Statements in which the resource exists as a subject.
PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
11
pubmed:dateCreated
2006-5-1
pubmed:abstractText
It is known that by binding to the FAS-associated death domain (FADD) protein and/or caspases-8 and -10 at the level of the death-inducing signaling complex (DISC), cellular FLICE-like inhibitory protein (c-FLIP) can prevent apoptosis triggered by death-inducing ligands. We investigated whether the c-FLIP splice variants, c-FLIP long [c-FLIP(L)] and c-FLIP short [c-FLIP(S)], play a role in Taxol-induced apoptosis. Our results showed that low Taxol concentrations triggered caspase-8- and caspase-10-dependent apoptosis in the CCRF-HSB-2 human lymphoblastic leukemia cell line, and induced the down-regulation of c-FLIP(S) and c-FLIP(L). Taxol decreased the expression of c-FLIP by a post-transcriptional and caspase-independent mechanism. To explore the distinct functions of the c-FLIP variants in Taxol-induced apoptosis, we transfected the cells with expression vectors carrying c-FLIP(L) and c-FLIP(S) in the sense orientation or c-FLIP(S) in the antisense orientation [c-FLIP(S)-AS]. Caspases-8 and -10 were more efficiently activated in the c-FLIP(S)-AS strain treated with 5-50nM Taxol, which revealed that c-FLIP regulates Taxol-induced apoptosis by interacting with these caspases. Furthermore, our data showed that increased expression of c-FLIP(L) or c-FLIP(S) reduced apoptosis at 5-50nM Taxol concentrations suggesting that both isoforms of c-FLIP prevent Taxol-induced apoptosis. These results revealed that Taxol induces apoptosis by down-regulating c-FLIP(S) and c-FLIP(L) expression.
pubmed:grant
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
IM
pubmed:chemical
pubmed:status
MEDLINE
pubmed:month
May
pubmed:issn
0006-2952
pubmed:author
pubmed:issnType
Print
pubmed:day
28
pubmed:volume
71
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
1551-61
pubmed:dateRevised
2007-11-15
pubmed:meshHeading
pubmed:year
2006
pubmed:articleTitle
Cellular FLICE-like inhibitory protein (c-FLIP): a novel target for Taxol-induced apoptosis.
pubmed:affiliation
Department of Pharmacology and Toxicology, Indiana University Cancer Research Institute, Indiana University School of Medicine, Indianapolis, IN 46202, USA.
pubmed:publicationType
Journal Article, Research Support, N.I.H., Extramural