Linked Life Data

12628743

Source:http://linkedlifedata.com/resource/pubmed/id/12628743

Statements in which the resource exists as a subject.
PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
2-3
pubmed:dateCreated
2003-3-11
pubmed:abstractText
Prominent among cell surface molecules capable of initiating apoptosis are members of the tumour necrosis factor (TNF) family of ligands and receptors. Death-inducing members of the TNF receptor family each contain a cytoplasmic 'death domain' (DD): a protein-protein interaction motif critical for engaging downstream components of the signal transduction machinery. Following activation of these receptors by their cognate ligands, a death-inducing signalling complex (DISC) is formed by recruitment of cytoplasmic DD-containing proteins to the receptor DD. The best-studied death-inducing ligand-receptor pairs are TNF/TNF receptor-1 (TNFR1) and CD95L/CD95 (Fas, Apo-1). A more recently identified member of the TNF ligand family is TNF-related apoptosis-inducing ligand (TRAIL), Apo-2L, which induces apoptosis in a number of tumour cell lines, yet is relatively non-toxic to normal cells. Consistent with its lack of toxicity, TRAIL is constitutively expressed in many human tissues. This raises the conundrum of why tumour cells are sensitive to TRAIL-mediated apoptosis and normal tissues resistant. One possibility lies in the existence of a family of four membrane-bound TRAIL receptors (TRAIL-R1-R4), which although able to bind TRAIL, differ in their ability to transduce the death signal. Recently, this hypothesis has been challenged based on poor correlations between TRAIL receptor expression and TRAIL sensitivity. This suggests that other factors, such as TRAIL-induced NF-kappaB activation or death inhibitors including c-FLIP, are involved in determining differential sensitivity to TRAIL. We have investigated TRAIL sensitivity in primary tumour cells together with TRAIL-induced signalling pathways in both sensitive and resistant cell lines. Our results and their implications for the potential use of TRAIL in cancer therapy are discussed.
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
IM
pubmed:chemical
http://linkedlifedata.com/resource/pubmed/chemical/Apoptosis Regulatory Proteins, http://linkedlifedata.com/resource/pubmed/chemical/CASP8 and FADD-Like Apoptosis..., http://linkedlifedata.com/resource/pubmed/chemical/CFLAR protein, human, http://linkedlifedata.com/resource/pubmed/chemical/Carrier Proteins, http://linkedlifedata.com/resource/pubmed/chemical/Intracellular Signaling Peptides..., http://linkedlifedata.com/resource/pubmed/chemical/Membrane Glycoproteins, http://linkedlifedata.com/resource/pubmed/chemical/NF-kappa B, 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/TNFSF10 protein, human, http://linkedlifedata.com/resource/pubmed/chemical/Tumor Necrosis Factor-alpha
pubmed:status
MEDLINE
pubmed:month
Apr
pubmed:issn
0378-4274
pubmed:author
pubmed:issnType
Print
pubmed:day
4
pubmed:volume
139
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
89-97
pubmed:dateRevised
2006-11-15
pubmed:meshHeading
pubmed:year
2003
pubmed:articleTitle
TRAIL-induced signalling and apoptosis.
pubmed:affiliation
MRC Toxicology Unit, Hodgkin Building, University of Leicester, Lancaster Road, Leicester LE19HN, UK. mm21@le.ac.uk
pubmed:publicationType
Journal Article, Review