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http://hdl.handle.net/2445/171364
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DC Field | Value | Language |
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dc.contributor.author | Colomer, Carlota | - |
dc.contributor.author | Margalef, Pol | - |
dc.contributor.author | Villanueva Garatachea, Alberto | - |
dc.contributor.author | Vert, Anna | - |
dc.contributor.author | Pecharroman, Irene | - |
dc.contributor.author | Sole, Laura | - |
dc.contributor.author | González Farré, Mónica | - |
dc.contributor.author | Alonso, Josune | - |
dc.contributor.author | Montagut Viladot, Clara | - |
dc.contributor.author | Martínez Iniesta, María | - |
dc.contributor.author | Bertran, Joan | - |
dc.contributor.author | Borràs, Eva | - |
dc.contributor.author | Iglesias, Mar | - |
dc.contributor.author | Sabidó Aguadé, Eduard | - |
dc.contributor.author | Bigas Salvans, Anna | - |
dc.contributor.author | Boulton, Simon J. | - |
dc.contributor.author | Espinosa, Lluís | - |
dc.date.accessioned | 2020-10-20T13:42:44Z | - |
dc.date.available | 2020-10-20T13:42:44Z | - |
dc.date.issued | 2019-08-22 | - |
dc.identifier.uri | http://hdl.handle.net/2445/171364 | - |
dc.description.abstract | Phosphorylated IKKα(p45) is a nuclear active form of the IKKα kinase that is induced by the MAP kinases BRAF and TAK1 and promotes tumor growth independent of canonical NF-κB signaling. Insights into the sources of IKKα(p45) activation and its downstream substrates in the nucleus remain to be defined. Here, we discover that IKKα(p45) is rapidly activated by DNA damage independent of ATM-ATR, but dependent on BRAF-TAK1-p38-MAPK, and is required for robust ATM activation and efficient DNA repair. Abolishing BRAF or IKKα activity attenuates ATM, Chk1, MDC1, Kap1, and 53BP1 phosphorylation, compromises 53BP1 and RIF1 co-recruitment to sites of DNA lesions, and inhibits 53BP1-dependent fusion of dysfunctional telomeres. Furthermore, IKKα or BRAF inhibition synergistically enhances the therapeutic potential of 5-FU and irinotecan to eradicate chemotherapy-resistant metastatic human tumors in vivo. Our results implicate BRAF and IKKα kinases in the DDR and reveal a combination strategy for cancer treatment. | - |
dc.format.extent | 20 p. | - |
dc.format.mimetype | application/pdf | - |
dc.language.iso | eng | - |
dc.publisher | Cell Press | - |
dc.relation.isformatof | Reproducció del document publicat a: https://doi.org/10.1016/j.molcel.2019.05.036 | - |
dc.relation.ispartof | Molecular Cell, 2019, vol. 75, num. 4, p. 669-682 | - |
dc.relation.uri | https://doi.org/10.1016/j.molcel.2019.05.036 | - |
dc.rights | cc by-nc-nd (c) Colomer et al., 2019 | - |
dc.rights.uri | http://creativecommons.org/licenses/by-nc-nd/3.0/es/ | * |
dc.source | Articles publicats en revistes (Institut d'lnvestigació Biomèdica de Bellvitge (IDIBELL)) | - |
dc.subject.classification | Càncer | - |
dc.subject.classification | Reparació de l'ADN | - |
dc.subject.other | Cancer | - |
dc.subject.other | DNA repair | - |
dc.title | IKKα Kinase Regulates the DNA Damage Response and Drives Chemo-resistance in Cancer | - |
dc.type | info:eu-repo/semantics/article | - |
dc.type | info:eu-repo/semantics/publishedVersion | - |
dc.date.updated | 2020-10-13T10:23:39Z | - |
dc.relation.projectID | info:eu-repo/grantAgreement/EC/H2020/702430/EU//RTEL1inHHS | - |
dc.relation.projectID | info:eu-repo/grantAgreement/EC/H2020/742437/EU//TelMetab | - |
dc.rights.accessRights | info:eu-repo/semantics/openAccess | - |
dc.identifier.pmid | 31302002 | - |
Appears in Collections: | Articles publicats en revistes (Institut d'lnvestigació Biomèdica de Bellvitge (IDIBELL)) |
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File | Description | Size | Format | |
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ColomerC.pdf | 6.95 MB | Adobe PDF | View/Open |
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