dc.creator | Belmonte Fernández, Alejandro | es |
dc.creator | Herrero Ruiz, Joaquín | es |
dc.creator | Galindo Moreno, María | es |
dc.creator | Limón Mortés, María Cristina | es |
dc.creator | Mora Santos, María del Mar | es |
dc.creator | Sáez, Carmen | es |
dc.creator | Japón, Miguel A. | es |
dc.creator | Tortolero García, María Dolores | es |
dc.creator | Romero Portillo, Francisco | es |
dc.date.accessioned | 2023-09-13T14:51:16Z | |
dc.date.available | 2023-09-13T14:51:16Z | |
dc.date.issued | 2023 | |
dc.identifier.citation | Belmonte Fernández, A., Herrero Ruiz, J., Galindo Moreno, M., Limón Mortés, M.C., Mora Santos, M.d.M., Sáez, C.,...,Romero Portillo, F. (2023). Cisplatin-induced Cell Death Increases the degradation of the MRE11-RAD50-NBS1 Complex Through the Autophagy/lysosomal Pathway. Cell Death and Differentiation, 30 (2), 488-499. https://doi.org/10.1038/s41418-022-01100-1. | |
dc.identifier.issn | 1350-9047 | es |
dc.identifier.issn | 1476-5403 | es |
dc.identifier.uri | https://hdl.handle.net/11441/148900 | |
dc.description.abstract | Cisplatin and other platinum-based anticancer agents are among the most widely used chemotherapy drugs in the treatment of different types of cancer. However, it is common to find patients who respond well to treatment at first but later relapse due to the appearance of resistance to cisplatin. Among the mechanisms responsible for this phenomenon is the increase in DNA damage repair. Here, we elucidate the effect of cisplatin on the MRN (MRE11-RAD50-NBS1) DNA damage sensor complex. We found that the tumor suppressor FBXW7 is a key factor in controlling the turnover of the MRN complex by inducing its degradation through lysosomes. Inhibition of lysosomal enzymes allowed the detection of the association of FBXW7-dependent ubiquitylated MRN with LC3 and the autophagy adaptor p62/SQSTM1 and the localization of MRN in lysosomes. Furthermore, cisplatin-induced cell death increased MRN degradation, suggesting that this complex is one of the targets that favor cell death. These findings open the possibility of using the induction of the degradation of the MRN complex after genotoxic damage as a potential therapeutic strategy to eliminate tumor cells. | es |
dc.description.sponsorship | Ministerio de Ciencia e Innovación SAF2017-87358-C2-1/2-R, PID2020-118774RB-C21, PID2020-118774RB-C22 | es |
dc.description.sponsorship | Junta de Andalucía 2021/BIO-211, 101024268 | es |
dc.format | application/pdf | es |
dc.format.extent | 12 p. | es |
dc.language.iso | eng | es |
dc.publisher | Springer Nature | es |
dc.relation.ispartof | Cell Death and Differentiation, 30 (2), 488-499. | |
dc.rights | Atribución 4.0 Internacional | * |
dc.rights.uri | http://creativecommons.org/licenses/by/4.0/ | * |
dc.title | Cisplatin-induced Cell Death Increases the degradation of the MRE11-RAD50-NBS1 Complex Through the Autophagy/lysosomal Pathway | es |
dc.type | info:eu-repo/semantics/article | es |
dcterms.identifier | https://ror.org/03yxnpp24 | |
dc.type.version | info:eu-repo/semantics/publishedVersion | es |
dc.rights.accessRights | info:eu-repo/semantics/openAccess | es |
dc.contributor.affiliation | Universidad de Sevilla. Departamento de Microbiología | es |
dc.relation.projectID | SAF2017-87358-C2-1/2-R | es |
dc.relation.projectID | PID2020-118774RB-C21 | es |
dc.relation.projectID | PID2020-118774RB-C22 | es |
dc.relation.projectID | 2021/BIO-211 | es |
dc.relation.projectID | 2021/BIO-211 | es |
dc.relation.projectID | 101024268 | es |
dc.relation.publisherversion | https://dx.doi.org/10.1038/s41418-022-01100-1 | es |
dc.identifier.doi | 10.1038/s41418-022-01100-1 | es |
dc.journaltitle | Cell Death and Differentiation | es |
dc.publication.volumen | 30 | es |
dc.publication.issue | 2 | es |
dc.publication.initialPage | 488 | es |
dc.publication.endPage | 499 | es |
dc.contributor.funder | Ministerio de Ciencia e Innovación (MICIN). España | es |
dc.contributor.funder | Junta de Andalucía | es |
dc.description.awardwinning | Premio Mensual Publicación Científica Destacada de la US. Facultad de Biología | |