| Modulation of the Fas-apoptosis-signalling pathway by functional polymorphisms at Fas, FasL and Fadd and their implication in T-cell lymphoblastic lymphoma susceptibility. | |
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MedLine Citation:
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PMID: 20889682 Owner: NLM Status: MEDLINE |
Abstract/OtherAbstract:
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In previous reports, we described germ line functional polymorphisms that differentiate Fas and FasL genes in two mouse strains (SEG/Pas and C57BL/6J) exhibiting extreme differences in susceptibility to γ radiation-induced T-cell lymphomas. Here, we provide new data reinforcing the importance of the extrinsic pathway of apoptosis mediated by Fas in T-cell lymphoma development and about the functional significance of polymorphisms located at intracellular and extracellular domains of Fas and FasL. Using DNA recombinant technology, we generate chimerical Fas and FasL proteins by combination of protein regions derived from the two strains and demonstrate that any Fas-FasL interaction involving chimerical proteins drive cell apoptosis to a significant lower extent than the wild-type SEG/Pas and C57BL/6J Fas-FasL systems. In addition, we report new polymorphisms in the coding sequence of Fadd and demonstrate that the interaction between Fas and Fadd is significantly stronger if Fas and Fadd are of SEG/Pas origin compared with the C57BL/6J system. Altogether, these results suggest a model in which functional polymorphisms at the three genes collaborate on the global ability of the Fas/FasL system to induce apoptosis. A complete analysis of these three genes in the pathway appears to be a sine qua non condition to accurately predict the effectiveness of the Fas system and to estimate susceptibility to T-cell lymphoma. |
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Authors:
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María Villa-Morales; Elena González-Gugel; Marta N Shahbazi; Javier Santos; José Fernández-Piqueras |
Publication Detail:
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Type: Journal Article; Research Support, Non-U.S. Gov't Date: 2010-10-01 |
Journal Detail:
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Title: Carcinogenesis Volume: 31 ISSN: 1460-2180 ISO Abbreviation: Carcinogenesis Publication Date: 2010 Dec |
Date Detail:
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Created Date: 2010-12-01 Completed Date: 2011-01-06 Revised Date: - |
Medline Journal Info:
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Nlm Unique ID: 8008055 Medline TA: Carcinogenesis Country: England |
Other Details:
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Languages: eng Pagination: 2165-71 Citation Subset: IM |
Affiliation:
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Área de Biología Celular e Inmunología, Centro de Biología Molecular Severo Ochoa (CBMSO), Consejo Superior de Investigaciones Científicas-Universidad Autónoma de Madrid, Nicolás Cabrera 1, 28049-Madrid, Spain. |
Export Citation:
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| MeSH Terms | |
Descriptor/Qualifier:
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Animals Antigens, CD95 / genetics*, physiology Apoptosis* Fas Ligand Protein / genetics*, physiology Fas-Associated Death Domain Protein / chemistry, genetics*, physiology Genetic Predisposition to Disease* HEK293 Cells Humans In Situ Nick-End Labeling Mice Mice, Inbred C57BL Polymorphism, Genetic* Precursor T-Cell Lymphoblastic Leukemia-Lymphoma / etiology*, genetics Signal Transduction / physiology* |
| Chemical | |
Reg. No./Substance:
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0/Antigens, CD95; 0/Fas Ligand Protein; 0/Fas-Associated Death Domain Protein |
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine
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