• Search Research Projects
  • Search Researchers
  • How to Use
  1. Back to previous page

PRR発現調節に着目した癌抑制遺伝子p53による抗ウイルス免疫制御の分子基盤

Research Project

Project/Area Number 12J08328
Research Category

Grant-in-Aid for JSPS Fellows

Allocation TypeSingle-year Grants
Section国内
Research Field Immunology
Research InstitutionKumamoto University

Principal Investigator

田浦 学  熊本大学, エイズ学研究センター, 特別研究員(PD)

Project Period (FY) 2012-04-01 – 2015-03-31
Project Status Completed (Fiscal Year 2014)
Budget Amount *help
¥3,960,000 (Direct Cost: ¥3,600,000、Indirect Cost: ¥360,000)
Fiscal Year 2014: ¥1,560,000 (Direct Cost: ¥1,200,000、Indirect Cost: ¥360,000)
Fiscal Year 2013: ¥1,200,000 (Direct Cost: ¥1,200,000)
Fiscal Year 2012: ¥1,200,000 (Direct Cost: ¥1,200,000)
Keywords癌抑制遺伝子 / PRR / TLR / エイズ / HIV-1 / 潜伏感染 / HIV抑制因子 / COMMD1 / 自然免疫 / p53 / I_KB-α / Murr1 / Rb / E2F1 / HHV8
Outline of Annual Research Achievements

昨年度までの研究では,発癌ウイルスによる自然免疫抑制機構の解明を目的に,発癌ウイルスにより機能が抑制される癌抑制遺伝子p53およびRbによる自然免疫制御機構を解明した.また病原ウイルス潜伏感染における自然免疫制御機構の機能解析を目的に,エイズ原因ウイルスHIV-1に着目し,HIV-1潜伏感染においてCOMMD1/Murr1発現誘導によりTLRおよびサイトカインシグナル応答が顕著に抑制されることを明らかにし,潜伏感染における自然免疫機構の関与を示した.
本年度は,これまでHIV抑制因子として知られていたCOMMD1のHIV-1潜伏感染における機能解明を目的とした.その結果,COMMD1はHIV-1潜伏感染を安定化することが示された.特に興味深いことに,COMMD1の発現を抑制すると,潜伏感染していたHIV-1が再活性化し,潜伏感染細胞から放出されることを明らかにした.さらに,詳細な細胞内シグナル解析より,HIV-1潜伏感染細胞ではJAK/PI3Kシグナルの活性化によりCOMMD1が転写誘導されることを示した.
以上,本研究では宿主の抗ウイルス自然免疫応答を切り口に展開してきた.その成果として,癌抑制遺伝子p53およびRbによるPRRの発現および機能制御系を示した(Mol. Cell. Biol., 2012). また,エイズ治療の最適化を目的としたART副作用研究より,副作用誘導性を考慮した創薬研究の可能性を示した(Free Radic. Biol. Med., 2013).さらにHIV-1潜伏感染に焦点を当てた研究は,HIV抑制因子の1つであるCOMMD1のHIV-1初回感染および潜伏感染における長短二面性を明らかにすることで, HIV抑制因子の定義そのものを再検証する必要性を示唆した( J. Virol., 2015; 熊本大学プレスリリース; 熊本日々新聞).

Research Progress Status

26年度が最終年度であるため、記入しない。

Strategy for Future Research Activity

26年度が最終年度であるため、記入しない。

Report

(3 results)
  • 2014 Annual Research Report
  • 2013 Annual Research Report
  • 2012 Annual Research Report
  • Research Products

    (23 results)

All 2015 2014 2013 2012 Other

All Journal Article (13 results) (of which Peer Reviewed: 13 results,  Open Access: 2 results,  Acknowledgement Compliant: 1 results) Presentation (7 results) Remarks (3 results)

  • [Journal Article] Inhibition of HIV-1 entry by the tricyclic coumarin GUT-70 through the modification of membrane fluidity.2015

    • Author(s)
      Matsuda K, Hattori S, Kariya R, Komizu Y, Kudo E, Goto H, Taura M, Ueoka R, Kimura S, Okada S.
    • Journal Title

      Biochemical and Biophysical Research Communications

      Volume: 457(3) Issue: 3 Pages: 288-94

    • DOI

      10.1016/j.bbrc.2014.12.102

    • Related Report
      2014 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] COMMD1/Murr1 reinforces HIV-1 latent infection through IκB-α stabilization.2015

    • Author(s)
      Taura M, Kudo E, Kariya R, Goto H, Matsuda K, Hattori S, Vaeteewoottacharn K, McDonald F, Suico MA, Shuto T, Kai H, Okada S.
    • Journal Title

