Toso, a cell surface, specific regulator of Fas-induced apoptosis in T cells

Immunity. 1998 Apr;8(4):461-71. doi: 10.1016/s1074-7613(00)80551-8.


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.

Publication types

  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Adaptor Proteins, Signal Transducing*
  • Amino Acid Sequence
  • Apoptosis / physiology*
  • Apoptosis Regulatory Proteins
  • Base Sequence
  • CASP8 and FADD-Like Apoptosis Regulating Protein
  • Carrier Proteins / genetics
  • Carrier Proteins / metabolism
  • Caspase 8
  • Caspase 9
  • Caspases*
  • Cloning, Molecular
  • Cysteine Endopeptidases / metabolism
  • DNA Primers / genetics
  • Fas-Associated Death Domain Protein
  • Humans
  • Intracellular Signaling Peptides and Proteins*
  • Lymphocyte Activation
  • Membrane Proteins / chemistry
  • Membrane Proteins / genetics
  • Membrane Proteins / physiology*
  • Molecular Sequence Data
  • Polymerase Chain Reaction
  • Sequence Homology, Amino Acid
  • Signal Transduction
  • T-Lymphocytes / cytology*
  • T-Lymphocytes / immunology
  • T-Lymphocytes / physiology*
  • Tumor Necrosis Factor-alpha / metabolism
  • fas Receptor / metabolism*


  • Adaptor Proteins, Signal Transducing
  • Apoptosis Regulatory Proteins
  • CASP8 and FADD-Like Apoptosis Regulating Protein
  • CFLAR protein, human
  • Carrier Proteins
  • DNA Primers
  • FADD protein, human
  • FCMR protein, human
  • Fas-Associated Death Domain Protein
  • Intracellular Signaling Peptides and Proteins
  • Membrane Proteins
  • Tumor Necrosis Factor-alpha
  • fas Receptor
  • CASP8 protein, human
  • CASP9 protein, human
  • Caspase 8
  • Caspase 9
  • Caspases
  • Cysteine Endopeptidases

Associated data

  • GENBANK/AF057557