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Functional analysis of truncated Notch 1 gene products generated by insertions of mouse mammary tumor proviruses in development of mouse lymphomas.

Research Project

Project/Area Number 09470084
Research Category

Grant-in-Aid for Scientific Research (B)

Allocation TypeSingle-year Grants
Section一般
Research Field Virology
Research InstitutionKYOTO UNIVERSITY

Principal Investigator

YANAGAWA Shin-ichi  Kyoto Univ., Inst.Virus Res., Instructor, ウイルス研究所, 助手 (70183978)

Co-Investigator(Kenkyū-buntansha) ISHIMOTO Akinori  Kyoto Univ., Inst.Virus Res., Professor, ウイスル研究所, 教授 (50073127)
HONJO Tasuku  Kyoto Univ., Dep.of Med., Professor, 医学研究科, 教授 (80090504)
Project Period (FY) 1997 – 1998
Project Status Completed (Fiscal Year 1998)
Budget Amount *help
¥9,000,000 (Direct Cost: ¥9,000,000)
Fiscal Year 1998: ¥4,200,000 (Direct Cost: ¥4,200,000)
Fiscal Year 1997: ¥4,800,000 (Direct Cost: ¥4,800,000)
KeywordsNotch / Mouse Mammary Tumor Virus / Viral Oncology / Lymphoma / IAP / Murine leukemia Virus / notch
Research Abstract

The Notch gene family encodes a transmembrane receptor that controls cell fate decisions throughout development in Drosophila and vertebrate. The amino terminus of Notch proteins encodes the extra-cellular domain and contains as many as 36 repeats of EGF-like motif involved in ligand binding and three copies of Notch/lin-12 motif of unknown function. The intracellular portion of Notch is characterized by six tandem copies of cdcl0/ankyrin motif thought to be involved in protein-protein interaction. Four Notch family (Notch 1 to Notch 4) members are known in mouse. Although Notch receptors are activated by a family of ligands such as Delta, they may also be constitutively activated by truncation of the extracellular domain. Because chromo-somal translocation associated with a subset of human T cell acute lymphoblastic leukemias results in overexpression of truncated Notch 1 lacking the EGF-like repeats. Similar truncated form of Notch 4 function as oncogenic protein in mouse mammary tumor virus (MMTV) induced mammary tumor. We report here frequent insertions of MMTV proviruses with LTR rearrangement in the Notch 1 gene in the thymomas induced by these MMTV LTR mutants. MMTV provirus insertions resulted in expression of truncated proteins consist of intracellular part of Notch 1 .Furthermore intracytoplasmic A particle (IAP), a mouse retrotransposon insertion in the Notch 4 gene was found in a spontaneous mammary tumor in BALB/C mouse. Similar to Notch 1 rearrangement described above, IAP transposition led to overexpression of truncated Notch 4 protein composed of 14 amino acids from IAP gag sequence followed by the cytoplasmic domain of Notch 4. We are testing transformation activities of these truncated Notch proteins.

Report

(3 results)
  • 1998 Annual Research Report   Final Research Report Summary
  • 1997 Annual Research Report
  • Research Products

    (15 results)

All Other

All Publications (15 results)

  • [Publications] Shin-ichi Yanagawa: "Accumulation of Armadillo Induced by Wingless, Dishevelled, and Dominant-negative Zeste-white 3 leods to Elevated DE-Codherin in Drosophila Clone 8 Wing Disc Cells." The Journal of Biological Chemistry. 272. 25243-25251 (1997)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1998 Final Research Report Summary
  • [Publications] Shin-ichi Yanagawa: "Identification and Characterization of a Novel Line of Drosophila Schneider S_2 Cells That Respond to Wingless signaling." The Journal of Biological Chemistry. 273. 32353-32359 (1998)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1998 Final Research Report Summary
  • [Publications] Jong-Seo Lee: "IAP Mediated Activation of Notch4/int-3 Gene in a Mouse Mammary Tumor : Generation of Trancated Notch4/int3 mRNAs by Retroviral Splicing Events." Journal of Virology. 73. in press (1999)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1998 Final Research Report Summary
  • [Publications] 柳川, 伸一: "Wnt/wingless蛋白質のシグナル伝達経路" 実験医学. 15. 2006-2012 (1997)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1998 Final Research Report Summary
  • [Publications] 柳川, 伸一: "Wingless/Wnt蛋白質のシグナル伝達機構" 蛋白質・核酸・酵素. 42. 22-30 (1997)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1998 Final Research Report Summary
  • [Publications] Yanagawa, S.-i., Lee, J.-S., Haruna, T., Oda, H., Uemura, T., Takeichi, M., and Ishimoto, A.: "Accumulation of Armadillo induced by wingless, Dishevelled and dominant negative Zeste-white 3 leads to elevation of DE-cadherin in Drosophila clone-8 wing disc cells." J.Biol.Chem.272,40. 25243-25251 (1997)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1998 Final Research Report Summary
  • [Publications] Yanagawa, S.-i., Lee, J.-S., and Ishimoto, A.: "Identification and characterization of a novel Drosophila Schneider S2 cells that respond to Wingless signaling." J.Biol.Chem.273,48. 3253-3259 (1998)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1998 Final Research Report Summary
  • [Publications] Lee, J.-S., Haruna, T., Ishimoto, A., Honjo, T., and Yanagawa, S.-i.: "IAP Mediated Activation of Notch4/int3 Gene in a Mouse Mammary Tumor : Generation of Truncated Notch4/int3 mRNAs by Retroviral Splicing Events." J.Virol.73,6(in press). (1999)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1998 Final Research Report Summary
  • [Publications] Yanagawa, S.-i.: "Wnt/Wingless Signal transduction pathway(Review in Japanese)" Experimental Medicine. 15. 2006-2012 (1997)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1998 Final Research Report Summary
  • [Publications] Yanagawa, S.-i.: "Signal Transduction Mechanism of Wingless/Wnt proteins(Review in Japanese)" Protein, Nucleic Acid, Enzyme. 42. 22-30 (1997)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1998 Final Research Report Summary
  • [Publications] Shin-ichi Yanagawa: "Identification and Characterization of a Novel Line of Drosophila Schneider S_2 Cells That Respond to Wingless Signaling." The Journal of Biological Chemistry. 273・48. 32353-32359 (1998)

    • Related Report
      1998 Annual Research Report
  • [Publications] Jong-Seo Lee: "IAP Mediated Activation of Notch 4/int-3 Gene in a Mammary Tumor : Generation of Truncated Notch4/int-3 mRNAs by Retroviral Splicing E xents" Journal of Virology. 73・6(in press). (1999)

    • Related Report
      1998 Annual Research Report
  • [Publications] Shin-ichi Yanagawa: "Accumulation of Armadillo Induced by Wingless,Dishevelled,and Dominant-negative Zeste-white3 Leads to Elevated DE-codherin in Drosophila clone 8 wing Disc Cells." The Journal of Biological Chemistry. 272・40. 25243-25251 (1997)

    • Related Report
      1997 Annual Research Report
  • [Publications] 柳川伸一: "Wnt/Winglessタンパク質のシグナル伝達経路" 羊土社・実験医学. 15・16. 2006-2012 (1997)

    • Related Report
      1997 Annual Research Report
  • [Publications] 柳川伸一: "Wingless/Wnt蛋白質のシグナル伝達機構" 共立出版・蛋白質,核酸,酵素. 42・1. 22-30 (1997)

    • Related Report
      1997 Annual Research Report

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Published: 1997-04-01   Modified: 2016-04-21  

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