Document Detail

The mouse cell surface protein TOSO regulates Fas/Fas ligand-induced apoptosis through its binding to Fas-associated death domain.
MedLine Citation:
PMID:  15632112     Owner:  NLM     Status:  MEDLINE    
Mouse TOSO, the homologue of human TOSO gene, was cloned and characterized in the present study. Using immunofluorescence confocal microscopy we localized TOSO to the cytoplasmic membrane of expressing cells. Using stably transfected mouse TOSO (mTOSO)-expressing Jurkat cells, we show that TOSO protects cells from Fas/Fas ligand- and tumor necrosis factor-induced apoptosis but not from TNF-related apoptosis-inducing ligand-induced apoptosis. The Fas-induced activation of caspase-8 was significantly inhibited by the expression of mTOSO. Using deletion mutants and glutathione S-transferase pull-down approaches, we have shown that mTOSO regulates apoptosis by directly binding to Fas-associated death domain through its C-terminal domain, suggesting the disruption of death-inducing signaling complex formation as mechanism of action. Furthermore, we have expressed mTOSO in transgenic mice and show that mTOSO overexpressing primary T lymphocytes are resistant to Fas/Fas ligand-induced apoptosis.
Yahui Song; Chaim O Jacob
Publication Detail:
Type:  Journal Article; Research Support, Non-U.S. Gov't     Date:  2005-01-04
Journal Detail:
Title:  The Journal of biological chemistry     Volume:  280     ISSN:  0021-9258     ISO Abbreviation:  J. Biol. Chem.     Publication Date:  2005 Mar 
Date Detail:
Created Date:  2005-03-07     Completed Date:  2005-04-19     Revised Date:  2006-11-15    
Medline Journal Info:
Nlm Unique ID:  2985121R     Medline TA:  J Biol Chem     Country:  United States    
Other Details:
Languages:  eng     Pagination:  9618-26     Citation Subset:  IM    
Department of Medicine, University of Southern California School of Medicine, Los Angeles, California 90089, USA.
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MeSH Terms
Amino Acid Sequence
Antigens, CD95 / physiology
Apoptosis Regulatory Proteins
Base Sequence
Carrier Proteins / chemistry*,  genetics,  metabolism*
Cloning, Molecular
DNA Primers
Membrane Proteins / chemistry*,  genetics,  metabolism*
Mice, Transgenic
Molecular Sequence Data
Receptors, Tumor Necrosis Factor / physiology
Sequence Alignment
Sequence Homology, Amino Acid
T-Lymphocytes / physiology*
Reg. No./Substance:
0/Antigens, CD95; 0/Apoptosis Regulatory Proteins; 0/Carrier Proteins; 0/DNA Primers; 0/Fas protein, mouse; 0/Membrane Proteins; 0/Receptors, Tumor Necrosis Factor; 0/TOSO protein, mouse; 0/toso protein, human

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