Functional analysis of truncated Notch 1 gene products generated by insertions of mouse mammary tumor proviruses in development of mouse lymphomas.
| Project/Area Number |
09470084
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| Research Category |
Grant-in-Aid for Scientific Research (B)
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| Allocation Type | Single-year Grants |
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| Section | 一般 |
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| Research Field |
Virology
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| Research Institution | KYOTO UNIVERSITY |
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Principal Investigator |
YANAGAWA Shin-ichi Kyoto Univ., Inst.Virus Res., Instructor, ウイルス研究所, 助手 (70183978)
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| 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)
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| Project Period (FY) |
1997 – 1998
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| Project Status |
Completed (Fiscal Year 1998)
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| 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)
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| Keywords | Notch / Mouse Mammary Tumor Virus / Viral Oncology / Lymphoma / IAP / Murine leukemia Virus / notch |
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| 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.
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Report
(3 results)
Research Products
(15 results)
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[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)
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[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)
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Related Report
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