| Project/Area Number |
21790516
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| Research Category |
Grant-in-Aid for Young Scientists (B)
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| Allocation Type | Single-year Grants |
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| Research Field |
Applied pharmacology
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| Research Institution | Tohoku University |
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Principal Investigator |
KAKUDO Yuichi Tohoku University, 加齢医学研究所, 助教 (10396484)
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| Project Period (FY) |
2009 – 2010
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| Project Status |
Completed (Fiscal Year 2010)
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| Budget Amount *help |
¥4,160,000 (Direct Cost: ¥3,200,000、Indirect Cost: ¥960,000)
Fiscal Year 2010: ¥1,690,000 (Direct Cost: ¥1,300,000、Indirect Cost: ¥390,000)
Fiscal Year 2009: ¥2,470,000 (Direct Cost: ¥1,900,000、Indirect Cost: ¥570,000)
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| Keywords | 薬物治療学 / 分子標的治療 / p53 / 機能獲得変異 / S121F / DRAM / hotspot mutation / 機能獲得 / RNA遺伝子 |
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| Research Abstract |
So far, "super p53" mutants of several gain-of-function mutants have been reported as mutants exhibiting more potent ability to induce apoptosis than wild-type p53. The super p53s may provide a clue for development novel therapeutic targets, but the major mechanism underlying the super p53-dependent apoptosis remains unclear. To identify critical gene(s) in the mechanism, we performed comprehensive and comparative expression analysis in p53-null Saos-2 cells with conditional expression of wild-type p53 and S121F, previously reported as a super p53 mutant. We identified damage-regulated autophagy modulator (DRAM) as one of the genes that were more upregulated by S121F than wild-type p53. Although knockdown of DRAM was not sufficient for reducing the ability of S121F to induce apoptosis, overexpression of DRAM enhanced the ability in a wild-type p53-dependent manner. Here, we show that DRAM is an important gene for the enhancement of p53-dependent apoptosis.
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