2000 Fiscal Year Annual Research Report

細胞周期の制御異常

Research Project

Project/Area Number	12215020
Research Category	Grant-in-Aid for Scientific Research on Priority Areas (C)
Research Institution	The University of Tokyo
Principal Investigator	秋山徹東京大学, 分子細胞生物学研究所, 教授 (70150745)
Co-Investigator(Kenkyū-buntansha)	畑裕東京医科歯科大学, 医学部, 教授 (80313237)
Keywords	癌 / 癌抑制遺伝子 / APC / Wntシグナル / Asef / ICAT / 細胞接着 / 細胞膜裏打ち蛋白質
Research Abstract	がん細胞における細胞周期制御異常の機構を明らかにすることを目的として、大腸癌のがん抑制遺伝子APC、Wntシグナル伝達経路および上皮細胞間結合の裏打ち蛋白質BAP1/MAGIの機能を明らかにすることを目的として研究を進め以下のような結果を得た。 1)Rac特異的なGEF活性をもつAPC結合蛋白質Ascfが、細胞運動の亢進を引き起こす活性をもつことを明らかにした。 2)Wntシグナルを負に制御するb-catenin結合蛋白質ICATは、APC、b-cateninまたはAxinに変異のある癌細胞特異的に細胞周期の停止を引き起こす活性をもつことを明らかにした。 ICATノックアウトマウスは脳、頭蓋骨などの形成に異常がみられた。 3)b-cateninに結合する新規蛋白質L9が、b-catenin-Tcf4複合体の活性を増強しWntシグナルを正に制御することを明らかにした。 4)APC-DLG複合体にさらに結合する新規蛋白質2種類を見出し機能を解析した。 5)b-catenin-TCF4複合体の標的遺伝子の単離を試み、候補遺伝子を単離した。 6)上皮細胞間結合の裏打ち蛋白質BAP1/MAGI-1の極性をもった細胞内局在にはC末端領域が必要十分であることを見出した。 7)上皮細胞の接着斑などの裏打ち蛋白質でカテニンファミリーに属するp0071にPDZドメインをもつ新規の裏打ち蛋白質PAPINが結合することを見出した。さらに、PAPINにはLIM領域をもつDRALが結合することを明らかにした

Research Products
(16 results)

All Other

All Publications (16 results)

[Publications] T.Ishidate: "The APC-hDLG Complex Negatively Regulates Cell Cycle Progression from the G0/G1 to SPhase."Oncogene. 19. 365-372 (2000)
[Publications] H.Nakagawa: "EB3, a novel member of the EB1 family preferentially expressed in the central nervous system, bins to a CNS-specific."Oncogene. 19. 210-216 (2000)
[Publications] H.Nakagawa: "APCL, a central nervous system-specific homolog of adenomatous polysois coli tumor suppressor, binds to p53-binding protein 2 and translocates."Cancer Res.. 60. 101-105 (2000)
[Publications] K.Kawahara.: "Downregulation of b-catenin by the Colorectal Tumor Suppressor APC Requires Association with Axin and β-catenin."J.Biol.Chem. 275. 8369-8374 (2000)
[Publications] T.Akiyama: "Wht/β-catenin signaling."Cytokine & Growth Factor Reviews. 11. 273-282 (2000)
[Publications] H.Yanai: "The Colorectal Tumor Suppressor APC is Present in the NMDA-receptor-PDS-95 Complex in the Brain."Genes Cells. 5. 815-822 (2000)
[Publications] Y.Kawasaki: "Asef, a Link between the Tumor Suppressor APC and G-protain Signaling."Science. 289. 1194-1197 (2000)
[Publications] H.Haraguchi: "The hDLG-associated protein DAP interacts with dynein light chain and neuronal nitric oxide synthase."Gene Cells. 5. 905-911 (2000)
[Publications] Y.Dabashi: "APC protein is required for initiation of neuronal differentiation in rat pheochromocytoma PC12 cells."Biochem.Biopys.Res.Commun.. 279. 685-691 (2000)
[Publications] T.Senda: "Expression of APC in the mouse kideney and its colocalization with A-canenin and hDLG."J.Histochem.Cytochem.. (in press).
[Publications] Kohu,K.: "Localization of the Novel GAP Family Protein SPAL in Epithelial Cells."Acta Histochem.Cytochem.. (in press).
[Publications] Kakinuma,N: "APC is Colocalized with β-catenin and hDLG in the Henle's Loop of the Mouse Kidney."Acta Histochem.Cytochem.. (in press).
[Publications] Tago,K.: "Inhibition of Wntsignaling by ICAT, a Novel β-catenin-interacting Protein."Gense Dev.. 14. 1741-1749 (2000)
[Publications] Nishimura,W: "Localization of BAP1/MAGI1 at adherens junctions in NRK cell : the polarized targeting mediated by the carboxyl-teminal PDZ domains."J.Cell.Physiol.. 185. 358-365 (2000)
[Publications] Deguchi,M: "PAPIN : a novel multiple PDZ protein interacting with neural plakophilin-related armadillo-repeat protein/β-catenin and P0071"J.Biol.Chem.. 275. 29875-29880 (2000)
[Publications] yao,I.: "Association of membrane-associated guanylate kinase-interacting protein-1 with Raf-1."Biochem.Biophys.Res.Commun. 270. 538-542 (2000)

