Inhibition of NF‐κB induces a switch from CD95L‐dependent to CD95L‐independent and JNK‐mediated apoptosis in T cells
Copyright policy )Inhibition of NF‐κB induces a switch from CD95L‐dependent to CD95L‐independent and JNK‐mediated apoptosis in T cells
NF‐κB is a crucial transcription factor regulating apoptosis sensitivity and resistance. It has been shown that inhibition of NF‐κB in T lymphocytes leads to sensitization towards apoptosis. The underlying molecular mechanism is not entirely understood. Therefore, we investigated T cell receptor (TCR) stimulated apoptosis in T cells in which NF‐κB activity is blocked by an inhibitor or IκBα overexpression. We show that enhanced apoptosis upon TCR stimulation is caspase‐ and JNK‐dependent, but independent of the CD95/CD95L system. Generation of reactive oxygen species (ROS) induced sustained JNK phosphorylation by inactivation of MAP kinase phosphatase 7 (MKP7). Sustained JNK activation causes upregulation of the pro‐apototic protein BIM. Thus, inhibition of NF‐κB causes a switch from classical activation‐induced cell death (AICD) to CD95L‐independent apoptosis.
Fas Ligand Protein, MAP kinase phosphatase, T-Lymphocytes, Receptors, Antigen, T-Cell, Apoptosis, Gene Expression Regulation, Enzymologic, Jurkat Cells, Proto-Oncogene Proteins, Humans, Bcl-2-Like Protein 11, T cell receptor signaling, Ionomycin, JNK Mitogen-Activated Protein Kinases, NF-kappa B, Membrane Proteins, I-kappa B Kinase, Enzyme Activation, Dual-Specificity Phosphatases, Mitogen-Activated Protein Kinase Phosphatases, JNK, Reactive oxygen species, Apoptosis Regulatory Proteins, Reactive Oxygen Species, Signal Transduction
Fas Ligand Protein, MAP kinase phosphatase, T-Lymphocytes, Receptors, Antigen, T-Cell, Apoptosis, Gene Expression Regulation, Enzymologic, Jurkat Cells, Proto-Oncogene Proteins, Humans, Bcl-2-Like Protein 11, T cell receptor signaling, Ionomycin, JNK Mitogen-Activated Protein Kinases, NF-kappa B, Membrane Proteins, I-kappa B Kinase, Enzyme Activation, Dual-Specificity Phosphatases, Mitogen-Activated Protein Kinase Phosphatases, JNK, Reactive oxygen species, Apoptosis Regulatory Proteins, Reactive Oxygen Species, Signal Transduction
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