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dc.contributor.authorMartí, Juan Manuel
dc.contributor.authorGarcía Díaz, Ángel
dc.contributor.authorDelgado Bellido, Daniel
dc.contributor.authorO'Valle Ravassa, Francisco Javier 
dc.contributor.authorGonzález Flores, Ariannys
dc.contributor.authorOliver Pozo, Francisco Javier
dc.date.accessioned2021-06-14T06:52:08Z
dc.date.available2021-06-14T06:52:08Z
dc.date.issued2021-02-01
dc.identifier.citationJuan Manuel Martí, Angel Garcia-Diaz, Daniel Delgado-Bellido, Francisco O'Valle, Ariannys González-Flores, Onintza Carlevaris, José Manuel Rodríguez-Vargas, Jean Christophe Amé, Françoise Dantzer, George L. King, Klaudia Dziedzic, Edurne Berra, E. de Álava, A.T. Amaral, Ester M. Hammond, F. Javier Oliver, Selective modulation by PARP-1 of HIF-1α-recruitment to chromatin during hypoxia is required for tumor adaptation to hypoxic conditions, Redox Biology, Volume 41, 2021, 101885, ISSN 2213-2317, [https://doi.org/10.1016/j.redox.2021.101885]es_ES
dc.identifier.urihttp://hdl.handle.net/10481/69143
dc.descriptionThis work was supported by Junta de Andalucia, project of Excellence from Junta de Andalucia P10-CTS-0662, P12-CTS-383 to FJO, Spanish Ministry of Economy and Competitiveness SAF2012-40011C02-01, SAF2015-70520-R, RTI2018-098968-B-I00, RTICC RD12/0036/0026 and CIBER Cancer ISCIII CB16/12/00421 to FJO. EB1s lab is supported by the Basque Department of Industry, Tourism and Trade (Etortek) and the MINECO (CB16/12/00421) grants. Fundacion Domingo Martinez (call 2019).es_ES
dc.descriptionWe would like to acknowledge Laura L´opez for technical assistance; Eduardo Andr´es and Laura Terr´on (Bioinformatic core IPBLN, CSIC) and Pan Hui (Bioinformatic Core, Joslin Diabetes center, Harvard Medical School).es_ES
dc.description.abstractBackground: 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_ES
dc.description.sponsorshipJunta de Andalucia P10-CTS-0662 P12-CTS-38es_ES
dc.description.sponsorshipSpanish Ministry of Economy and Competitiveness SAF2012-40011-C02-01 SAF2015-70520- R RTI2018-098968-B-I00 RTICC RD12/0036/0026es_ES
dc.description.sponsorshipCIBER Cancer ISCIII CB16/12/00421es_ES
dc.description.sponsorshipBasque Department of Industry, Tourism and Trade (Etortek)es_ES
dc.description.sponsorshipMINECO CB16/12/00421es_ES
dc.description.sponsorshipFundacion Domingo Martinezes_ES
dc.language.isoenges_ES
dc.publisherElsevieres_ES
dc.rightsAtribución-NoComercial-SinDerivadas 3.0 España*
dc.rights.urihttp://creativecommons.org/licenses/by-nc-nd/3.0/es/*
dc.subjectHypoxiaes_ES
dc.subjectPARP-1es_ES
dc.subjectPARylationes_ES
dc.subjectChIP-seqes_ES
dc.subjectTumor microenvironmentes_ES
dc.titleSelective modulation by PARP-1 of HIF-1α-recruitment to chromatin during hypoxia is required for tumor adaptation to hypoxic conditionses_ES
dc.typeinfo:eu-repo/semantics/articlees_ES
dc.rights.accessRightsinfo:eu-repo/semantics/openAccesses_ES
dc.identifier.doi10.1016/j.redox.2021.101885
dc.type.hasVersioninfo:eu-repo/semantics/publishedVersiones_ES


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