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The role of UBR4/HPV16 E7 interaction in cancer

Research Project

Project/Area Number 25430119
Research Category

Grant-in-Aid for Scientific Research (C)

Allocation TypeMulti-year Fund
Section一般
Research Field Tumor biology
Research InstitutionKanazawa Medical University

Principal Investigator

TASAKI Takafumi  金沢医科大学, 総合医学研究所, 准教授 (70629815)

Project Period (FY) 2013-04-01 – 2016-03-31
Project Status Completed (Fiscal Year 2015)
Budget Amount *help
¥5,330,000 (Direct Cost: ¥4,100,000、Indirect Cost: ¥1,230,000)
Fiscal Year 2015: ¥1,040,000 (Direct Cost: ¥800,000、Indirect Cost: ¥240,000)
Fiscal Year 2014: ¥1,560,000 (Direct Cost: ¥1,200,000、Indirect Cost: ¥360,000)
Fiscal Year 2013: ¥2,730,000 (Direct Cost: ¥2,100,000、Indirect Cost: ¥630,000)
Keywordsパピローマウイルス / がん / E7 / UBR4 / 代謝的安定性 / N-end rule pathway / UBR box domain / HPV16 E7 / がん化 / 子宮頸がん / HPVE7 / UBR box / UBR box protein / Ubiquitin / Protein regulation / HPV16E7 / cancer
Outline of Final Research Achievements

Cervical cancer is caused by certain types of human papilloma virus. The viral E7 is a small 98-amino acid protein that binds various cellular proteins in a host cell. Among these interaction proteins, UBR4 is a huge approx. 5800-amino acids protein. This study found out that the E7 binds to UBR4 via the conservative UBR box domain in UBR4. The UBR box domain is involved in a physiological role of UBR4. Next, we investigated a metabolic stability of the E7 in genetically modified UBR4-deficient cells. The E7 was significantly unstable in the UBR4-lacking cells. Our results suggest that the E7 forms a stable complex with the UBR4 and the complex regulates the viral cancer activity in host cells.

Report

(4 results)
  • 2015 Annual Research Report   Final Research Report ( PDF )
  • 2014 Research-status Report
  • 2013 Research-status Report
  • Research Products

    (12 results)

All 2016 2015 2014 2013

All Journal Article (6 results) (of which Peer Reviewed: 6 results) Presentation (6 results)

  • [Journal Article] Suppressive effect of topoisomerase inhibitors on JC polyomavirus propagation in human neuroblastoma cells.2016

    • Author(s)
      Nukuzuma S, Nakamichi K, Kameoka M, Sugiura S, Nukuzuma C, Tasaki T, Takegami T.
    • Journal Title

      Microbiol Immunol.

      Volume: 60 Issue: 4 Pages: 253-260

    • DOI

      10.1111/1348-0421.12372

    • NAID

      40020808909

    • Related Report
      2015 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Replication of IMR-32-adapted JC virus clones in human embryonic kidney cells.2015

    • Author(s)
      Nukuzuma S, Sugiura S, Nakamichi K, Kameoka M, Nukuzuma C, Tasaki T, Takegami T.
    • Journal Title

      Microbiol Immunol.

      Volume: 59 Issue: 4 Pages: 238-242

    • DOI

      10.1111/1348-0421.12243

    • Related Report
      2015 Annual Research Report 2014 Research-status Report
    • Peer Reviewed
  • [Journal Article] TNF-alpha stimulates efficient JC virus replication in neuroblastoma cells2014

    • Author(s)
      Nukuzuma, S. Nakamichi, K. Kameoka, M. Sugiura, S. Nukuzuma, C. Tasaki, T. Takegami, T.
    • Journal Title

      J Med Virol

      Volume: XX Issue: 12 Pages: 2026-2032

    • DOI

      10.1002/jmv.23886

    • Related Report
      2014 Research-status Report
    • Peer Reviewed
  • [Journal Article] UBR box N-recognin-4 (UBR4), an N-recognin of the N-end rule pathway, and its role in yolk sac vascular development and autophagy2013

