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Functional analysis of ubiquitin ligase RNF126

Research Project

Project/Area Number 17K10432
Research Category

Grant-in-Aid for Scientific Research (C)

Allocation TypeMulti-year Fund
Section一般
Research Field Radiation science
Research InstitutionTohoku University

Principal Investigator

Ishida Noriko  東北大学, 東北メディカル・メガバンク機構, 助教 (10361073)

Co-Investigator(Kenkyū-buntansha) 中川 直  山陽小野田市立山口東京理科大学, 薬学部, 講師 (30707013)
Project Period (FY) 2017-04-01 – 2021-03-31
Project Status Completed (Fiscal Year 2020)
Budget Amount *help
¥4,680,000 (Direct Cost: ¥3,600,000、Indirect Cost: ¥1,080,000)
Fiscal Year 2019: ¥1,430,000 (Direct Cost: ¥1,100,000、Indirect Cost: ¥330,000)
Fiscal Year 2018: ¥1,560,000 (Direct Cost: ¥1,200,000、Indirect Cost: ¥360,000)
Fiscal Year 2017: ¥1,690,000 (Direct Cost: ¥1,300,000、Indirect Cost: ¥390,000)
KeywordsDNA損傷修復 / ユビキチン / E3リガーゼ / タンパク分解 / ノックアウトマウス / ユビキチンリガーゼ / 放射線 / ゲノム / 蛋白質分解 / DNA修復
Outline of Final Research Achievements

It was reported that E3 ligase RNF126 ubiquitinates Ku80, which plays an important role in DSB repair, and promotes the completion of repair (Ishida N et al. Mol Cell Biol. 2017; 37: e00347-16).
As a result of producing and analyzing RNF126 knockout (KO) mice, a decrease in T cells and sperm was observed. It was also confirmed that the phenotype obtained using the human cell line can be reproduced in KO mouse primary cells. Furthermore, as a result of producing and analyzing RNF126 CKO mice, it was clarified that RNF126 plays an important role in germ cell development in the testis.

Academic Significance and Societal Importance of the Research Achievements

ヒト細胞における、DNA損傷修復に重要なKu複合体を分解制御する新たな因子RNF126を発見・論文報告したことにより、DNA修復の二重鎖切断修復メカニズムの理解に貢献できた。また、RNF126のマウス個体レベルでの機能、T細胞や精子細胞分化における重要性を明らかにしたことより、T細胞維持や精子形成におけるユビキチンリガーゼやタンパク分解の理解に貢献できる可能性に繋がった。

Report

(5 results)
  • 2020 Annual Research Report   Final Research Report ( PDF )
  • 2019 Research-status Report
  • 2018 Research-status Report
  • 2017 Research-status Report
  • Research Products

    (25 results)

All 2020 2019 2018 2017 Other

All Journal Article (18 results) (of which Int'l Joint Research: 3 results,  Peer Reviewed: 18 results,  Open Access: 10 results) Presentation (6 results) (of which Int'l Joint Research: 3 results,  Invited: 2 results) Remarks (1 results)

  • [Journal Article] Landscape of electrophilic and inflammatory stress-mediated gene regulation in human lymphoblastoid cell lines2020

    • Author(s)
      Ishida Noriko、Aoki Yuichi、Katsuoka Fumiki、Nishijima Ichiko、Nobukuni Takahiro、Anzawa Hayato、Bin Li、Tsuda Miyuki、Kumada Kazuki、Kudo Hisaaki、Terakawa Takahiro、Otsuki Akihito、Kinoshita Kengo、Yamashita Riu、Minegishi Naoko、Yamamoto Masayuki
    • Journal Title

      Free Radical Biology and Medicine

      Volume: 161 Pages: 71-83

    • DOI

      10.1016/j.freeradbiomed.2020.09.023

    • Related Report
      2020 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] The Autism-Related Protein SETD5 Controls Neural Cell Proliferation through Epigenetic Regulation of rDNA Expression.2020

    • Author(s)
      Nakagawa T, Hattori S, Nobuta R, Kimura R, Nakagawa M, Matsumoto M, Nagasawa Y, Funayama R, Miyakawa T, Inada T, Osumi N, Nakayama KI, Nakayama K.
    • Journal Title

      iScience

      Volume: 23 Issue: 4 Pages: 101030-101030

    • DOI

      10.1016/j.isci.2020.101030

    • Related Report
      2020 Annual Research Report 2019 Research-status Report
    • Peer Reviewed / Open Access
  • [Journal Article] A multi-ethnic meta-analysis identifies novel genes, including ACSL5, associated with amyotrophic lateral sclerosis.2020

