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ER stress triggers apoptosis by activating BH3-only protein Bim
被引:1207
作者:

Puthalakath, Hamsa
论文数: 0 引用数: 0
h-index: 0
机构: Walter & Eliza Hall Inst Med Res, Melbourne, Vic 3050, Australia

O'Reilly, Lorraine A.
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h-index: 0
机构: Walter & Eliza Hall Inst Med Res, Melbourne, Vic 3050, Australia

Gunn, Priscilla
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h-index: 0
机构: Walter & Eliza Hall Inst Med Res, Melbourne, Vic 3050, Australia

Lee, Lily
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h-index: 0
机构: Walter & Eliza Hall Inst Med Res, Melbourne, Vic 3050, Australia

Kelly, Priscilla N.
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h-index: 0
机构: Walter & Eliza Hall Inst Med Res, Melbourne, Vic 3050, Australia

Huntington, Nicholas D.
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机构: Walter & Eliza Hall Inst Med Res, Melbourne, Vic 3050, Australia

Hughes, Peter D.
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机构: Walter & Eliza Hall Inst Med Res, Melbourne, Vic 3050, Australia

Michalak, Ewa M.
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机构: Walter & Eliza Hall Inst Med Res, Melbourne, Vic 3050, Australia

McKimm-Breschkin, Jennifer
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机构: Walter & Eliza Hall Inst Med Res, Melbourne, Vic 3050, Australia

Motoyama, Noburo
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h-index: 0
机构: Walter & Eliza Hall Inst Med Res, Melbourne, Vic 3050, Australia

Gotoh, Tomomi
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h-index: 0
机构: Walter & Eliza Hall Inst Med Res, Melbourne, Vic 3050, Australia

Akira, Shizuo
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h-index: 0
机构: Walter & Eliza Hall Inst Med Res, Melbourne, Vic 3050, Australia

Bouillet, Philippe
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h-index: 0
机构: Walter & Eliza Hall Inst Med Res, Melbourne, Vic 3050, Australia

Strasser, Andreas
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h-index: 0
机构:
Walter & Eliza Hall Inst Med Res, Melbourne, Vic 3050, Australia Walter & Eliza Hall Inst Med Res, Melbourne, Vic 3050, Australia
机构:
[1] Walter & Eliza Hall Inst Med Res, Melbourne, Vic 3050, Australia
[2] Univ Melbourne, Dept Med Biol, Melbourne, Vic, Australia
[3] CSIRO, Div Mol & Hlth Technol, Melbourne, Vic, Australia
[4] Natl Ctr Geriatr & Gerontol, Natl Inst Longev Sci, Dept Geriatr Med, Aichi, Japan
[5] Kumamoto Univ, Dept Mol Genet, Kumamoto 8608556, Japan
[6] Osaka Univ, Dept Host Def, Suita, Osaka 5650871, Japan
[7] Univ Melbourne, Dept Biochem, Bio21, Parkville, Vic 3052, Australia
[8] Inst Pasteur, Dept Immunol, Cytokine & Lymphoid Dev Unit, F-75724 Paris, France
来源:
关键词:
D O I:
10.1016/j.cell.2007.04.027
中图分类号:
Q5 [生物化学];
Q7 [分子生物学];
学科分类号:
071010 ;
081704 ;
摘要:
Endoplasmic reticulum ( ER) stress caused by misfolded proteins or cytotoxic drugs can kill cells and although activation of this pathway has been implicated in the etiology of certain degenerative disorders its mechanism remains unresolved. Bim, a proapoptotic BH3-onlymember of the Bcl-2 family is required for initiation of apoptosis induced by cytokine deprivation or certain stress stimuli. Its proapoptotic activity can be regulated by several transcriptional or posttranslational mechanisms, such as ERK-mediated phosphorylation, promoting its ubiquitination and proteasomal degradation. We found that Bim is essential for ER stress-induced apoptosis in a diverse range of cell types both in culture and within the whole animal. ER stress activates Bim through two novel pathways, involving protein phosphatase 2A-mediated dephosphorylation, which prevents its ubiquitination and proteasomal degradation and CHOP-C/EBP alpha-mediated direct transcriptional induction. These results define the molecular mechanisms of ER stress-induced apoptosis and identify targets for therapeutic intervention in ER stress-related diseases.
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页码:1337 / 1349
页数:13
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