    • Author(s)
      Tasaki T, Kim ST, Zakrzewska A, Lee BE, Kang MJ, Yoo YD, Cha-Molstad HJ, Hwang J, Soung NK, Sung KS, Kim SH, Nguyen MD, Sun M, Yi EC, Kim BY, Kwon YT
    • Journal Title

      Proc Natl Acad Sci USA

      Volume: 110 Issue: 10 Pages: 3800-3805

    • DOI

      10.1073/pnas.1217358110

    • Related Report
      2013 Research-status Report
    • Peer Reviewed
  • [Journal Article] The N-end rule proteolytic system in autophagy2013

    • Author(s)
      Kim ST, Tasaki T, Zakrzewska A, Yoo YD, Sa Sung K, Kim SH, Cha-Molstad H, Hwang J, Kim KA, Kim BY, Kwon YT
    • Journal Title

      Autophagy

      Volume: 9 Issue: 7 Pages: 1100-1103

    • DOI

      10.4161/auto.24643

    • Related Report
      2013 Research-status Report
    • Peer Reviewed
  • [Journal Article] he N-end rule and retroviral infection: no effect on integrase2013

    • Author(s)
      Boso G, Tasaki T, Kwon YT, Somia NV
    • Journal Title

      Virol J

      Volume: 13 Issue: 1 Pages: 233-233

    • DOI

      10.1186/1743-422x-10-233

    • Related Report
      2013 Research-status Report
    • Peer Reviewed
  • [Presentation] UBR4-E7相互作用はUBR box領域を介している2015

    • Author(s)
      田崎隆史
    • Organizer
      第38回日本分子生物学会
    • Place of Presentation
      神戸ポートアイランド(兵庫県神戸市)
    • Year and Date
      2015-12-01
    • Related Report
      2015 Annual Research Report
  • [Presentation] デオキシヌクレオチド類似体EdAPによる抗日本脳炎ウイルス作用2015

    • Author(s)
      田崎 隆史、北川 陽子、大類 洋、菅原二三男、奴久妻聡一、竹上 勉
    • 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
    • Related Report
      2015 Annual Research Report
  • [Presentation] D-ribose誘導体EdAPによる日本脳炎ウイルス複製阻害2015

    • Author(s)
      田崎 隆史、北川 陽子、大類 洋、菅原二三男、竹上 勉
    • Organizer
      第50回日本脳炎ウイルス生態学研究会
    • Place of Presentation
      ホテル京都エミナース(京都府京都市)
    • Year and Date
      2015-05-15
    • Related Report
      2015 Annual Research Report
  • [Presentation] 宿主細胞内pHによる日本脳炎ウイルス複製調節機構2014

    • Author(s)
      田崎隆史、北川陽子、堀貴代江、奴久妻聡一、竹上勉
    • Organizer
      第62回日本ウイルス学会学術集会
    • Place of Presentation
      パシフィコ横浜会議センター(神奈川県横浜市)
    • Year and Date
      2014-11-10 – 2014-11-12
    • Related Report
      2014 Research-status Report
  • [Presentation] UBR-box protein UBR4の分子生物学2014

    • Author(s)
      田崎隆史、Yong Tae Kwon、竹上勉
    • Organizer
      日本生化学会北陸支部第32回大会
    • Place of Presentation
      富山大学杉谷キャンパス(富山県富山市)
    • Year and Date
      2014-05-24
    • Related Report
      2014 Research-status Report
  • [Presentation] UBR4, and N-recognin of the N-end rule pathway, and its role in yolk sac vascular development and autophagy2013

    • Author(s)
      T.Tasaki, ST. Kim, A. Zakrzewska, YT. Kwon
    • Organizer
      THE 35th NAITO CONFERENCE on The Ubiquitin-Proteasome System: From Basic Mechanisms to Phathophysiological Roles
    • Place of Presentation
      シャトレーゼガトーキングダムサッポロ(北海道札幌市)
    • Related Report
      2013 Research-status Report

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Published: 2014-07-25   Modified: 2019-07-29  

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