| Project/Area Number |
17591718
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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 |
Obstetrics and gynecology
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| Research Institution | The University of Tokyo |
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Principal Investigator |
KUGU Koji The University of Tokyo, The University of Tokyo Hospital, Assistant Professor (30322051)
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| Co-Investigator(Kenkyū-buntansha) |
YANO Tetsu THE UNIVERSITY OF TOKYO, The University of Tokyo Hospital, Associate Professor (90251264)
OSUGA Yutaka THE UNIVERSITY OF TOKYO, The University of Tokyo Hospital, Assistant Professor (80260496)
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| Project Period (FY) |
2005 – 2007
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| Project Status |
Completed (Fiscal Year 2007)
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| Budget Amount *help |
¥3,600,000 (Direct Cost: ¥3,300,000、Indirect Cost: ¥300,000)
Fiscal Year 2007: ¥1,300,000 (Direct Cost: ¥1,000,000、Indirect Cost: ¥300,000)
Fiscal Year 2006: ¥1,000,000 (Direct Cost: ¥1,000,000)
Fiscal Year 2005: ¥1,300,000 (Direct Cost: ¥1,300,000)
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| Keywords | ovarian function / apoptosis / malignant tumor / anti-cancer drug |
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| Research Abstract |
Caspases, a family of aspartic acid-specific cysteine proteases, are considered to be death effectors that possess an obligate specificity for cleavage of target proteins at aspartate residues in diverse cell lineages. They take part in the final steps of cell death committal via their unique ability to cleave a wide spectrum of homeostatic proteins. Among these targets are nuclear and cytoskeletal proteins., although it remains to be established whether cleavage of these proteins is required for the execution of all cell deaths.
We further showed that nitric oxide (NO) inhibited Fas/Fas ligand system-induced apoptosis by suppressing activation of the caspases, pointing to a cross-talk between Fas/Fas ligand system-induced apoptosis pathway and NO-mediated antiapoptotic pathway in ovarian follicle atresia through rat granulose cell culture system.
hScrib, human homologue of Drosophila neoplastic tumor suppressor, was identified as a target of human papilloma-virus E6 oncoprotein for the ubiquitin-mediated degradation. We report that hScrib is a novel death substrate targeted by caspase. Full-length hScrib was cleaved by caspase during death ligands-induced apoptosis, which generates a p170 C-terminal fragments in Hela cells. The reported results indicate that caspase-dependent cleavage of hScrib in a critical step for detachment of cell contact during the process of apoptosis.
Further investigations into the mechanisms of ovarian follicle apoptosis on the basis of the present results may bring pathogenesis of ovarian failure into light, which should be a great breakthrough for reproductive medicine.
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