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Identification of proteolytic signaling pathways regulating reprogramming during iPS cell generation

Research Project

Project/Area Number 16K15811
Research Category

Grant-in-Aid for Challenging Exploratory Research

Allocation TypeMulti-year Fund
Research Field Dental engineering/Regenerative dentistry
Research InstitutionTohoku University

Principal Investigator

Inuzuka Hiroyuki  東北大学, 歯学研究科, 准教授 (20335863)

Co-Investigator(Kenkyū-buntansha) 福本 敏  東北大学, 歯学研究科, 教授 (30264253)
福島 秀文  東北大学, 歯学研究科, 准教授 (70412624)
Research Collaborator SAWASAKI Tatsuya  愛媛大学, プロテオサイエンスセンター, 教授
SHIMIZU Kouhei  東北大学, 大学院歯学研究科, 助教
Project Period (FY) 2016-04-01 – 2018-03-31
Project Status Completed (Fiscal Year 2017)
Budget Amount *help
¥3,380,000 (Direct Cost: ¥2,600,000、Indirect Cost: ¥780,000)
Fiscal Year 2017: ¥1,690,000 (Direct Cost: ¥1,300,000、Indirect Cost: ¥390,000)
Fiscal Year 2016: ¥1,690,000 (Direct Cost: ¥1,300,000、Indirect Cost: ¥390,000)
KeywordsSKP2 / Ubiquitination / iPS cells / iPS / iPS細胞 / 蛋白質分解 / ユビキチン-プロテアソーム系 / iPS 細胞 / エピゲノム修飾
Outline of Final Research Achievements

Direct reprogramming of somatic cells to iPS cells involves global changes in epigenetic modification and gene expression. SKP2 E3 ligase is reported to play essential roles in epigenetic transcriptional regulation through degrading histone methyltransferases including MLL, PR-SET7, and CARM1. Here, to characterize the role of SKP2 signaling in human iPS generation, we conducted a screening of SKP2 interacting proteins and identified a RING-family protein as the E3 ligase of SKP2. Furthermore, we found that the protein levels of SKP2 and the RING E3 ligase are associated with the process of iPS generation. These data suggest that the identified E3 cascade may play important roles in epigenetic reprogramming of somatic to iPS cells.

Report

(3 results)
  • 2017 Annual Research Report   Final Research Report ( PDF )
  • 2016 Research-status Report
  • Research Products

    (13 results)

All 2018 2017 2016 Other

All Int'l Joint Research (2 results) Journal Article (7 results) (of which Int'l Joint Research: 7 results,  Peer Reviewed: 7 results,  Open Access: 1 results) Presentation (4 results) (of which Int'l Joint Research: 1 results,  Invited: 2 results)

  • [Int'l Joint Research] Beth Israel Deaconess Medical Center(米国)

    • Related Report
      2017 Annual Research Report
  • [Int'l Joint Research] Beth Israel Deaconess Medical Center(米国)

    • Related Report
      2016 Research-status Report
  • [Journal Article] Skp2-dependent reactivation of AKT drives resistance to PI3K inhibitors2018

    • Author(s)
      Clement Emilie、Inuzuka Hiroyuki、Nihira Naoe T.、Wei Wenyi、Toker Alex
    • Journal Title

      Science Signaling

      Volume: 11 Issue: 521 Pages: 3810-3810

    • DOI

      10.1126/scisignal.aao3810

    • Related Report
      2017 Annual Research Report
    • Peer Reviewed / Int'l Joint Research
  • [Journal Article] NOTCH2 Hajdu-Cheney Mutations Escape SCFFBW7-Dependent Proteolysis to Promote Osteoporosis.2017

    • Author(s)
      Fukushima H, Shimizu K, Watahiki A, Hoshikawa S, Kosho T, Oba D, Sakano S, Arakaki M
    • Journal Title

      Mol Cell

      Volume: Nov 16;68(4) Issue: 4 Pages: 645-658

    • DOI

      10.1016/j.molcel.2017.10.018

    • Related Report
      2017 Annual Research Report
    • Peer Reviewed / Open Access / Int'l Joint Research
  • [Journal Article] Prostate cancer-associated SPOP mutations confer resistance to BET inhibitors through stabilization of BRD42017

    • Author(s)
      Dai X, Gan W, Li X, Wang S, Zhang W, Huang L, Liu S, Zhong Q, Guo J, Zhang J, Chen T, Shimizu K, Beca F, Blattner M, Vasudevan D, Buckley DL, Qi J, Buser L, Liu P, Inuzuka H, Beck AH, Wang L, Wild PJ, Garraway LA, Rubin MA, Barbieri CE, Wong KK, Muthuswamy SK, Huang J, Chen Y, Bradner JE, Wei W
    • Journal Title

