| Project/Area Number |
18390002
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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 |
Chemical pharmacy
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| Research Institution | Kyoto University |
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Principal Investigator |
UESUGI Motonari Kyoto University, Institute for Chemical Research, Professor (10402926)
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| Project Period (FY) |
2006 – 2007
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| Project Status |
Completed (Fiscal Year 2007)
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| Budget Amount *help |
¥16,780,000 (Direct Cost: ¥15,100,000、Indirect Cost: ¥1,680,000)
Fiscal Year 2007: ¥7,280,000 (Direct Cost: ¥5,600,000、Indirect Cost: ¥1,680,000)
Fiscal Year 2006: ¥9,500,000 (Direct Cost: ¥9,500,000)
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| Keywords | Chemical Biology / Chemical genetics / bioactive small molecules / protein target / liver cancer / fat synthesis |
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| Research Abstract |
Our laboratory has been discovering bioactive small molecules by screening chemical libraries of synthetic molecules. The goal of this research program is to explore intracellular signaling pathways that are related to cancer and metabolic diseases by using two unique synthetic molecules we previously discovered, chromeceptin and fatostatin. The research outcomes during the two-year funding period are summarized below :
(1) Chromeceptin is a small molecule that blocks the insulin-like growth factor (IGF)-dependent growth of liver cancer cells. Chromeceptin binds to a protein called MFP-2 and selectively activates transcription factor STAT6 which stimulates the expression of IGF-inhibiting genes. We purified an enzyme X that binds MFP-2 only in the presence of chromeceptin. Our experiments indicate that this ternary association induces the activation of kinase Z, resulting in the phosphorylation of STAT6.
(2) Fatostatin is a small molecule that inhibits fat synthesis in cells and animals. This thiazole derivative blocks the activation of transcription factor sterol-responsive element binding protein (SREBP). We purified and identified a protein that binds to fatostatin. Microsequence analyses showed that the binding protein is protein X. The interaction between fatostatin and protein X impairs the translocation of SREBP from ER to Golgi apparatus, and thereby blocks the activation of SREBP, which activate the expression of fat synthesis genes.
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