Document Detail


Prominent dominant negative effect of a mutant Fas molecule lacking death domain on cell-mediated induction of apoptosis.
MedLine Citation:
PMID:  15488945     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
Using a panel of transfectant B lymphoma cells expressing varying amounts of the mutant Fas together with the endogenous wild type Fas, semi-quantitative studies on the dominant negative effect of a murine mutant Fas molecule lacking death domain were carried out. In anti-Fas antibody-mediated induction of apoptosis, the mutant molecules exerted significant dominant-negative effect only when their expression level was comparable to or higher than that of wild type molecules, or when exposed to low amounts of the antibody. The inhibitory effect was accompanied by the failure in DISC formation in spite of Fas aggregation. When they were subjected to T cell-mediated Fas-based induction of apoptosis, however, the dominant negative effect was prominent such that the expression of even a small amount of the mutant molecules resulted in significant inhibition. Such a strong inhibitory effect explains the dominant phenotype of this type of mutant Fas molecules in ALPS heterozygous patients and also implies that the physiological effectors for Fas in vivo are cells, i.e., FasL-expressing activated T cells.
Authors:
Aya Yokota; Emiko Takeuchi; Misao Iizuka; Yuko Ikegami; Hajime Takayama; Nobukata Shinohara
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Publication Detail:
Type:  Journal Article    
Journal Detail:
Title:  Molecular immunology     Volume:  42     ISSN:  0161-5890     ISO Abbreviation:  Mol. Immunol.     Publication Date:  2005 Jan 
Date Detail:
Created Date:  2004-10-18     Completed Date:  2005-01-13     Revised Date:  2006-11-15    
Medline Journal Info:
Nlm Unique ID:  7905289     Medline TA:  Mol Immunol     Country:  England    
Other Details:
Languages:  eng     Pagination:  71-8     Citation Subset:  IM    
Affiliation:
Department of Immunology, Kitasato University School of Medicine, 1-15-1 Kitasato, Sagamihara, Kanagawa 228-8555, Japan.
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MeSH Terms
Descriptor/Qualifier:
Animals
Antibodies, Monoclonal / pharmacology
Antigens, CD95 / chemistry,  genetics*,  physiology
Apoptosis / genetics*
Cell Communication
Cell Line, Tumor
Fas Ligand Protein
Genes, Dominant / physiology*
Lymphoma, B-Cell / pathology
Membrane Glycoproteins / pharmacology
Mice
Mutation*
Phenotype
Protein Structure, Tertiary
Signal Transduction / drug effects
T-Lymphocytes / physiology
Transfection
Chemical
Reg. No./Substance:
0/Antibodies, Monoclonal; 0/Antigens, CD95; 0/Fas Ligand Protein; 0/Fasl protein, mouse; 0/Membrane Glycoproteins

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