| pubmed-article:19432816 | rdf:type | pubmed:Citation | lld:pubmed |
| pubmed-article:19432816 | lifeskim:mentions | umls-concept:C0086418 | lld:lifeskim |
| pubmed-article:19432816 | lifeskim:mentions | umls-concept:C0667830 | lld:lifeskim |
| pubmed-article:19432816 | lifeskim:mentions | umls-concept:C0162638 | lld:lifeskim |
| pubmed-article:19432816 | lifeskim:mentions | umls-concept:C0017636 | lld:lifeskim |
| pubmed-article:19432816 | lifeskim:mentions | umls-concept:C1556138 | lld:lifeskim |
| pubmed-article:19432816 | lifeskim:mentions | umls-concept:C1330957 | lld:lifeskim |
| pubmed-article:19432816 | lifeskim:mentions | umls-concept:C1621443 | lld:lifeskim |
| pubmed-article:19432816 | lifeskim:mentions | umls-concept:C1704686 | lld:lifeskim |
| pubmed-article:19432816 | lifeskim:mentions | umls-concept:C0596311 | lld:lifeskim |
| pubmed-article:19432816 | lifeskim:mentions | umls-concept:C2587213 | lld:lifeskim |
| pubmed-article:19432816 | lifeskim:mentions | umls-concept:C0180459 | lld:lifeskim |
| pubmed-article:19432816 | lifeskim:mentions | umls-concept:C1705370 | lld:lifeskim |
| pubmed-article:19432816 | pubmed:issue | 6A | lld:pubmed |
| pubmed-article:19432816 | pubmed:dateCreated | 2010-7-23 | lld:pubmed |
| pubmed-article:19432816 | pubmed:abstractText | To explore the molecular mechanisms by which glioblastomas are resistant to tumour necrosis factor-related apoptosis-inducing ligand (TRAIL), we examined TRAIL signalling pathways in the tumours. TRAIL has four membrane-anchored receptors, death receptor 4/5 (DR4/5) and decoy receptor 1/2 (DcR1/2). Of these receptors, only DR5 was expressed consistently in glioblastoma cell lines and tumour tissues, ruling out the role of DcR1/2 in TRAIL resistance. Upon TRAIL binding, DR5 was homotrimerized and recruited Fas-associated death domain (FADD) and caspase-8 for the assembly of death-inducing signalling complex (DISC) in the lipid rafts of the plasma membrane. In the DISC, caspase-8 was cleaved and initiated apoptosis by cleaving downstream caspases in TRAIL-sensitive glioblastoma cells. In TRAIL-resistant cells, however, DR5-mediated DISC was modified by receptor-interacting protein (RIP), cellular FADD-like interleukin-1beta-converting enzyme inhibitory protein (c-FLIP) and phosphoprotein enriched in diabetes or in astrocyte-15 (PED/PEA-15). This DISC modification occurred in the non-raft fractions of the plasma membrane and resulted in the inhibition of caspase-8 cleavage and activation of nuclear factor-kappaB (NF-kappaB). Treatment of resistant cells with parthenolide, an inhibitor of inhibitor of kappaB (I-kappaB), eliminated TRAIL-induced NF-kappaB activity but not TRAIL resistance. In contrast, however, targeting of RIP, c-FLIP or PED/PEA-15 with small interfering RNA (siRNA) led to the redistribution of the DISC from non-rafts to lipid rafts and eliminated the inhibition of caspase-8 cleavage and thereby TRAIL resistance. Taken together, this study indicates that the DISC modification by RIP, c-FLIP and PED/PEA-15 is the most upstream event in TRAIL resistance in glioblastomas. | lld:pubmed |
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| pubmed-article:19432816 | pubmed:language | eng | lld:pubmed |
| pubmed-article:19432816 | pubmed:journal | http://linkedlifedata.com/r... | lld:pubmed |
| pubmed-article:19432816 | pubmed:citationSubset | IM | lld:pubmed |
| pubmed-article:19432816 | pubmed:chemical | http://linkedlifedata.com/r... | lld:pubmed |
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| pubmed-article:19432816 | pubmed:status | MEDLINE | lld:pubmed |
| pubmed-article:19432816 | pubmed:month | Jun | lld:pubmed |
| pubmed-article:19432816 | pubmed:issn | 1582-4934 | lld:pubmed |
| pubmed-article:19432816 | pubmed:author | pubmed-author:HaoChunhaiC | lld:pubmed |
| pubmed-article:19432816 | pubmed:author | pubmed-author:OlsonJeffrey... | lld:pubmed |
| pubmed-article:19432816 | pubmed:author | pubmed-author:TseMargaret... | lld:pubmed |
| pubmed-article:19432816 | pubmed:author | pubmed-author:PhuphanichSur... | lld:pubmed |
| pubmed-article:19432816 | pubmed:author | pubmed-author:SunShi YongSY | lld:pubmed |
| pubmed-article:19432816 | pubmed:author | pubmed-author:SongJin HJH | lld:pubmed |
| pubmed-article:19432816 | pubmed:author | pubmed-author:BellailAnita... | lld:pubmed |
| pubmed-article:19432816 | pubmed:issnType | Electronic | lld:pubmed |
| pubmed-article:19432816 | pubmed:volume | 14 | lld:pubmed |
| pubmed-article:19432816 | pubmed:owner | NLM | lld:pubmed |
| pubmed-article:19432816 | pubmed:authorsComplete | Y | lld:pubmed |
| pubmed-article:19432816 | pubmed:pagination | 1303-17 | lld:pubmed |
| pubmed-article:19432816 | pubmed:dateRevised | 2011-9-26 | lld:pubmed |
