| Project/Area Number |
10480201
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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 |
Cell biology
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| Research Institution | KYUSHU UNIVERSITY |
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Principal Investigator |
KITAGAWA Masatoshi Medical Institute of Bioregulation, Kyushu University, Assoc. Prof., 生体防御医学研究所, 助教授 (50294971)
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| Co-Investigator(Kenkyū-buntansha) |
NAKAYAMA Keiichi Medical Institute of Bioregulation, Kyushu University, Professor, 生体防御医学研究所, 教授 (80291508)
HATAKEYAMA Shigetsugu Medical Institute of Bioregulation, Kyushu University, Research Assoc., 生体防御医学研究所, 助手 (70294973)
NAKAYAMA Keiko Medical Institute of Bioregulation, Kyushu University, Assoc. Prof., 生体防御医学研究所, 助教授 (60294972)
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| Project Period (FY) |
1998 – 1999
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| Project Status |
Completed (Fiscal Year 1999)
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| Budget Amount *help |
¥2,500,000 (Direct Cost: ¥2,500,000)
Fiscal Year 1999: ¥2,500,000 (Direct Cost: ¥2,500,000)
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| Keywords | β-catenin / ubiquitination / proteasome / colon cancer / 蛋白分解 / F-box蛋白質 / IκBα / 細胞周期 |
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| Research Abstract |
We study the mechanisms of growth promotion via ubiquitin-dependent proteolysis. β-catenin plays an essential role for growth regulation and colon cancer formation. Cytoplasmic β-catenin is regulated by ubiquitin-proteasome system via Wnt signaling pathway. In this study, we identified FWD1, an ubiquitin ligase for β-catenin. FWD1 formed a complex with β-catenin, axin, APC, GSK3βvia its WD40 repeats in the phosphorylation-dependent manner. Furthermore, FED1 also bound with Skp1 and Cull as an ubiquitination machinery named SCF through its F-box. The SCFィイD1FWD1ィエD1 complex ubiquitinated the β-catenin in vivo as well as in vitro. Immunohistchemical analysis indicated that transfection of FWD1 decreased the level of cytoplasmic β-catenin in SW480 colon cancer cell line. These findings suggest that FWD1 is useful for gene-therapy against colon cancer.
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