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Mechanisms of degradation of human papillomavirus DNA helicase E1

Research Project

Project/Area Number 26460564
Research Category

Grant-in-Aid for Scientific Research (C)

Allocation TypeMulti-year Fund
Section一般
Research Field Virology
Research InstitutionNational Institute of Infectious Diseases

Principal Investigator

Kukimoto Iwao  国立感染症研究所, 病原体ゲノム解析研究センター, 室長 (70291127)

Project Period (FY) 2014-04-01 – 2018-03-31
Project Status Completed (Fiscal Year 2017)
Budget Amount *help
¥5,070,000 (Direct Cost: ¥3,900,000、Indirect Cost: ¥1,170,000)
Fiscal Year 2016: ¥1,560,000 (Direct Cost: ¥1,200,000、Indirect Cost: ¥360,000)
Fiscal Year 2015: ¥1,170,000 (Direct Cost: ¥900,000、Indirect Cost: ¥270,000)
Fiscal Year 2014: ¥2,340,000 (Direct Cost: ¥1,800,000、Indirect Cost: ¥540,000)
Keywordsヒトパピローマウイルス / 子宮頸癌 / ユビキチン / タンパク質分解 / ユビキチン化 / プロテアソーム / 蛋白質分解 / ウイルス複製
Outline of Final Research Achievements

Genome replication of human papillomavirus requires viral replicative DNA helicase E1, and regulation of intracellular E1 levels is important for controlling the virus life cycle. This study aimed to elucidate viral and cellular mechanisms of regulating E1 levels. We found that E1 was degraded in a manner dependent on its own ATPase activity, and that E1 was poly-ubiquitinated and degraded via the proteasome pathway. We further demonstrated that intracellular E1 levels were up-regulated with the treatment of tankyrase inhibitor XAV939, although the potential target of XAX939 for E1 up-regulation was not tankyrase but poly-ADP-ribose polymerase 1 (PARP1), suggesting that PARP1 is involved in negative regulation of E1 function.

Report

(5 results)
  • 2017 Annual Research Report   Final Research Report ( PDF )
  • 2016 Research-status Report
  • 2015 Research-status Report
  • 2014 Research-status Report
  • Research Products

    (39 results)

All 2018 2017 2016 2015 2014 Other

All Journal Article (12 results) (of which Int'l Joint Research: 1 results,  Peer Reviewed: 11 results,  Open Access: 9 results,  Acknowledgement Compliant: 2 results) Presentation (26 results) (of which Int'l Joint Research: 7 results,  Invited: 1 results) Remarks (1 results)

  • [Journal Article] Within-Host Variations of Human Papillomavirus Reveal APOBEC-Signature Mutagenesis in the Viral Genome2018

    • Author(s)
      Hirose Yusuke、Onuki Mamiko、Tenjimbayashi Yuri、Mori Seiichiro、Ishii Yoshiyuki、Takeuchi Takamasa、Tasaka Nobutaka、Satoh Toyomi、Morisada Tohru、Iwata Takashi、Miyamoto Shingo、Matsumoto Koji、Sekizawa Akihiko、Kukimoto Iwao
    • Journal Title

      Journal of Virology

      Volume: 印刷中 Issue: 12

    • DOI

      10.1128/jvi.00017-18

    • Related Report
      2017 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] Whole-genome analysis of human papillomavirus genotypes 52 and 58 isolated from Japanese women with cervical intraepithelial neoplasia and invasive cervical cancer2017

    • Author(s)
      Tenjimbayashi Yuri、Onuki Mamiko、Hirose Yusuke、Mori Seiichiro、Ishii Yoshiyuki、Takeuchi Takamasa、Tasaka Nobutaka、Satoh Toyomi、Morisada Tohru、Iwata Takashi、Miyamoto Shingo、Matsumoto Koji、Sekizawa Akihiko、Kukimoto Iwao
    • Journal Title

      Infectious Agents and Cancer

      Volume: 12 Issue: 1 Pages: 44-44

    • DOI

      10.1186/s13027-017-0155-4

    • NAID

      120007128848

    • Related Report
      2017 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] Human Papillomavirus 16 E6 Upregulates APOBEC3B via the TEAD Transcription Factor.2017

