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rdf:type |
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lifeskim:mentions |
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pubmed:issue |
5
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pubmed:dateCreated |
2003-11-24
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pubmed:abstractText |
Tumour necrosis factor-related apoptosis-inducing ligand (TRAIL) effectively kills tumour cells but not normal cells. We investigated TRAIL sensitivity and the TRAIL-induced apoptosis signalling pathway in a panel of B-lymphocytic leukaemia cell lines. Depending upon TRAIL sensitivity, leukaemia cells could be divided into three groups: highly sensitive, moderately sensitive and resistant. TRAIL receptor-2 (DR5) plays an important role in transducing apoptosis signals. DR5 was internalized into the cytoplasm where it recruited FAS-associated death domain protein (FADD) under TRAIL stimulation in both sensitive and resistant cells. However, the active form of caspase-8 was recruited to FADD and only sensitive cells showed increased caspase-8 activity upon TRAIL stimulation. The caspase-8 specific inhibitor, Z-IETD, impaired caspase-8 activation and completely abrogated TRAIL-induced apoptosis. These results suggest that TRAIL resistance in B-lymphocytic leukaemia cells is due to negative regulation at the level of caspase-8 activation and that caspase-8 activation is an indispensable process in TRAIL-induced apoptosis. However, FADD-like interleukin-1 beta-converting enzyme inhibitory protein (c-FLIPL) was similarly expressed and down-regulated after TRAIL stimulation in both sensitive and resistant cells. Interestingly, in some cell lines, TRAIL sensitivity and caspase-8 activity was enhanced or restored with the treatment of cycloheximide (CHX). In addition, X-linked inhibitor of apoptosis (XIAP) levels decreased significantly and rapidly following treatment with CHX. Down-regulation of XIAP may be responsible for enhancement or restoration of TRAIL sensitivity after CHX treatment in B-lymphocytic leukaemia cells.
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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/Apoptosis Regulatory Proteins,
http://linkedlifedata.com/resource/pubmed/chemical/Arabidopsis Proteins,
http://linkedlifedata.com/resource/pubmed/chemical/CASP8 and FADD-Like Apoptosis...,
http://linkedlifedata.com/resource/pubmed/chemical/CASP8 protein, human,
http://linkedlifedata.com/resource/pubmed/chemical/CASP9 protein, human,
http://linkedlifedata.com/resource/pubmed/chemical/CFLAR protein, human,
http://linkedlifedata.com/resource/pubmed/chemical/Carrier Proteins,
http://linkedlifedata.com/resource/pubmed/chemical/Caspase 8,
http://linkedlifedata.com/resource/pubmed/chemical/Caspase 9,
http://linkedlifedata.com/resource/pubmed/chemical/Caspases,
http://linkedlifedata.com/resource/pubmed/chemical/Cycloheximide,
http://linkedlifedata.com/resource/pubmed/chemical/Cysteine Proteinase Inhibitors,
http://linkedlifedata.com/resource/pubmed/chemical/Fad7 protein, Arabidopsis,
http://linkedlifedata.com/resource/pubmed/chemical/Fatty Acid Desaturases,
http://linkedlifedata.com/resource/pubmed/chemical/Intracellular Signaling Peptides...,
http://linkedlifedata.com/resource/pubmed/chemical/Membrane Glycoproteins,
http://linkedlifedata.com/resource/pubmed/chemical/Oligopeptides,
http://linkedlifedata.com/resource/pubmed/chemical/Protein Synthesis Inhibitors,
http://linkedlifedata.com/resource/pubmed/chemical/Proteins,
http://linkedlifedata.com/resource/pubmed/chemical/Receptors, TNF-Related...,
http://linkedlifedata.com/resource/pubmed/chemical/Receptors, Tumor Necrosis Factor,
http://linkedlifedata.com/resource/pubmed/chemical/TNF-Related Apoptosis-Inducing...,
http://linkedlifedata.com/resource/pubmed/chemical/TNFRSF10B protein, human,
http://linkedlifedata.com/resource/pubmed/chemical/TNFSF10 protein, human,
http://linkedlifedata.com/resource/pubmed/chemical/Tumor Necrosis Factor-alpha,
http://linkedlifedata.com/resource/pubmed/chemical/X-Linked Inhibitor of Apoptosis...,
http://linkedlifedata.com/resource/pubmed/chemical/XIAP protein, human,
http://linkedlifedata.com/resource/pubmed/chemical/benzyloxycarbonyl-isoleucyl-glutamyl...
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pubmed:status |
MEDLINE
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pubmed:month |
Dec
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pubmed:issn |
0007-1048
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pubmed:author |
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pubmed:issnType |
Print
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pubmed:volume |
123
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pubmed:owner |
NLM
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pubmed:authorsComplete |
Y
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pubmed:pagination |
921-32
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pubmed:dateRevised |
2009-11-19
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pubmed:meshHeading |
pubmed-meshheading:14632785-Apoptosis,
pubmed-meshheading:14632785-Apoptosis Regulatory Proteins,
pubmed-meshheading:14632785-Arabidopsis Proteins,
pubmed-meshheading:14632785-Blotting, Western,
pubmed-meshheading:14632785-CASP8 and FADD-Like Apoptosis Regulating Protein,
pubmed-meshheading:14632785-Carrier Proteins,
pubmed-meshheading:14632785-Caspase 8,
pubmed-meshheading:14632785-Caspase 9,
pubmed-meshheading:14632785-Caspases,
pubmed-meshheading:14632785-Cell Line,
pubmed-meshheading:14632785-Cycloheximide,
pubmed-meshheading:14632785-Cysteine Proteinase Inhibitors,
pubmed-meshheading:14632785-Drug Resistance, Neoplasm,
pubmed-meshheading:14632785-Enzyme Activation,
pubmed-meshheading:14632785-Fatty Acid Desaturases,
pubmed-meshheading:14632785-Humans,
pubmed-meshheading:14632785-Intracellular Signaling Peptides and Proteins,
pubmed-meshheading:14632785-Leukemia, B-Cell,
pubmed-meshheading:14632785-Membrane Glycoproteins,
pubmed-meshheading:14632785-Oligopeptides,
pubmed-meshheading:14632785-Protein Synthesis Inhibitors,
pubmed-meshheading:14632785-Proteins,
pubmed-meshheading:14632785-Receptors, TNF-Related Apoptosis-Inducing Ligand,
pubmed-meshheading:14632785-Receptors, Tumor Necrosis Factor,
pubmed-meshheading:14632785-Signal Transduction,
pubmed-meshheading:14632785-TNF-Related Apoptosis-Inducing Ligand,
pubmed-meshheading:14632785-Tumor Necrosis Factor-alpha,
pubmed-meshheading:14632785-X-Linked Inhibitor of Apoptosis Protein
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pubmed:year |
2003
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pubmed:articleTitle |
Chemical sensitization and regulation of TRAIL-induced apoptosis in a panel of B-lymphocytic leukaemia cell lines.
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pubmed:affiliation |
Department of Pediatrics, Mie University School of Medicine, Tsu, Mie, Japan.
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pubmed:publicationType |
Journal Article
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