The apoptosis inhibitory domain of FE65-like protein 1 regulates both apoptotic and caspase-independent programmed cell death mediated by tumor necrosis factor.
Tumor necrosis factor (TNF) can induce caspase-dependent (apoptotic) and caspase-independent pathways to programmed cell death (PCD). Here, we demonstrate that stable transfection of a cDNA encompassing the C-terminal apoptosis inhibitory domain (AID) of FE65-like protein 1 into mouse L929 fibrosarcoma cells protects from caspase-independent as well as from apoptotic PCD induced by TNF. We show that the AID does not protect from caspase-independent PCD elicited by 1-methyl-3-nitro-1-nitrosoguanidine, suggesting that the AID might prevent cell death by affecting assembly of the death inducing signaling complex of the 55 kDa TNF receptor or clustering of the receptor itself. Interference with caspase-independent PCD mediated by the sphingolipid ceramide further increases protection conferred by the AID, as does the antioxidant butylated hydroxyanisole, implicating ceramide and reactive oxygen species as potential factors interacting with caspase-independent PCD regulated by the AID.
Lange
Arne
A
Institut für Immunologie, Universitätsklinikum Schleswig-Holstein Campus Kiel, Michaelisstr. 5, 24105 Kiel, Germany.
Thon
Lutz
L
Mathieu
Sabine
S
Adam
Dieter
D
D048868:Adaptor Proteins, Signal Transducing / Q000737:chemistry* / Q000378:metabolism; D000595:Amino Acid Sequence; D000818:Animals; D000975:Antioxidants / Q000494:pharmacology; D017209:Apoptosis; D001483:Base Sequence; D020169:Caspases / Q000378:metabolism*; D016923:Cell Death; D002460:Cell Line; D045744:Cell Line, Tumor; D002470:Cell Survival; D002518:Ceramides / Q000378:metabolism; D003001:Cloning, Molecular; D004305:Dose-Response Relationship, Drug; D005822:Genetic Vectors; D006801:Humans; D015151:Immunoblotting; D051379:Mice; D008969:Molecular Sequence Data; D009604:Nitrosoguanidines / Q000494:pharmacology; D016133:Polymerase Chain Reaction; D017434:Protein Structure, Tertiary; D017382:Reactive Oxygen Species; D017386:Sequence Homology, Amino Acid; D013107:Sphingolipids / Q000737:chemistry; D013997:Time Factors; D014162:Transfection; D014409:Tumor Necrosis Factor-alpha / Q000378:metabolism*
C466684:APBB2 protein, human; D048868:Adaptor Proteins, Signal Transducing; D000975:Antioxidants; D002518:Ceramides; D009604:Nitrosoguanidines; D017382:Reactive Oxygen Species; D013107:Sphingolipids; D014409:Tumor Necrosis Factor-alpha; C063048:1,3-dimethyl-2-cyano-1-nitrosoguanidine; D020169:Caspases