| Project/Area Number |
14037257
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| Research Category |
Grant-in-Aid for Scientific Research on Priority Areas
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| Allocation Type | Single-year Grants |
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| Review Section |
Biological Sciences
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| Research Institution | Kumamoto University |
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Principal Investigator |
TERADA Kazutoyo (2006) Kumamoto University, Dept. Mol Genet., Grad. Sch. Med. Sci., Associate Professor (00253724)
森 正敬 (2002-2005) 熊本大学, 大学院医学薬学研究部, 教授 (40009650)
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| Co-Investigator(Kenkyū-buntansha) |
GOTOH Tomomi Kumamoto Univ., Dept. Mol. Genet., Grad. Sch. Med. Sci, Lecturer (20264286)
YANO Masato Kumamoto Univ., Dept. Mol. Genet., Grad. Sch. Med. Sci., Assistant Professor (60315299)
寺田 和豊 熊本大学, 大学院医学薬学研究部, 助教授 (00253724)
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| Project Period (FY) |
2002 – 2006
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| Project Status |
Completed (Fiscal Year 2006)
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| Budget Amount *help |
¥128,900,000 (Direct Cost: ¥128,900,000)
Fiscal Year 2006: ¥24,600,000 (Direct Cost: ¥24,600,000)
Fiscal Year 2005: ¥24,600,000 (Direct Cost: ¥24,600,000)
Fiscal Year 2004: ¥26,100,000 (Direct Cost: ¥26,100,000)
Fiscal Year 2003: ¥26,100,000 (Direct Cost: ¥26,100,000)
Fiscal Year 2002: ¥27,500,000 (Direct Cost: ¥27,500,000)
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| Keywords | mitochondria / Omi / ER stress / CHOP / apoptosis / Bcl-2 / t-Bid / Bim / Hsp70 / Hsp40 / 熱耐性 / カスパーゼ / XBP-1 / 精子形成 / アンドロジェン受容体 / LPS / 一酸化窒素 / Akiraマウス / 神経細胞死 / Bax / 分子シャペロン / ノックアウトマウス / 糖尿病 |
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| Research Abstract |
The mitochondrial serine protease Omi/HtrA2 has a proapoptotic role in mammalian cells. However, neither the topology nor the processing of Omi in mitochondria is clearly understood. To determine the topology of Omi in the mitochondrial IMS, EGFP fusions were expressed with the entire N-terminal segment of full-length Omi, and that without the transmembrane region in the cells. As a result, the transmembrane region determines the topology of Omi in the IMS and anchors the pro form into the inner membrane. Mature Omi largely exists in the IMS as a soluble form. The processing sites of the precursor protein were examined, and we could reveal the importance of three arginine residues for the processing of the N-terminal segment of Omi. (BBRC 2007)
Anti-apoptotic Bcl-2 localizes in the membranes of mitochondria and endoplasmic reticulum (ER) and resists a broad range of apoptotic stimuli. However, the precise function of Bcl-2 in ER is still unclear. We herein examined the anti-apoptotic potencies of Bcl-2 in mitochondria and ER in vitro. The mitochondria isolated from HeLa cells, which have little or practically no Bcl-2, were apoptosis-competent. That is, membrane-bound Bax was activated and cytochrome c was released. In the presence of tBid, Bcl-2 in mitochondria and ER are similarly potent in inhibiting Bax-associated apoptosis of other mitochondria, but are regulated by tBid differently. (ECR 2007)
Bim, a proapoptotic BH3-only member of the Bcl-2 family is required for initiation of apoptosis. We found that Bim is essential for ER stress-induced apoptosis through two novel pathways, involving protein phosphatase 2A-mediated dephosphorylation, which prevents its ubiquitination and proteasomal degradation and CHOP-C/EBP-mediated direct transcriptional induction. (Cell 2007)
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