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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| Project Status |
Completed (Fiscal Year 2003)
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| Budget Amount *help |
¥3,400,000 (Direct Cost: ¥3,400,000)
Fiscal Year 2003: ¥1,800,000 (Direct Cost: ¥1,800,000)
Fiscal Year 2002: ¥1,600,000 (Direct Cost: ¥1,600,000)
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| Keywords | Ras / Apoptosis / ミトコンドリア |
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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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Report
(3 results)
Research Products
(15 results)
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[Publications] Kitanaka C, Kato K, Ijiri R, Sakurada K, Tomiyama A, Noguchi K, Nagashima Y, Nakagawara A, Momoi T, Toyoda Y, Kigasawa H, Nishi T, Shirouzu M, Yokoyama S, Tanaka Y, Kuchino Y: "Increased Ras expression and caspase-independent neuroblastoma cell death : possible mechanism of spontaneous neuroblastoma regression"Journal of the National Cancer Institute. 94. 58-68 (2002)
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[Publications] Mochizuki T, Asai A, Saito N, Tanaka S, Katagiri H, Asano T, Nakane M, Tamura A, Kuchino Y, Kitanaka C, Kirino T: "Akt protein kinase inhibits non-apoptotic programmed cell death induced by ceramide"Journal of Biological Chemistry. 277. 2790-2797 (2002)
