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rdf:type |
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lifeskim:mentions |
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pubmed:issue |
10
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pubmed:dateCreated |
2006-5-4
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pubmed:abstractText |
The HTLV-1 transactivator protein Tax is essential for malignant transformation of CD4 T cells, ultimately leading to adult T-cell leukemia/lymphoma (ATL). Malignant transformation may involve development of apoptosis resistance. In this study we investigated the molecular mechanisms by which HTLV-1 Tax confers resistance toward CD95-mediated apoptosis. We show that Tax-expressing T-cell lines derived from HTLV-1-infected patients express elevated levels of c-FLIP(L) and c-FLIP(S). The levels of c-FLIP correlated with resistance toward CD95-mediated apoptosis. Using an inducible system we demonstrated that both resistance toward CD95-mediated apoptosis and induction of c-FLIP are dependent on Tax. In addition, analysis of early cleavage of the BH3-only Bcl-2 family member Bid, a direct caspase-8 substrate, revealed that apoptosis is inhibited at a CD95 death receptor proximal level in Tax-expressing cells. Finally, using siRNA we directly showed that c-FLIP confers Tax-mediated resistance toward CD95-mediated apoptosis. In conclusion, our data suggest an important mechanism by which expression of HTLV-1 Tax may lead to immune escape of infected T cells and, thus, to persistent infection and transformation.
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pubmed:language |
eng
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pubmed:journal |
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pubmed:citationSubset |
AIM
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pubmed:chemical |
http://linkedlifedata.com/resource/pubmed/chemical/Antigens, CD95,
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/DNA Primers,
http://linkedlifedata.com/resource/pubmed/chemical/Gene Products, tax,
http://linkedlifedata.com/resource/pubmed/chemical/Intracellular Signaling Peptides...,
http://linkedlifedata.com/resource/pubmed/chemical/Recombinant Fusion Proteins,
http://linkedlifedata.com/resource/pubmed/chemical/bcl-X Protein
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pubmed:status |
MEDLINE
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pubmed:month |
May
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pubmed:issn |
0006-4971
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pubmed:author |
pubmed-author:BaumannSvenS,
pubmed-author:BleuminkMarcM,
pubmed-author:BoschValerieV,
pubmed-author:FasStefanie CSC,
pubmed-author:GiaisiMarcoM,
pubmed-author:HoltkotteDeniseD,
pubmed-author:KrammerPeter HPH,
pubmed-author:KruegerAndreasA,
pubmed-author:Li-WeberMinM,
pubmed-author:MerlingAnetteA,
pubmed-author:StumpfChristineC
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pubmed:issnType |
Print
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pubmed:day |
15
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pubmed:volume |
107
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pubmed:owner |
NLM
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pubmed:authorsComplete |
Y
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pubmed:pagination |
3933-9
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pubmed:dateRevised |
2006-11-15
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pubmed:meshHeading |
pubmed-meshheading:16403915-Antigens, CD95,
pubmed-meshheading:16403915-Apoptosis,
pubmed-meshheading:16403915-Base Sequence,
pubmed-meshheading:16403915-CASP8 and FADD-Like Apoptosis Regulating Protein,
pubmed-meshheading:16403915-DNA Primers,
pubmed-meshheading:16403915-Gene Deletion,
pubmed-meshheading:16403915-Gene Products, tax,
pubmed-meshheading:16403915-Human T-lymphotropic virus 1,
pubmed-meshheading:16403915-Humans,
pubmed-meshheading:16403915-Intracellular Signaling Peptides and Proteins,
pubmed-meshheading:16403915-Jurkat Cells,
pubmed-meshheading:16403915-Kinetics,
pubmed-meshheading:16403915-Recombinant Fusion Proteins,
pubmed-meshheading:16403915-bcl-X Protein
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pubmed:year |
2006
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pubmed:articleTitle |
HTLV-1 Tax protects against CD95-mediated apoptosis by induction of the cellular FLICE-inhibitory protein (c-FLIP).
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pubmed:affiliation |
Tumorimmunology Program, German Cancer Research Center, Im Neuenheimer Feld 280, 69120 Heidelberg, Germany.
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pubmed:publicationType |
Journal Article,
Research Support, Non-U.S. Gov't
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