Document Detail

The adaptor protein TRIP6 antagonizes Fas-induced apoptosis but promotes its effect on cell migration.
MedLine Citation:
PMID:  20876301     Owner:  NLM     Status:  MEDLINE    
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.
Yun-Ju Lai; Victor T G Lin; Ying Zheng; Etty N Benveniste; Fang-Tsyr Lin
Publication Detail:
Type:  Journal Article; Research Support, N.I.H., Extramural; Research Support, Non-U.S. Gov't     Date:  2010-09-27
Journal Detail:
Title:  Molecular and cellular biology     Volume:  30     ISSN:  1098-5549     ISO Abbreviation:  Mol. Cell. Biol.     Publication Date:  2010 Dec 
Date Detail:
Created Date:  2010-11-08     Completed Date:  2010-12-06     Revised Date:  2013-07-03    
Medline Journal Info:
Nlm Unique ID:  8109087     Medline TA:  Mol Cell Biol     Country:  United States    
Other Details:
Languages:  eng     Pagination:  5582-96     Citation Subset:  IM    
Department of Cell Biology, University of Alabama at Birmingham, Birmingham, Alabama 35294-0005, USA.
Export Citation:
APA/MLA Format     Download EndNote     Download BibTex
MeSH Terms
Actins / 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
LIM Domain Proteins
Lysophospholipids / pharmacology
Models, Biological
Neoplasm Invasiveness / genetics,  physiopathology
Signal Transduction
Transcription Factor RelA / genetics,  physiology
Transcription Factors / chemistry,  genetics,  physiology*
Tyrosine / chemistry
Grant Support
Reg. No./Substance:
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/LIM Domain Proteins; 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

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine

Previous Document:  Progesterone receptor induces ErbB-2 nuclear translocation to promote breast cancer growth via a nov...
Next Document:  Why Dom34 stimulates growth of cells with defects of 40S ribosomal subunit biosynthesis.