| Project/Area Number |
12480211
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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 |
Molecular biology
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| Research Institution | KYUSHU UNIVERSITY |
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Principal Investigator |
NAKAYAMA Keiko Medical Institute of Bioregulation, Kyushu University, Ass. Prof., 生体防御医学研究所, 助教授 (60294972)
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| Co-Investigator(Kenkyū-buntansha) |
HATAKEYAMA Shigetsugu Medical Institute of Bioregulation, Kyushu University, Ass. Prof., 生体防御医学研究所, 助教授 (70294973)
NAKAYAMA Kei-ichi Medical Institute of Bioregulation, Kyushu University, Prof., 生体防御医学研究所, 教授 (80291508)
KITAGAWA Masatoshi Hamamatsu Medical Univ., Dept. of Medicine, Prof., 医学部, 教授 (50294971)
小南 欽一郎 九州大学, 生体防御医学研究所, 助手 (80304830)
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| Project Period (FY) |
2000 – 2001
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| Project Status |
Completed (Fiscal Year 2001)
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| Budget Amount *help |
¥14,600,000 (Direct Cost: ¥14,600,000)
Fiscal Year 2001: ¥5,000,000 (Direct Cost: ¥5,000,000)
Fiscal Year 2000: ¥9,600,000 (Direct Cost: ¥9,600,000)
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| Keywords | Ubiquitin Ligase / knock-out mouse / Skp2 / Cul-1 / Skp1 / p27 / F-box protein / SCF複合体 / 中心体 / ユビキチン化 |
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| Research Abstract |
1) We have reported that F-box protein, FWD1 works as a ubiquitin ligase on the degradation of lκB or β-catenin. FWD1 constitutes SCF complex with Cul-1, Skp1, and Rbx1. In this study, we generated knock-out mice of Cul-1 and Skp1, which are components of SCF complex, and another F-box protein, Skp2. Analysis of these mice shows the biological role of protein degradation by SCF complex system, one category of proteolysis by ubiquitin-proteasome system.
2) Skp2 is a ubiquitin ligase of cyclin E and p27^<Kip1>. In Skp2 knock-out mice, cyclin E and p27^<Kip1> was accumulated abnormally. Cells in the mutant mice contain markedly enlarged nuclei with polyploidy and multiple centrosomes, and show a reduced growth rate and increased apoptosis.
3) We generated and characterized mice lacking both Skp2 and p27^<Kip1>. The Skp2^<-/->p27^<-/-> mice did not exhibit the overreplication phenotype, suggesting hat p27^<Kip1> accumulation is required for its development.
4) Cul-1 and Skp1 knock-out mice are died between on embryonic day 5.5 and 6.5. In these embryos, cyclin E is accumulated. It is postulated that Cul-1 and Skp1 are common components of SCF complex and relate to degradation of many kinds of protein. Early embryonic death of knock-out mice supports that SCF complex participate in many kinds of protein degradation system.
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