1997 Fiscal Year Annual Research Report

がん抑制遺伝子の作用機構

Research Project

Project/Area Number	06283215
Research Category	Grant-in-Aid for Scientific Research on Priority Areas
Research Institution	Osaka University
Principal Investigator	秋山徹大阪大学, 微生物病研究所, 教授 (70150745)
Co-Investigator(Kenkyū-buntansha)	石館宇夫東京大学, 分子細胞生物学研究所, 助手
Keywords	がん抑制遺伝子 / 大腸癌 / APC / hDLG / b-catenin / D2 / Axin / WT1
Research Abstract	1)大腸がんのがん抑制遺伝子APCの産物はarm motifでSrcによりM期にリン酸化されるSam68と細胞周期を通して核内で複合体を形成していることを見い出した。2)先年度APCと結合することを明らかにしたDrosophilaのがん抑制遺伝子dlgのヒトホモログの産物(hDLG)のPDZドメインにDrosophilaのがん抑制遺伝子fatのヒトホモログの産物、Wnt受容体Frizzled5および7、リボゾーム受容体が結合すること、guanylate kinase(GK)ドメインにはGAP活性をもつ蛋白質が結合することを明らかにした。3)hDLGのSH3ドメインとHOOKドメイン-GKドメインが分子内で結合していることを見出した。4)hDLGが高発癌性ヒトパピローマウイルスのE6と結合すること、hDLGと結合できないmutant E6は細胞形質転換活性がないことを明らかにした。5)b-catenin (armadillo)に結合するDrosophilaの蛋白質D2を見い出した。D2はb-catenin,APC,GSK-3と結合しWnt/Winglessシグナル伝達経路を負に制御する活性を示した。6)胎児期に体軸の重複を起こすmutantマウスで変異を起こしている。AxinがD2のマウスホモログで、やはりb-catenin、APC、GSK-3と結合しb-cateninの分解を誘導する活性をもつことを見い出した。7)Wnt/Winglessシグナル伝達経路を正に制御するb-catenin結合蛋白質D6を見い出した。8)WT1の急性白血病における異常発現の意識を明らかにするために、WT1を発現していない白血病細胞株にWT1を過剰発現し表現形質の変化を検討し、白血病細胞株の種類によりG1 arrestとapotosis、分化阻害等異なった反応を示すことを明らかにした。

Research Products
(16 results)

All Other

All Publications (16 results)

[Publications] K.Satoh, et al.: "DAP-1,a novel protein that interacts with the guanylate kinase-like domains of DLG and PSD-95." Genes to Cells. 2. 415-424 (1997)
[Publications] T.Ishidate, et al.: "Identification of a novel nuclear localization signal in Sam68." FEBS LETTERS. 409. 237-241 (1997)
[Publications] M.Moriyama, et al.: "The BCL-6 protein is phosphorylated at multiple sites in its serine-and proline-clustered region by mitogen activated protein kinase(MAPK)in vivo." Oncogene. 14. 2465-2474 (1997)
[Publications] T,Kiyono, et al.: "Binding of high risk HPV E6 oncoproteins to PDZ-domain-containing proteins." Proc.Natl.Acad.Sci.USA. 94. 11616-11612 (1997)
[Publications] Y.Murata, et al.: "The Wilms tumor suppressor gene WT1 induces G1 arrest and apoptosis in myeloblastic leukemia M1 cells." FEBS LLETTERS.409. 41-45 (1997)
[Publications] H.Shibata, et al.: "Rapid colorectal adenoma formation initiated by conditional targeting of the Apc gene." Science. 278. 120-123 (1997)
[Publications] M.Takemura, et al.: "Phosphorylated retinoblastoma protein stimulates DNA polymerase" Oncogene. 15. 2483-2492 (1997)
[Publications] Y.Dobashi, et al.: "The Wilms tumor protein is persistently associated with the nuclear matrix throughout the cell cycle." Mol.Cell.Biochem.171. 121-126 (1997)
[Publications] I.Miyashiro, et al.: "Midkine expression in human breast cancers: Expression of truncated form." Breast Can.Res.Treatment. 43. 1-6 (1997)
[Publications] K.Kagawa, et al.: "Overexpression of GML promotes radiation-induced cell cycle arrest and apoptosis." Biochem.Biophys.Res.Commun.241. 481-485 (1997)
[Publications] Y.Dobashi, et al.: "Cell cycle control with minimal participation of CDK2 in a murine fibrosarcoma clone cultured in protein-free medium." Biochem.Biophys.Res.Commun.232. 622-625 (1997)
[Publications] J.Adachi, et al.: "Growth suppression of non-small cell lung carcinoma cells by the introduction of the p16INK4A gene." Int J.Cancer. 10. 33-39
[Publications] T.Senda, et al.: "Expression and localization of the APC tumor suppressor protein in the nervous system." Neuroscience. 83. 857-866 (1998)
[Publications] T.Yamagami, et al.: "Suppression of Wilms tumor gene(WT1)expression induces G2/M arest in leukemic cells." Leukemia Res.(in press).
[Publications] T.Senda, et al.: "Association of the MCC(Mutated in colorectal cancer)gene product to the plasma membrane and membrane organelles." Medical Electron Microscopy in press.
[Publications] K.Inoue, et al.: "Wilms'tumor gene(WT1) competes with defferentiation-induced signal in hematopoietic progenitor cells." Blood. (in press).

