| Project/Area Number |
24592514
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| Research Category |
Grant-in-Aid for Scientific Research (C)
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| Allocation Type | Multi-year Fund |
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| Section | 一般 |
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| Research Field |
Obstetrics and gynecology
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| Research Institution | Kyoto University |
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Principal Investigator |
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| Project Period (FY) |
2012-04-01 – 2015-03-31
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| Project Status |
Completed (Fiscal Year 2014)
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| Budget Amount *help |
¥5,200,000 (Direct Cost: ¥4,000,000、Indirect Cost: ¥1,200,000)
Fiscal Year 2014: ¥1,040,000 (Direct Cost: ¥800,000、Indirect Cost: ¥240,000)
Fiscal Year 2013: ¥2,080,000 (Direct Cost: ¥1,600,000、Indirect Cost: ¥480,000)
Fiscal Year 2012: ¥2,080,000 (Direct Cost: ¥1,600,000、Indirect Cost: ¥480,000)
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| Keywords | gankyrin / mononeddylation / S6 ATPase / 26S proteasome / polyubiquitylation / synthetic biology / mdm2 / p53 / NEDD8 / E3 ubiquitin ligase / pRB / 卵巣がん / ガンキリン / プロテアソーム / 卵巣癌 / 癌遺伝子 |
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| Outline of Final Research Achievements |
In ovarian cancers, gankyrin and Nedd8 are overexpressed. In vitro gankyrin neddylation assay (bacteria-expressed and purified E1, E2, Mdm2, Nedd8, gankyrin, ATP) produces gankyrin mononeddylation, that is verified by western blot of anti-gankyrin antibody and anti-Nedd8 antibody. Due to synthetic biological method, polycistronic affinity-tagged gankyrin, Nedd8, E1, E2, and Mdm2 are expressed into Rosetta bacterial cells. Gankyrin mononeddylation occurs. This expressed and purified mononeddylated gankyrin enhances p53 and pRB polyubiquitylation and 26S proteasome-mediated protein degradation. This effect is enhanced by full-length S6 ATPase co-expression. However it is suppressed by C-terminal truncated S6 ATPase mutant.
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