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

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.

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Acknowledgements

We are grateful to Pola Linzmayer, Wolfgang W Müller, Christine Stumpf and Simone Stößer for expert technical assistance. We thank Drs Weigand and Sebens for taking blood samples. We also thank all our blood donors.

This work was supported by grants from Sonderforschungsbereich der deutschen Forschungsgemeinschaft SFB 601 and 405, Deutsches Krebsforschungszentrum/Israeli Minister of Science (DKFZ/MOS) (Ca86), Deutsch-Israelische Projektkooperation (DIP), and the Sander Stiftung.

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Correspondence to Peter H Krammer.

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Baumann, S., Hess, J., Eichhorst, S. et al. An unexpected role for FosB in activation-induced cell death of T cells. Oncogene 22, 1333–1339 (2003). https://doi.org/10.1038/sj.onc.1206126

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