Modifications and intracellular trafficking of FADD/MORT1 and caspase-8 after stimulation of T lymphocytes
- Author(s)
- O'Reilly, LA; Divisekera, U; Newton, K; Scalzo, K; Kataoka, T; Puthalakath, H; Ito, M; Huang, DCS; Strasser, A;
- Details
- Publication Year 2004-07,Volume 11,Issue #7,Page 724-736
- Journal Title
- CELL DEATH AND DIFFERENTIATION
- Publication Type
- Journal Article
- Abstract
- 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.
- Publisher
- NATURE PUBLISHING GROUP
- Keywords
- DEATH DOMAIN PROTEIN; DOMINANT INTERFERING MUTANT; FAS-MEDIATED APOPTOSIS; CELL-ACTIVATION; SIGNALING COMPLEX; MEMBRANE RAFTS; BCL-2 FAMILY; TRANSGENIC MICE; MOTOR COMPLEX; LIPID RAFTS
- Publisher's Version
- https://doi.org/10.1038/sj.cdd.4401408
- Terms of Use/Rights Notice
- Refer to copyright notice on published article.
Creation Date: 2004-07-01 12:00:00