      Journal of Virology

      Volume: 89(5) Issue: 5 Pages: 2643-58

    • DOI

      10.1128/jvi.03105-14

    • Related Report
      2014 Annual Research Report
    • Peer Reviewed / Acknowledgement Compliant
  • [Journal Article] Targeting VEGF and Interleukin-6 for controlling malignant effusion of primary effusion lymphoma.2015

    • Author(s)
      Goto H, Kudo E, Kariya R, Taura M, Katano H, Okada S.
    • Journal Title

      Journal of Cancer Research and Clinical Oncology

      Volume: 141(3) Issue: 3 Pages: 465-74

    • DOI

      10.1007/s00432-014-1842-9

    • Related Report
      2014 Annual Research Report
    • Peer Reviewed
  • [Journal Article] The transcription factor MEF/ELF4 is dually modulated by p53-MDM2 axis and MEF-MDM2 autoregulatory mechanism.2014

    • Author(s)
      Suico MA, Fukuda R, Miyakita R, Koyama K, Taura M, Shuto T, Kai H.
    • Journal Title

      The Journal of Biological Chemistry

      Volume: 289(38) Issue: 38 Pages: 26143-54

    • DOI

      10.1074/jbc.m114.580209

    • Related Report
      2014 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] Efficacy of anti-CD47 antibody-mediated phagocytosis with macrophages against primary effusion lymphoma.2014

    • Author(s)
      Goto H, Kojima Y, Matsuda K, Kariya R, Taura M, Kuwahara K, Nagai H, Katano H, Okada S.
    • Journal Title

      The European Journal of Cancer

      Volume: 50(10) Issue: 10 Pages: 1836-46

    • DOI

      10.1016/j.ejca.2014.03.004

    • Related Report
      2014 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Inhibition of HIV-1 replication by a tricyclinc coumarin GUT-70 in acutely and chronically infected cells.2014

    • Author(s)
      Kudo E, Taura M, Matusda K, Shimamoto M, Kariya R, Goto H, Hattori S, Kimura S, Okada S.
    • Journal Title

      Cancer Letters

      Volume: 342(1) Issue: 1 Pages: 52-59

    • DOI

      10.1016/j.canlet.2013.08.045

    • Related Report
      2013 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Comparative analysis of ER stress response into HIV protease inhibitors : Lopinavir but not Darunavir induces potent ER stress response via ROS/JNK pathway.2013

    • Author(s)
      Taura M, Kariya R, Kudo E, Goto H, Iwawaki T, Amano M, Suico MA, Kai H, Mitsuya H, Okada S.
    • Journal Title

      Free Radical Biology and Medicine

      Volume: 65 Pages: 778-788

    • DOI

      10.1016/j.freeradbiomed.2013.08.161

    • Related Report
      2013 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Perturbation of proteasome function by bortezomib leading to ER stress-induced apoptotic cell death in cholangiocarcinoma.2013

    • Author(s)
      Vaeteewoottacharn K, Kariya R, Matsuda K, Taura M, Wongkham C, Wongkham S, Okada S.
    • Journal Title

      Journal of Cancer Research and Clinical Oneology

      Volume: 139(9) Issue: 9 Pages: 1551-1562

    • DOI

      10.1007/s00432-013-1473-6

    • Related Report
      2013 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Mild electrical stimulation at 0.1-ms pulse width induces p53 protein phosphorylation and G2 arrest in human epithelial cells.2013

    • Author(s)
      Fukuda ft, Suico MA, Koyama K, Omachi K, Kai Y, Matsuyama S, Mitsutake K, Taura M, Mo rino-Koga S, Shuto T, Kai H.
    • Journal Title

      Journal of Biological Chemistry

      Volume: 288(22) Issue: 22 Pages: 16117-16126

    • DOI

      10.1074/jbc.m112.442442

    • Related Report
      2013 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Inhibition of HIV-1 replication by a tricyclinc coumarin GUT-70 in acutely and chronically infected cells.2013

    • Author(s)
      Kudo E., et.al.
    • Journal Title

      Bioorganic & Medical Chemistry Letters

      Volume: 23(3) Issue: 3 Pages: 606-609

    • DOI

      10.1016/j.bmcl.2012.12.034

    • Related Report
      2012 Annual Research Report
    • Peer Reviewed
  • [Journal Article] STT3B-dependent posttranslational N-glycosylation as a surveillance system for secretory protein.2012

