期刊
CELL DEATH AND DIFFERENTIATION
卷 11, 期 7, 页码 724-736出版社
NATURE PUBLISHING GROUP
DOI: 10.1038/sj.cdd.4401408
关键词
apoptosis; caspase-8; FADD(MORT1); monoclonal antibody; signal transduction
资金
- NCI NIH HHS [CA80188] Funding Source: Medline
The adaptor protein FADD/MORT1 is essential for apoptosis induced by 'death receptors', such as Fas (APO-1/CD95), mediating aggregation and autocatalytic activation of caspase-8. Perhaps surprisingly, FADD and caspase-8 are also critical for mitogen-induced proliferation of T lymphocytes. We generated novel monoclonal antibodies specific for mouse FADD and caspase-8 to investigate whether cellular responses, apoptosis or proliferation, might be explained by differences in post-translational modification and subcellular localisation of these proteins. During both apoptosis signalling and mitogenic activation, FADD and caspase-8 aggregated in multiprotein complexes and formed caps at the plasma membrane but they did not colocalise with lipid rafts. Interestingly, mitogenic stimulation, but not Fas ligation, induced a unique post-translational modification of FADD. These different modifications may determine whether FADD and caspase-8 induce cell death or proliferation.
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