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http://hdl.handle.net/2445/190635
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DC Field | Value | Language |
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dc.contributor.author | Fernández-Majada, Vanesa | - |
dc.contributor.author | Welz, Patrick-Simon | - |
dc.contributor.author | Ermolaeva, Maria | - |
dc.contributor.author | Schell, Michael | - |
dc.contributor.author | Adam, Alexander | - |
dc.contributor.author | Dietlein, Felix | - |
dc.contributor.author | Komander, David | - |
dc.contributor.author | Büttner, Reinhard | - |
dc.contributor.author | Thomas, Roman K. | - |
dc.contributor.author | Schumacher, Björn | - |
dc.contributor.author | Pasparakis, Manolis | - |
dc.date.accessioned | 2022-11-09T17:37:07Z | - |
dc.date.available | 2022-11-09T17:37:07Z | - |
dc.date.issued | 2016 | - |
dc.identifier.issn | 2041-1723 | - |
dc.identifier.uri | http://hdl.handle.net/2445/190635 | - |
dc.description.abstract | The tumour suppressor CYLD is a deubiquitinase previously shown to inhibit NF-κB, MAP kinase and Wnt signalling. However, the tumour suppressing mechanisms of CYLD remain poorly understood. Here we show that loss of CYLD catalytic activity causes impaired DNA damage-induced p53 stabilization and activation in epithelial cells and sensitizes mice to chemical carcinogen-induced intestinal and skin tumorigenesis. Mechanistically, CYLD interacts with and deubiquitinates p53 facilitating its stabilization in response to genotoxic stress. Ubiquitin chain-restriction analysis provides evidence that CYLD removes K48 ubiquitin chains from p53 indirectly by cleaving K63 linkages, suggesting that p53 is decorated with complex K48/K63 chains. Moreover, CYLD deficiency also diminishes CEP-1/p53-dependent DNA damage-induced germ cell apoptosis in the nematode Caenorhabditis elegans. Collectively, our results identify CYLD as a deubiquitinase facilitating DNA damage-induced p53 activation and suggest that regulation of p53 responses to genotoxic stress contributes to the tumour suppressor function of CYLD. | - |
dc.format.extent | 14 p. | - |
dc.format.mimetype | application/pdf | - |
dc.language.iso | eng | - |
dc.publisher | Nature Publishing Group | - |
dc.relation.isformatof | Reproducció del document publicat a: https://doi.org/10.1038/ncomms12508 | - |
dc.relation.ispartof | Nature Communications, 2016, vol. 7 | - |
dc.relation.uri | https://doi.org/10.1038/ncomms12508 | - |
dc.rights | cc-by (c) Fernández-Majada, Vanesa et al., 2016 | - |
dc.rights.uri | https://creativecommons.org/licenses/by/4.0/ | - |
dc.source | Articles publicats en revistes (Patologia i Terapèutica Experimental) | - |
dc.subject.classification | Apoptosi | - |
dc.subject.classification | Carcinogènesi | - |
dc.subject.classification | Experimentació animal | - |
dc.subject.other | Apoptosis | - |
dc.subject.other | Carcinogenesis | - |
dc.subject.other | Animal experimentation | - |
dc.title | The tumor suppressor CYLD regulates the p53 DNA damage response | - |
dc.type | info:eu-repo/semantics/article | - |
dc.type | info:eu-repo/semantics/publishedVersion | - |
dc.identifier.idgrec | 700997 | - |
dc.date.updated | 2022-11-09T17:37:07Z | - |
dc.relation.projectID | info:eu-repo/grantAgreement/EC/FP7/223151/EU//INFLA-CARE | - |
dc.relation.projectID | info:eu-repo/grantAgreement/EC/FP7/260383/EU//GENSTAGE | - |
dc.relation.projectID | info:eu-repo/grantAgreement/EC/FP7/309756/EU//UBSPECIFIC | - |
dc.relation.projectID | info:eu-repo/grantAgreement/EC/FP7/316354/EU//CODEAGE | - |
dc.relation.projectID | info:eu-repo/grantAgreement/EC/FP7/316390/EU//ADDRESS | - |
dc.relation.projectID | info:eu-repo/grantAgreement/EC/FP7/316964/EU//MARRIAGE | - |
dc.relation.projectID | info:eu-repo/grantAgreement/EC/FP7/323040/EU//EPINFLAM | - |
dc.rights.accessRights | info:eu-repo/semantics/openAccess | - |
dc.identifier.pmid | 27561390 | - |
Appears in Collections: | Articles publicats en revistes (Patologia i Terapèutica Experimental) |
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700997.pdf | 1.58 MB | Adobe PDF | View/Open |
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