2000 Fiscal Year Annual Research Report

細胞周期の制御異常

Principal Investigator

秋山 徹 東京大学, 分子細胞生物学研究所, 教授 (70150745)

Research Products

[Publications] T.Ishidate: "The APC-hDLG Complex Negatively Regulates Cell Cycle Progression from the G0/G1 to SPhase."Oncogene. 19. 365-372 (2000)

[Publications] H.Nakagawa: "EB3, a novel member of the EB1 family preferentially expressed in the central nervous system, bins to a CNS-specific."Oncogene. 19. 210-216 (2000)

[Publications] H.Nakagawa: "APCL, a central nervous system-specific homolog of adenomatous polysois coli tumor suppressor, binds to p53-binding protein 2 and translocates."Cancer Res.. 60. 101-105 (2000)

[Publications] K.Kawahara.: "Downregulation of b-catenin by the Colorectal Tumor Suppressor APC Requires Association with Axin and β-catenin."J.Biol.Chem. 275. 8369-8374 (2000)

[Publications] T.Akiyama: "Wht/β-catenin signaling."Cytokine & Growth Factor Reviews. 11. 273-282 (2000)

[Publications] H.Yanai: "The Colorectal Tumor Suppressor APC is Present in the NMDA-receptor-PDS-95 Complex in the Brain."Genes Cells. 5. 815-822 (2000)

[Publications] Y.Kawasaki: "Asef, a Link between the Tumor Suppressor APC and G-protain Signaling."Science. 289. 1194-1197 (2000)

[Publications] H.Haraguchi: "The hDLG-associated protein DAP interacts with dynein light chain and neuronal nitric oxide synthase."Gene Cells. 5. 905-911 (2000)

[Publications] Y.Dabashi: "APC protein is required for initiation of neuronal differentiation in rat pheochromocytoma PC12 cells."Biochem.Biopys.Res.Commun.. 279. 685-691 (2000)

[Publications] T.Senda: "Expression of APC in the mouse kideney and its colocalization with A-canenin and hDLG."J.Histochem.Cytochem.. (in press).

[Publications] Kohu,K.: "Localization of the Novel GAP Family Protein SPAL in Epithelial Cells."Acta Histochem.Cytochem.. (in press).

[Publications] Kakinuma,N: "APC is Colocalized with β-catenin and hDLG in the Henle's Loop of the Mouse Kidney."Acta Histochem.Cytochem.. (in press).

[Publications] Tago,K.: "Inhibition of Wntsignaling by ICAT, a Novel β-catenin-interacting Protein."Gense Dev.. 14. 1741-1749 (2000)

[Publications] Nishimura,W: "Localization of BAP1/MAGI1 at adherens junctions in NRK cell : the polarized targeting mediated by the carboxyl-teminal PDZ domains."J.Cell.Physiol.. 185. 358-365 (2000)

[Publications] Deguchi,M: "PAPIN : a novel multiple PDZ protein interacting with neural plakophilin-related armadillo-repeat protein/β-catenin and P0071"J.Biol.Chem.. 275. 29875-29880 (2000)

[Publications] yao,I.: "Association of membrane-associated guanylate kinase-interacting protein-1 with Raf-1."Biochem.Biophys.Res.Commun. 270. 538-542 (2000)

秋山徹東京大学, 分子細胞生物学研究所, 教授 (70150745)