    • Author(s)
      Nakamura R, Misawa K, Tohnai G, Nakatochi M, Furuhashi S, Atsuta N, Hayashi N, Yokoi D, Watanabe H, Watanabe H, Katsuno M, Izumi Y, Kanai K, Hattori N, Morita M, Taniguchi A, Kano O, Oda M, Shibuya K, Kuwabara S, Suzuki N, Aoki M, Ohta Y, Yamashita T, Abe K, Hashimoto R, Aiba I, Okada Y, Nagasaki M, Sobue G. et al.,
    • Journal Title

      Commun Biol.

      Volume: 23 Issue: 1 Pages: 526-526

    • DOI

      10.1038/s42003-020-01251-2

    • NAID

      120007178464

    • Related Report
      2020 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] Identification of Dominant Transcripts in Oxidative Stress Response by a Full-Length Transcriptome Analysis2020

    • Author(s)
      Otsuki Akihito、Okamura Yasunobu、Aoki Yuichi、Ishida Noriko、Kumada Kazuki、Minegishi Naoko、Katsuoka Fumiki、Kinoshita Kengo、Yamamoto Masayuki
    • Journal Title

      Molecular and Cellular Biology

      Volume: 41 Issue: 2 Pages: 1-18

    • DOI

      10.1128/mcb.00472-20

    • Related Report
      2020 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] Knockout Mouse Models Provide Insight into the Biological Functions of CRL1 Components.2020

    • Author(s)
      Nakagawa T, Nakayama K, Nakayama KI.
    • Journal Title

      Adv Exp Med Biol.

      Volume: 1217 Pages: 147-171

    • DOI

      10.1007/978-981-15-1025-0_10

    • ISBN
      9789811510243, 9789811510250
    • Related Report
      2020 Annual Research Report 2019 Research-status Report
    • Peer Reviewed
  • [Journal Article] An Amyotrophic Lateral Sclerosis-Associated Mutant of C21ORF2 Is Stabilized by NEK1-Mediated Hyperphosphorylation and the Inability to Bind FBXO32020

    • Author(s)
      Watanabe Y, Nakagawa T, Akiyama T, Nakagawa M, Suzuki N, Warita H, Aoki M, Nakayama K.
    • Journal Title

      iScience

      Volume: 23 Issue: 9 Pages: 1-15

    • DOI

      10.1016/j.isci.2020.101491

    • Related Report
      2020 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] USP15 suppresses tumor immunity via deubiquitylation and inactivation of TET22020

    • Author(s)
      Chen LL, Smith MD, Lv L, Nakagawa T, Li Z, Sun SC, Brown NG, Xiong Y, Xu YP.
    • Journal Title

      Science Advances

      Volume: 6 Issue: 38 Pages: 1-13

    • DOI

      10.1126/sciadv.abc9730

    • Related Report
      2020 Annual Research Report
    • Peer Reviewed / Open Access / Int'l Joint Research
  • [Journal Article] Longitudinal plasma amino acid profiling with maternal genomic background throughout human pregnancy2020

    • Author(s)
      M Shirota, D Saigusa, R Yamashita, Y Kato, M Matsumoto, J Yamagishi, N Ishida, K Kumada, Y Oe, H Kudo, J Yokozawa, Y Kuroki, I Motoike, F Katsuoka, M Nagasaki, S Koshiba, K Nakayama, O Tanabe, J Yasuda, S Kure, K Kinoshita, H Metoki, S Kuriyama, N Yaegashi, M Yamamoto, J Sugawara
    • Journal Title

      Medical Mass Spectrometry

      Volume: 4 Pages: 36-49

    • NAID

      130007897968

    • Related Report
      2020 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Longitudinal plasma amino acid profiling with maternal genomic background throughout human pregnancy2020

    • Author(s)
      Shirota M, Saigusa D, Yamashita R, Kato Y, Matsumoto M, Yamagishi J, Ishida N, Kumada K, Oe Y, Kudo H, Yokozawa J, Kuroki Y, Motoike I, Katsuoka F, Nagasaki M, Koshiba S, Nakayama K, Tanabe O, Yasuda J, Kure S, Kinoshita K, Metoki H, Kuriyama S, Yaegashi N, Yamamoto M, Sugawara J
    • Journal Title