    • Author(s)
      Mori S, Takeuchi T, Ishii Y, Yugawa T, Kiyono T, Nishina H, Kukimoto I.
    • Journal Title

      Journal of Virology

      Volume: 91 Issue: 6

    • DOI

      10.1128/jvi.02413-16

    • Related Report
      2016 Research-status Report
    • Peer Reviewed / Open Access
  • [Journal Article] Comparison of methods using paraffin‐embedded tissues and exfoliated cervical cells to evaluate human papillomavirus genotype attribution2016

    • Author(s)
      Fujii T, Torii Y, Kukimoto I, Saito M, Iwata T, Takahashi H, Ichikawa R, Kawai S, Otani S, Aoki D
    • Journal Title

      Cancer Sci

      Volume: 107(10) Issue: 10 Pages: 1520-1526

    • DOI

      10.1111/cas.13030

    • Related Report
      2016 Research-status Report
    • Peer Reviewed / Open Access / Acknowledgement Compliant
  • [Journal Article] Genetic Variations of Human Papillomavirus Type 16: Implications for Cervical Carcinogenesis2015

    • Author(s)
      I. Kukimoto and M. Muramatsu.
    • Journal Title

      Japanese Journal of Infectious Diseases

      Volume: 68 Issue: 3 Pages: 169-175

    • DOI

      10.7883/yoken.JJID.2014.584

    • NAID

      130005070792

    • ISSN
      1344-6304, 1884-2836
    • Related Report
      2015 Research-status Report
    • Peer Reviewed / Open Access
  • [Journal Article] Hypermutation in the E2 gene of human papillomavirus type 16 in cervical intraepithelial neoplasia.2015

    • Author(s)
      Kukimoto I, Mori S, Aoyama S, Wakae K, Muramatsu M, Kondo K.
    • Journal Title

      Journal of Medical Virology

      Volume: 87 Issue: 10 Pages: 1754-1760

    • DOI

      10.1002/jmv.24215

    • Related Report
      2015 Research-status Report
    • Peer Reviewed
  • [Journal Article] Detection of hypermutated human papillomavirus type 16 genome by Next-Generation Sequencing.2015

    • Author(s)
      Wakae K, Aoyama S, Wang Z, Kitamura K, Liu G, Monjurul AM, Koura M, Imayasu M, Sakamoto N, Nakamura M, Kyo S, Kondo S, Fujiwara H, Yoshizaki T, Kukimoto I, Yamaguchi K, Shigenobu S, Nishiyama T, Muramatsu M.
    • Journal Title

      Virology

      Volume: 485 Pages: 460-466

    • DOI

      10.1016/j.virol.2015.08.017

    • Related Report
      2015 Research-status Report
    • Peer Reviewed / Open Access / Int'l Joint Research / Acknowledgement Compliant
  • [Journal Article] APOBEC3A and 3C decrease human papillomavirus 16 pseudovirion infectivity.2015

    • Author(s)
      Ahasan MM, Wakae K, Wang Z, Kitamura K, Liu G, Koura M, Imayasu M, Sakamoto N, Hanaoka K, Nakamura M, Kyo S, Kondo S, Fujiwara H, Yoshizaki T, Mori S, Kukimoto I, Muramatsu M.
    • Journal Title

      Biochem Biophys Res Commun.

      Volume: 457 Issue: 3 Pages: 295-9

    • DOI

      10.1016/j.bbrc.2014.12.103

    • Related Report
      2014 Research-status Report
    • Peer Reviewed / Open Access
  • [Journal Article] Identification of APOBEC3B promoter elements responsible for activation by human papillomavirus type 16 E62015

    • Author(s)
      Mori, S., T. Takeuchi, Y. Ishii, and I. Kukimoto.
    • Journal Title

      Biochemical and Biophysical Research Communications

      Volume: 460 Issue: 3 Pages: 555-560

    • DOI

      10.1016/j.bbrc.2015.03.068

    • Related Report
      2014 Research-status Report
    • Peer Reviewed
  • [Journal Article] Characterization of novel transcripts of human papillomavirus type 16 using cap analysis gene expression technology2015

