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Oncogene. 2003 Mar 6;22(9):1333-9.

An unexpected role for FosB in activation-induced cell death of T cells.

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1
Tumor Immunology Program, Heidelberg, Germany.

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.

PMID:
12618758
DOI:
10.1038/sj.onc.1206126
[Indexed for MEDLINE]
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