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2007 Fiscal Year Final Research Report Summary

Characterization of the molecular mechanisms of Akt activation

Research Project

Project/Area Number 17370044
Research Category

Grant-in-Aid for Scientific Research (B)

Allocation TypeSingle-year Grants
Section一般
Research Field Functional biochemistry
Research InstitutionHokkaido University

Principal Investigator

NOGUCHI Masayuki  Hokkaido University, Institute for Genetic Medicine, Professor (40359477)

Co-Investigator(Kenkyū-buntansha) NOGUCHI Masayuki  Hokkaido University, Institute for Genetic Medicine, Professor (40359477)
Project Period (FY) 2005 – 2007
KeywordsGene / Cancer / Enzyme reaction / Nucleic acid / Protein
Research Abstract

Serine threonine kinase Akt, also called PKB (Protein Kinase B), plays a central role in the regulation of intracellular survival. Deregulation of this Akt signaling pathway underlies various human neoplastic diseases. Recently, the protooncogene TCL1 (T cell leukemia 1), with a previously unknown physiological function, was shown to interact with the Akt pleckstrin homology domain, enhancing Akt kinase activity; hence, it functions as an Akt kinase co-activator. In contrast to pathological conditions in which the TCL1 gene is highly activated in various human neoplasmic diseases, the physiological expression of TCL1 is tightly limited to early developmental cells as well as various developmental stages of immune cells. The NBRE (Nerve Growth Factor Responsive Element) of the proximal TCL1 promoter sequences can regulate the restricted physiological expression of TCL1 in a negative feedback mechanism. Further, based on the NMR structural studies of Akt-TCL1 protein complexes, an inhibitory peptide, "Akt-in," consisting of the βA strand of TCL1, has been identified and has therapeutic potential. Our study together promote substantial understanding of TCL1-Akt functional interaction and the biological action of the protooncogene TCL1 family and the new suppressive drug specific for Akt, a core intracellular survival regulator.

  • Research Products

    (24 results)

All 2008 2007 2006 2005 Other

All Journal Article (6 results) (of which Peer Reviewed: 4 results) Presentation (15 results) Book (2 results) Remarks (1 results)

  • [Journal Article] Regulation of the PI3K-Akt Network: Current Status and a Promise for the Treatment of Human Diseases.2008

    • Author(s)
      M. Noguchi
    • Journal Title

      Curr Sig. Thera (In press)

    • Description
      「研究成果報告書概要(和文)」より
    • Peer Reviewed
  • [Journal Article] The roles of the PI3K-AKT network in infectious Diseases.2008

    • Author(s)
      M. Noguchi
    • Journal Title

      Jpn J. Infect Dis. (In press)

    • Description
      「研究成果報告書概要(和文)」より
    • Peer Reviewed
  • [Journal Article] The roles of the PI3K-AKT network in infectious Diseases.2008

    • Author(s)
      M. Noguchi
    • Journal Title

      Jpn J. Infect Dis.

    • Description
      「研究成果報告書概要(欧文)」より
  • [Journal Article] Protooncogene TCL1: More than just as a co-activator for Akt.2007

    • Author(s)
      M. Noguchi
    • Journal Title

      FASEB J. 21

      Pages: 2273-2284

    • Description
      「研究成果報告書概要(和文)」より
    • Peer Reviewed
  • [Journal Article] Fusion of Biotechnology and Biology2007

    • Author(s)
      M. Noguchi
    • Journal Title

      Hokkaido University Press

      Pages: 305-315

    • Description
      「研究成果報告書概要(欧文)」より
  • [Journal Article] Identification of NBRE (nerve growth factor responsive element) of the TCL1 promoter as a novel negative regulatory element.2006

    • Author(s)
      M. Hiromura
    • Journal Title

      J. Biol. Chem. 281

      Pages: 27753-27764

    • Description
      「研究成果報告書概要(和文)」より
    • Peer Reviewed
  • [Presentation] PI3K-AKT Network as a Therapeutic Target For Human Disease.2007

    • Author(s)
      M. Noguchi
    • Organizer
      IDDST・2007
    • Place of Presentation
      西安(中国)・古都新世界大酒店
    • Year and Date
      2007-11-08
    • Description
      「研究成果報告書概要(和文)」より
  • [Presentation] PI3K-AKT Network as a Therapeutic Target for Human Disease.2007

    • Author(s)
      M. Noguchi
    • Organizer
      IDDST 2007
    • Place of Presentation
      Grand New World Hotel, Xi'an, China
    • Year and Date
      2007-11-08
    • Description
      「研究成果報告書概要(欧文)」より
  • [Presentation] Protooncogene TCL1: More than just as a co-activator for Akt.2007

    • Author(s)
      M. Noguchi
    • Organizer
      日本癌学会
    • Place of Presentation
      横浜・パシフィコ横浜
    • Year and Date
      2007-10-03
    • Description
      「研究成果報告書概要(和文)」より
  • [Presentation] Protooncogene TCL1: More than just a co-activator for Akt.2007

