Abstract
The CD95 (APO-1/Fas) system plays a major role in induction of apoptosis in lymphoid and nonlymphoid tissues. The CD95 (APO-1/Fas) ligand (CD95L) is induced in response to a variety of signals including TCR/CD3 stimulation or application of chemotherapeutic drugs. Here we report that an AP-1 site located in the 5' untranslated region of the CD95L gene is required for TCR/CD3-mediated induction of the human CD95L promoter. Electrophoretic mobility shift assays using nuclear extracts of Jurkat T cells as well as TCR/CD3-restimulated primary human T cells demonstrated specific binding of AP-1, predominantly composed of c-Jun and FosB, to this sequence. Ectopic expression of transdominant negative Jun mutants strongly reduced CD95L promoter activity and activation-induced cell death (AICD), confirming the functional significance of FosB/c-Jun binding. Thus, our results demonstrate an important novel function for FosB dimerized with c-Jun in TCR/CD3-mediated AICD in human T cells.
Publication types
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Research Support, Non-U.S. Gov't
MeSH terms
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5' Untranslated Regions / genetics*
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Bacterial Proteins / physiology*
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Dimerization
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Fas Ligand Protein
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Gene Expression Regulation, Neoplastic
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Genes, Dominant
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Genes, jun
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Humans
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Jurkat Cells / cytology
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Jurkat Cells / metabolism
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Lymphocyte Activation / physiology*
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Membrane Glycoproteins / biosynthesis
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Membrane Glycoproteins / genetics*
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Membrane Glycoproteins / physiology
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Neoplasm Proteins / physiology
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Promoter Regions, Genetic / genetics
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Proto-Oncogene Proteins c-fos*
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Proto-Oncogene Proteins c-jun / physiology*
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Receptor-CD3 Complex, Antigen, T-Cell / immunology*
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Recombinant Fusion Proteins / physiology
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T-Lymphocytes / cytology*
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T-Lymphocytes / metabolism
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Transcription Factor AP-1 / physiology*
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Transfection
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fas Receptor / physiology
Substances
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5' Untranslated Regions
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Bacterial Proteins
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FASLG protein, human
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FOSB protein, human
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Fas Ligand Protein
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Membrane Glycoproteins
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Neoplasm Proteins
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Proto-Oncogene Proteins c-fos
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Proto-Oncogene Proteins c-jun
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Receptor-CD3 Complex, Antigen, T-Cell
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Recombinant Fusion Proteins
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Transcription Factor AP-1
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fas Receptor