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dc.contributor.author | Martín-Guerrero, Sandra M | |
dc.contributor.author | Casado, Pedro | |
dc.contributor.author | Hijazi Vega, Maruan | |
dc.contributor.author | Rajeeve, Vinothini | |
dc.contributor.author | Plaza-Díaz, Julio | |
dc.contributor.author | Abadía-Molina, Francisco | |
dc.contributor.author | Navascués, Julio | |
dc.contributor.author | Cuadros, Miguel A | |
dc.contributor.author | Cutillas, Pedro R | |
dc.contributor.author | Martín-Oliva, David | |
dc.date.accessioned | 2024-01-31T12:46:59Z | |
dc.date.available | 2024-01-31T12:46:59Z | |
dc.date.issued | 2020-12-11 | |
dc.identifier.citation | Martín-Guerrero, S. M., Casado, P., Hijazi, M., Rajeeve, V., Plaza-Díaz, J., Abadía-Molina, F., ... & Martín-Oliva, D. (2020). PARP-1 activation after oxidative insult promotes energy stress-dependent phosphorylation of YAP1 and reduces cell viability. Biochemical Journal, 477(23), 4491-4513. https://doi.org/10.1042/BCJ20200525 | es_ES |
dc.identifier.issn | 0264-6021 | |
dc.identifier.uri | http://hdl.handle.net/10366/155107 | |
dc.description.abstract | [EN]Poly(ADP-ribose) polymerase 1 (PARP-1) is a nuclear enzyme that catalyze the transfer of ADP-ribose units from NAD+ to several target proteins involved in cellular stress responses. Using WRL68 (HeLa derivate) cells, we previously showed that PARP-1 activation induced by oxidative stress after H2O2 treatment lead to depletion of cellular NAD+ and ATP, which promoted cell death. In this work, LC-MS/MS-based phosphoproteomics in WRL68 cells showed that the oxidative damage induced by H2O2 increased the phosphorylation of YAP1, a transcriptional co-activator involved in cell survival, and modified the phosphorylation of other proteins involved in transcription. Genetic or pharmacological inhibition of PARP-1 in H2O2-treated cells reduced YAP1 phosphorylation and degradation and increased cell viability. YAP1 silencing abrogated the protective effect of PARP-1 inhibition, indicating that YAP1 is important for the survival of WRL68 cells exposed to oxidative damage. Supplementation of NAD+ also reduced YAP1 phosphorylation, suggesting that the loss of cellular NAD+ caused by PARP-1 activation after oxidative treatment is responsible for the phosphorylation of YAP1. Finally, PARP-1 silencing after oxidative treatment diminished the activation of the metabolic sensor AMPK. Since NAD+ supplementation reduced the phosphorylation of some AMPK substrates, we hypothesized that the loss of cellular NAD+ after PARP-1 activation may induce an energy stress that activates AMPK. In summary, we showed a new crucial role of PARP-1 in the response to oxidative stress in which PARP-1 activation reduced cell viability by promoting the phosphorylation and degradation of YAP1 through a mechanism that involves the depletion of NAD+. | es_ES |
dc.language.iso | eng | es_ES |
dc.publisher | Portland Press | es_ES |
dc.subject | Oxidative Stress | es_ES |
dc.subject | Cell survival | es_ES |
dc.subject.mesh | Oxidative Stress | * |
dc.subject.mesh | Cell Survival | * |
dc.subject.mesh | NAD | * |
dc.subject.mesh | Phosphorylation | * |
dc.subject.mesh | AMP-Activated Protein Kinases | * |
dc.subject.mesh | Humans | * |
dc.subject.mesh | HeLa Cells | * |
dc.subject.mesh | Hydrogen Peroxide | * |
dc.subject.mesh | Transcription Factors | * |
dc.title | PARP-1 activation after oxidative insult promotes energy stress-dependent phosphorylation of YAP1 and reduces cell viability | es_ES |
dc.type | info:eu-repo/semantics/article | es_ES |
dc.relation.publishversion | https://doi.org/10.1042/BCJ20200525 | es_ES |
dc.identifier.doi | 10.1042/BCJ20200525 | |
dc.rights.accessRights | info:eu-repo/semantics/openAccess | es_ES |
dc.identifier.pmid | 33146386 | |
dc.identifier.essn | 1470-8728 | |
dc.journal.title | The Biochemical Journal | es_ES |
dc.volume.number | 477 | es_ES |
dc.issue.number | 23 | es_ES |
dc.page.initial | 4491 | es_ES |
dc.page.final | 4513 | es_ES |
dc.type.hasVersion | info:eu-repo/semantics/publishedVersion | es_ES |
dc.subject.decs | proteina cinasas activadas por AMP | * |
dc.subject.decs | peróxido de hidrógeno | * |
dc.subject.decs | NAD | * |
dc.subject.decs | estrés oxidativo | * |
dc.subject.decs | humanos | * |
dc.subject.decs | células HeLa | * |
dc.subject.decs | factores de transcripción | * |
dc.subject.decs | supervivencia celular | * |
dc.subject.decs | fosforilación | * |