    • Author(s)
      Taguchi A, Nagasaka K, Kawana K, Hashimoto K, Kusumoto-Matsuo R, Plessy C, Miranda T, Nakamura H, Bonetti A, Oda K, Kukimoto I, Carninci P, Banks L, Osuga Y, Fujii T,
    • Journal Title

      J Virol

      Volume: 89 Issue: 4 Pages: 2448

    • DOI

      10.1128/jvi.03433-14

    • Related Report
      2014 Research-status Report
    • Peer Reviewed / Open Access
  • [Journal Article] Human papillomavirus genotype distribution in cervical intraepithelial neoplasia grade 2/3 and invasive cervical cancer in Japanese women2014

    • Author(s)
      Azuma Y, Kusumoto-Matsuo R, Takeuchi F, Uenoyama A, Kondo K, Tsunoda H, Nagasaka K, Kawana K, Morisada T, Iwata T, Aoki D, Kukimoto I
    • Journal Title

      Japan J Clin Oncol,

      Volume: 44 Issue: 10 Pages: 910

    • DOI

      10.1093/jjco/hyu112

    • Related Report
      2014 Research-status Report
    • Peer Reviewed / Open Access
  • [Journal Article] HPVワクチン2014

    • Author(s)
      柊元 巌
    • Journal Title

      臨床と微生物

      Volume: 41 Pages: 725-729

    • Related Report
      2014 Research-status Report
  • [Presentation] APOBEC変異導入を介したヒトパピローマウイルス発癌機構2018

    • Author(s)
      柊元 巌
    • Organizer
      日本薬学会第138年会
    • Related Report
      2017 Annual Research Report
    • Invited
  • [Presentation] Detection of HPV L1 gene expression in cervical exfoliated cells from CIN patients by RT-PCR using consensus primers2017

    • Author(s)
      K. Kawana, A. Taguchi, K. Adachi, D. Maeda, S. Mori, I. Kukimoto, T. Iwata, A. and Mitsuhashi.
    • Organizer
      31st International Papillomavirus Conference
    • Place of Presentation
      Cape Town, South Africa
    • Year and Date
      2017-02-28
    • Related Report
      2016 Research-status Report
    • Int'l Joint Research
  • [Presentation] Upregulation of APOBEC3B cytidine deaminase by HPV E6 and E7 via the TEAD transcription factor2017

    • Author(s)
      Kukimoto I, Tenjimbayashi Y, Hirose Y, Onuki M, Matsumoto K, Mori S.
    • Organizer
      DNA tumour virus meeting
    • Related Report
      2017 Annual Research Report
    • Int'l Joint Research
  • [Presentation] Intra-patient variation of human papillomavirus genomes revealed by deep sequencing2017

    • Author(s)
      Hirose Y, Tenjimbayashi Y, Onuki M, Minaguchi T, Iwata T, Matsumoto K, Kukimoto I.
    • Organizer
      第76回日本癌学会学術総会
    • Related Report
      2017 Annual Research Report
  • [Presentation] Whole-genome analysis of human papillomavirus 52 and 58 in Japanese women2017

    • Author(s)
      Tenjimbayashi Y, Hirose Y, Onuki M, Nakao S, Iwata T, Matsumoto K, Kukimoto I.
    • Organizer
      第76回日本癌学会学術総会
    • Related Report
      2017 Annual Research Report
  • [Presentation] MicroRNAs extracted from cervical mucus or exfoliated cells are promising biomarkers for cervical cancer screening2017

    • Author(s)
      Fujii T, Kukimoto I.
    • Organizer
      第76回日本癌学会学術総会
    • Related Report
      2017 Annual Research Report
  • [Presentation] Whole-genome analysis of human papillomavirus 52/58 isolated from Japanese women with cervical intraepithelial neoplasia and invasive cervical cancer2017

    • Author(s)
      Kukimoto I, Tenjimbayashi Y, Hirose Y, Onuki M, Iwata T, Matsumoto K.
    • Organizer
      AOGIN 2017
    • Related Report
      2017 Annual Research Report
    • Int'l Joint Research
  • [Presentation] Whole-genome analysis of HPV52/58 isolated from Japanese women with cervical intraepithelial neoplasia and invasive cervical cancer2017

