| Project/Area Number |
15390100
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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 |
Pathological medical chemistry
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| Research Institution | The University of Tokyo |
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Principal Investigator |
AKIYAMA Tetsu The University of Tokyo, Institute of Molecular and Cellular Biosciences, Professor, 分子細胞生物学研究所, 教授 (70150745)
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| Project Period (FY) |
2003 – 2004
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| Project Status |
Completed (Fiscal Year 2004)
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| Budget Amount *help |
¥15,400,000 (Direct Cost: ¥15,400,000)
Fiscal Year 2004: ¥4,200,000 (Direct Cost: ¥4,200,000)
Fiscal Year 2003: ¥11,200,000 (Direct Cost: ¥11,200,000)
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| Keywords | RNA-binding protein / p53 / TGF-b / apoptosis / Bim / KHドメイン / 標的遺伝子 / ノックアウトマウス / TPA / 発現誘導 |
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| Research Abstract |
We identified and characterized a novel gene termed D8 that is involved in the induction of apoptosis and obtained the following results :
1)Overexpression of D8 in tumor cell lines such as HepG2 resulted in the induction of apoptosis. Knockdown experiments using RNAi revealed that D8 is required for p53 and TGF-β-mediated induction of apoptosis
2)Treatment of cells with anticancer reagents such as 5FU and adriamycin resulted in the induction of D8 expression. Knockdown of D8 inhibited 5FU-and adriamycin-induced apoptosis.
3)Bim, a family member of the BH3 only family of proteins, was found to bind to the KH domain of D8. Knockdown experiments using RNAi revealed that Bim is important for D8-mediated apoptosis
4)D8 was found to stabilize the Bim mRNA.
5)To generate D8 knockdown mice, we established ES cell lines lacking the D8 gene.
6)We found that D8 possesses three family members.
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