| Project/Area Number |
14599001
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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 |
細胞死(アポトーシス)
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| Research Institution | Tokyo Medical and Dental University |
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Principal Investigator |
ADACHI Takahiro Tokyo Medical and Dental University, Medical Research Institute, Associate Prof., 難治疾患研究所, 助教授 (50222625)
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| Co-Investigator(Kenkyū-buntansha) |
TSUBATA Takeshi Tokyo Medical and Dental University, School ob Biomedical Science, Prof., 大学院・疾患生命科学研究部, 教授 (80197756)
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| Project Period (FY) |
2002 – 2003
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| Project Status |
Completed (Fiscal Year 2003)
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| Budget Amount *help |
¥3,100,000 (Direct Cost: ¥3,100,000)
Fiscal Year 2003: ¥1,200,000 (Direct Cost: ¥1,200,000)
Fiscal Year 2002: ¥1,900,000 (Direct Cost: ¥1,900,000)
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| Keywords | apoptosis / cell cycle / kip1 / cyclin dependent kinase inhibitor / Kip1 |
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| Research Abstract |
It has been shown that cell cycle has relevance to apoptosis. Effect of cell cycle arrest on apoptosis is controversial upon cell types or stimuli. Previously we found that treatment with L-mimosine or enforced expression of Kip 1 induced cell cycle arrest at G 1 phase and apoptosis in various types of cells including mouse B lymphoma line WEHI-23 I. But so far, molecular mechanism of the connection between cell cycle and apoptosis remains unclear. Therefore, we tried to isolate genes related to cell cycle arrest-induced apoptosis. We generated that cDNA library from WEHI-23 1 cells or, spleen cells by using retrovirus vectors and introduced into WEHI-23 I cells. Cells were treated with L-mimosine and integrated cDNA fragments were recovered from the live cells by PCR. We obtained three independent partial c-Myc cDNA fragments were inserted into the vector as antisense direction. Expression of these constructs in WEHI-23 1 cells repressed c-Myc expression and inhibited Kip i-induced apoptosis. Moreover, overexpression of c-Myc augmented Kip 1-induced apoptosis and inhibition of c-Myc by enforced expression of Mad4 reversed it. These results indicated that c-Myc is a crucial molecule which decide cell fate upon cell cycle arrest. Furthermore, we obtained cDNA fragments that inhibit cell cycle arrest-induced apoptosis. Analyses of these fragments are in progress.
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