| DJ-1 inhibits TRAIL-induced apoptosis by blocking pro-caspase-8 recruitment to FADD. | |
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MedLine Citation:
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PMID: 21785459 Owner: NLM Status: Publisher |
Abstract/OtherAbstract:
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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. |
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Authors:
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K Fu; H Ren; Y Wang; E Fei; H Wang; G Wang |
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Publication Detail:
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Type: JOURNAL ARTICLE Date: 2011-7-25 |
Journal Detail:
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Title: Oncogene Volume: - ISSN: 1476-5594 ISO Abbreviation: - Publication Date: 2011 Jul |
Date Detail:
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Created Date: 2011-7-25 Completed Date: - Revised Date: - |
Medline Journal Info:
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Nlm Unique ID: 8711562 Medline TA: Oncogene Country: - |
Other Details:
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Languages: ENG Pagination: - Citation Subset: - |
Affiliation:
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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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