| Project/Area Number |
16370060
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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 |
Functional biochemistry
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| Research Institution | Hamamatsu University School of Medicine |
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Principal Investigator |
KITAGAWA Masatoshi Hamamatsu University School of Medicine, Department of Biochemistry 1, Professor, 医学部, 教授 (50294971)
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| Co-Investigator(Kenkyū-buntansha) |
KITAGAWA Kyoko Hamamatsu University School of Medicine, Department of Biochemistry 1, Research Fellow, 医学部, 助手 (20299605)
UCHIDA Chiharu Hamamatsu University School of Medicine, Department of Biochemistry 1, Research Fellow, 医学部, 助手 (60223567)
ODA Toshiaki Hamamatsu University School of Medicine, Department of Biochemistry 1, Associate Professor, 医学部, 助教授 (90126805)
HATTORI Takayuki Hamamatsu University School of Medicine, Department of Biochemistry 1, Post-doctorial Fellow, 医学部, COE研究員 (50377751)
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| Project Period (FY) |
2004 – 2005
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| Project Status |
Completed (Fiscal Year 2005)
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| Budget Amount *help |
¥15,500,000 (Direct Cost: ¥15,500,000)
Fiscal Year 2005: ¥5,300,000 (Direct Cost: ¥5,300,000)
Fiscal Year 2004: ¥10,200,000 (Direct Cost: ¥10,200,000)
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| Keywords | Cell cycle / RB / ubiquitin / プロテアソーム / RBタンパク質 / 癌化 / Mdm2 |
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| Research Abstract |
Retinoblastoma gene product (pRB) plays critical roles in regulation of the cell cycle and tumor suppression. It is known that downregulation of pRB can stimulate carcinogenesis via abrogation of the pRB pathway, although the mechanism has not been elucidated. In this study, we found that Mdm2, a ubiquitin ligase for p53, promoted ubiquitin-dependent degradation of pRB. pRB was efficiently ubiquitinated by wild-type Mdm2 in vivo as well as in vitro, but other RB family proteins were not. Mutant Mdm2 with a substitution in the RING finger domain showed dominant-negative stabilization of pRB. Both knockout and knockdown of Mdm2 caused accumulation of pRB. Moreover, Mdm2 inhibited pRB-mediated flat formation of Saos-2 cells. Downregulation of pRB expression was correlated with a high level of expression of Mdm2 in human lung cancers. These results suggest that Mdm2 regulates function of pRB via ubiquitin-dependent degradation of pRB.
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