• Search Research Projects
  • Search Researchers
  • How to Use
  1. Back to previous page

Development of cell-response selective regulation of TGF-βsignaling

Research Project

Project/Area Number 22390052
Research Category

Grant-in-Aid for Scientific Research (B)

Allocation TypeSingle-year Grants
Section一般
Research Field General medical chemistry
Research InstitutionUniversity of Yamanashi

Principal Investigator

MIYAZAWA Keiji  山梨大学, 大学院・医学工学総合研究部, 教授 (40209896)

Co-Investigator(Renkei-kenkyūsha) MOTIZUKI Mitsuyoshi  山梨大学, 大学院・医学工学総合研究部, 助教 (90174341)
XU Zhaojun  山梨大学, 大学院・医学工学総合研究部, 助教 (00345703)
Project Period (FY) 2010 – 2012
Project Status Completed (Fiscal Year 2012)
Budget Amount *help
¥18,720,000 (Direct Cost: ¥14,400,000、Indirect Cost: ¥4,320,000)
Fiscal Year 2012: ¥5,460,000 (Direct Cost: ¥4,200,000、Indirect Cost: ¥1,260,000)
Fiscal Year 2011: ¥5,720,000 (Direct Cost: ¥4,400,000、Indirect Cost: ¥1,320,000)
Fiscal Year 2010: ¥7,540,000 (Direct Cost: ¥5,800,000、Indirect Cost: ¥1,740,000)
Keywords細胞内シグナル伝達 / 細胞増殖因子 / シグナル伝達 / 細胞運動性 / Pin1 / ペプチドブロッカー
Research Abstract

Transforming growth factor (TGF)-β plays crucial roles in embryonic development and adult tissue homeostasis by eliciting various cellular responses in target cells. TGF- β signaling is principally mediated through receptor-activated Smad proteins, which regulate expression of target genes in cooperation with other DNA-binding transcription factors (Smad cofactors). In this study, we found that the basic helix-loop-helix transcription factor Olig1 is a Smad cofactor involved in TGF-β-induced cell motility. We also observed that cooperation of Smad2/3 with Olig1 is regulated by a peptidyl-prolyl cis/trans isomerase, Pin1. We further found that Olig1 interacts with the L3 loop ofSmad3. Using a synthetic peptide corresponding to the L3 loop of Smad3, we succeeded in selectively inhibiting TGF-β-induced cell motility. These findings may lead to a new strategy for selective regulation of TGF-β-induced cellular responses.

Report

(4 results)
  • 2012 Annual Research Report   Final Research Report ( PDF )
  • 2011 Annual Research Report
  • 2010 Annual Research Report
  • Research Products

    (36 results)

All 2013 2012 2011 2010 Other

All Journal Article (19 results) (of which Peer Reviewed: 19 results) Presentation (13 results) Book (1 results) Remarks (3 results)

  • [Journal Article] Oligodendrocyte transcription factor 1 (Olig1) is a Smad cofactor involved in cell motility induced by transforming growth factor-β.2013

    • Author(s)
      Motizuki, M., Isogaya, K., Miyake, K., Ikushima, K., Kubota, T., Miyazono, K., Saitoh, M., and Miyazawa, K
    • Journal Title

      J. Biol. Chem

      Volume: (in press)

    • Related Report
      2012 Final Research Report
    • Peer Reviewed
  • [Journal Article] Basolateral BMP signaling in polarized epithelial cells2013

    • Author(s)
      Saitoh, M., Shirakihara, T., Fukasawa, A., Horiguchi, K., Sakamoto, K., Sugiya, H., Beppu, H., Fujita, Y., Morita, I., Miyazono, K., and Miyazawa, K
    • Journal Title

      PLosONE

      Volume: 8

    • Related Report
      2012 Final Research Report
    • Peer Reviewed
  • [Journal Article] Basolateral BMP signaling in polarized epithelial cells.2013

    • Author(s)
      Saitoh, M.
    • Journal Title

      PLOS ONE

      Volume: in press

    • Related Report
      2012 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Transcriptional and post-transcriptional regulation in TGF-β-mediated epithelial-mesenchymal transition.2012