1997 Fiscal Year Annual Research Report

がん抑制遺伝子の作用機構

Principal Investigator

秋山 徹 大阪大学, 微生物病研究所, 教授 (70150745)

Research Products

[Publications] K.Satoh, et al.: "DAP-1,a novel protein that interacts with the guanylate kinase-like domains of DLG and PSD-95." Genes to Cells. 2. 415-424 (1997)

[Publications] T.Ishidate, et al.: "Identification of a novel nuclear localization signal in Sam68." FEBS LETTERS. 409. 237-241 (1997)

[Publications] M.Moriyama, et al.: "The BCL-6 protein is phosphorylated at multiple sites in its serine-and proline-clustered region by mitogen activated protein kinase(MAPK)in vivo." Oncogene. 14. 2465-2474 (1997)

[Publications] T,Kiyono, et al.: "Binding of high risk HPV E6 oncoproteins to PDZ-domain-containing proteins." Proc.Natl.Acad.Sci.USA. 94. 11616-11612 (1997)

[Publications] Y.Murata, et al.: "The Wilms tumor suppressor gene WT1 induces G1 arrest and apoptosis in myeloblastic leukemia M1 cells." FEBS LLETTERS.409. 41-45 (1997)

[Publications] H.Shibata, et al.: "Rapid colorectal adenoma formation initiated by conditional targeting of the Apc gene." Science. 278. 120-123 (1997)

[Publications] M.Takemura, et al.: "Phosphorylated retinoblastoma protein stimulates DNA polymerase" Oncogene. 15. 2483-2492 (1997)

[Publications] Y.Dobashi, et al.: "The Wilms tumor protein is persistently associated with the nuclear matrix throughout the cell cycle." Mol.Cell.Biochem.171. 121-126 (1997)

[Publications] I.Miyashiro, et al.: "Midkine expression in human breast cancers: Expression of truncated form." Breast Can.Res.Treatment. 43. 1-6 (1997)

[Publications] K.Kagawa, et al.: "Overexpression of GML promotes radiation-induced cell cycle arrest and apoptosis." Biochem.Biophys.Res.Commun.241. 481-485 (1997)

[Publications] Y.Dobashi, et al.: "Cell cycle control with minimal participation of CDK2 in a murine fibrosarcoma clone cultured in protein-free medium." Biochem.Biophys.Res.Commun.232. 622-625 (1997)

[Publications] J.Adachi, et al.: "Growth suppression of non-small cell lung carcinoma cells by the introduction of the p16INK4A gene." Int J.Cancer. 10. 33-39

[Publications] T.Senda, et al.: "Expression and localization of the APC tumor suppressor protein in the nervous system." Neuroscience. 83. 857-866 (1998)

[Publications] T.Yamagami, et al.: "Suppression of Wilms tumor gene(WT1)expression induces G2/M arest in leukemic cells." Leukemia Res.(in press).

[Publications] T.Senda, et al.: "Association of the MCC(Mutated in colorectal cancer)gene product to the plasma membrane and membrane organelles." Medical Electron Microscopy in press.

[Publications] K.Inoue, et al.: "Wilms'tumor gene(WT1) competes with defferentiation-induced signal in hematopoietic progenitor cells." Blood. (in press).

秋山徹大阪大学, 微生物病研究所, 教授 (70150745)