      Medical Mass Spectrometry

      Volume: in press

    • NAID

      130007897968

    • Related Report
      2019 Research-status Report
    • Peer Reviewed
  • [Journal Article] Biobank Establishment and Sample Management in the Tohoku Medical Megabank Project2019

    • Author(s)
      Minegishi Naoko、Nishijima Ichiko、Nobukuni Takahiro、Kudo Hisaaki、Ishida Noriko、Terakawa Takahiro、Kumada Kazuki、Yamashita Riu、Katsuoka Fumiki、Ogishima Soichi、Suzuki Kichiya、Sasaki Makoto、Satoh Mamoru、Tohoku Medical Megabank Project Study Group、Yamamoto Masayuki
    • Journal Title

      The Tohoku Journal of Experimental Medicine

      Volume: 248 Issue: 1 Pages: 45-55

    • DOI

      10.1620/tjem.248.45

    • NAID

      130007652672

    • ISSN
      0040-8727, 1349-3329
    • Related Report
      2019 Research-status Report
    • Peer Reviewed / Open Access
  • [Journal Article] A low-frequency IL4R locus variant in Japanese patients with intravenous immunoglobulin therapy-unresponsive Kawasaki disease.2019

    • Author(s)
      Yuji Amano, Yohei Akazawa, Jun Yasud, Kazuhisa Yoshino, Katsuhiko Kojima, Norimoto Kobayashi, Satoshi Matsuzaki, Masao Nagasaki, Yosuke Kawai, Naoko Minegishi, Noriko Ishida, Noriko Motoki, Akira Hachiya, Yozo Nakazawa, Masayuki Yamamoto, Kenichi Koike, Toshikazu Takeshita
    • Journal Title

      Pediatr Rheumatol

      Volume: 17 Issue: 1 Pages: 1-11

    • DOI

      10.1186/s12969-019-0337-2

    • NAID

      120007113478

    • Related Report
      2019 Research-status Report
    • Peer Reviewed / Open Access
  • [Journal Article] Pathogenic mutations in the ALS gene CCNF cause cytoplasmic mislocalization of Cyclin F and elevated VCP ATPase activity.2019

    • Author(s)
      Yu Y, Nakagawa T, Morohoshi A, Nakagawa M, Ishida N, Suzuki N, Aoki M, Nakayama K.
    • Journal Title

      Hum Mol Genet

      Volume: 28 Issue: 20 Pages: 3486-3497

    • DOI

      10.1093/hmg/ddz119

    • Related Report
      2019 Research-status Report
    • Peer Reviewed
  • [Journal Article] Aberrant axon branching via Fos-B dysregulation in FUS-ALS motor neurons.2019

    • Author(s)
      Akiyama T, Suzuki N, Ishikawa M, Fujimori K, Sone T, Kawada J, Funayama R, Fujishima F, Mitsuzawa S, Ikeda K, Ono H, Shijo T, Osana S, Shirota M, Nakagawa T, et al.
    • Journal Title

      EBioMedicine

      Volume: 45 Pages: 362-378

    • DOI

      10.1016/j.ebiom.2019.06.013

    • Related Report
      2019 Research-status Report
    • Peer Reviewed / Open Access
  • [Journal Article] The ubiquitin ligase subunit β-TrCP in Sertoli cells is essential for spermatogenesis in mice.2019

    • Author(s)
      Morohoshi, A., Nakagawa, T., Nakano, S., Nagasawa, Y., Nakayama, K.
    • Journal Title

      Dev Biol.

      Volume: 445 Issue: 2 Pages: 178-188

    • DOI

      10.1016/j.ydbio.2018.10.023

    • Related Report
      2018 Research-status Report
    • Peer Reviewed
  • [Journal Article] Transforming Growth Factor β-Induced Proliferative Arrest Mediated by TRIM26-Dependent TAF7 Degradation and Its Antagonism by MYC.2018

    • Author(s)
      Nakagawa T, Hosogane M, Nakagawa M, Morohoshi A, Funayama R, Nakayama K.
    • Journal Title

      Mol Cell Biol

      Volume: 38 Issue: 5

    • DOI

      10.1128/mcb.00449-17

    • Related Report
      2017 Research-status Report
    • Peer Reviewed
  • [Journal Article] Ubiquitylation of Ku80 by RNF126 Promotes Completion of Nonhomologous End Joining-Mediated DNA Repair.2017

