Elevated A20 promotes TNF-induced and RIPK1-dependent intestinal epithelial cell death.
DC Field | Value | Language |
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dc.contributor.author | Garcia-Carbonell, Ricard | - |
dc.contributor.author | Wong, Jerry | - |
dc.contributor.author | Kim, Ju Youn | - |
dc.contributor.author | Close, Lisa Abernathy | - |
dc.contributor.author | Boland, Brigid S. | - |
dc.contributor.author | Wong, Thomas L. | - |
dc.contributor.author | Harris, Philip A. | - |
dc.contributor.author | Ho, Samuel B. | - |
dc.contributor.author | Das, Soumita | - |
dc.contributor.author | Ernst, Peter B. | - |
dc.contributor.author | Sasik, Roman | - |
dc.contributor.author | Sandborn, William J. | - |
dc.contributor.author | Bertin, John | - |
dc.contributor.author | Gough, Pete J. | - |
dc.contributor.author | Chang, John T. | - |
dc.contributor.author | Kelliher, Michelle | - |
dc.contributor.author | Boone, David | - |
dc.contributor.author | Guma, Monica | - |
dc.contributor.author | Karin, Michael | - |
dc.date.accessioned | 2023-08-16T07:40:32Z | - |
dc.date.available | 2023-08-16T07:40:32Z | - |
dc.date.issued | 2018-09 | - |
dc.identifier.issn | 0027-8424 | - |
dc.identifier.issn | 1091-6490 | - |
dc.identifier.uri | https://scholarworks.bwise.kr/erica/handle/2021.sw.erica/114020 | - |
dc.description.abstract | Intestinal epithelial cell (IEC) death is a common feature of inflammatory bowel disease (IBD) that triggers inflammation by compromising barrier integrity. In many patients with IBD, epithelial damage and inflammation are TNF-dependent. Elevated TNF production in IBD is accompanied by increased expression of the TNFAIP3 gene, which encodes A20, a negative feedback regulator of NF-κB. A20 in intestinal epithelium from patients with IBD coincided with the presence of cleaved caspase-3, and A20 transgenic (Tg) mice, in which A20 is expressed from an IEC-specific promoter, were highly susceptible to TNF-induced IEC death, intestinal damage, and shock. A20-expressing intestinal organoids were also susceptible to TNF-induced death, demonstrating that enhanced TNF-induced apoptosis was a cell-autonomous property of A20. This effect was dependent on Receptor Interacting Protein Kinase 1 (RIPK1) activity, and A20 was found to associate with the Ripoptosome complex, potentiating its ability to activate caspase- 8. A20-potentiated RIPK1-dependent apoptosis did not require the A20 deubiquitinase (DUB) domain and zinc finger 4 (ZnF4), which mediate NF-κB inhibition in fibroblasts, but was strictly dependent on ZnF7 and A20 dimerization. We suggest that A20 dimers bind linear ubiquitin to stabilize the Ripoptosome and potentiate its apoptosis-inducing activity. © 2018 National Academy of Sciences. All rights reserved. | - |
dc.language | 영어 | - |
dc.language.iso | ENG | - |
dc.publisher | National Academy of Sciences | - |
dc.title | Elevated A20 promotes TNF-induced and RIPK1-dependent intestinal epithelial cell death. | - |
dc.type | Article | - |
dc.publisher.location | 미국 | - |
dc.identifier.doi | 10.1073/pnas.1810584115 | - |
dc.identifier.scopusid | 2-s2.0-85054034649 | - |
dc.identifier.wosid | 000445545200020 | - |
dc.identifier.bibliographicCitation | Proceedings of the National Academy of Sciences of the United States of America, v.115, no.39, pp E9192 - E9200 | - |
dc.citation.title | Proceedings of the National Academy of Sciences of the United States of America | - |
dc.citation.volume | 115 | - |
dc.citation.number | 39 | - |
dc.citation.startPage | E9192 | - |
dc.citation.endPage | E9200 | - |
dc.type.docType | 정기학술지(Article(Perspective Article포함)) | - |
dc.description.isOpenAccess | N | - |
dc.description.journalRegisteredClass | sci | - |
dc.description.journalRegisteredClass | scie | - |
dc.description.journalRegisteredClass | scopus | - |
dc.relation.journalResearchArea | Science & Technology - Other Topics | - |
dc.relation.journalWebOfScienceCategory | Multidisciplinary Sciences | - |
dc.subject.keywordAuthor | A20 | - |
dc.subject.keywordAuthor | Apoptosis | - |
dc.subject.keywordAuthor | Inflammatory bowel disease | - |
dc.subject.keywordAuthor | Intestinal epithelial cells | - |
dc.subject.keywordAuthor | RIPK1 | - |
dc.identifier.url | https://www.scopus.com/record/display.uri?eid=2-s2.0-85054034649&origin=inward&txGid=d9bb5b20922f8cb298be582d2aa3a334 | - |
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