    • Author(s)
      Kukimoto I, Tenjimbayashi Y, Hirose Y, Onuki M, Iwata T, Matsumoto K.
    • Organizer
      第65回日本ウイルス学会学術集会
    • Related Report
      2017 Annual Research Report
  • [Presentation] Persistent expression of a broadly neutralizing monoclonal antibody against HPVs by AAV-mediated gene transfer2017

    • Author(s)
      Mori S, Kotani O, Takeuchi T, Ishii Y, Kukimoto I.
    • Organizer
      第65回日本ウイルス学会学術集会
    • Related Report
      2017 Annual Research Report
  • [Presentation] Activation of human APOBEC3B promoter by HPV16 E6 through TEAD transcription factors2016

    • Author(s)
      S. Mori, T. Kiyono, H. Nishina, and I. Kukimoto.
    • Organizer
      第64回日本ウイルス学会学術集会
    • Place of Presentation
      札幌
    • Year and Date
      2016-10-24
    • Related Report
      2016 Research-status Report
  • [Presentation] TEAD-dependent, YAP/TAZ-independent activation of human APOBEC3B promoter by HPV16 E62016

    • Author(s)
      S. Mori, H. Nishina, and I. Kukimoto.
    • Organizer
      第75回日本癌学会学術総会
    • Place of Presentation
      横浜
    • Year and Date
      2016-10-07
    • Related Report
      2016 Research-status Report
  • [Presentation] Estimation of HPV genotype attribution using cervical exfoliated cells for monitoring the efficacy of HPV vaccines2016

    • Author(s)
      T. Fujii, I. Kukimoto, T. Iwata, and D. Aoki.
    • Organizer
      第75回日本癌学会学術総会
    • Place of Presentation
      横浜
    • Year and Date
      2016-10-07
    • Related Report
      2016 Research-status Report
  • [Presentation] Mechanism of multiple lysine 48-linked ubiquitin chain synthesis by E6AP2016

    • Author(s)
      Y. Masuda, Y. Saeki, S. Yanaka, H. Kawai, I. Kukimoto, K. Kato, K. Tanaka, C. Masutani.
    • Organizer
      FASEB Science Research Conference, UBIQUITIN & CELLULAR REGULATION
    • Place of Presentation
      Montana, U.S.A.
    • Year and Date
      2016-06-12
    • Related Report
      2016 Research-status Report
    • Int'l Joint Research
  • [Presentation] HECTタイプユビキチンリガーゼによるK48ユビキチン鎖合成の分子機構2015

    • Author(s)
      増田雄司、柊元 巌、益谷央豪
    • Organizer
      第38回日本分子生物学会年会/第88回日本生化学会大会合同大会
    • Place of Presentation
      神戸
    • Year and Date
      2015-12-01
    • Related Report
      2015 Research-status Report
  • [Presentation] The L2 capsid protein of HPV16 promotes viral uncoating by inhibiting virus entry into the Golgi body through the L2-TRAPPC8 interaction2015

    • Author(s)
      Y. Ishii, S. Mori, T. Takeuchi, and I. Kukimoto.
    • Organizer
      第68回日本ウイルス学会学術集会
    • Place of Presentation
      福岡
    • Year and Date
      2015-11-23
    • Related Report
      2015 Research-status Report
  • [Presentation] Hypermutation in the E2 Gene of HPV16 in Cervical Intraepithelial Neoplasia2015

    • Author(s)
      I. Kukimoto, S. Mori, and K. Kondo.
    • Organizer
      第74回日本癌学会学術総会
    • Place of Presentation
      名古屋
    • Year and Date
      2015-10-08
    • Related Report
      2015 Research-status Report
  • [Presentation] The significance of the existence of novel HPV16 derived antisense RNAs and the TSS-switch of HPV16 transcriptomes2015

    • Author(s)
      A. Taguchi, K. Nagasaka, K. Kawana, H. Nakamura, I. Kukimoto, K. Oda, and T. Fujii.
    • Organizer
      第74回日本癌学会学術総会
    • Place of Presentation
      名古屋
    • Year and Date
      2015-10-08
    • Related Report
      2015 Research-status Report
  • [Presentation] Mechanism of Lysine 48-linked Multiple Ubiquitin Chain Synthesis by an HECT Ubiquitin Ligase2015

