1996 Fiscal Year Annual Research Report

前白血病状態進展にかかわる転写因子異常の解析

Research Project

Project/Area Number	08671215
Research Category	Grant-in-Aid for Scientific Research (C)
Research Institution	The University of Tokyo
Principal Investigator	三谷絹子東京大学, 医学部・附属病院, 助手 (50251244)
Co-Investigator(Kenkyū-buntansha)	黒川峰夫東京大学, 医学部・附属病院, 医員小川誠司東京大学, 医学部・附属病院, 医員田中智之東京大学, 医学部・附属病院, 助手 (50227154) 宮川清東京大学, 医学部・附属病院, 助手 (40200133) 平井久丸東京大学, 医学部・附属病院, 助教授 (90181130)
Keywords	骨髄異形成症候群 / t(11;19)(q.23;P13.1) / MLL / MEN / 転写因子 / 伸長因子
Research Abstract	進展期MDS症例に観察されるt(11;19)(q23;p13.1)の分子解析を行うことにより、新規融合遺伝子MLL/MENのクローニングを行った。MLLはAT hooksと2つのzinc finger domainsを有する転写因子であり、t(11;19)転座の結果、2つのzinc finger domainsを失っていた。一方、MENは849個のアミノ酸をコードする新規遺伝子であり、t(11;19)転座の結果、N末の45個のアミノ酸を失っていた。その後、MENはRNAポリメラーゼII伸長因子をコードしていることが報告された(Shilatifard,A.,et al.,Science271,1873-1876,1996)。私たちは、maltose-binding protein fusion及びGST fusionの形で大腸菌に発現させたMLL及びMEN蛋白質をウサギに免疫して、ポリクローナル抗体を得た。MLL/MEN、tMLL(患者白血病細胞で発現が期待される2つのzinc finger domains以下のシークエンスを失った短縮型のMLL)、MENのそれぞれのcDNAをCos7細胞に遺伝子導入し、この抗体を用いて蛋白質の発現を確認した。MLL/MEN、tMLL、MENはそれぞれ230kD,180kD,80kDの蛋白質として検出された。免疫組織染色の結果これらの蛋白質は主に核内に存在することが明らかになった。細胞を核分画と細胞質分画に分離して行ったウエスタン解析によっても、同様の結果が確認された。t(11;19)転座により形成されるMLL/MENは核内の転写制御の異常により前白血病を進展させるものと考えられた。

Research Products

(12 results)

All Other

All Publications (12 results)

[Publications] Krokawa M: "Overexpression of the humman AML1b proto-oncoprotein leads to neoplastic transformation of NIH3T3 cells." Oncogene. 12. 883-892 (1996)
[Publications] Sasaki K: "TPO/c-MPL ligand induces tyrosine phosphorylation multiple cellular proteins including proto-oncogene produckts,VAV and c-CBL,and RAS signaling molecules." Biochem.Biophys.Res.Commun.216. 338-347 (1996)
[Publications] Yamagata T: "A novel interferon regulatory family transcription factor,ICSAT/Pip/LSIRF,that negatively regulates the activity if interferon-regulated genes." Mol.Cell.Biol.16. 1283-1294 (1996)
[Publications] Tanaka T: "The extracellular signal-regulated kinase pathway phoshorylates AML1,an acute myeloid leukemia gene product,and potentially regulates its transactivation ability." Mol.Cell.Biol.16. 3967-3979 (1996)
[Publications] Ogwa S: "Structurally altered Evi-1 prorein generated in the 3q26q21 syndrome.21GC05:Oncogene" 13. 183-191 (1996)
[Publications] Kurokawa M: "A conserved cystein residue in the runt homology domiain of AML1 is required for the DNA binding ability and the transforming activity on fibroblasts." J.Biol.Chem.271. 16870-16876 (1996)
[Publications] Yamagata T: "Eleveted plated count features the variant type of BCR/ABL junction in chronic myelogenous leukaemia." Br.J.Haematol.94. 370-372 (1996)
[Publications] MITANI K: "Chromosomal abnormalities and oncogenes." Int.J.Hematol.63. 81-93 (1996)
[Publications] Ogawa S: "Increased Evi-1 expression is frequently observed in blastic crisis of chronic myelocytic leukemia." Leukemia. 10. 788-794 (1996)
[Publications] Hirai H: "cell cycle regulator genes in human leukemias." Proceedings of The First Fukuoka International Symposium on Medical Science;An approach to disease.131-141 (1996)
[Publications] Hirai H: "Recent progress in molecular mechanisms of leukemogenesis:The cyclin-dependent kinase 4-inhibitor gene in human leukemias." Proceedings of The XVIII Symposium of the International Association for Comparative Research on Leukemia and Related Disease. (in press). (1996)
[Publications] Ueno H: "Growth and survival signals transmitted via distinct NPXY motifs within leukocyte.tyrosine kinase,an insulin receptor-related tyrosine kinase." J.Biol.Chem.271. 27707-27714 (1996)

