| Peroxiredoxin 6 interferes with TRAIL-induced death-inducing signaling complex formation by binding to death effector domain caspase. | |
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MedLine Citation:
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PMID: 20829884 Owner: NLM Status: MEDLINE |
Abstract/OtherAbstract:
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Tumor necrosis factor-related apoptosis-inducing ligand (TRAIL) is a promising cancer therapeutic agent with cancer-selective apoptogenic activity. It evokes the canonical caspase-mediated cell death pathway through death-inducing signaling complex (DISC) formation. We identified that Peroxiredoxin 6 (Prx6) interacts with caspase-10 and caspase-8 via the death effector domain (DED). Prx6 suppresses TRAIL-mediated cell death in human cancer cells, but not that induced by intrinsic apoptosis inducers such as etoposide, staurosporine, or A23187. Among Prx1-6 members, only Prx6 binds to DED caspases and is most effective in suppressing TRAIL or DED caspase-induced cell death. The antiapoptotic activity of Prx6 against TRAIL is not likely associated with its peroxidase activity but is associated with its ability to bind to DED caspases. Increased expression of Prx6 enhances the binding of Prx6 to caspase-10 but reduces TRAIL-induced DISC formation and subsequently caspase activation. Interestingly, Prx6 is highly upregulated in metastatic gastric cancer cells, which are relatively resistant to TRAIL as compared with primary cancer cells. Downregulation of Prx6 sensitizes the metastatic cancer cells to TRAIL-induced cell death. Taken together, these results suggest that Prx6 modulates TRAIL signaling as a negative regulator of caspase-8 and caspase-10 in DISC formation of TRAIL-resistant metastatic cancer cells. |
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Authors:
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H Choi; J-W Chang; Y-K Jung |
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Publication Detail:
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Type: Journal Article; Research Support, Non-U.S. Gov't Date: 2010-09-10 |
Journal Detail:
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Title: Cell death and differentiation Volume: 18 ISSN: 1476-5403 ISO Abbreviation: Cell Death Differ. Publication Date: 2011 Mar |
Date Detail:
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Created Date: 2011-02-14 Completed Date: 2011-05-31 Revised Date: 2012-03-01 |
Medline Journal Info:
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Nlm Unique ID: 9437445 Medline TA: Cell Death Differ Country: England |
Other Details:
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Languages: eng Pagination: 405-14 Citation Subset: IM |
Affiliation:
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Creative Research Initiative (CRI)-Acceleration Research, School of Biological Science/Bio-Max Institute, Seoul National University, 599 Gwanak-ro, Gwanak-gu, Seoul 151-747, Republic of Korea. |
Export Citation:
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| MeSH Terms | |
Descriptor/Qualifier:
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Caspase 10
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chemistry*,
metabolism* Caspase 8 / chemistry*, metabolism* Cell Death / drug effects Death Domain Receptor Signaling Adaptor Proteins / metabolism* Drug Resistance, Neoplasm / drug effects Enzyme Activation / drug effects HeLa Cells Humans Neoplasm Metastasis Peroxiredoxin VI / metabolism* Protein Binding / drug effects Protein Structure, Tertiary Signal Transduction / drug effects Stomach Neoplasms / pathology TNF-Related Apoptosis-Inducing Ligand / pharmacology* Tumor Necrosis Factor-alpha / pharmacology Up-Regulation |
| Chemical | |
Reg. No./Substance:
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0/Death Domain Receptor Signaling Adaptor Proteins; 0/TNF-Related Apoptosis-Inducing Ligand; 0/Tumor Necrosis Factor-alpha; EC 1.11.1.15/Peroxiredoxin VI; EC 3.4.22.-/Caspase 10; EC 3.4.22.-/Caspase 8 |
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine
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