    • Author(s)
      Sato T., et.al.
    • Journal Title

      Molecular Cell

      Volume: 47(1) Issue: 1 Pages: 99-110

    • DOI

      10.1016/j.molcel.2012.04.015

    • Related Report
      2012 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Antitumor effect of berberine against primary effusion lymphoma via inhibition of NF-_kB pathway.2012

    • Author(s)
      Goto H., et.al.
    • Journal Title

      Cancer Science

      Volume: 103(4) Issue: 4 Pages: 775-781

    • DOI

      10.1111/j.1349-7006.2012.02212.x

    • Related Report
      2012 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Rb/E2F1 regulates the innate immune receptor Toll-like receptor 3 in epithelial cells2012

    • Author(s)
      Taura M., et.al.
    • Journal Title

      Molecular and Cellular Biology

      Volume: 32(8) Issue: 8 Pages: 1581-1590

    • DOI

      10.1128/mcb.06454-11

    • Related Report
      2012 Annual Research Report
    • Peer Reviewed
  • [Presentation] 宿主制御因子COMMD1によるIκB-αの安定化を介したHIV-1の潜伏感染の制御2014

    • Author(s)
      工藤恵理子,田浦学,岡田誠治
    • Organizer
      第62回 日本ウイルス学会学術集会
    • Place of Presentation
      パシフィコ横浜
    • Year and Date
      2014-11-10 – 2014-11-12
    • Related Report
      2014 Annual Research Report
  • [Presentation] The role of HIV-1 restriction factor Murr 1 in HIV-1 latently infected cells.2013

    • Author(s)
      Taura M, Kudo E, Goto H, Okada S.
    • Organizer
      2013 ASCB annual meeting
    • Place of Presentation
      New Orleans Convention Center, New Orleans, LA, USA
    • Year and Date
      2013-12-16
    • Related Report
      2013 Annual Research Report
  • [Presentation] The role of HIV-1 restriction factor Murrlin HIV-1 latently infected cells.2013

    • Author(s)
      田浦学、工藤恵里子、後藤裕樹、岡田誠治
    • Organizer
      第42回日本免疫学会学術集会
    • Place of Presentation
      幕張メッセ, 千葉市, 千葉県
    • Year and Date
      2013-12-12
    • Related Report
      2013 Annual Research Report
  • [Presentation] The role of HIV-1 restriction factor Murrl in HIV-1 latently infected cells.2013

    • Author(s)
      田浦学、工藤恵里子、後藤裕樹、岡田誠治
    • Organizer
      第27回日本エイズ学会学術集会・総会
    • Place of Presentation
      熊本市国際交流会館, 熊本市, 熊本県
    • Year and Date
      2013-11-21
    • Related Report
      2013 Annual Research Report
  • [Presentation] Comparative analysis of ER stress response into HIV protease inhibitors:Lopinavir but not Darunavir induces potent ER stress response viaROS/JNK pathway.2012

    • Author(s)
      Taura M., et.al.
    • Organizer
      2012 ASCB annual meeting
    • Place of Presentation
      Moscone Center, SanFrancisco, CA, USA
    • Year and Date
      2012-12-16
    • Related Report
      2012 Annual Research Report
  • [Presentation] p53 regulates the ETS transcription factor MEF/Elf4 via MDM2.2012

    • Author(s)
      Suico M., et.al.
    • Organizer
      2012 ASCB annual meeting
    • Place of Presentation
      Moscone Center, SanFrancisco, CA, USA
    • Year and Date
      2012-12-16
    • Related Report
      2012 Annual Research Report
  • [Presentation] 副作用誘導因子である小胞体ストレスに着目したHIV protease inhibitorの評価2012

    • Author(s)
      田浦学、刈谷龍昇、工藤恵里子、後藤裕樹、岡田誠治
    • Organizer
      第26回日本エイズ学会
    • Place of Presentation
      慶応義塾大学日吉キャンパス横浜市,神奈川県
    • Year and Date
      2012-11-26
    • Related Report
      2012 Annual Research Report
  • [Remarks] 熊本大学エイズ学研究センター 岡田プロジェクト研究室

    • URL

      http://www.caids.kumamoto-u.ac.jp/data/okada/default.html

    • Related Report
      2014 Annual Research Report
  • [Remarks]

    • URL

      http://www.caids.kumamoto-u.ac.jp/data/okada/default.html

    • Related Report
      2013 Annual Research Report
  • [Remarks]

    • URL

      http://www.caids.kumamoto-u.ac.jp/data/okada/default.html

    • Related Report
      2012 Annual Research Report

URL: 

Published: 2013-04-25   Modified: 2024-03-26  

Information User Guide FAQ News Terms of Use Attribution of KAKENHI

Powered by NII kakenhi