| Apoptosis-associated release of Smac/DIABLO from mitochondria requires active caspases and is blocked by Bcl-2. | |
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MedLine Citation:
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PMID: 11726499 Owner: NLM Status: MEDLINE |
Abstract/OtherAbstract:
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Smac/DIABLO is a mitochondrial protein that potentiates some forms of apoptosis, possibly by neutralizing one or more members of the IAP family of apoptosis inhibitory proteins. Smac has been shown to exit mitochondria and enter the cytosol during apoptosis triggered by UV- or gamma-irradiation. Here, we report that Smac/DIABLO export from mitochondria into the cytosol is provoked by cytotoxic drugs and DNA damage, as well as by ligation of the CD95 death receptor. Mitochondrial efflux of Smac/DIABLO, in response to a variety of pro-apoptotic agents, was profoundly inhibited in Bcl-2-overexpressing cells. Thus, in addition to modulating apoptosis-associated mitochondrial cytochrome c release, Bcl-2 also regulates Smac release, suggesting that both molecules may escape via the same route. However, whereas cell stress-associated mitochondrial cytochrome c release was largely caspase independent, release of Smac/DIABLO in response to the same stimuli was blocked by a broad-spectrum caspase inhibitor. This suggests that apoptosis-associated cytochrome c and Smac/DIABLO release from mitochondria do not occur via the same mechanism. Rather, Smac/DIABLO efflux from mitochondria is a caspase-catalysed event that occurs downstream of cytochrome c release. |
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Authors:
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C Adrain; E M Creagh; S J Martin |
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Publication Detail:
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Type: Journal Article; Research Support, Non-U.S. Gov't |
Journal Detail:
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Title: The EMBO journal Volume: 20 ISSN: 0261-4189 ISO Abbreviation: EMBO J. Publication Date: 2001 Dec |
Date Detail:
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Created Date: 2001-11-29 Completed Date: 2002-01-17 Revised Date: 2009-11-18 |
Medline Journal Info:
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Nlm Unique ID: 8208664 Medline TA: EMBO J Country: England |
Other Details:
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Languages: eng Pagination: 6627-36 Citation Subset: IM |
Affiliation:
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Molecular Cell Biology Laboratory, Department of Genetics, The Smurfit Institute, Trinity College, Dublin 2, Ireland. |
Export Citation:
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APA/MLA Format Download EndNote Download BibTex |
| MeSH Terms | |
Descriptor/Qualifier:
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Antibiotics, Antineoplastic
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pharmacology Antigens, CD95 / metabolism Apoptosis* / drug effects, radiation effects Carrier Proteins / biosynthesis* Caspases / antagonists & inhibitors, metabolism* Cell Line Cytochrome c Group / metabolism Cytosol / metabolism DNA Damage Dactinomycin / pharmacology Daunorubicin / pharmacology Enzyme Activation Enzyme Inhibitors / pharmacology Gamma Rays Hela Cells Humans Intracellular Signaling Peptides and Proteins Jurkat Cells Kinetics Microscopy, Fluorescence Mitochondria / metabolism* Mitochondrial Proteins / biosynthesis* Models, Biological Protein Binding Protein Synthesis Inhibitors / pharmacology Protein Transport Proto-Oncogene Proteins c-bcl-2 / metabolism* Staurosporine / pharmacology Subcellular Fractions / metabolism Time Factors Tissue Distribution Ultraviolet Rays |
| Chemical | |
Reg. No./Substance:
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0/Antibiotics, Antineoplastic; 0/Antigens, CD95; 0/Carrier Proteins; 0/Cytochrome c Group; 0/DIABLO protein, human; 0/Enzyme Inhibitors; 0/Intracellular Signaling Peptides and Proteins; 0/Mitochondrial Proteins; 0/Protein Synthesis Inhibitors; 0/Proto-Oncogene Proteins c-bcl-2; 20830-81-3/Daunorubicin; 50-76-0/Dactinomycin; 62996-74-1/Staurosporine; EC 3.4.22.-/Caspases |
| Comments/Corrections | |
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