| The adaptor protein TRIP6 antagonizes Fas-induced apoptosis but promotes its effect on cell migration. | |
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MedLine Citation:
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PMID: 20876301 Owner: NLM Status: MEDLINE |
Abstract/OtherAbstract:
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The Fas/CD95 receptor mediates apoptosis but is also capable of triggering nonapoptotic signals. However, the mechanisms that selectively regulate these opposing effects are not yet fully understood. Here we demonstrate that the activation of Fas or stimulation with lysophosphatidic acid (LPA) induces cytoskeletal reorganization, leading to the association of Fas with actin stress fibers and the adaptor protein TRIP6. TRIP6 binds to the cytoplasmic juxtamembrane domain of Fas and interferes with the recruitment of FADD to Fas. Furthermore, through physical interactions with NF-κB p65, TRIP6 regulates nuclear translocation and the activation of NF-κB upon Fas activation or LPA stimulation. As a result, TRIP6 antagonizes Fas-induced apoptosis and further enhances the antiapoptotic effect of LPA in cells that express high levels of TRIP6. On the other hand, TRIP6 promotes Fas-mediated cell migration in apoptosis-resistant glioma cells. This effect is regulated via the Src-dependent phosphorylation of TRIP6 at Tyr-55. As TRIP6 is overexpressed in glioblastomas, this may have a significant impact on enhanced NF-κB activity, resistance to apoptosis, and Fas-mediated cell invasion in glioblastomas. |
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Authors:
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Yun-Ju Lai; Victor T G Lin; Ying Zheng; Etty N Benveniste; Fang-Tsyr Lin |
Publication Detail:
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Type: Journal Article; Research Support, N.I.H., Extramural; Research Support, Non-U.S. Gov't Date: 2010-09-27 |
Journal Detail:
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Title: Molecular and cellular biology Volume: 30 ISSN: 1098-5549 ISO Abbreviation: Mol. Cell. Biol. Publication Date: 2010 Dec |
Date Detail:
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Created Date: 2010-11-08 Completed Date: 2010-12-06 Revised Date: 2011-07-28 |
Medline Journal Info:
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Nlm Unique ID: 8109087 Medline TA: Mol Cell Biol Country: United States |
Other Details:
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Languages: eng Pagination: 5582-96 Citation Subset: IM |
Affiliation:
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Department of Cell Biology, University of Alabama at Birmingham, Birmingham, Alabama 35294-0005, USA. |
Export Citation:
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APA/MLA Format Download EndNote Download BibTex |
| MeSH Terms | |
Descriptor/Qualifier:
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Actins
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metabolism Active Transport, Cell Nucleus Adaptor Proteins, Signal Transducing / chemistry, genetics, physiology* Antigens, CD95 / chemistry, genetics, physiology* Apoptosis / drug effects, genetics, physiology* Cell Line, Tumor Cell Movement / drug effects, genetics, physiology* Fas-Associated Death Domain Protein / genetics, physiology Glioma / genetics, pathology, physiopathology HEK293 Cells Humans Lysophospholipids / pharmacology Models, Biological Neoplasm Invasiveness / genetics, physiopathology Phosphorylation Signal Transduction Transcription Factor RelA / genetics, physiology Transcription Factors / chemistry, genetics, physiology* Tyrosine / chemistry |
| Grant Support | |
ID/Acronym/Agency:
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CA13148-35/CA/NCI NIH HHS; NS066332/NS/NINDS NIH HHS; T32-NS48039/NS/NINDS NIH HHS |
| Chemical | |
Reg. No./Substance:
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0/Actins; 0/Adaptor Proteins, Signal Transducing; 0/Antigens, CD95; 0/FADD protein, human; 0/FAS protein, human; 0/Fas-Associated Death Domain Protein; 0/Lysophospholipids; 0/RELA protein, human; 0/Transcription Factor RelA; 0/Transcription Factors; 0/thyroid-hormone-receptor interacting protein; 22002-87-5/lysophosphatidic acid; 55520-40-6/Tyrosine |
| Comments/Corrections | |
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