| Project/Area Number |
09044249
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| Research Category |
Grant-in-Aid for international Scientific Research
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| Allocation Type | Single-year Grants |
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| Section | Joint Research |
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| Research Field |
Developmental biology
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| Research Institution | Institute of Development, Aging and Cancer, Tohoku University |
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Principal Investigator |
SATAKE Masanobu Institute of Development, Aging and Cancer, Tohoku University, Professor, 加齢医学研究所, 教授 (50178688)
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| Co-Investigator(Kenkyū-buntansha) |
CHIBA Natsuko Institute of Development, Aging and Cancer, Tohoku University, Postdoctoral Fell, 加齢医学研究所, 非常勤研究員
NIKI Masaru Institute of Development, Aging and Cancer, Tohoku University, Instructor, 加齢医学研究所, 助手 (60241626)
WATANABE Toshio Institute of Development, Aging and Cancer, Tohoku University, Associate Profess, 加齢医学研究所, 助教授 (60201208)
JAYNES Jim トマス, ジェファソン大学・キンメル癌研究所, 助教授
JIM Jaynes Thomas Jefferson University, Kimmel Cancer Institute, Associate Professor
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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 |
¥4,600,000 (Direct Cost: ¥4,600,000)
Fiscal Year 1998: ¥2,200,000 (Direct Cost: ¥2,200,000)
Fiscal Year 1997: ¥2,400,000 (Direct Cost: ¥2,400,000)
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| Keywords | transcription factor / hematopoietic stem cell / acute myeloid leukemia / T lymphocytes / AML1 / PEBP2beta / runt / AML1 / CBFβ / キメラ遺伝子 / 細胞骨格 / アポトーシス |
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| Research Abstract |
The PEBP2 transcription factor functions as a heterodimer composed of the alpha and beta subunits. The alpha subunit is responsible for the DNA binding activity of PEBP2, which is furthermore enhanced by interacting with the beta subunit. The AML1 gene, encoding the alpha subunit of PEBP2, corresponds to the mammalian homologue of Drosophila runt gene, a gene involved in Segmentation, neural development and sex determination in fly. The mammalian PEBP2beta gene encoding the beta subunit of PEBP2 represents a runt-partner gene. Both the AMI.I and PEBP2beta genes are involved in chromosomal rearrangements associated which human acute myeloid leukemia. As a result of translocation and/or inversion, the chimeric genes are generated.
The study was carried out to reveal the functions of mammalian runt and runt-partner genes in cell differentiation, transformation and development. The results are summarized as follows.
l)The PEBP2 transcription factor is indispensable and functions in a dose dependent manner for the hematopoietic development in the embryonic aorta-gonad-mesonephros region.
2)The product of the chimeric gene associate with human AML and involving the PEBP2beta gene impairs the architecture of cytoplasmic cytoskeleton.
3)A dose of AML1 transcription factor is critical in deternuning the quality of T cell receptor-mediated signal to cell survival or cell death.
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