    • Author(s)
      Saitoh,, M. and Miyazawa, K
    • Journal Title

      J. Biochem

      Volume: 151 Pages: 563-571

    • NAID

      10031166097

    • Related Report
      2012 Final Research Report
    • Peer Reviewed
  • [Journal Article] Structure of dominant-negative helix-loop-helix transcriptional regulator HHM representing the autoinhibition state2012

    • Author(s)
      Ishii, R., Seto, A., Isogaya, K., Seto, A., Koinuma, D., Watanabe, Y., Arisaka, F., Yaguchi, S., Ikushima, H., Dohmae, N., Miyazono, K., Miyazawa, K., Ishitani, R., and Nureki, O.
    • Journal Title

      EMBO J

      Volume: 31 Pages: 2541-2552

    • Related Report
      2012 Final Research Report
    • Peer Reviewed
  • [Journal Article] TGF-βdrives epithelial-mesenchymal transition through δEF1-mediated downregulation of ESRP2012

    • Author(s)
      Horiguchi, K., Sakamoto, K., Koinuma, D., Semba, K., Inoue, A., Inoue, S., Fujii, H., Yamaguchi, A., Miyazawa,K., Miyazono K., and Saitoh, M
    • Journal Title

      Oncogene

      Volume: 31 Pages: 3190-3201

    • Related Report
      2012 Final Research Report
    • Peer Reviewed
  • [Journal Article] Transcriptional and post-transcriptional regulation in TGF-β-mediated epithelial-mesenchymal transition.2012

    • Author(s)
      Saitoh, M.
    • Journal Title

      J. Biochem.

      Volume: 151 Issue: 6 Pages: 563-571

    • DOI

      10.1093/jb/mvs040

    • Related Report
      2012 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Structure of a dominant-negative helix-loop-helix transcriptional regulator suggests mechanisms of autoinhibition2012

    • Author(s)
      Ishii R
    • Journal Title

      EMBO Journal

      Volume: 31 Issue: 11 Pages: 2541-2552

    • DOI

      10.1038/emboj.2012.77

    • Related Report
      2011 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Glioma-initiating cells retain their tumorigenicity through integration of the Sox axis and Oct42011

    • Author(s)
      Ikushima, H., Todo, T., Ino, Y., Takahashi, M., Saito, N., Miyazawa, K., and Miyazono, K
    • Journal Title

      J. Biol. Chem

      Volume: 286 Pages: 41434-41441

    • Related Report
      2012 Final Research Report
    • Peer Reviewed
  • [Journal Article] RB1CC1 positively regulates TGF-βsignaling through modulation of Arkadia E3 ubiquitin ligase activity2011

    • Author(s)
      Koinuma, D., Shinozaki, M., Nagano, Y., Ikushima, H., Horiguchi, K., Goto, K., Chano, T., Saitoh, M., Imamura, T., Miyazono, K., and Miyazawa, K
    • Journal Title

      J. Biol. Chem

      Volume: 286 Pages: 32502-32512

    • Related Report
      2012 Final Research Report
    • Peer Reviewed
  • [Journal Article] Suppression of p53 activity through the cooperative action of Ski and histone deacetylase SIRT12011

    • Author(s)
      Inoue, Y., Iemura, S-i., Natsume, T., Miyazawa, K., and Imamura, T.
    • Journal Title

      J. Biol. Chem

      Volume: 286 Pages: 6311-6320

    • Related Report
      2012 Final Research Report
    • Peer Reviewed
  • [Journal Article] TGF-βregulates FGF receptor isoform switching and epithelial-mesenchymal transition2011

    • Author(s)
      Shirakihara, T., Horiguchi, K., Miyazawa, K., Ehata, S., Shibata, T., Morita, I., Miyazono, K., and Saitoh, M
    • Journal Title

      EMBO J

      Volume: 30 Pages: 783-795

    • Related Report
      2012 Final Research Report
    • Peer Reviewed
  • [Journal Article] RB1CC1 protein positively regulates transforming growth factor-beta signaling through the modulation of Arkadia E3 ubiquitin ligase activity2011

