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2009 Fiscal Year Final Research Report

Functional analysis of the C-treminal frangment of membrane-anchored growth factors

Research Project

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Project/Area Number 17014068
Research Category

Grant-in-Aid for Scientific Research on Priority Areas

Allocation TypeSingle-year Grants
Review Section Biological Sciences
Research InstitutionEhime University

Principal Investigator

HIGASHIYAMA Shigeki  Ehime University, 大学院・医学系研究科, 教授 (60202272)

Co-Investigator(Kenkyū-buntansha) MORIMOTO Chie  安田女子大学, 薬学部, 講師 (10332826)
HIEDA Miki  大阪大学, 大学院・医学系研究科, 特任助教 (00380254)
INOUE Hirofumi  愛媛大学, 大学院・医学系研究科, 講師 (70321635)
Project Period (FY) 2005 – 2009
Keywordsシグナル伝達と遺伝子発現 / 膜型増殖因子 / shedding / CTFシグナル / 転写リプレッサー / レトログレード小胞輸送
Research Abstract

We analyzed the function of C-terminal fragment (CTF) signals which are evoked by the shedding of a representative membrane-anchored growth factor proHB-EGF. We found that (1) the CTF of proHB-EGF was internalized into cytosol by endocytosis and localized at the innernuclear membrane by retrograde vesicle transport, (2) the CTF regulated several gene expression essential for cell growth promotion by interacting with and regulating gene repressors, and (3) the CTF signal was constitutively active in some tumor cell lines.

  • Research Products

    (16 results)

All 2009 2008 2007 2005 Other

All Journal Article (10 results) Presentation (3 results) Remarks (1 results) Patent(Industrial Property Rights) (2 results)

  • [Journal Article] Mitochondrial reactive oxygen species mediate GPCR-induced TACE/ADAM17-dependent transforming growth factor-alpha shedding.2009

    • Author(s)
      Myers TJ, Higashiyama S
    • Journal Title

      Mol Biol Cell. 20(24)

      Pages: 5236-49

  • [Journal Article] Generation and characterization of conditional heparin-binding EGF-like growth factor knockout mice.2009

    • Author(s)
      Oyagi A, Higashiyama S
    • Journal Title

      PLoS One. 4(10)

      Pages: e7461

  • [Journal Article] Promyelocytic leukemia zinc finger protein regulates interferon-mediated innate immunity.2009

    • Author(s)
      Xu D, Higashiyama S
    • Journal Title

      Immunity 30(6)

      Pages: 802-16

  • [Journal Article] Insufficiency of pro-heparin-binding epidermal growth factor-like growth factor shedding enhances hypoxic cell death in H9c2 cardiomyoblasts via the activation of caspase-3 and c-Jun N-terminal kinase.2009

    • Author(s)
      Uetani T, Inoue H, Higashiyama S
    • Journal Title

      J Biol Chem. 284(18)

      Pages: 12399-409

  • [Journal Article] Plasma-membrane-anchored growth factor pro-amphiregulin binds A-type lamin and regulates global transcription.2008

    • Author(s)
      Isokane M, Hieda M, Higashiyama S
    • Journal Title

      J Cell Sci. 121(Pt21)

      Pages: 3608-18

  • [Journal Article] Membrane-anchored growth factor, HB-EGF, on the cell surface targeted to the inner nuclear membrane.2008

    • Author(s)
      Hieda M, Higashiyama S
    • Journal Title

      J Cell Biol. 180(4)

      Pages: 763-9

  • [Journal Article] Membrane-anchored growth factors, the epidermal growth factor family: beyond receptor ligands.2008

    • Author(s)
      Higashiyama S
    • Journal Title

      Cancer Sci 99(2)

      Pages: 214-20

  • [Journal Article] An intermediary role of proHB-EGF shedding in growth factor-induced c-Myc gene expression.2008

    • Author(s)
      Nanba D, Inoue H, Higashiyama S
    • Journal Title

      J Cell Physiol. 214(2)

      Pages: 465-73

  • [Journal Article] he carboxyl-terminal fragment of pro-HB-EGF reverses Bcl6-mediated gene repression.2007

    • Author(s)
      Kinugasa Y, Hieda M, Hori M, Higashiyama S
    • Journal Title

      J Biol Chem. 282(20)

      Pages: 14797-806

  • [Journal Article] Pre-B-cell leukemia transcription factor 1 is a major target of promyelocytic leukemia zinc-finger-mediated melanoma cell growth suppression.2007

    • Author(s)
      Shiraishi K, Inoue H, Higashiyama S
    • Journal Title

      Oncogene 26(3)

      Pages: 339-48

  • [Presentation] Inner nuclear membrane targeting of membrane-anchored growth factors and transcriptional regulation (Invited).2009

    • Author(s)
      Shigeki Higashiyama
    • Organizer
      Gordon Research Conference "Signal Transduction within the Nucleus"
    • Place of Presentation
      Ventura, CA, USA
    • Year and Date
      20090329-20090403
  • [Presentation] A zinc finger transcription factor regulates vascular sprouting through the downregulation of Notch signaling in vascular endothelial cells.2009

    • Author(s)
      Hidetaka Ohnuki, Hirofumi Inoue, Hironao Nakayama, Shinji Fukuda, Shigeki Higashiyama
    • Organizer
      Keystone Symposia -Angiogenesis and Lymphangiogenesis in Cancer-
    • Place of Presentation
      Big Sky Resort, Big Sky, Montana, USA (Hidetaka Ohnuki received Keystone Symposia Scholarship Award, NIH, National Cancer Institute Grant #1R13CA135834-01. )
    • Year and Date
      20090106-20090111
  • [Presentation] Ectodomain shedding of membrane-anchored growth factor HB-EGF by ADAM and HB-EGF-C terminal fragment signaling.2005

    • Author(s)
      Shigeki Higahsiyama
    • Organizer
      The Kennedy institute of Rheumatology Symposium, Metalloproteinases
    • Place of Presentation
      Biology and Pathology, London, UK
    • Year and Date
      20051121-20051122
  • [Remarks]

    • URL

      http://www.m.ehime-u.ac.jp/school/biochem2/index.html

  • [Patent(Industrial Property Rights)] 新規ユビキチンリガーゼ及びその利用法2009

    • Inventor(s)
      東山繁樹, 井上博文, 大貫秀隆
    • Industrial Property Rights Holder
      国立大学法人愛媛大学
    • Industrial Property Number
      特許・2009-277073
    • Filing Date
      2009-12-04
  • [Patent(Industrial Property Rights)] 血管新生制御剤, 及びそのスクリーニング方法、並びにスクリーニング用キット2008

    • Inventor(s)
      東山繁樹、井上博文、大貫秀隆
    • Industrial Property Rights Holder
      国立大学法人愛媛大学
    • Industrial Property Number
      特許・2008-208828
    • Filing Date
      2008-08-14

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Published: 2011-06-18   Modified: 2016-04-21  

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