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rdf:type |
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lifeskim:mentions |
umls-concept:C0017262,
umls-concept:C0035820,
umls-concept:C0037083,
umls-concept:C0079904,
umls-concept:C0185117,
umls-concept:C0205314,
umls-concept:C0332453,
umls-concept:C0385242,
umls-concept:C0679622,
umls-concept:C0851285,
umls-concept:C1710082,
umls-concept:C2911684
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pubmed:issue |
6
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pubmed:dateCreated |
2001-9-6
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pubmed:abstractText |
The NF-kappaB family of transcription factors functions broadly in the host control of immunoregulatory gene expression, inflammation, and apoptosis. Using Jurkat T cells engineered to inducibly express a transdominant repressor of IkappaBalpha, we examined the role of NF-kappaB in the regulation of cytokine and apoptotic gene expression. In this T cell model, as well as in primary T lymphocytes, expression of TNF-related apoptosis-inducing ligand (TRAIL) apoptotic signaling protein was dramatically down-regulated by inhibition of NF-kappaB binding activity. TRAIL acts through membrane death receptors to induce apoptosis of activated T lymphocytes and can be up-regulated by a variety of physiological and pharmacological inducers. However, regulation of TRAIL gene expression has not been defined. Treatment with TCR mimetics (PMA/ionomycin, PHA, and anti-CD3/CD28 Abs) resulted in a rapid increase in the expression of TRAIL mRNA and cell surface TRAIL protein. Induction of the transdominant repressor of IkappaBalpha dramatically down-regulated surface expression of TRAIL, indicating an essential role for NF-kappaB in the regulation of TRAIL. The induced expression of TRAIL was linked to a c-Rel binding site in the proximal TRAIL promoter at position -256 to -265; mutation of this site or an adjacent kappaB site resulted in a complete loss of the inducibility of the TRAIL promoter. The regulation of TRAIL expression by NF-kappaB may represent a general mechanism that contributes to the control of TRAIL-mediated apoptosis in T lymphocytes.
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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/Antibodies, Monoclonal,
http://linkedlifedata.com/resource/pubmed/chemical/Antigens, CD28,
http://linkedlifedata.com/resource/pubmed/chemical/Antigens, CD3,
http://linkedlifedata.com/resource/pubmed/chemical/Apoptosis Regulatory Proteins,
http://linkedlifedata.com/resource/pubmed/chemical/DNA-Binding Proteins,
http://linkedlifedata.com/resource/pubmed/chemical/I-kappa B Proteins,
http://linkedlifedata.com/resource/pubmed/chemical/Ionomycin,
http://linkedlifedata.com/resource/pubmed/chemical/Membrane Glycoproteins,
http://linkedlifedata.com/resource/pubmed/chemical/NF-kappa B,
http://linkedlifedata.com/resource/pubmed/chemical/NF-kappaB inhibitor alpha,
http://linkedlifedata.com/resource/pubmed/chemical/Neoplasm Proteins,
http://linkedlifedata.com/resource/pubmed/chemical/Phytohemagglutinins,
http://linkedlifedata.com/resource/pubmed/chemical/Proto-Oncogene Proteins c-rel,
http://linkedlifedata.com/resource/pubmed/chemical/RNA, Messenger,
http://linkedlifedata.com/resource/pubmed/chemical/RNA, Neoplasm,
http://linkedlifedata.com/resource/pubmed/chemical/Recombinant Fusion Proteins,
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/Tetradecanoylphorbol Acetate,
http://linkedlifedata.com/resource/pubmed/chemical/Tumor Necrosis Factor-alpha
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pubmed:status |
MEDLINE
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pubmed:month |
Sep
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pubmed:issn |
0022-1767
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pubmed:author |
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pubmed:issnType |
Print
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pubmed:day |
15
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pubmed:volume |
167
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pubmed:owner |
NLM
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pubmed:authorsComplete |
Y
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pubmed:pagination |
3164-73
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pubmed:dateRevised |
2008-11-21
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pubmed:meshHeading |
pubmed-meshheading:11544302-Amino Acid Substitution,
pubmed-meshheading:11544302-Antibodies, Monoclonal,
pubmed-meshheading:11544302-Antigens, CD28,
pubmed-meshheading:11544302-Antigens, CD3,
pubmed-meshheading:11544302-Apoptosis,
pubmed-meshheading:11544302-Apoptosis Regulatory Proteins,
pubmed-meshheading:11544302-DNA-Binding Proteins,
pubmed-meshheading:11544302-Gene Expression Regulation,
pubmed-meshheading:11544302-Gene Expression Regulation, Neoplastic,
pubmed-meshheading:11544302-Humans,
pubmed-meshheading:11544302-I-kappa B Proteins,
pubmed-meshheading:11544302-Ionomycin,
pubmed-meshheading:11544302-Jurkat Cells,
pubmed-meshheading:11544302-Membrane Glycoproteins,
pubmed-meshheading:11544302-Mutagenesis, Site-Directed,
pubmed-meshheading:11544302-NF-kappa B,
pubmed-meshheading:11544302-Neoplasm Proteins,
pubmed-meshheading:11544302-Phytohemagglutinins,
pubmed-meshheading:11544302-Promoter Regions, Genetic,
pubmed-meshheading:11544302-Proto-Oncogene Proteins c-rel,
pubmed-meshheading:11544302-RNA, Messenger,
pubmed-meshheading:11544302-RNA, Neoplasm,
pubmed-meshheading:11544302-Recombinant Fusion Proteins,
pubmed-meshheading:11544302-T-Lymphocytes,
pubmed-meshheading:11544302-TNF-Related Apoptosis-Inducing Ligand,
pubmed-meshheading:11544302-Tetradecanoylphorbol Acetate,
pubmed-meshheading:11544302-Transcription, Genetic,
pubmed-meshheading:11544302-Transfection,
pubmed-meshheading:11544302-Tumor Necrosis Factor-alpha
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pubmed:year |
2001
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pubmed:articleTitle |
Disruption of NF-kappaB signaling reveals a novel role for NF-kappaB in the regulation of TNF-related apoptosis-inducing ligand expression.
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pubmed:affiliation |
Terry Fox Molecular Oncology Group, Lady Davis Institute for Medical Research, McGill University, Montreal, Canada.
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pubmed:publicationType |
Journal Article,
Comparative Study,
Research Support, Non-U.S. Gov't
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