    • Author(s)
      Ishida N, Nakagawa T, Iemura SI, Yasui A, Shima H, Katoh Y, Nagasawa Y, Natsume T, Igarashi K, Nakayama K.
    • Journal Title

      Mol Cell Biol

      Volume: 37 Issue: 4

    • DOI

      10.1128/mcb.00347-16

    • Related Report
      2017 Research-status Report
    • Peer Reviewed
  • [Journal Article] Regulation of mitosis-meiosis transition by the ubiquitin ligase β-TrCP in male germ cells.2017

    • Author(s)
      Nakagawa T, Zhang T, Kushi R, Nakano S, Endo T, Nakagawa M, Yanagihara N, Zarkower D, Nakayama K.
    • Journal Title

      Development

      Volume: 144 Pages: 4137-4147

    • DOI

      10.1242/dev.158485

    • Related Report
      2017 Research-status Report
    • Peer Reviewed / Int'l Joint Research
  • [Journal Article] The SCFβ-TRCP E3 ubiquitin ligase complex targets Lipin1 for ubiquitination and degradation to promote hepatic lipogenesis.2017

    • Author(s)
      Shimizu K, Fukushima H, Ogura K, Lien EC, Nihira NT, Zhang J, North BJ, Guo A, Nagashima K, Nakagawa T, Hoshikawa S, Watahiki A, Okabe K, Yamada A, Toker A, Asara JM, Fukumoto S, Nakayama KI, Nakayama K, Inuzuka H, Wei W.
    • Journal Title

      Sci Signal. doi: 10.1126/scisignal.aah4117.

      Volume: 10 Issue: 460 Pages: 1-15

    • DOI

      10.1126/scisignal.aah4117

    • Related Report
      2017 Research-status Report
    • Peer Reviewed / Open Access / Int'l Joint Research
  • [Presentation] 自閉症関連タンパク質SETD5によるrDNAのエピジェネティック制御を介した神経細胞の増殖促進2020

    • Author(s)
      中川 直、中山 啓子
    • Organizer
      第10回武田科学振興財団 薬科学シンポジウム
    • Related Report
      2020 Annual Research Report
    • Int'l Joint Research
  • [Presentation] The Evaluation of Genomic Identity of the Cell Specimens in the TMM Biobank2019

    • Author(s)
      Kazuki Kumada, Noriko Ishida, Yuichi Aoki, Hisaaki Kudo, Riu Yamashita, Takahiro Nobukuni, Ichiko Nishijima, Takahiro Terakawa, Kengo Kinoshita, Masayuki Yamamoto, Naoko Minegishi
    • Organizer
      ISBER
    • Related Report
      2019 Research-status Report
    • Int'l Joint Research
  • [Presentation] 知的障害・自閉症関連因子SETD5によるrDNAのエピジェネティック制御2019

    • Author(s)
      中川直, 中山啓子
    • Organizer
      第42回日本分子生物学会
    • Related Report
      2019 Research-status Report
    • Invited
  • [Presentation] Processing, Storage and Management Systems of Cell Samples in TMM Biobank2018

    • Author(s)
      Noriko Ishida, Takahiro Nobukuni, Ichiko Nishijima, isaaki Kudo, Riu Yamashita, Takahiro Terakawa, Masayuki Yamamoto, Naoko Minegishi
    • Organizer
      Europe Biobank Week, Oral presentation, Topic 4C: Quality Assessment and Management of Samples and Data
    • Related Report
      2018 Research-status Report
    • Int'l Joint Research
  • [Presentation] ユビキチン化によるFACT複合体の機能制御2018

    • Author(s)
      中川 直、諸星 茜、中山 啓子
    • Organizer
      第41回日本分子生物学会年会、ワークショップ:ユビキチン on クロマチン
    • Related Report
      2018 Research-status Report
    • Invited
  • [Presentation] Mutation of cyclin F may contribute to Amyotrophic Lateral Sclerosis pathogenesis by affecting VCP2018

    • Author(s)
      Yujiao Yu. Akane Morohoshi, Tadashi Nakagawa, Keiko Nakayama
    • Organizer
      第41回日本分子生物学会年会、ポスター発表
    • Related Report
      2018 Research-status Report
  • [Remarks] 東北大学大学院医学系研究科 附属創生応用医学研究センター がん医学コアセンター 細胞増殖制御分野

    • URL

      http://www.devgen.med.tohoku.ac.jp/result/ronbun/index.html

    • Related Report
      2017 Research-status Report

URL: 

Published: 2017-04-28   Modified: 2022-01-27  

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