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Elucidation of signals and metabolic bases that regulate functions of plasma membrane microdomains

Research Project

Project/Area Number 25460385
Research Category

Grant-in-Aid for Scientific Research (C)

Allocation TypeMulti-year Fund
Section一般
Research Field Pathological medical chemistry
Research InstitutionThe University of Tokyo (2016)
Nagoya University (2013-2015)

Principal Investigator

Yamauchi Yoshio  東京大学, 大学院農学生命科学研究科(農学部), 特任准教授 (00444878)

Co-Investigator(Kenkyū-buntansha) 古川 鋼一  中部大学, 生命健康科学部, 教授 (80211530)
Co-Investigator(Renkei-kenkyūsha) UESUGI Motonari  京都大学, 物質-細胞統合システム拠点, 教授 (10402926)
Research Collaborator CHANG Ta-Yuan Chang  Geisel School of Medicine at Dartmouth, 教授
Project Period (FY) 2013-04-01 – 2017-03-31
Project Status Completed (Fiscal Year 2016)
Budget Amount *help
¥5,200,000 (Direct Cost: ¥4,000,000、Indirect Cost: ¥1,200,000)
Fiscal Year 2015: ¥1,560,000 (Direct Cost: ¥1,200,000、Indirect Cost: ¥360,000)
Fiscal Year 2014: ¥1,560,000 (Direct Cost: ¥1,200,000、Indirect Cost: ¥360,000)
Fiscal Year 2013: ¥2,080,000 (Direct Cost: ¥1,600,000、Indirect Cost: ¥480,000)
Keywords膜ドメイン / 脂質代謝 / シグナル / がん / シグナル伝達 / コレステロール / スフィンゴ糖脂質 / 代謝 / mTOR / 癌
Outline of Final Research Achievements

Plasma membrane microdomains (lipid rafts) play essential roles in cellular functions and in malignant properties of cancer cells. It is therefore important for developing therapeutic strategies for malignant tumor, to understand how functionality of lipid rafts is preserved in cancer cells. In this study, we showed that SREBP, a transcriptional factor that regulates lipid metabolism, functions as a crucial factor maintaining integrity of lipid rafts in and malignant properties of cancer cells. Furthermore, we revealed regulatory mechanisms that control the activation of SREBP at the endoplasmic reticulum.

Report

(5 results)
  • 2016 Annual Research Report   Final Research Report ( PDF )
  • 2015 Research-status Report
  • 2014 Research-status Report
  • 2013 Research-status Report
  • Research Products

    (34 results)

All 2017 2016 2015 2014 2013 Other

All Int'l Joint Research (2 results) Journal Article (9 results) (of which Int'l Joint Research: 7 results,  Peer Reviewed: 9 results,  Open Access: 3 results,  Acknowledgement Compliant: 4 results) Presentation (20 results) Book (3 results)

  • [Int'l Joint Research] ダートマス大学/イリノイ大学(米国)

    • Related Report
      2016 Annual Research Report
  • [Int'l Joint Research] ダートマス大学/イリノイ大学(米国)

    • Related Report
      2015 Research-status Report
  • [Journal Article] Methods for Monitoring ABCA1-Dependent Sterol Release2017

    • Author(s)
      Yamauchi Y, Yokoyama S, Chang TY
    • Journal Title

      Methods Mol Biol

      Volume: 1583 Pages: 257-273

    • DOI

      10.1007/978-1-4939-6875-6_19

    • ISBN
      9781493968732, 9781493968756
    • Related Report
      2016 Annual Research Report
    • Peer Reviewed / Int'l Joint Research / Acknowledgement Compliant
  • [Journal Article] Cellular Cholesterol Homeostasis in Alzheimer's Disease2017