1996 Fiscal Year Annual Research Report

前白血病状態進展にかかわる転写因子異常の解析

Principal Investigator

三谷 絹子 東京大学, 医学部・附属病院, 助手 (50251244)

Research Products

[Publications] Krokawa M: "Overexpression of the humman AML1b proto-oncoprotein leads to neoplastic transformation of NIH3T3 cells." Oncogene. 12. 883-892 (1996)

[Publications] Sasaki K: "TPO/c-MPL ligand induces tyrosine phosphorylation multiple cellular proteins including proto-oncogene produckts,VAV and c-CBL,and RAS signaling molecules." Biochem.Biophys.Res.Commun.216. 338-347 (1996)

[Publications] Yamagata T: "A novel interferon regulatory family transcription factor,ICSAT/Pip/LSIRF,that negatively regulates the activity if interferon-regulated genes." Mol.Cell.Biol.16. 1283-1294 (1996)

[Publications] Tanaka T: "The extracellular signal-regulated kinase pathway phoshorylates AML1,an acute myeloid leukemia gene product,and potentially regulates its transactivation ability." Mol.Cell.Biol.16. 3967-3979 (1996)

[Publications] Ogwa S: "Structurally altered Evi-1 prorein generated in the 3q26q21 syndrome.21GC05:Oncogene" 13. 183-191 (1996)

[Publications] Kurokawa M: "A conserved cystein residue in the runt homology domiain of AML1 is required for the DNA binding ability and the transforming activity on fibroblasts." J.Biol.Chem.271. 16870-16876 (1996)

[Publications] Yamagata T: "Eleveted plated count features the variant type of BCR/ABL junction in chronic myelogenous leukaemia." Br.J.Haematol.94. 370-372 (1996)

[Publications] MITANI K: "Chromosomal abnormalities and oncogenes." Int.J.Hematol.63. 81-93 (1996)

[Publications] Ogawa S: "Increased Evi-1 expression is frequently observed in blastic crisis of chronic myelocytic leukemia." Leukemia. 10. 788-794 (1996)

[Publications] Hirai H: "cell cycle regulator genes in human leukemias." Proceedings of The First Fukuoka International Symposium on Medical Science;An approach to disease.131-141 (1996)

[Publications] Hirai H: "Recent progress in molecular mechanisms of leukemogenesis:The cyclin-dependent kinase 4-inhibitor gene in human leukemias." Proceedings of The XVIII Symposium of the International Association for Comparative Research on Leukemia and Related Disease. (in press). (1996)

[Publications] Ueno H: "Growth and survival signals transmitted via distinct NPXY motifs within leukocyte.tyrosine kinase,an insulin receptor-related tyrosine kinase." J.Biol.Chem.271. 27707-27714 (1996)

三谷絹子東京大学, 医学部・附属病院, 助手 (50251244)