    • Author(s)
      Koinuma D
    • Journal Title

      Journal of Biological Chemistry

      Volume: 286 Issue: 37 Pages: 32502-32512

    • DOI

      10.1074/jbc.m111.227561

    • Related Report
      2011 Annual Research Report
    • Peer Reviewed
  • [Journal Article] TGF-β derives epithelial-mesenchymal transition through δEF1-mediated downregulation of ESRP2011

    • Author(s)
      堀口華奈
    • Journal Title

      Oncogene

      Volume: (掲載確定)(印刷中) Issue: 26 Pages: 3190-3201

    • DOI

      10.1038/onc.2011.493

    • Related Report
      2011 Annual Research Report
    • Peer Reviewed
  • [Journal Article] TGF-βregulates FGF receptor isoform switching and epithelial-mesenchvmal transition.2011

    • Author(s)
      Shirakihara, et al.
    • Journal Title

      EMBO J.

      Volume: 30 Pages: 783-795

    • Related Report
      2010 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Arkadia complexes with clathrin adaptor AP2 and regulates EGF signaling2010

    • Author(s)
      Mizutani, A., Saitoh, M., Imamura, T., Miyazawa, K., and Miyazono, K
    • Journal Title

      J..Biochem

      Volume: 148 Pages: 733-741

    • NAID

      10027879992

    • Related Report
      2012 Final Research Report
    • Peer Reviewed
  • [Journal Article] Smad7 inhibits transforming growth factor-βfamily type I receptors through two distinct modes of interaction2010

    • Author(s)
      Kamiya, Y., Miyazono, K., and Miyazawa, K
    • Journal Title

      Biol. Chem

      Volume: 285 Pages: 30804-30813

    • Related Report
      2012 Final Research Report
    • Peer Reviewed
  • [Journal Article] Smad7 inhibits transforming growth factor-βfamily type I receptors through two distinct modes of interaction2010

    • Author(s)
      Kamiya, et al.
    • Journal Title

      J. Biol. Chem.

      Volume: 285 Pages: 30804-30813

    • Related Report
      2010 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Identification of a phosphorylation site in c-Ski as serine 5152010

    • Author(s)
      Nagata, et al.
    • Journal Title

      J..Bioc.hem.

      Volume: 148 Pages: 423-427

    • Related Report
      2010 Annual Research Report
    • Peer Reviewed
  • [Presentation] TGF-βによる運動性促進に必須であるSmad-Olig1複合体形成はPin1によって制御される2012

    • Author(s)
      望月光由、斉藤正夫、宮澤恵二
    • Organizer
      第71回日本癌学会学術総会
    • Place of Presentation
      札幌
    • Year and Date
      2012-09-19
    • Related Report
      2012 Final Research Report
  • [Presentation] Pin1 regulates the cooperative action of Smad2/3 and Olig12012

    • Author(s)
      Keiji Miyazawa
    • Organizer
      Ludwig Foundation TGF-βmeeting
    • Place of Presentation
      Leiden, Nederland
    • Year and Date
      2012-08-29
    • Related Report
      2012 Final Research Report
  • [Presentation] Selective regulation of TGF-β-induced cellular responses: TGF-βFamily2012

    • Author(s)
      Keiji Miyazawa
    • Organizer
      Signal Network in Biologocal Functions The 1st International Symposium by JSPS Core-to-Core Program "Cooperative International Framework in TGF-βFamily Signaling"
    • Place of Presentation
      Tokyo
    • Year and Date
      2012-01-23
    • Related Report
      2012 Final Research Report
  • [Presentation] Selective regulation of TGF-β-induced cellular responses2012

    • Author(s)
      Keiji Miyazawa
    • Organizer
      TGF-β Family : Signal Network in Biologocal Functions The 1st International Symposium by JSPS Core-to-Core Program "Cooperative International Framework in TGF-β Family Signaling"
    • Place of Presentation
      東京大学小柴記念ホール(東京都)(招待講演)
    • Year and Date
      2012-01-23
    • Related Report
      2011 Annual Research Report
  • [Presentation] Smad共役因子Olig1はTGF-βにより誘導される細胞運動を制御する2011