    • Author(s)
      Chang TY, Yamauchi Y, Hasan M, Chang CC
    • Journal Title

      J Lipid Res

      Volume: 印刷中 Issue: 12 Pages: 2239-2254

    • DOI

      10.1194/jlr.r075630

    • Related Report
      2016 Annual Research Report
    • Peer Reviewed / Int'l Joint Research
  • [Journal Article] Raft-based interactions of gangliosides with a GPI-anchored receptor2016

    • Author(s)
      N. Komura, K. G. N. Suzuki, H. Ando, M. Konishi, M. Koikeda, A. Imamura, R. Chadda, T. K. Fujiwara, H. Tsuboi, R. Sheng, W. Cho, K. Furukawa, K. Furukawa, Y. Yamauchi, H. Ishida, A. Kusumi (Co-Corresponding Author), and M. Kiso
    • Journal Title

      Nat. Chem. Biol.

      Volume: in press Issue: 6 Pages: 402-410

    • DOI

      10.1038/nchembio.2059

    • Related Report
      2016 Annual Research Report
    • Peer Reviewed / Open Access / Int'l Joint Research
  • [Journal Article] Expression analysis of 0-series gangliosides in human cancer cell lines with monoclonal antibodies generated using knockout mice of ganglioside synthase genes2016

    • Author(s)
      Bhuiyan RH, Kondo Y, Yamaguchi T, Tokuda N, Ohkawa Y, Hashimoto N, Ohmi Y, Yamauchi Y, Furukawa K, Okajima T, Furukawa K
    • Journal Title

      Glycobiology

      Volume: 26 Issue: 9 Pages: 984-998

    • DOI

      10.1093/glycob/cww049

    • Related Report
      2016 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Increased expression levels of ppGalNAc-T13 in lung cancers: Significance in the prognostic diagnosis2016

    • Author(s)
      Nogimori K, Hori T, Kawaguchi K, Fukui T, Mii S, Nakada H, Matsumoto Y, Yamauchi Y, Takahashi M, Furukawa K, Tetsuya O, Yokoi K, Hasegawa Y, Furukawa K
    • Journal Title

      Int J Oncol

      Volume: 49 Issue: 4 Pages: 1369-1376

    • DOI

      10.3892/ijo.2016.3638

    • Related Report
      2016 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Expression of B4GALNT1, an essential glycosyltransferase for the synthesis of complex gangliosides, suppresses BACE1 degradation and modulates APP processing2016

    • Author(s)
      Yamaguchi T, Yamauchi Y, Furukawa K, Ohmi Y, Ohkawa Y, Zhang Q, Okajima T, Furukawa K
    • Journal Title

      Sci Rep

      Volume: 6 Issue: 1 Pages: 34505-34505

    • DOI

      10.1038/srep34505

    • Related Report
      2016 Annual Research Report
    • Peer Reviewed / Open Access / Int'l Joint Research / Acknowledgement Compliant
  • [Journal Article] ABCA1-dependent sterol release: sterol molecule specificity and potential membrane domain for HDL biogenesis2016

    • Author(s)
      Yamauchi Y, Yokoyama S, Chang TY.
    • Journal Title

      J Lipid Res

      Volume: 57 Issue: 1 Pages: 77-88

    • DOI

      10.1194/jlr.m063784

    • Related Report
      2015 Research-status Report
    • Peer Reviewed / Int'l Joint Research / Acknowledgement Compliant
  • [Journal Article] Raft-based interactions of gangliosides with a GPI-anchored receptor2016

    • Author(s)
      Komura N, Suzuki KG, Ando H, Konishi M, Koikeda M, Imamura A, Chadda R, Fujiwara TK, Tsuboi H, Sheng R, Cho W, Furukawa K, Furukawa K, Yamauchi Y, Ishida H, Kusumi A, Kiso M.
    • Journal Title

      Nature Chem Biol

      Volume: 印刷中

    • Related Report
      2015 Research-status Report
    • Peer Reviewed / Int'l Joint Research
  • [Journal Article] Deficiency in the Lipid Exporter ABCA1 Impairs Retrograde Sterol Movement and Disrupts Sterol Sensing at the Endoplasmic Reticulum2015

