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rdf:type |
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lifeskim:mentions |
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pubmed:issue |
7
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pubmed:dateCreated |
2001-5-23
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pubmed:abstractText |
Sympathetic neurons undergo protein synthesis-dependent apoptosis when deprived of nerve growth factor (NGF). Expression of SM-20 is up-regulated in NGF-deprived sympathetic neurons, and ectopic SM-20 is sufficient to promote neuronal death in the presence of NGF. We now report that SM-20 is a mitochondrial protein that promotes cell death through a caspase-dependent mechanism. SM-20 immunofluorescence was present in the cytoplasm in a punctate pattern that colocalized with cytochrome oxidase I and with mitochondria-selective dyes. Analysis of SM-20/dihydrofolate reductase fusion proteins revealed that the first 25 amino acids of SM-20 contain a functional mitochondrial targeting sequence. An amino-terminal truncated form of SM-20 was not restricted to mitochondria but instead localized throughout the cytosol and nucleus. Nevertheless, the truncated SM-20 retained the ability to induce neuronal death, similar to the wild type protein. SM-20-induced death was accompanied by caspase-3 activation and was blocked by a general caspase inhibitor. Additionally, overexpression of SM-20, under conditions where cell death is blocked by a general caspase inhibitor, did not result in widespread release of cytochrome c from mitochondria. These results indicate that SM-20 is a novel mitochondrial protein that may be an important mediator of neurotrophin-withdrawal-mediated cell death.
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pubmed:grant |
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pubmed:language |
eng
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pubmed:journal |
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pubmed:citationSubset |
IM
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pubmed:chemical |
http://linkedlifedata.com/resource/pubmed/chemical/Aspartic Acid,
http://linkedlifedata.com/resource/pubmed/chemical/Casp3 protein, mouse,
http://linkedlifedata.com/resource/pubmed/chemical/Caspase 3,
http://linkedlifedata.com/resource/pubmed/chemical/Caspases,
http://linkedlifedata.com/resource/pubmed/chemical/Cytochrome c Group,
http://linkedlifedata.com/resource/pubmed/chemical/DNA-Binding Proteins,
http://linkedlifedata.com/resource/pubmed/chemical/Egln1 protein, mouse,
http://linkedlifedata.com/resource/pubmed/chemical/Enzyme Inhibitors,
http://linkedlifedata.com/resource/pubmed/chemical/Immediate-Early Proteins,
http://linkedlifedata.com/resource/pubmed/chemical/Nerve Growth Factor,
http://linkedlifedata.com/resource/pubmed/chemical/Procollagen-Proline Dioxygenase,
http://linkedlifedata.com/resource/pubmed/chemical/benzyloxycarbonyl-aspartyl(O-methyl)...
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pubmed:status |
MEDLINE
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pubmed:month |
Feb
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pubmed:issn |
0021-9258
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pubmed:author |
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pubmed:issnType |
Print
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pubmed:day |
16
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pubmed:volume |
276
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pubmed:owner |
NLM
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pubmed:authorsComplete |
Y
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pubmed:pagination |
5085-92
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pubmed:dateRevised |
2011-9-2
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pubmed:meshHeading |
pubmed-meshheading:11060309-3T3 Cells,
pubmed-meshheading:11060309-Animals,
pubmed-meshheading:11060309-Apoptosis,
pubmed-meshheading:11060309-Aspartic Acid,
pubmed-meshheading:11060309-Caspase 3,
pubmed-meshheading:11060309-Caspases,
pubmed-meshheading:11060309-Cell Death,
pubmed-meshheading:11060309-Cell Line,
pubmed-meshheading:11060309-Cells, Cultured,
pubmed-meshheading:11060309-Cytochrome c Group,
pubmed-meshheading:11060309-DNA-Binding Proteins,
pubmed-meshheading:11060309-Enzyme Inhibitors,
pubmed-meshheading:11060309-Ganglia, Sympathetic,
pubmed-meshheading:11060309-Immediate-Early Proteins,
pubmed-meshheading:11060309-Mice,
pubmed-meshheading:11060309-Mitochondria,
pubmed-meshheading:11060309-Nerve Growth Factor,
pubmed-meshheading:11060309-Neurons,
pubmed-meshheading:11060309-Procollagen-Proline Dioxygenase,
pubmed-meshheading:11060309-Protein Transport,
pubmed-meshheading:11060309-Sequence Deletion
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pubmed:year |
2001
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pubmed:articleTitle |
SM-20 is a novel mitochondrial protein that causes caspase-dependent cell death in nerve growth factor-dependent neurons.
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pubmed:affiliation |
Department of Environmental Medicine, University of Rochester School of Medicine and Dentistry, Rochester, NY 14642, USA.
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pubmed:publicationType |
Journal Article,
Research Support, U.S. Gov't, P.H.S.,
Research Support, Non-U.S. Gov't
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