / オートファジー / 脳神経疾患 / TDP-43
Outline of Final Research Achievements

USP10 plays an important role in the formation of stress granule. I established systemic USP10-knockout (USP10-KO) mice. USP10-KO mice developed pancytopenia, and died within 300 days. This pancytopenia was completely restored by transplantation of normal bone marrows into USP10-KO mice. Furthermore, I found that apoptosis of hematopoietic stem cells is aggravated in USP10-KO mice. SCL (stem cell factor) inhibits the apoptosis of hematopoietic stem cells, but this inhibition was significantly attenuated by USP10 depletion in hematopoietic stem cells. USP10 mutants indicated that deubiquitinase activity of USP10 is critical for inhibition of apoptosis of hematopoietic stem cells. The present study suggests that USP10 and stress granules participate in the maintenance of hematopoietic stem cells.

Report

(4 results)
  • 2017 Annual Research Report   Final Research Report ( PDF )
  • 2016 Annual Research Report
  • 2015 Annual Research Report
  • Research Products

    (19 results)

All 2018 2017 2016 2015

All Journal Article (11 results) (of which Int'l Joint Research: 1 results,  Peer Reviewed: 11 results,  Open Access: 10 results,  Acknowledgement Compliant: 4 results) Presentation (8 results) (of which Invited: 1 results)

  • [Journal Article] MAGI-1 expression is decreased in several types of human T-cell leukemia cell lines, including adult T-cell leukemia.2018

    • Author(s)
      Kozakai T, Takahashi M, Higuchi M, Hara T, Saito K, Tanaka Y, Masuko M, Takizawa J, Sone H, Fujii M
    • Journal Title

      International Journal of Hematology

      Volume: 107(3) Issue: 3 Pages: 337-344

    • DOI

      10.1007/s12185-017-2359-1

    • Related Report
      2017 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] Sox2-dependent inhibition of p21 is associated with poor prognosis of endometrial cancer2017

    • Author(s)
      Yamawaki K, Ishiguro T, Mori Y, Yoshihara K, Suda K, Tamura R, Yamaguchi M, Sekine M, Kashima K, Higuchi M, Fujii M, Okamoto K, Enomoto T
    • Journal Title

      Cancer Sci.

      Volume: 108 Issue: 4 Pages: 632

    • DOI

      10.1111/cas.13196

    • URL

      https://localhost/en/publications/d793b480-f145-4a57-bd67-216acad6010f

    • Related Report
      2017 Annual Research Report 2016 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] USP10 Is an Essential Deubiquitinase for Hematopoiesis and Inhibits Apoptosis of Long-Term Hematopoietic Stem Cells.2016

    • Author(s)
      Higuchi M, Kawamura H, Matsuki H, Hara T, Takahashi M, Saito S, Saito K, Jiang S, Naito M, Kiyonari H, Fujii M.
    • Journal Title

      Stem Cell Reports

      Volume: 7 Issue: 6 Pages: 1116-1129

    • DOI

      10.1016/j.stemcr.2016.11.003

    • Related Report
      2016 Annual Research Report
    • Peer Reviewed / Open Access / Acknowledgement Compliant
  • [Journal Article] Human T-cell leukemia virus type 1 (HTLV-1) Tax1 oncoprotein but not HTLV-2 Tax2 induces the expression of OX40 ligand by interacting with p52/p100 and RelB.2016

    • Author(s)
      Motai Y, Takahashi M, Takachi T, Higuchi M, Hara T, Mizuguchi M, Aoyagi Y, Terai S, Tanaka Y, Fujii M.
    • Journal Title

      Virus Genes.

      Volume: 52 Issue: 1 Pages: 4-13

    • DOI

      10.1007/s11262-015-1277-7

    • Related Report
      2016 Annual Research Report 2015 Annual Research Report
    • Peer Reviewed / Open Access / Acknowledgement Compliant
  • [Journal Article] Induction of Cell Death by Human T-cell Leukemia Virus Type 1 Tax in a Cell Cycle-Dependent Manner.2016

    • Author(s)
      Mizuguchi M, Sasaki Y, Hara T, Higuchi M, Tanaka Y, Funato N, Tanaka N, Fujii M, Nakamura M.
    • Journal Title

      PLoS One

      Volume: 11 Issue: 2 Pages: 0148217-0148217

    • DOI

      10.1371/journal.pone.0148217

    • Related Report
      2016 Annual Research Report 2015 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] Osteopontin-integrin interaction as a novel molecular target for antibody-mediated immunotherapy in adult T-cell leukemia.2015

    • Author(s)
      1.Maeda N, Ohashi T, Chagan-Yasutan, H, Hattori T, Takahashi Y, Harigae, H, Hasegawa H, Yamada Y, Fujii M, Maenaka K, and Uede T.
    • Journal Title

      Retrovirology

      Volume: 12 Issue: 1 Pages: 99-99

    • DOI

      10.1186/s12977-015-0225-x

    • Related Report
      2015 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] Loss of NDRG2 enhanced activation of the NF-κB pathway by PTEN and NIK phosphorylation for ATL and other cancer development.2015

    • Author(s)
      Ichikawa T, Nakahata S, Fujii M, Iha H, Morishita K.
    • Journal Title

      Sci Rep

      Volume: 5 Issue: 1 Pages: 12841-12841

    • DOI

      10.1038/srep12841

    • Related Report
      2015 Annual Research Report
    • Peer Reviewed / Open Access / Int'l Joint Research / Acknowledgement Compliant
  • [Journal Article] Superoxide-Generating Nox5α Is Functionally Required for the Human T-Cell Leukemia Virus Type 1-Induced Cell Transformation Phenotype.2015

    • Author(s)
      Shigemura T, Shiohara M, Kato M, Furuta S, Kaneda K, Morishita K, Hasegawa H, Fujii M, Gorlach A, Koike K, Kamata T.
    • Journal Title

      J Virol.