    • Author(s)
      Yamauchi Y, Iwamoto N, Rogers MA, Abe-Dohmae S, Fujimoto T, Chang CC, Ishigami M, Kishimoto T, Kobayashi T, Ueda K, Furukawa K, Chang TY, Yokoyama S.
    • Journal Title

      J Biol Chem

      Volume: 290 Issue: 39 Pages: 23464-23477

    • DOI

      10.1074/jbc.m115.662668

    • Related Report
      2015 Research-status Report
    • Peer Reviewed / Open Access / Int'l Joint Research / Acknowledgement Compliant
  • [Presentation] ABCA1依存的HDL形成におけるステロール分子特異性と膜ドメイン2017

    • Author(s)
      山内祥生、横山信治,Ta-Yuan Chang
    • Organizer
      日本農芸化学会2017年度大会
    • Place of Presentation
      京都女子大学、京都府京都市
    • Year and Date
      2017-03-17
    • Related Report
      2016 Annual Research Report
  • [Presentation] SREBPプロセシングを阻害する新規低分子量化合物によって明らかになったヒトメラノーマ細胞におけるSREBP依存的なメバロン酸経路の重要性,ポスター2016

    • Author(s)
      山内祥生,太田晃成,渡邉瑞貴,五十嵐政智,佐藤隆一郎,上杉志成,古川鋼一
    • Organizer
      第39回日本分子生物学会年会
    • Place of Presentation
      パシフィコ横浜、神奈川県横浜市
    • Year and Date
      2016-11-30
    • Related Report
      2016 Annual Research Report
  • [Presentation] ABCトランスポーターABCA1はダイナミン依存性エンドサイトーシスを介したステロール逆行輸送を調節する2015

    • Author(s)
      山内祥生、岩本紀之、Maximillian A. Rogers, 堂前純子、藤本豊士、Catherine Chang、石神正登、岸本拓磨、小林俊秀、植田和光、古川鋼一、Ta-Yuan Chang、横山信治
    • 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
      神戸国際会議場、兵庫県神戸市
    • Year and Date
      2015-12-01
    • Related Report
      2015 Research-status Report
  • [Presentation] SCAPを標的とした新規低分子量化合物から明らかになったがん細胞におけるSREBP依存的メバロン酸経路の重要性2015

    • Author(s)
      山内祥生、太田晃成、渡辺瑞貴、五十嵐政智、上杉志成、古川鋼一
    • Organizer
      第74回日本癌学会学術総会
    • Place of Presentation
      名古屋国際会議場、愛知県名古屋市
    • Year and Date
      2015-10-08
    • Related Report
      2015 Research-status Report
  • [Presentation] ヒトmelanoma細胞におけるNeogenin細胞内ドメイン(NeICD)標的遺伝子の同定2015

    • Author(s)
      金子慶、大川祐樹、橋本登、大海雄介、山内 祥生、岡島徹也、小谷典弘、本家孝一、古川圭子、古川鋼一
    • Organizer
      第74回日本癌学会学術総会
    • Place of Presentation
      名古屋国際会議場、愛知県名古屋市
    • Year and Date
      2015-10-08
    • Related Report
      2015 Research-status Report
  • [Presentation] Expression and roles of asialo-series gangliosides in human cancer cell lines2015

    • Author(s)
      Robiul H. Bhuiyan, Yuji Kondo, Tokiaki Yamaguchi, Noriyo Tokuda, Yuki Ohkawa, Yuhsuke Ohmi, Yoshio Yamauchi, Keiko Furukawa, Tetsuya Okajima, Koichi Furukawa
    • Organizer
      第74回日本癌学会学術総会
    • Place of Presentation
      名古屋国際会議場、愛知県名古屋市
    • Year and Date
      2015-10-08
    • Related Report
      2015 Research-status Report
  • [Presentation] Neogenin細胞内領域(NeICD)は GD3発現メラノーマにおいて、癌悪性形質亢進に関与する2015

