dc.creator | Martí, Juan Manuel | es |
dc.creator | Garcia-Diaz, Angel | es |
dc.creator | Delgado-Bellido, Daniel | es |
dc.creator | O'Valle, Francisco | es |
dc.creator | González-Flores, Ariannys | es |
dc.creator | Carlevaris, Onintza | es |
dc.creator | Álava Casado, Enrique de | es |
dc.creator | Oliver, F. Javier | es |
dc.date.accessioned | 2022-09-23T15:48:16Z | |
dc.date.available | 2022-09-23T15:48:16Z | |
dc.date.issued | 2021 | |
dc.identifier.citation | Martí, J.M., Garcia-Diaz, A., Delgado-Bellido, D., O'Valle, F., González-Flores, A., Carlevaris, O.,...,Oliver, F.J. (2021). Selective modulation by PARP-1 of HIF-1α-recruitment to chromatin during hypoxia is required for tumor adaptation to hypoxic conditions. Redox Biology, 41 | |
dc.identifier.issn | 2213-2317 | es |
dc.identifier.uri | https://hdl.handle.net/11441/137348 | |
dc.description.abstract | Background: The adaptation to hypoxia is mainly controlled by the HIF transcription factors. Increased expression/
activity of HIF-1α correlates with poor prognosis in cancer patients. PARP-1 inhibitors are used in the clinic
to treat BRCAness breast/ovarian cancer and have been shown to regulate the hypoxic response; therefore, their
use could be expanded.
Methods: In this work by integrating molecular/cell biology approaches, genome-wide ChIP-seq, and patient
samples, we elucidate the extent to which PARP-1 exerts control over HIF-1-regulated genes.
Results: In human melanoma, PARP-1 and HIF-1α expression are strongly associated. In response to a hypoxic
challenge poly(ADP-ribose) (PAR) is synthesized, HIF-1α is post-transcriptionally modified (PTM) and stabilized
by PARylation at specific K/R residues located at its C-terminus. Using an unbiased ChIP-seq approach we
demonstrate that PARP-1 dictates hypoxia-dependent HIF-recruitment to chromatin in a range of HIF-regulated
genes while analysis of HIF-binding motifs (RCGTG) reveals a restriction on the recognition of hypoxia
responsive elements in the absence of PARP-1. Consequently, the cells are poorly adapted to hypoxia, showing a
reduced fitness during hypoxic induction.
Conclusions: These data characterize the fine-tuning regulation by PARP-1/PARylation of HIF activation and
suggest that PARP inhibitors might have therapeutic potential against cancer types displaying HIF-1α overactivation. | es |
dc.description.sponsorship | Junta de Andalucía | es |
dc.description.sponsorship | Ministerio de Economía. España | es |
dc.format | application/pdf | es |
dc.format.extent | 15 p. | es |
dc.language.iso | eng | es |
dc.publisher | Elsevier | es |
dc.relation.ispartof | Redox Biology, 41 | |
dc.rights | Attribution-NonCommercial-NoDerivatives 4.0 Internacional | * |
dc.rights.uri | http://creativecommons.org/licenses/by-nc-nd/4.0/ | * |
dc.subject | Hypoxia | es |
dc.subject | PARP-1 | es |
dc.subject | PARylation | es |
dc.subject | ChIP-seq | es |
dc.subject | Tumor microenvironment | es |
dc.title | Selective modulation by PARP-1 of HIF-1α-recruitment to chromatin during hypoxia is required for tumor adaptation to hypoxic conditions | 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 Citología e Histología Normal y Patológica | es |
dc.relation.projectID | P10-CTS-0662 | es |
dc.relation.projectID | P12-CTS-383 | es |
dc.relation.projectID | SAF2012-40011- C02-01 | es |
dc.relation.projectID | SAF2015-70520- R | es |
dc.relation.projectID | RTI2018-098968-B-I00 | es |
dc.relation.projectID | RTICC RD12/ 0036/0026 | es |
dc.relation.publisherversion | https://www.sciencedirect.com/science/article/pii/S2213231721000331?via%3Dihub | es |
dc.identifier.doi | 10.1016/j.redox.2021.101885 | es |
dc.journaltitle | Redox Biology | es |
dc.publication.volumen | 41 | es |