      Nature Medicine

      Volume: 23 Issue: 9 Pages: 1063-1071

    • DOI

      10.1038/nm.4378

    • Related Report
      2017 Annual Research Report
    • Peer Reviewed / Int'l Joint Research
  • [Journal Article] FBW7 loss promotes chromosomal instability and tumorigenesis via Cyclin E1/CDK2-mediated phosphorylation of CENP-A2017

    • Author(s)
      Takada M, Zhang W, Suzuki A, Kuroda T, Yu Z, Inuzuka H, Gao D, Wan L, Zhuang M, Hu L, Zhai B, Fry C, Bloom K, Li G, Karpen G, Wei W, Zhang Q
    • Journal Title

      Cancer Research

      Volume: 77 Issue: 18 Pages: 4881-4893

    • DOI

      10.1158/0008-5472.can-17-1240

    • Related Report
      2017 Annual Research Report
    • Peer Reviewed / Int'l Joint Research
  • [Journal Article] Acetylation-dependent regulation of MDM2 E3 ligase activity dictates its oncogenic function.2017

    • Author(s)
      2.Nihira NT, Ogura K, Shimizu K, North BJ, Zhang J, Gao D, Inuzuka H, Wei W.
    • Journal Title

      Science Signaling

      Volume: 10 Issue: 466

    • DOI

      10.1126/scisignal.aai8026

    • Related Report
      2017 Annual Research Report
    • Peer Reviewed / Int'l Joint Research
  • [Journal Article] The APC/C E3 Ligase Complex Activator FZR1 Restricts BRAF Oncogenic Function2017

    • Author(s)
      Wan L, Chen M, Cao J, Dai X, Yin Q, Zhang J, Song SJ, Lu Y, Liu J, Inuzuka H, Katon JM, Berry K, Fung J, Ng C, Liu P, Song MS, Xue L, Bronson RT, Kirschner MW, Cui R, Pandolfi PP, Wei W
    • Journal Title

      Cancer Discovery

      Volume: 7 Issue: 4 Pages: 424-441

    • DOI

      10.1158/2159-8290.cd-16-0647

    • Related Report
      2017 Annual Research Report
    • Peer Reviewed / Int'l Joint Research
  • [Journal Article] G1 cyclins link proliferation, pluripotency and differentiation of embryonic stem cells2017

    • Author(s)
      Lijun Liu, Wojciech Michowski, Hiroyuki Inuzuka, Kouhei Shimizu, Naoe Taira Nihira, Joel M. Chick, Na Li, Yan Geng, Alice Y. Meng, Alban Ordureau, Aleksandra Kolodziejczyk, Keith L. Ligon, Roderick T. Bronson, Kornelia Polyak, J. Wade Harper, Steven P. Gygi, Wenyi Wei, Piotr Sicinski
    • Journal Title

      Nature Cell Biology

      Volume: 19 Issue: 3 Pages: 177-188

    • DOI

      10.1038/ncb3474

    • Related Report
      2016 Research-status Report
    • Peer Reviewed / Int'l Joint Research
  • [Presentation] タンパク質分解から考える骨及び脂質代謝制御2017

    • Author(s)
      犬塚 博之
    • Organizer
      第55回日本小児歯科学会大会(シンポジウム)
    • Related Report
      2017 Annual Research Report
    • Invited
  • [Presentation] Multiple functions of SCF E3 ligase and its implications as a therapeutic target2017

    • Author(s)
      犬塚 博之
    • Organizer
      第15回 松山国際学術シンポジウム
    • Related Report
      2017 Annual Research Report
    • Int'l Joint Research / Invited
  • [Presentation] 抗アポトーシスタンパク質MCL1の安定性制御におけるアセチル化の役割2017

    • Author(s)
      清水 康平、犬塚 博之、福島 秀文、福本 敏
    • Organizer
      第59回歯科基礎医学会学術大会
    • Related Report
      2017 Annual Research Report
  • [Presentation] BHD症候群関連タンパク質FNIP2のプロテアソーム依存的な量的調節機構の解析2016

    • Author(s)
      綿引 麻美、星川 聖良、犬塚 博之、江草 宏、福島 秀文
    • Organizer
      第39回 日本分子生物学会年会
    • Place of Presentation
      横浜
    • Year and Date
      2016-11-30
    • Related Report
      2016 Research-status Report

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Published: 2016-04-21   Modified: 2019-03-29  

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