    • Author(s)
      金子慶、大川祐樹、橋本登、大海雄介、山内 祥生、岡島徹也、小谷典弘、本家孝一、古川圭子、古川鋼一
    • Organizer
      第34回日本糖質学会年会
    • Place of Presentation
      東京大学、東京都文京区
    • Year and Date
      2015-07-31
    • Related Report
      2015 Research-status Report
  • [Presentation] mTORシグナルは小胞体での脂質センシングを制御し、がん細胞のリポジェニックフェノタイプを増強する2014

    • Author(s)
      山内 祥生、五十嵐 政智、太田晃成、古川 鋼一
    • Organizer
      第87回日本生化学会大会
    • Place of Presentation
      国立京都国際会館、京都府京都市
    • Year and Date
      2014-10-15 – 2014-10-18
    • Related Report
      2014 Research-status Report
  • [Presentation] GD3発現メラノーマにおけるNeogeninの悪性形質創出メカニズム2014

    • Author(s)
      金子慶、大川祐樹、橋本登、大海雄介、小川光貴、山内 祥生、小谷典弘、本家孝一、古川圭子、古川鋼一
    • Organizer
      第87回日本生化学会大会
    • Place of Presentation
      国立京都国際会館、京都府京都市
    • Year and Date
      2014-10-15 – 2014-10-18
    • Related Report
      2014 Research-status Report
  • [Presentation] ガングリオシドによるAPP切断とその切断断片による酸化ストレス応答の制御2014

    • Author(s)
      山口世堯、山内祥生、松本康之、橋本登、大海雄介、近藤裕史、古川圭子、古川鋼一
    • Organizer
      第87回日本生化学会大会
    • Place of Presentation
      国立京都国際会館、京都府京都市
    • Year and Date
      2014-10-15 – 2014-10-18
    • Related Report
      2014 Research-status Report
  • [Presentation] SREBPのプロセシングを標的とした新規低分子化合物はメラノーマ細胞の悪性形質を抑制する2014

    • Author(s)
      太田晃成、山内祥生、山口世堯、渡辺瑞貴、古川圭子、上杉志成、古川鋼一
    • Organizer
      第73回日本癌学会学術総会
    • Place of Presentation
      パシフィコ横浜、神奈川県横浜市
    • Year and Date
      2014-09-25 – 2014-09-27
    • Related Report
      2014 Research-status Report
  • [Presentation] Establishment of anti-GD1alpha mAbs and expression analysis of asialo-series gangliosides in human cancer cell lines2014

    • Author(s)
      Robiul H. Bhuiyan, Yuji Kondo, Tokiaki Yamaguchi, Noriyo Tokuda, Yoshio Yamauchi, Keiko Furukawa, Tetsuya Okajima, Koichi Furukawa
    • Organizer
      第73回日本癌学会学術総会
    • Place of Presentation
      パシフィコ横浜、神奈川県横浜市
    • Year and Date
      2014-09-25 – 2014-09-27
    • Related Report
      2014 Research-status Report
  • [Presentation] スフィンゴ糖脂質の生合成におけるp24タンパク質の役割2014

    • Author(s)
      山内祥生、Alkmini Papadopoulou、古川鋼一
    • Organizer
      第33回日本糖質学会年会
    • Place of Presentation
      名古屋大学、愛知県名古屋市
    • Year and Date
      2014-08-10 – 2014-08-12
    • Related Report
      2014 Research-status Report
  • [Presentation] ガングリオシドGM1によるAPPの切断とその切断断片により誘導される細胞死の制御2013

