2003 Fiscal Year Final Research Report Summary
Molecular mechanisms involved in non-apoptotic programmed cell death regulation
| Project/Area Number |
14580708
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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 |
Cell biology
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| Research Institution | National Cancer Center Research Institute |
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Principal Investigator |
KITANAKA Chifumi National Cancer Center Research Institute, Biology Division, Section Head, 生物学部, 室長 (70260320)
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| Project Period (FY) |
2002 – 2003
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| Keywords | Ras / Apoptosis |
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| Research Abstract |
We used the in vitro model system for Ras-dependent non-apoptotic programmed cell death and dissected the molecular mechanism involved in the regulation of Ras-induced non-apoptotic programmed cell death. In general, caspase-independent, non-apoptotic programmed cell deaths are known to be mitochondria-dependent We therefore examined whether mitochondria is involved in Ras-induced non-apoptotic programmed cell death. We found no evidence of increased permeability of mitochondrial membrane during Ras-induced cell death, and Ras-induced cell death was inhibited neither by Bcl-xL nor by vMIA, which are known to be potent inhitibors of mitochondrial cell death. These results indicated that Ras-induced cell death belongs to a novel type of non-apoptotic programmed cell death that has never been reported. Dissection of the intracellular signaling pathway activated by Ras using Ras effector loop mutant revealed that the Pl3K pathway plays a critical role in the transduction of the death signal. Screening of pharmacological agents that inhibit or promote Ras-induced cell death identified Toxin B of Clostridium difficile as a potent inhibitor of Ras-induced cell death, suggesting that the Rho family of proteins may play an important role in the regulation of Ras-induced cell death. Use of dominant-negative mutants of the Rho family proteins revealed that Rac among others may have a key role in Ras-induced non-apoptotic programmed cell death.
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Research Products
(8 results)