      Volume: 89 Issue: 17 Pages: 9080-9

    • DOI

      10.1128/jvi.00983-15

    • Related Report
      2015 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] RASAL3, a novel hematopoietic RasGAP protein, regulates the number and functions of NKT cells.2015

    • Author(s)
      Saito S, Kawamura T, Higuchi M, Kobayashi T, Yoshita-Takahashi M, Yamazaki M, Abe M, Sakimura K, Kanda Y, Kawamura H, Jiang S, Naito M, Yoshizaki T, Takahashi M, Fujii M.
    • Journal Title

      Eur J Immunol.

      Volume: in press Issue: 5 Pages: 1512-1523

    • DOI

      10.1002/eji.201444977

    • Related Report
      2015 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Kruppel-like factor 2 represses transcription of the telomerase catalytic subunit hTERT in human T cells.2015

    • Author(s)
      Hara T, Mizuguchi M, Fujii M, Nakamura M.
    • Journal Title

      J Biol Chem

      Volume: 290(14) Issue: 14 Pages: 8758-8763

    • DOI

      10.1074/jbc.m114.610386

    • Related Report
      2015 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] Human T-cell leukemia virus type 1 Tax oncoprotein represses the expression of the BCL11B tumor suppressor in T-cells2015

    • Author(s)
      Takachi T, Takahashi M, Takahashi-Yoshita M, Higuchi M, Obata M, Mishima Y, Okuda S, Tanaka Y, Matsuoka M, Saitoh A, Green PL, Fujii M.
    • Journal Title

      Cance Science

      Volume: 106(4) Issue: 4 Pages: 461-465

    • DOI

      10.1111/cas.12618

    • NAID

      120006844098

    • Related Report
      2015 Annual Research Report
    • Peer Reviewed / Open Access / Acknowledgement Compliant
  • [Presentation] Signal transduction of reactive oxygen species in HAM and ATL2017

    • Author(s)
      藤井雅寛、高橋雅彦、樋口雅也
    • Organizer
      日本HTLV-1学会学術集会
    • Related Report
      2017 Annual Research Report
    • Invited
  • [Presentation] Stress granules and autophagy control degradation of neuropathogenic RNA-binding proteins2017

    • Author(s)
      Masahiro Fujii, Toshifumi Hara, Masaya Higuchi, Osamu Onodera, Masahiko Takahashi
    • Organizer
      日本神経科学学会
    • Related Report
      2017 Annual Research Report
  • [Presentation] ストレス顆粒とオートファジーによる酸化ストレスの制御機構2017

    • Author(s)
      藤井雅寛, 原敏文、樋口雅也、高橋雅彦
    • Organizer
      日本抗加齢医学会
    • Related Report
      2017 Annual Research Report
  • [Presentation] 脱ユビキチン化酵素USP10はHematopoietic stem cellの恒常性維持に必須である2016

    • Author(s)
      川村 宏樹、樋口 雅也、藤井 雅寛
    • Organizer
      日本生体防御学会
    • Place of Presentation
      九州大学(福岡県福岡市)
    • Year and Date
      2016-07-07
    • Related Report
      2016 Annual Research Report
  • [Presentation] HTLV-1 Tax1 oncoprotein but not HTLV-2 Tax2 induces the expression of OX40 ligand by interacting with p52/p100 and RelB2015

    • Author(s)
      Masahiro Fujii, Yosuke Motai, Masaya Higuchi, Toshifumi Hara, Masahiko Takahashi
    • Organizer
      第63回日本ウイルス学会学術集会
    • Place of Presentation
      福岡国際会議場(福岡県福岡市)
    • Year and Date
      2015-11-22
    • Related Report
      2015 Annual Research Report
  • [Presentation] Ubiquitin Specific Protease 10 is essential for hematopoietic stem cell maintenance2015

    • Author(s)
      Masaya Higuchi, Hiroki Kawamura, Toshifumi Hara, Masahiko Takahashi, Masahiro Fujii
    • Organizer
      第77回日本血液学会学術集会
    • Place of Presentation
      ホテル日航金沢(石川県金沢市)
    • Year and Date
      2015-10-16
    • Related Report
      2015 Annual Research Report
  • [Presentation] Loss of NDRG2 enhanced activation of the NF-κB pathway by PTEN and NIK phosphorylation for ATLL development2015

    • Author(s)
      Ichikawa T, Nakahata S, Fujii M, Iha H, Morishita K.
    • Organizer
      第74回日本癌学会学術総会
    • Place of Presentation
      名古屋国際会議場(愛知県名古屋市)
    • Year and Date
      2015-10-08
    • Related Report
      2015 Annual Research Report
  • [Presentation] HTLV-1のTax1はHTLV-2のTax2とは異なる細胞遺伝子の発現をNF-kB2を介して誘導する2015

    • Author(s)
      藤井雅寛、罇陽介、原俊文、高橋雅彦
    • Organizer
      第2回日本HTLV-1学会学術集会
    • Place of Presentation
      東京大学医科学研究所(東京都港区)
    • Year and Date
      2015-08-22
    • Related Report
      2015 Annual Research Report

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Published: 2015-04-16   Modified: 2019-05-15  

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