    • Author(s)
      山口世堯、山内祥生、松本康之、大川祐樹、大海雄介、橋本登、近藤裕史、古川圭子、古川鋼一
    • Organizer
      第32回日本糖質学会年会
    • Place of Presentation
      大阪国際交流センター、大阪市
    • Related Report
      2013 Research-status Report
  • [Presentation] The lipogenic phenotype of human melanoma cells expressing ganglioside GD3 is regulated by mTOR-mediated lipid sensing at the ER2013

    • Author(s)
      山内祥生、五十嵐政智、古川鋼一
    • Organizer
      第86回日本生化学会大会
    • Place of Presentation
      パシフィコ横浜、横浜市
    • Related Report
      2013 Research-status Report
  • [Presentation] GD3発現メラノーマの悪性形質におけるNeogeninの機能2013

    • Author(s)
      金子慶、大川祐樹、橋本登、大海雄介、山内祥生、小谷典弘、本家孝一、古川圭子、古川鋼一
    • Organizer
      第86回日本生化学会大会
    • Place of Presentation
      パシフィコ横浜、横浜市
    • Related Report
      2013 Research-status Report
  • [Presentation] ガングリオシドによるamyloid β precursor protein(APP) の切断パターンの制御及びAPP切断断片が細胞の健常性に与える影響2013

    • Author(s)
      山口 世堯、山内 祥生、松本 康之、大川 祐樹、大海 雄介、橋本  登、近藤 裕史、古川 圭子、古川 鋼一
    • Organizer
      第86回日本生化学会大会
    • Place of Presentation
      パシフィコ横浜、横浜市
    • Related Report
      2013 Research-status Report
  • [Presentation] mTOR signaling regulates sterol regulatory element binding proteins by mediating lipid sensing2013

    • Author(s)
      Yoshio Yamauchi, Masatomo Igarashi, Koichi Furukawa
    • Organizer
      第72回日本癌学会学術総会
    • Place of Presentation
      パシフィコ横浜、横浜市
    • Related Report
      2013 Research-status Report
  • [Presentation] Roles of Neogenin in GD3-expressing human melanoma cells2013

    • Author(s)
      Kei Kaneko, Yuki Ohkawa, Noboru Hashimoto, Yusuke Ohmi, Yoshio Yamauchi, Norihiro Kotani, Koichi Honke, Keiko Furukawa, Koichi Furukawa
    • Organizer
      第72回日本癌学会学術総会
    • Place of Presentation
      パシフィコ横浜、横浜市
    • Related Report
      2013 Research-status Report
  • [Presentation] スフィンゴ糖脂質合成の調節におけるp24タンパク質の関与の検討2013

    • Author(s)
      山内祥生、山口世堯、藤田盛久、木下タロウ、古川鋼一
    • Organizer
      第36回日本分子生物学会年会
    • Place of Presentation
      神戸国際会議場、神戸市
    • Related Report
      2013 Research-status Report
  • [Book] Glycoscience: Biology and Medicine2015

    • Author(s)
      Furukawa K, Ohmi Y, Ohkawa Y, Hashimoto N, Yamauchi Y, Tajima O, Furukawa K
    • Total Pages
      1569
    • Publisher
      Springer Japan
    • Related Report
      2015 Research-status Report
  • [Book] Glycoscience: Biology and Medicine2014

    • Author(s)
      Koichi Furukawa, Yuhsuke Ohmi, Yuki Ohkawa, Noboru Hashimoto, Yoshio Yamauchi, Orie Tajima, Keiko Furukawa
    • Publisher
      Springer Japan
    • Related Report
      2014 Research-status Report
  • [Book] Handbook of Glycosyltransferases and Related Genes2014

    • Author(s)
      Koichi Furukawa, Keiko Furukawa, Yuhsuke Ohmi, Yuki Ohkawa, Yoshio Yamauchi, Noboru Hashimoto, Orie Tajima
    • Total Pages
      1707
    • Publisher
      Springer Japan
    • Related Report
      2014 Research-status Report

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Published: 2014-07-25   Modified: 2022-01-24  

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