Cellular FLIP Long Form Augments Caspase Activity and Death of T Cells through Heterodimerization with and Activation of Caspase-8
Copyright policy )Cellular FLIP Long Form Augments Caspase Activity and Death of T Cells through Heterodimerization with and Activation of Caspase-8
AbstractCaspase activity is required not only for the death of T cells, but also for their activation. A delicate balance of caspase activity is thus required during T cell activation at a level that will not drive cell death. How caspase activity is initiated and regulated during T cell activation is not known. One logical candidate for this process is cellular FLIP long form (c-FLIPL), because it can block caspase-8 recruitment after Fas (CD95) ligation as well as directly heterodimerize with and activate caspase-8. The current findings demonstrate that after T cell activation, caspase-8 and c-FLIPL associate in a complex enriched for active caspases. This occurs coincidently with the cleavage of two known caspase-8 substrates, c-FLIPL and receptor interacting protein 1. Caspase activity is higher in wild-type CD8+ than CD4+ effector T cells. Increased expression of c-FLIPL results in augmented caspase activity in resting and effector T cells to levels that provoke cell death, especially of the CD8 subset. c-FLIPL is thus not only an inhibitor of cell death by Fas, it can also act as a principal activator of caspases independently of Fas.
- Institute of Biochemistry Switzerland
- University of Lausanne Switzerland
- ETH Zurich Switzerland
- University of Vermont United States
CD4-Positive T-Lymphocytes, Caspase 8, DNA, Complementary, Base Sequence, Cell Death, T-Lymphocytes, CASP8 and FADD-Like Apoptosis Regulating Protein, Intracellular Signaling Peptides and Proteins, Mice, Transgenic, CD8-Positive T-Lymphocytes, In Vitro Techniques, Lymphocyte Activation, Enzyme Activation, Mice, Inbred C57BL, Mice, Caspases, Animals, fas Receptor, Dimerization, Cell Proliferation
CD4-Positive T-Lymphocytes, Caspase 8, DNA, Complementary, Base Sequence, Cell Death, T-Lymphocytes, CASP8 and FADD-Like Apoptosis Regulating Protein, Intracellular Signaling Peptides and Proteins, Mice, Transgenic, CD8-Positive T-Lymphocytes, In Vitro Techniques, Lymphocyte Activation, Enzyme Activation, Mice, Inbred C57BL, Mice, Caspases, Animals, fas Receptor, Dimerization, Cell Proliferation
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