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rdf:type |
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lifeskim:mentions |
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pubmed:issue |
8
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pubmed:dateCreated |
2009-7-21
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pubmed:abstractText |
Apoptosis is central to the interaction between pathogenic mycobacteria and host macrophages. Caspase-8-dependent apoptosis of infected macrophages, which requires activation of the mitogen-activated protein (MAP) kinase p38, lowers the spread of mycobacteria. Here we establish a link between the release of tumor necrosis factor (TNF) and mycobacteria-mediated macrophage apoptosis. TNF activated a pathway involving the kinases ASK1, p38 and c-Abl. This pathway led to phosphorylation of FLIP(S), which facilitated its interaction with the E3 ubiquitin ligase c-Cbl. This interaction triggered proteasomal degradation of FLIP(S), which promoted activation of caspase-8 and apoptosis. Our findings identify a previously unappreciated signaling pathway needed for Mycobacterium tuberculosis-triggered macrophage cell death.
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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/CASP8 and FADD-Like Apoptosis...,
http://linkedlifedata.com/resource/pubmed/chemical/CBL protein, human,
http://linkedlifedata.com/resource/pubmed/chemical/Caspase 8,
http://linkedlifedata.com/resource/pubmed/chemical/Cbl protein, mouse,
http://linkedlifedata.com/resource/pubmed/chemical/MAP Kinase Kinase Kinase 5,
http://linkedlifedata.com/resource/pubmed/chemical/MAP3K5 protein, human,
http://linkedlifedata.com/resource/pubmed/chemical/Proteasome Endopeptidase Complex,
http://linkedlifedata.com/resource/pubmed/chemical/Proto-Oncogene Proteins c-abl,
http://linkedlifedata.com/resource/pubmed/chemical/Proto-Oncogene Proteins c-cbl,
http://linkedlifedata.com/resource/pubmed/chemical/Tumor Necrosis Factor-alpha,
http://linkedlifedata.com/resource/pubmed/chemical/p38 Mitogen-Activated Protein...
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pubmed:status |
MEDLINE
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pubmed:month |
Aug
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pubmed:issn |
1529-2916
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pubmed:author |
pubmed-author:BasuJoyotiJ,
pubmed-author:BasuSanchitaS,
pubmed-author:ChatterjeeGargiG,
pubmed-author:IchijoHidenoriH,
pubmed-author:KumawatKuldeepK,
pubmed-author:KunduManikuntalaM,
pubmed-author:LangdonWallace YWY,
pubmed-author:NoguchiTakuyaT,
pubmed-author:PathakShreshS,
pubmed-author:PathakSushil KumarSK,
pubmed-author:TakedaKohsukeK,
pubmed-author:ThienChristine B FCB
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pubmed:issnType |
Electronic
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pubmed:volume |
10
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pubmed:owner |
NLM
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pubmed:authorsComplete |
Y
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pubmed:pagination |
918-26
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pubmed:dateRevised |
2011-11-2
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pubmed:meshHeading |
pubmed-meshheading:19597496-Animals,
pubmed-meshheading:19597496-Apoptosis,
pubmed-meshheading:19597496-CASP8 and FADD-Like Apoptosis Regulating Protein,
pubmed-meshheading:19597496-Caspase 8,
pubmed-meshheading:19597496-Cell Line,
pubmed-meshheading:19597496-Cell Proliferation,
pubmed-meshheading:19597496-Humans,
pubmed-meshheading:19597496-MAP Kinase Kinase Kinase 5,
pubmed-meshheading:19597496-Macrophages,
pubmed-meshheading:19597496-Mice,
pubmed-meshheading:19597496-Mice, Knockout,
pubmed-meshheading:19597496-Mycobacterium tuberculosis,
pubmed-meshheading:19597496-Phosphorylation,
pubmed-meshheading:19597496-Proteasome Endopeptidase Complex,
pubmed-meshheading:19597496-Protein Binding,
pubmed-meshheading:19597496-Proto-Oncogene Proteins c-abl,
pubmed-meshheading:19597496-Proto-Oncogene Proteins c-cbl,
pubmed-meshheading:19597496-Signal Transduction,
pubmed-meshheading:19597496-Tumor Necrosis Factor-alpha,
pubmed-meshheading:19597496-Ubiquitination,
pubmed-meshheading:19597496-p38 Mitogen-Activated Protein Kinases
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pubmed:year |
2009
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pubmed:articleTitle |
A TNF- and c-Cbl-dependent FLIP(S)-degradation pathway and its function in Mycobacterium tuberculosis-induced macrophage apoptosis.
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pubmed:affiliation |
Department of Chemistry, Bose Institute, Kolkata, India.
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pubmed:publicationType |
Journal Article,
Research Support, Non-U.S. Gov't
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