Toso, a cell surface, specific regulator of Fas-induced apoptosis in T cells.
Fas is a surface receptor that can transmit signals for apoptosis. Using retroviral cDNA library-based functional cloning we identified a gene, toso, that blocks Fas-mediated apoptosis. Toso expression was confined to lymphoid cells and was enhanced after cell-specific activation processes in T cells. Toso appeared limited to inhibition of apoptosis mediated by members of the TNF receptor family and was capable of inhibiting T cell self-killing induced by TCR activation processes that up-regulate Fas ligand. We mapped the effect of Toso to inhibition of caspase-8 processing, the most upstream caspase activity in Fas-mediated signaling, potentially through activation of cFLIP. Toso therefore serves as a novel regulator of Fas-mediated apoptosis and may act as a regulator of cell fate in T cells and other hematopoietic lineages.
Hitoshi
Y
Y
Department of Molecular Pharmacology, Stanford University School of Medicine, California 94305, USA.
Lorens
J
J
Kitada
S I
SI
Fisher
J
J
LaBarge
M
M
Ring
H Z
HZ
Francke
U
U
Reed
J C
JC
Kinoshita
S
S
Nolan
G P
GP
D048868:Adaptor Proteins, Signal Transducing; D000595:Amino Acid Sequence; D017209:Apoptosis / Q000502:physiology*; D051017:Apoptosis Regulatory Proteins; D001483:Base Sequence; D053446:CASP8 and FADD-Like Apoptosis Regulating Protein; D002352:Carrier Proteins / Q000235:genetics / Q000378:metabolism; D053181:Caspase 8; D053453:Caspase 9; D020169:Caspases; D003001:Cloning, Molecular; D003546:Cysteine Endopeptidases / Q000378:metabolism; D017931:DNA Primers / Q000235:genetics; D053200:Fas-Associated Death Domain Protein; D006801:Humans; D047908:Intracellular Signaling Peptides and Proteins; D008213:Lymphocyte Activation; D008565:Membrane Proteins / Q000737:chemistry / Q000235:genetics / Q000502:physiology*; D008969:Molecular Sequence Data; D016133:Polymerase Chain Reaction; D017386:Sequence Homology, Amino Acid; D015398:Signal Transduction; D013601:T-Lymphocytes / Q000166:cytology* / Q000276:immunology / Q000502:physiology*; D014409:Tumor Necrosis Factor-alpha / Q000378:metabolism; D019014:fas Receptor / Q000378:metabolism*
D048868:Adaptor Proteins, Signal Transducing; D051017:Apoptosis Regulatory Proteins; D053446:CASP8 and FADD-Like Apoptosis Regulating Protein; C506386:CFLAR protein, human; D002352:Carrier Proteins; D017931:DNA Primers; C505533:FADD protein, human; C112037:FCMR protein, human; D053200:Fas-Associated Death Domain Protein; D047908:Intracellular Signaling Peptides and Proteins; D008565:Membrane Proteins; D014409:Tumor Necrosis Factor-alpha; D019014:fas Receptor; C505530:CASP8 protein, human; C506433:CASP9 protein, human; D053181:Caspase 8; D053453:Caspase 9; D020169:Caspases; D003546:Cysteine Endopeptidases