| Project/Area Number |
14571189
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| Research Category |
Grant-in-Aid for Scientific Research (C)
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| Allocation Type | Single-year Grants |
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| Section | 一般 |
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| Research Field |
Digestive surgery
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| Research Institution | HAMAMATSU UNIVERSITY SCHOOL OF MEDICINE |
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Principal Investigator |
KAMIYA Kinji HAMAMATSU UNIVERSITY, Medicine, Instructor, 医学部附属病院, 助手 (20324361)
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| Co-Investigator(Kenkyū-buntansha) |
KITAGAWA Masatoshi HAMAMATSU UNIVERSITY, Medicine, Professor, 医学部, 教授 (50294971)
KONNO Hiroyuki HAMAMATSU UNIVERSITY, Medicine, Associate Professor, 医学部, 助教授 (00138033)
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| Project Period (FY) |
2002 – 2003
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| Project Status |
Completed (Fiscal Year 2003)
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| Budget Amount *help |
¥3,300,000 (Direct Cost: ¥3,300,000)
Fiscal Year 2003: ¥1,300,000 (Direct Cost: ¥1,300,000)
Fiscal Year 2002: ¥2,000,000 (Direct Cost: ¥2,000,000)
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| Keywords | Ubiquitin ligase / p27^<Kip1> / procinosis / Cell cycle / gastric cancer / p27^<Kip1> / ユビキチン / Skp2 / 大腸癌 / p27^<kip1>ノックアウトヒトがん細胞 / 腫瘍転移増殖能 / マイクロアレイ |
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| Research Abstract |
Ubiquitin-proteasome pathway is a key system that controls cellular levels of number of proteins. This pathway is responsible not only for the degradation of short-lived proteins but also tumor suppressors, transcription factors and cell cycle proteins. Ubiquitin-protein ligases determine the substrate specificity of ubiquitination. In this study, we analyzed the molecular mechanisms of proteolytic degradation of Cdk inhibitory protein p27^<Kip1>. Furthermore, we tried to experimentally demonstrate that down-regulation of p27^<Kip1> promoted tumor progression.
In this study, we found that Cks1, a subcomponent of SCF-Skp2 ubiquitin ligase for p27-degradation, was post-translationally regulated by ubiquitin-proteasome pathway. We also found high expression of Cks1 in human lung cancers. Therefore, altered degradation of Cks1 proteins is thought to promote growth and malignancy of cancer. Next, we experimentally demonstrate that down-regulation of p27^<Kip1> promoted tumor progression in node mice using the model cell lines which shawed down-regulated expression of p27^<Kip1>.
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