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rdf:type |
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lifeskim:mentions |
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pubmed:issue |
9
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pubmed:dateCreated |
2002-9-2
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pubmed:databankReference |
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pubmed:abstractText |
Although Jun amino-terminal kinase (JNK) is known to mediate a physiological stress signal that leads to cell death, the exact role of the JNK pathway in the mechanisms underlying intrinsic cell death is largely unknown. Here we show through a genetic screen that a mutant of Drosophila melanogaster tumour-necrosis factor receptor-associated factor 1 (DTRAF1) is a dominant suppressor of Reaper-induced cell death. We show that Reaper modulates the JNK pathway through Drosophila inhibitor-of-apoptosis protein 1 (DIAP1), which negatively regulates DTRAF1 by proteasome-mediated degradation. Reduction of JNK signals rescues the Reaper-induced small eye phenotype, and overexpression of DTRAF1 activates the Drosophila ASK1 (apoptosis signal-regulating kinase 1; a mitogen-activated protein kinase kinase kinase) and JNK pathway, thereby inducing cell death. Overexpresson of DIAP1 facilitates degradation of DTRAF1 in a ubiquitin-dependent manner and simultaneously inhibits activation of JNK. Expression of Reaper leads to a loss of DIAP1 inhibition of DTRAF1-mediated JNK activation in Drosophila cells. Taken together, our results indicate that DIAP1 may modulate cell death by regulating JNK activation through a ubiquitin#150;proteasome pathway.
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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/Drosophila Proteins,
http://linkedlifedata.com/resource/pubmed/chemical/Inhibitor of Apoptosis Proteins,
http://linkedlifedata.com/resource/pubmed/chemical/JNK Mitogen-Activated Protein...,
http://linkedlifedata.com/resource/pubmed/chemical/MAP Kinase Kinase Kinase 5,
http://linkedlifedata.com/resource/pubmed/chemical/MAP Kinase Kinase Kinases,
http://linkedlifedata.com/resource/pubmed/chemical/Mitogen-Activated Protein Kinases,
http://linkedlifedata.com/resource/pubmed/chemical/Peptides,
http://linkedlifedata.com/resource/pubmed/chemical/Proteins,
http://linkedlifedata.com/resource/pubmed/chemical/TNF Receptor-Associated Factor 1,
http://linkedlifedata.com/resource/pubmed/chemical/reaper protein, Drosophila,
http://linkedlifedata.com/resource/pubmed/chemical/thread protein, Drosophila
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pubmed:status |
MEDLINE
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pubmed:month |
Sep
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pubmed:issn |
1465-7392
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pubmed:author |
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pubmed:issnType |
Print
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pubmed:volume |
4
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pubmed:owner |
NLM
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pubmed:authorsComplete |
Y
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pubmed:pagination |
705-10
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pubmed:dateRevised |
2009-11-19
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pubmed:meshHeading |
pubmed-meshheading:12198495-Animals,
pubmed-meshheading:12198495-Animals, Genetically Modified,
pubmed-meshheading:12198495-Apoptosis,
pubmed-meshheading:12198495-Base Sequence,
pubmed-meshheading:12198495-Drosophila Proteins,
pubmed-meshheading:12198495-Drosophila melanogaster,
pubmed-meshheading:12198495-Enzyme Activation,
pubmed-meshheading:12198495-Eye,
pubmed-meshheading:12198495-Genes, Insect,
pubmed-meshheading:12198495-Inhibitor of Apoptosis Proteins,
pubmed-meshheading:12198495-JNK Mitogen-Activated Protein Kinases,
pubmed-meshheading:12198495-MAP Kinase Kinase Kinase 5,
pubmed-meshheading:12198495-MAP Kinase Kinase Kinases,
pubmed-meshheading:12198495-Mitogen-Activated Protein Kinases,
pubmed-meshheading:12198495-Molecular Sequence Data,
pubmed-meshheading:12198495-Mutation,
pubmed-meshheading:12198495-Peptides,
pubmed-meshheading:12198495-Phenotype,
pubmed-meshheading:12198495-Proteins,
pubmed-meshheading:12198495-TNF Receptor-Associated Factor 1
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pubmed:year |
2002
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pubmed:articleTitle |
Reaper-mediated inhibition of DIAP1-induced DTRAF1 degradation results in activation of JNK in Drosophila.
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pubmed:affiliation |
Laboratory for Cell Recovery Mechanisms, RIKEN Brain Science Institute, 2-1 Hirosawa, Wako, Saitama 351-0198, Japan.
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pubmed:publicationType |
Journal Article,
Research Support, Non-U.S. Gov't
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