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Inhibition of NF‐κB induces a switch from CD95L‐dependent to CD95L‐independent and JNK‐mediated apoptosis in T cells
Author(s) -
Kießling Michael K.,
Linke Björn,
Brechmann Markus,
Süss Dorothee,
Krammer Peter H.,
Gülow Karsten
Publication year - 2010
Publication title -
febs letters
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.593
H-Index - 257
eISSN - 1873-3468
pISSN - 0014-5793
DOI - 10.1016/j.febslet.2010.10.047
Subject(s) - apoptosis , microbiology and biotechnology , downregulation and upregulation , phosphorylation , kinase , t cell receptor , fas receptor , nf κb , chemistry , signal transduction , phosphatase , caspase 8 , caspase , programmed cell death , t cell , biology , immunology , biochemistry , immune system , gene
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.
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