2006 Fiscal Year Final Research Report Summary
Functional analysis of chaperones in mammals
| 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 Kumamoto University, Dept. Mol Genet., Grad. Sch. Med. Sci., Associate Professor (00253724)
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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)
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| Project Period (FY) |
2002 – 2006
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| Keywords | mitochondria / Omi / ER stress / CHOP / apoptosis / Bcl-2 / t-Bid / Bim |
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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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[Journal Article] A. Strasser ER Stress Triggers Apoptosis by Activating BH3-Only Protein Bim2007
Author(s)
H. Puthalakath, L.A. O'Reilly, P.Gunn, L. Lee, EN. Kelly, N.D. Huntington, P.D. Hughes, E.M. Michalak, J. McKimm-Breschkin, N. Motoyama, T. Gotoh. S. Akira, P. Bouillet
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Journal Title
Cell 129(7)
Pages: 1337-1349
Description
「研究成果報告書概要(欧文)」より
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