FADD/MORT1, a signal transducer that can promote cell death or cell growth.
FADD/MORT1 is a cytosolic adaptor protein which is critical for signalling from CD95 (Fas/APO-1) and certain other members of the tumour necrosis factor receptor (TNF-R) family (called 'death receptors'). Two protein interaction domains have been identified in FADD/MORT1. The C-terminal 'death domain' is needed for recruitment of FADD/MORT1 to ligated 'death receptors' and the N-terminal 'death effector domain' mediates oligomerisation and activation of caspase-8 zymogens. Caspase-8 activates other cysteine proteases by cleavage and this starts a proteolytic cascade which constitutes the 'point of no return' in apoptosis signalling. Experiments in mice lacking FADD/MORT1 function proved that this adaptor is required for CD95- and TNF-RI-transduced cell death but is dispensable for other pathways to apoptosis. Surprisingly, FADD/MORT1 is also essential for mitogen-induced proliferation of T-lymphocytes. Therapeutic activation of FADD/MORT1 function may be used to kill unwanted cells in cancer or autoimmunity and its suppression may help prevent cell death in certain degenerative disorders.
Walter and Eliza Hall Institute of Medical Research, Post Office Royal Melbourne Hospital, Vic., Australia. strasser@wehi.edu.au
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D000818:Animals; D029681:Arabidopsis Proteins; D016923:Cell Death; D002455:Cell Division; D044943:Fatty Acid Desaturases / Q000737:chemistry / Q000502:physiology*; D015870:Gene Expression; D006801:Humans; D051379:Mice; D008822:Mice, Transgenic; D008954:Models, Biological; D011499:Protein Processing, Post-Translational; D015398:Signal Transduction
D029681:Arabidopsis Proteins; D044943:Fatty Acid Desaturases; C084083:Fad7 protein, Arabidopsis