An unexpected role for FosB in activation-induced cell death of T cells.
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.
Baumann
Sven
S
Tumor Immunology Program, Heidelberg, Germany.
Hess
Jochen
J
Eichhorst
Sören T
ST
Krueger
Andreas
A
Angel
Peter
P
Krammer
Peter H
PH
Kirchhoff
Sabine
S
D020121:5' Untranslated Regions / Q000235:genetics*; D001426:Bacterial Proteins / Q000502:physiology*; D019281:Dimerization; D053222:Fas Ligand Protein; D015972:Gene Expression Regulation, Neoplastic; D005799:Genes, Dominant; D016758:Genes, jun; D006801:Humans; D019169:Jurkat Cells / Q000166:cytology / Q000378:metabolism; D008213:Lymphocyte Activation / Q000502:physiology*; D008562:Membrane Glycoproteins / Q000096:biosynthesis / Q000235:genetics* / Q000502:physiology; D009363:Neoplasm Proteins / Q000502:physiology; D011401:Promoter Regions, Genetic / Q000235:genetics; D016760:Proto-Oncogene Proteins c-fos; D016755:Proto-Oncogene Proteins c-jun / Q000502:physiology*; D017260:Receptor-CD3 Complex, Antigen, T-Cell / Q000276:immunology*; D011993:Recombinant Fusion Proteins / Q000502:physiology; D013601:T-Lymphocytes / Q000166:cytology* / Q000378:metabolism; D018808:Transcription Factor AP-1 / Q000502:physiology*; D014162:Transfection; D019014:fas Receptor / Q000502:physiology
D020121:5' Untranslated Regions; D001426:Bacterial Proteins; C505661:FASLG protein, human; C064269:FOSB protein, human; D053222:Fas Ligand Protein; D008562:Membrane Glycoproteins; D009363:Neoplasm Proteins; D016760:Proto-Oncogene Proteins c-fos; D016755:Proto-Oncogene Proteins c-jun; D017260:Receptor-CD3 Complex, Antigen, T-Cell; D011993:Recombinant Fusion Proteins; D018808:Transcription Factor AP-1; D019014:fas Receptor