Requirement for Casper (c-FLIP) in Regulation of Death Receptor–Induced Apoptosis and Embryonic Development
Copyright policy )Requirement for Casper (c-FLIP) in Regulation of Death Receptor–Induced Apoptosis and Embryonic Development
Casper (c-FLIP) associates with FADD and caspase-8 in signaling complexes downstream of death receptors like Fas. We generated Casper-deficient mice and cells and noted a duality in the physiological functions of this molecule. casper-/- embryos do not survive past day 10.5 of embryogenesis and exhibit impaired heart development. This phenotype is reminiscent of that reported for FADD-/- and caspase-8-/- embryos. However, unlike FADD-/- and caspase-8-/- cells, casper-/- embryonic fibroblasts are highly sensitive to FasL- or TNF-induced apoptosis and show rapid induction of caspase activities. NF-kappaB and JNK/SAPK activation is intact in TNF-stimulated casper-/- cells. These results suggest that Casper has two distinct roles: to cooperate with FADD and caspase-8 during embryonic development and to mediate cytoprotection against death factor-induced apoptosis.
- Amgen (United States) United States
- University of Colorado Cancer Center United States
- Ontario Institute for Cancer Research Canada
- Amgen (Canada) Canada
- University of Toronto Canada
Male, Immunology, CASP8 and FADD-Like Apoptosis Regulating Protein, Apoptosis, Cell Line, Embryonic and Fetal Development, Mice, Immunology and Allergy, Animals, Mice, Knockout, Caspase 8, Caspase 3, Intracellular Signaling Peptides and Proteins, JNK Mitogen-Activated Protein Kinases, Heart, Caspase 9, Enzyme Activation, Mice, Inbred C57BL, Infectious Diseases, Caspases, Female, Mitogen-Activated Protein Kinases, Carrier Proteins
Male, Immunology, CASP8 and FADD-Like Apoptosis Regulating Protein, Apoptosis, Cell Line, Embryonic and Fetal Development, Mice, Immunology and Allergy, Animals, Mice, Knockout, Caspase 8, Caspase 3, Intracellular Signaling Peptides and Proteins, JNK Mitogen-Activated Protein Kinases, Heart, Caspase 9, Enzyme Activation, Mice, Inbred C57BL, Infectious Diseases, Caspases, Female, Mitogen-Activated Protein Kinases, Carrier Proteins
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