    • Author(s)
      望月光由、齋藤正夫、宮澤恵二
    • Organizer
      第70回日本癌学会学術総会
    • Place of Presentation
      名古屋
    • Year and Date
      2011-10-04
    • Related Report
      2012 Final Research Report
  • [Presentation] Smad共役因子Olig1はTGF-βにより誘導される細胞運動を制御する2011

    • Author(s)
      望月光由
    • Organizer
      第70回日本癌学会学術総会
    • Place of Presentation
      名古屋国際会議場(愛知県)
    • Year and Date
      2011-10-04
    • Related Report
      2011 Annual Research Report
  • [Presentation] Olig1 is a Smad cofactor that mediates TGF-β-induced cell motility2011

    • Author(s)
      Keiji Miyazawa
    • Organizer
      Ludwig Foundation TGF-βmeeting
    • Place of Presentation
      Uppsala, Sweden
    • Year and Date
      2011-08-18
    • Related Report
      2012 Final Research Report
  • [Presentation] How to achieve cellular-response-selective regulation of TGF-βsignaling2011

    • Author(s)
      Keiji Miyazawa
    • Organizer
      KSBMB
    • Place of Presentation
      Seoul, Korea
    • Year and Date
      2011-05-17
    • Related Report
      2012 Final Research Report
  • [Presentation] Olig1 is an essential transcription factor for the TGF-β-induced cell migration2010

    • Author(s)
      Mitsuyoshi Motizuki, Masao Saitoh, and Keiji Miyazawa
    • Organizer
      BMB2010
    • Place of Presentation
      Kobe
    • Year and Date
      2010-12-07
    • Related Report
      2012 Final Research Report
  • [Presentation] The role of Smad-Olig1 transcription complex in TGF-βsignaling2010

    • Author(s)
      Keiji Miyazawa
    • Organizer
      Ludwig Foundation TGF-βmeeting
    • Place of Presentation
      Leiden, Nederland
    • Year and Date
      2010-09-02
    • Related Report
      2012 Final Research Report
  • [Presentation] An-Id-like molecule, Maid, is a cellular-response selective regulator of TGF-βsignaling2010

    • Author(s)
      Keiji Miyazawa
    • Organizer
      藤原セミナー
    • Place of Presentation
      苫小牧
    • Year and Date
      2010-07-15
    • Related Report
      2012 Final Research Report 2010 Annual Research Report
  • [Presentation] Pin1 regualtes the cooperative action of Smad2/3 and Olig1

    • Author(s)
      Keiji Miyazawa
    • Organizer
      Ludwig foundation TGF-beta meeting
    • Place of Presentation
      Leiden University Medical Center (Leiden, Holland)
    • Related Report
      2012 Annual Research Report
  • [Presentation] TGF-β enhances cell migration through the Pin1-regualted Smad-Olig1 transcriptional complex.

    • Author(s)
      望月光由
    • Organizer
      第71回日本癌学会学術総会
    • Place of Presentation
      札幌市教育文化会館(札幌市)
    • Related Report
      2012 Annual Research Report
  • [Book] がん増殖と悪性化の分子機構2012

    • Author(s)
      澤恵二
    • Total Pages
      13
    • Publisher
      化学同人
    • Related Report
      2012 Final Research Report
  • [Remarks]

    • URL

      http://www.med.yamanashi.ac.jp/basic/bioche02/bioch2.html

    • Related Report
      2012 Final Research Report
  • [Remarks] 生化学講座第2教室

    • URL

      http://www.med.yamanashi.ac.jp/basic/bioche02/bioch2.html

    • Related Report
      2012 Annual Research Report
  • [Remarks]

    • URL

      http://www.med.yamanashi.ac.jp/basic/bioche02/

    • Related Report
      2011 Annual Research Report

URL: 

Published: 2010-08-23   Modified: 2019-07-29  

Information User Guide FAQ News Terms of Use Attribution of KAKENHI

Powered by NII kakenhi