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DJ-1 inhibits TRAIL-induced apoptosis by blocking pro-caspase-8 recruitment to FADD.
MedLine Citation:
PMID:  21785459     Owner:  NLM     Status:  Publisher    
Abstract/OtherAbstract:
DJ-1 was initially identified as an oncogene product involved in human tumorigenesis in cooperation with Ras. Increased DJ-1 expression is associated with tumorigenesis in many cancers, whereas the loss of DJ-1 function is linked to an autosomal recessive form of Parkinson's disease (PD). It has been reported that DJ-1 protects cells from TRAIL (tumor necrosis factor-related apoptosis-inducing ligand)-induced apoptosis. However, the mechanism by which DJ-1 is involved is still largely unknown. Here we show that DJ-1 inhibits TRAIL-induced apoptosis by blocking Fas-associated protein death domain (FADD)-mediated pro-caspase-8 activation. Wild-type DJ-1, but not the PD-associated mutant L166P, binds to FADD to inhibit the formation of the death-inducing signaling complex (DISC). DJ-1 competes with pro-caspase-8 to bind to FADD at the death effector domain, thereby repressing the recruitment and activation of pro-caspase-8 to the active form of caspase-8. Thus, our study suggests that DJ-1 protects against TRAIL-induced apoptosis through the regulation of DISC formation.Oncogene advance online publication, 25 July 2011;doi:10.1038/onc.2011.315.
Authors:
K Fu; H Ren; Y Wang; E Fei; H Wang; G Wang
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Publication Detail:
Type:  JOURNAL ARTICLE     Date:  2011-7-25
Journal Detail:
Title:  Oncogene     Volume:  -     ISSN:  1476-5594     ISO Abbreviation:  -     Publication Date:  2011 Jul 
Date Detail:
Created Date:  2011-7-25     Completed Date:  -     Revised Date:  -    
Medline Journal Info:
Nlm Unique ID:  8711562     Medline TA:  Oncogene     Country:  -    
Other Details:
Languages:  ENG     Pagination:  -     Citation Subset:  -    
Affiliation:
Laboratory of Molecular Neuropathology, Department of Neurobiology, Key Laboratory of Brain Function and Disease and School of Life Sciences, University of Science & Technology of China, Chinese Academy of Sciences, Hefei, Anhui, PR China.
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