1998 Fiscal Year Final Research Report Summary
Functions of the runt gene family in development
| 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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| Keywords | transcription factor / hematopoietic stem cell / acute myeloid leukemia / T lymphocytes / AML1 / PEBP2beta / runt |
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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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[Publications] Niki, M., Okada, H., Takano, H., Kuno, J., Tani, K., Hibino, H., Asano, S., Ito, Y., Satake, M.and Noda, T.: "Hematopoiesis in the fetal liver is impaired by targeted mutagenesis of a gene encoding a non-DNA binding subunit of the transcription factor, PEBP2/CBF." Proc.Natl.Acad.Sci.USA.94. 5697-5702 (1997)
Description
「研究成果報告書概要(欧文)」より
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[Publications] Chiba, N., Watanabe, T., Nomura, S., Tanaka, Y., Minowa, M., Niki, M., Kanamaru, R.and Satake, M.: "Differentiation dependent expression and distinct subcellular localization of the protooncogene product, PEBP2beta/CBFbeta, in muscle development." Oncogene. 14. 2543-2552 (1997)
Description
「研究成果報告書概要(欧文)」より
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[Publications] Tanaka, Y., Watanabe, T., Chiba, N., Niki, M., Kuroiwa, Y., Nishihira, T., Satomi, S., Ito, Y.and Satake, M.: "The protooncogene product, PEBP2beta/CBFbeta, is mainly located in the cytoplasm and has an affinity with cytoskeletal structures." Oncogene. 15. 677-683 (1997)
Description
「研究成果報告書概要(欧文)」より
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[Publications] Tanaka, Y., Fujii, M., Hayashi, K., Chiba, N., Akaishi, T., Shineha, R., Nishihira, T., Satomi, S., Ito, Y., Watanabe, T.and Satake, M.: "The chimeric protein, PEBP2beta/CBFbeta-SMMHC,disorganizes cytoplasmic stress fibers and inhibits transcriptional activation." Oncogene. 17. 699-708 (1998)
Description
「研究成果報告書概要(欧文)」より
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[Publications] Fujii, M., Hayashi, K., Niki, M., Chiba, N., Megro, K., Endo, K., Kameoka, J., Ito, S., Abe, K., Watanabe, T.and Satake, M.: "Overexpression of AML1 renders a T hybridoma resistant to T cell receptor-mediated apoptosis." Oncogene. 17. 1813-1820 (1998)
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「研究成果報告書概要(欧文)」より
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[Publications] Okada, H., Watanabe, T., Niki, M., Takano, H., Chiba, N., Yanai, N., Tani, K., Hibino, H., Asano, S., Mucenski, M.L., Ito, Y., Noda, T.and Satake, M.: "AML1 (-1-) embryos do not express certain hematopoiesis-related gene transcripts including those of the PU.1 gene." Oncogene. 17. 2287-2293 (1998)
Description
「研究成果報告書概要(欧文)」より