    • Author(s)
      M. Noguchi
    • Organizer
      JAPANESE CANCER ASSOCIATION
    • Place of Presentation
      Pacifico Yokohama, Yokohama
    • Year and Date
      2007-10-03
    • Description
      「研究成果報告書概要(欧文)」より
  • [Presentation] 細胞死と増殖を介した生体ホメオスターシス制御の破綻と疾病2007

    • Author(s)
      野口 昌幸
    • Organizer
      日本適応医学会
    • Place of Presentation
      札幌・北海道大学
    • Year and Date
      2007-06-09
    • Description
      「研究成果報告書概要(和文)」より
  • [Presentation] Deregulation of cell death and survival and human diseases2007

    • Author(s)
      M. Noguchi
    • Organizer
      Japan Society for Adaptation Medicine
    • Place of Presentation
      Hokkaido University, Sapporo
    • Year and Date
      2007-06-09
    • Description
      「研究成果報告書概要(欧文)」より
  • [Presentation] Identification of NBRE (nerve growth factor responsive element) of the TCL1 promoter as a novel negative regulatory element.2007

    • Author(s)
      M. Noguchi
    • Organizer
      Keystone Symposia
    • Place of Presentation
      サンタフェ(米国)・ヒルトン サンタフェ
    • Year and Date
      2007-02-16
    • Description
      「研究成果報告書概要(和文)」より
  • [Presentation] Identification of NBRE (nerve growth factor responsive element) of the TCL1 promoter as a novel negative regulatory element2007

    • Author(s)
      M. Noguchi
    • Organizer
      Keystone Symposia
    • Place of Presentation
      Hilton Hotel Santa Fe, Santa Fe, USA
    • Year and Date
      2007-02-16
    • Description
      「研究成果報告書概要(欧文)」より
  • [Presentation] Identification of NBRE (nerve growth factor responsive element) of the TCL1 promoter as a novel negative regulatory element.2006

    • Author(s)
      野口 昌幸
    • Organizer
      日本免疫学会
    • Place of Presentation
      大阪・大阪国際会議場
    • Year and Date
      2006-12-12
    • Description
      「研究成果報告書概要(和文)」より
  • [Presentation] Identification of NBRE (nerve growth factor responsive element) of the TCL1 promoter as a novel negative regulatory element.2006

    • Author(s)
      野口 昌幸
    • Organizer
      日本分子生物学会
    • Place of Presentation
      名古屋・名古屋国際会議場
    • Year and Date
      2006-12-07
    • Description
      「研究成果報告書概要(和文)」より
  • [Presentation] Identification of NBRE (nerve growth factor responsive element) of the TCL1 promoter as a novel negative regulatory element.2006

    • Author(s)
      M. Noguchi
    • Organizer
      Japanese Society of Immunology
    • Place of Presentation
      Grand Cube Osaka, Osaka
    • Year and Date
      2006-10-12
    • Description
      「研究成果報告書概要(欧文)」より
  • [Presentation] Identification of NBRE (nerve growth factor responsive element) of the TCL1 promoter as a novel negative regulatory element.2006

    • Author(s)
      M. Noguchi
    • Organizer
      The Molecular Biology Society of Japan
    • Place of Presentation
      Fukuoka Dome, Fukuoka
    • Year and Date
      2006-10-07
    • Description
      「研究成果報告書概要(欧文)」より
  • [Presentation] AKTの活性化と癌2006

    • Author(s)
      野口 昌幸
    • Organizer
      日本癌学会
    • Place of Presentation
      横浜・パシフィコ横浜
    • Year and Date
      2006-09-30
    • Description
      「研究成果報告書概要(和文)」より
  • [Presentation] AKT活性化補助因子であるプロトオンコジンTCL1の遺伝子発現調節機構2005

    • Author(s)
      野口 昌幸
    • Organizer
      日本分子生物学会
    • Place of Presentation
      福岡・福岡ドーム
    • Year and Date
      2005-12-09
    • Description
      「研究成果報告書概要(和文)」より
  • [Presentation] Gene regulation of the protooncogene TCL12005

    • Author(s)
      M. Noguchi
    • Organizer
      The Molecular Biology Society of Japan
    • Place of Presentation
      Fukuoka Dome, Fukuoka
    • Year and Date
      2005-10-09
    • Description
      「研究成果報告書概要(欧文)」より
  • [Book] Regulation of the PI3K-Akt Network: Current Status and a Promise for the Treatment of Human Diseases.2008

    • Author(s)
      M. Noguchi
    • Publisher
      Curr Sig. Thera
    • Description
      「研究成果報告書概要(欧文)」より
  • [Book] バイオとナノの融合II2007

    • Author(s)
      野口 昌幸
    • Total Pages
      305-315
    • Publisher
      北海道大学出版会
    • Description
      「研究成果報告書概要(和文)」より
  • [Remarks] 「研究成果報告書概要(和文)」より

    • URL

      http://www.igm.hokudai.ac.jp/hu_ifgm_cb/index.html

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Published: 2010-02-04  

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