| Prominent dominant negative effect of a mutant Fas molecule lacking death domain on cell-mediated induction of apoptosis. | |
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MedLine Citation:
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PMID: 15488945 Owner: NLM Status: MEDLINE |
Abstract/OtherAbstract:
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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. |
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Authors:
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Aya Yokota; Emiko Takeuchi; Misao Iizuka; Yuko Ikegami; Hajime Takayama; Nobukata Shinohara |
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Publication Detail:
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Type: Journal Article |
Journal Detail:
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Title: Molecular immunology Volume: 42 ISSN: 0161-5890 ISO Abbreviation: Mol. Immunol. Publication Date: 2005 Jan |
Date Detail:
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Created Date: 2004-10-18 Completed Date: 2005-01-13 Revised Date: 2006-11-15 |
Medline Journal Info:
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Nlm Unique ID: 7905289 Medline TA: Mol Immunol Country: England |
Other Details:
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Languages: eng Pagination: 71-8 Citation Subset: IM |
Affiliation:
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Department of Immunology, Kitasato University School of Medicine, 1-15-1 Kitasato, Sagamihara, Kanagawa 228-8555, Japan. |
Export Citation:
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| MeSH Terms | |
Descriptor/Qualifier:
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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:
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0/Antibodies, Monoclonal; 0/Antigens, CD95; 0/Fas Ligand Protein; 0/Fasl protein, mouse; 0/Membrane Glycoproteins |
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine
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