CDK2-dependent activation of PARP-1 is required for hormonal gene regulation in breast cancer cells
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- dc.contributor.author Wright, Roni H.G.ca
- dc.contributor.author Castellano, Giancarloca
- dc.contributor.author Bonet Martínez, Jaume, 1982-ca
- dc.contributor.author Le Dily, Françoisca
- dc.contributor.author Font Mateu, Jofre, 1977-ca
- dc.contributor.author Ballaré, Cecilia Juliaca
- dc.contributor.author Nacht, A. Silvinaca
- dc.contributor.author Soronellas, Danielca
- dc.contributor.author Oliva Miguel, Baldomeroca
- dc.contributor.author Beato, Miguelca
- dc.date.accessioned 2015-12-10T13:25:13Z
- dc.date.available 2015-12-10T13:25:13Z
- dc.date.issued 2012
- dc.description.abstract Eukaryotic gene regulation implies that transcription factors gain access to genomic information via poorly understood processes involving activation and targeting of kinases, histone-modifying enzymes, and chromatin remodelers to chromatin. Here we report that progestin gene regulation in breast cancer cells requires a rapid and transient increase in poly-(ADP)-ribose (PAR), accompanied by a dramatic decrease of cellular NAD that could have broad implications in cell physiology. This rapid increase in nuclear PARylation is mediated by activation of PAR polymerase PARP-1 as a result of phosphorylation by cyclin-dependent kinase CDK2. Hormone-dependent phosphorylation of PARP-1 by CDK2, within the catalytic domain, enhances its enzymatic capabilities. Activated PARP-1 contributes to the displacement of histone H1 and is essential for regulation of the majority of hormone-responsive genes and for the effect of progestins on cell cycle progression. Both global chromatin immunoprecipitation (ChIP) coupled with deep sequencing (ChIP-seq) and gene expression analysis show a strong overlap between PARP-1 and CDK2. Thus, progestin gene regulation involves a novel signaling pathway that connects CDK2-dependent activation of PARP-1 with histone H1 displacement. Given the multiplicity of PARP targets, this new pathway could be used for the pharmacological management of breast cancer.ca
- dc.description.sponsorship The experimental work was supported by grants from the Departament d’Innovació Universitat i Empresa (DIUiE), Ministerio de Educación y Ciencia (MEC) BMC 2003-02902, Consolider (CSD2006-00049), Fondo de Investigación Sanitaria (FIS) PI0411605 and CP04/00087, FEDER BIO2008-0205, and EU IP HEROIC.
- dc.format.mimetype application/pdfca
- dc.identifier.citation Wright RH, Castellano G, Bonet J, Le Dily F, Font-Mateu J, Ballaré C et al. CDK2-dependent activation of PARP-1 is required for hormonal gene regulation in breast cancer cells. Genes & Development. 2012;26(17):1972-83. DOI: 10.1101/gad.193193.112ca
- dc.identifier.doi http://dx.doi.org/10.1101/gad.193193.112
- dc.identifier.issn 0890-9369
- dc.identifier.uri http://hdl.handle.net/10230/25368
- dc.language.iso engca
- dc.publisher Cold Spring Harbor Laboratory Press (CSHL Press)ca
- dc.relation.ispartof Genes & Development. 2012;26(17):1972-83
- dc.relation.projectID info:eu-repo/grantAgreement/ES/1PN/BMC2003-02902
- dc.relation.projectID info:eu-repo/grantAgreement/ES/2PN/CSD2006-00049
- dc.rights © 2012 Genome Research by Cold Spring Harbor Laboratory Press. Published version available at http://genome.cshlp.org.ca
- dc.rights.accessRights info:eu-repo/semantics/openAccessca
- dc.subject.keyword Mouse mammary tumor virus
- dc.subject.keyword Progesterone receptor
- dc.subject.keyword Transcriptional regulation
- dc.subject.keyword Histone H1
- dc.subject.keyword PARP-1
- dc.subject.keyword Chromatin remodeling
- dc.subject.other Regulació genèticaca
- dc.subject.other Enzimsca
- dc.subject.other Mama -- Càncerca
- dc.title CDK2-dependent activation of PARP-1 is required for hormonal gene regulation in breast cancer cellsca
- dc.type info:eu-repo/semantics/articleca
- dc.type.version info:eu-repo/semantics/publishedVersionca