2002 Fiscal Year Final Research Report Summary
STUDY OF HISTONE ACETYLATION REGULATION IN LEUKEMOGENESIS
| Project/Area Number |
12470207
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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 |
Hematology
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| Research Institution | National Cancer Center Research Institute |
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Principal Investigator |
KITABAASHI Issay National Cancer Center Research Institute, Molecular Oncology Division, Chief, 分子腫瘍学部, 部長 (20261175)
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| Co-Investigator(Kenkyū-buntansha) |
清水 喜美子 国立がんセンター研究所, 分子腫瘍学部, 主任研究官 (00161414)
MOROHOSHI Fumiko National Cancer Center Research Institute, Molecular Oncology Division, Researcher, 分子腫瘍学部, 研究員 (20157944)
MOROHOSHI Fumiko National Cancer Center Research Institute, molecular Oncology Division, Senior Researcher (20157944)
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| Project Period (FY) |
2000 – 2002
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| Keywords | leukemia / AML1 / PML / transcription / cell differentiation / MOZ |
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| Research Abstract |
Chromosome translocations are frequently found in human leukemia and resultant fusion proteins and/or disregulation of specific gene expressions are involved in leukemogenesis. We found that the p300 and MOZ genes, which enocode histone acetyltransferases, are fused by t(8;22) translocation that were found in therapy-related acute myeloid leukemia (AML). The AML1 gene is the most frequent target of the chromosome translocation in acute leukemia and encodes a transcription factor that is essential for definitive hematopojesis. We purified the AML1 complex and found that various proteins including. p300, MOZ, PML as well as CBFb, were involed in the complex. MOZ strongly stimulated the AML1-dependent transcription. In contrast, MOZ-CBP, a product of t(8;16) translocation associated with AML, inhibited the transcription. Among PML isoforms, PML-I specifically interacted with AML1 and recruited AML1 and p300 into nuclear bodies to stimulates AML1-dependent transcription. The facts that components of the AMLi complex such as CBFb, p300, MOZ and p300/CBP are targets of leukemia-associated translocation suggest that the AML1 complex is the main target of the translocation and dysfunction of the complex might be important for pathogenesis of leukemia.
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[Publications] Kitabayashi, I., Aikawa, Y., Yokoyama, A., Hosoda, F., Nagai, M., Kakazu, N., Abe T., Ohki, M.: "Fusion of MOZ and p300 histone acetyltransferases in acute monocytic leukemia with a t(8;22)(p11;q13) chromosome translocation."Leukemia. 15. 89-94 (2001)
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「研究成果報告書概要(和文)」より
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[Publications] Yokoyama, T, Tanaka, M, Matsuda, G, Kato, K, Kanamori, M, Kawasaki, H, Hirano, H, Kitabayashi, I, Ohki, M, Hirai, K, Kawaguchi, Y.: "Identification of major phosphorylation sites of Epstein-Barr virus nuclear antigen leader protein (EBNA-LP): ability of EBNA-LP to induce latent membrane protein 1 cooperatively with EBNA-2 is regulated by phosphorylation."J Virol.. 75. 5119-5128 (2001)
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[Publications] Morohoshi, F., Mitani, S., Mitsuhashi, N., Kitabayashi., I., Takahashi, E., Suzuki., M., Munakata, N., Ohki, M.: "Structure and expression pattern of a human MTG8/ETO family gene, MTGR1."Gene. 241. 287-295 (2001)
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[Publications] Shimizu, K., Kitayashi, I., Kamada, N., Abe, T., Maseki, N., Suzukaawa, K., Ohki, M.: "AML1-MTG8 leukemic protein induces the expression of granulocyte colony-stimulating factor (G-CSF) receptor through the up-regulation of CCAT/enhancer binding protein epsilon."Blood. 96. 288-296 (2000)
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[Publications] Murasawa, S, Matsubara, H, Mori, Y, Masaki, H, Tsutsumi, Y, Shibasaki, Y, Kitabatashi, I, Tanaka, Y, fujiyama, S, Koyama, Y, Fujiyama, A, Iba, S, Iwasaka, T.: "Angiotensin II initiates tyrosine kinase Pyk2-dependent signaling leading to activation of Rac1-mediated c-Jun NH2-terminal kinase."J.Biol Chem.. 275. 26856-26863 (2000)
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「研究成果報告書概要(和文)」より