    • Author(s)
      Y. Masuda, I. Kukimoto, C. Masutani
    • Organizer
      EMBO Conference on Ubiquitin and ubiquitin-like modifiers: From molecular mechanisms to human diseases
    • Place of Presentation
      Cavtat
    • Year and Date
      2015-09-18
    • Related Report
      2015 Research-status Report
    • Int'l Joint Research
  • [Presentation] Mechanisms of APOBEC3B Promoter Activation by HPV16 E62015

    • Author(s)
      S. Mori, T. Takeuchi, Y. Ishii, and I. Kukimoto.
    • Organizer
      International Papillomavirus Conference
    • Place of Presentation
      Lisbon
    • Year and Date
      2015-09-17
    • Related Report
      2015 Research-status Report
    • Int'l Joint Research
  • [Presentation] Hypermutation in the E2 Gene of HPV16 in Cervical Intraepithelial Neoplasia2015

    • Author(s)
      I. Kukimoto, K. Kondo, M. Muramatsu, and S. Mori.
    • Organizer
      DNA Tumour Virus Meeting
    • Place of Presentation
      Trieste
    • Year and Date
      2015-07-21
    • Related Report
      2015 Research-status Report
    • Int'l Joint Research
  • [Presentation] ヒトパピローマウイルス16型E6/E7によるAPOBEC3Bプロモーターの活性化機構2014

    • Author(s)
      森 清一郎、竹内 隆正、石井 克幸、柊元 巌
    • Organizer
      第62回日本ウイルス学会学術集会
    • Place of Presentation
      横浜
    • Year and Date
      2014-11-12
    • Related Report
      2014 Research-status Report
  • [Presentation] APOBEC3はHPV16 Pseudovirionの感染性を低下させる2014

    • Author(s)
      若江 亨祥、Ahasan M Monjurul、王 哲、喜多村 晃一、森 清一郎、柊元 巌、中村 充弘、藤原 浩、村松 正道
    • Organizer
      第62回日本ウイルス学会学術集会
    • Place of Presentation
      横浜
    • Year and Date
      2014-11-12
    • Related Report
      2014 Research-status Report
  • [Presentation] ヒトパピローマウイルス16型のがん蛋白質E6/E7によるAPOBEC3Bプロモーターの活性化2014

    • Author(s)
      森 清一郎、柊元 巌
    • Organizer
      第73回日本癌学会学会学術総会
    • Place of Presentation
      横浜
    • Year and Date
      2014-09-25
    • Related Report
      2014 Research-status Report
  • [Presentation] 日本人女性のCIN2/3および子宮頸部浸潤癌でのHPV遺伝子型分布2014

    • Author(s)
      柊元 巌、近藤 一成、岩田 卓、川名 敬
    • Organizer
      第73回日本癌学会学会学術総会
    • Place of Presentation
      横浜
    • Year and Date
      2014-09-25
    • Related Report
      2014 Research-status Report
  • [Presentation] Wee1 binds to and stabilizes the E1 helicase of human papillomavirus type 162014

    • Author(s)
      Kusumoto-Matsuo R, Mori S, Maehama T, Kukimoto I.
    • Organizer
      29th International Papillomavirus Conference
    • Place of Presentation
      シアトル
    • Year and Date
      2014-08-25
    • Related Report
      2014 Research-status Report
  • [Presentation] Characterization of novel transcripts of human papillomavirus type 16 and host interactions using CAGE technology2014

    • Author(s)
      Taguchi A, Nagasaka K, Kawana K, Hashimoto K, Kusumoto-Matsuo R, Kamoto H, Bonetti A, Kukimoto I, Carninci P, Banks L, Osuga Y, Fujii T.
    • Organizer
      29th International Papillomavirus Conference
    • Place of Presentation
      シアトル
    • Year and Date
      2014-08-24
    • Related Report
      2014 Research-status Report
  • [Remarks] 国立感染症研究所年報 平成28年度

    • URL

      https://www.niid.go.jp/niid/images/annual/h28/201620.pdf

    • Related Report
      2017 Annual Research Report

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Published: 2014-04-04   Modified: 2019-03-29  

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