Regulation of antivirus innate immunity by stress granules

• Project/Area Number: 26670222
• Research Category: Grant-in-Aid for Challenging Exploratory Research
• Allocation Type: Multi-year Fund
• Research Field: Virology
• Research Institution: Niigata University
• Principal Investigator: Fujii Masahiro 新潟大学, 医歯学系, 教授 (30183099)
• Research Collaborator: HIGUCHI Masaya ; TAKAHASHI Masahiko
• Project Period (FY): 2014-04-01 – 2016-03-31
• Project Status: Completed (Fiscal Year 2015)
• Budget Amount: ¥3,640,000 (Direct Cost: ¥2,800,000、Indirect Cost: ¥840,000); Fiscal Year 2015: ¥1,820,000 (Direct Cost: ¥1,400,000、Indirect Cost: ¥420,000); Fiscal Year 2014: ¥1,820,000 (Direct Cost: ¥1,400,000、Indirect Cost: ¥420,000)
• Keywords: stress granules / HTLV-1 / Tax / USP10 / G3BP1 / ストレス顆粒 / G3BP2 / ROS

Outline of Final Research Achievements

USP10 is a component of stress granules. We established systemic USP10-knockout (KO) mice. USP10-KO mice developed bone marrow failure and severe anemia. Bone marrow failure in these USP10-KO mice was associated with reductions of hematopoietic stem cells（HSCs). Such USP10-KO HSCs exhibited enhanced apoptosis. These results suggest that USP10 is essential for hematopoiesis and functions by inhibiting apoptosis of HSCs, thereby regulating anti-viral immunity.

Research Products

• [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
  • Peer Reviewed / Open Access
• [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
  • Peer Reviewed / Open Access / Acknowledgement Compliant
• [Journal Article] Human T-cell leukemia virus type 1 Tax oncoprotein represses the expression of the BCL11B tumor suppressor in T-cells (2015)
  • 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
  • Peer Reviewed / Open Access / Acknowledgement Compliant
• [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
  • Peer Reviewed
• [Journal Article] Downregulation of proapoptotic Bim augments IL-2-independent T-cell transformation by human T-cell leukemia virus type-1 Tax. (2014)
  • Author(s): Higuchi M, Takahashi M, Tanaka Y, Fujii M.
  • Journal Title: Cancer Med. Volume: 3 Issue: 6 Pages: 1605-1614
  • DOI: 10.1002/cam4.329
  • Peer Reviewed / Open Access / Acknowledgement Compliant
• [Presentation] HTLV-1 Tax oncoprotein but not HTLV-2 Tax2 induces the expression of OX40 ligand by interacting with p52/p100 and RelB (2015)
  • Author(s): Fujii M、Motai Y, Takachi T, Higuchi M, Hara T, Takahashi M
  • Organizer: 第63回日本ウイルス学会
  • Place of Presentation: 福岡国際会議場（福岡県福岡市）
  • Year and Date: 2015-11-22
• [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、原敏文、高橋雅彦
  • Organizer: HTLV-1学会
  • Place of Presentation: 東京大学医科学研究所(東京都港区）
  • Year and Date: 2015-08-22
• [Presentation] 新規RasGAP蛋白RASAL3の生体内機能解析 (2014)
  • Author(s): 齋藤卓、樋口雅也、藤井雅寛
  • Organizer: 第37回日本分子生物学会年会
  • Place of Presentation: パシフィコ横浜
  • Year and Date: 2014-11-25
• [Presentation] HTLV-1 Taxによる細胞周期依存的な遺伝子発現の解析 (2014)
  • Author(s): 水口真理子、樋口雅也、藤井雅寛、中村正孝
  • Organizer: 第73回日本癌学会学術総会
  • Place of Presentation: パシフィコ横浜
  • Year and Date: 2014-09-25
• [Presentation] USP10はボルテゾミブによるATL細胞のアポトーシスを抑制する (2014)
  • Author(s): 藤井雅寛、髙橋真奈美、原敏文、樋口雅也、髙橋雅彦
  • 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 講堂
  • Year and Date: 2014-08-22 – 2014-08-24
• [Remarks] ウイルス学分野
  • URL: http://www.med.niigata-u.ac.jp/vir/welcome.htm
• [Remarks] ウイルス学研究活動
  • URL: http://www.med.niigata-u.ac.jp/contents/research/kiso/virus.html