Please use this identifier to cite or link to this item: http://hdl.handle.net/2445/155233
Full metadata record
DC FieldValueLanguage
dc.contributor.authorAlbero, Robert-
dc.contributor.authorEnjuanes, Anna-
dc.contributor.authorDemajo, Santiago-
dc.contributor.authorCastellano, Giancarlo-
dc.contributor.authorPinyol, Magda-
dc.contributor.authorGarcía, Noelia-
dc.contributor.authorCapdevila, Cristina-
dc.contributor.authorClot, Guillem-
dc.contributor.authorSuárez-Cisneros, Helena-
dc.contributor.authorShimada, Mariko-
dc.contributor.authorKarube, Kennosuke-
dc.contributor.authorLópez-Guerra, Mónica-
dc.contributor.authorColomer Pujol, Dolors-
dc.contributor.authorBeà Bobet, Sílvia M.-
dc.contributor.authorMartín-Subero, José Ignacio-
dc.contributor.authorCampo Güerri, Elias-
dc.contributor.authorJares Gerboles, Pedro-
dc.date.accessioned2020-04-14T14:00:52Z-
dc.date.available2020-04-14T14:00:52Z-
dc.date.issued2018-08-31-
dc.identifier.issn0021-9738-
dc.identifier.urihttp://hdl.handle.net/2445/155233-
dc.description.abstractCyclin D1 is an oncogene frequently overexpressed in human cancers that has a dual function as cell cycle and transcriptional regulator, although the latter is widely unexplored. Here, we investigated the transcriptional role of cyclin D1 in lymphoid tumor cells with cyclin D1 oncogenic overexpression. Cyclin D1 showed widespread binding to the promoters of most actively transcribed genes, and the promoter occupancy positively correlated with the transcriptional output of targeted genes. Despite this association, the overexpression of cyclin D1 in lymphoid cells led to a global transcriptional downmodulation that was proportional to cyclin D1 levels. This cyclin D1-dependent global transcriptional downregulation was associated with a reduced nascent transcription and an accumulation of promoter-proximal paused RNA polymerase II (Pol II) that colocalized with cyclin D1. Concordantly, cyclin D1 overexpression promoted an increase in the Poll II pausing index. This transcriptional impairment seems to be mediated by the interaction of cyclin D1 with the transcription machinery. In addition, cyclin D1 overexpression sensitized cells to transcription inhibitors, revealing a synthetic lethality interaction that was also observed in primary mantle cell lymphoma cases. This finding of global transcriptional dysregulation expands the known functions of oncogenic cyclin D1 and suggests the therapeutic potential of targeting the transcriptional machinery in cyclin D1-overexpressing tumors.-
dc.format.extent17 p.-
dc.format.mimetypeapplication/pdf-
dc.language.isoeng-
dc.publisherAmerican Society for Clinical Investigation-
dc.relation.isformatofReproducció del document publicat a: https://doi.org/10.1172/JCI96520-
dc.relation.ispartofJournal of Clinical Investigation, 2018, vol. 128, num. 9, p. 4132-4147-
dc.relation.urihttps://doi.org/10.1172/JCI96520-
dc.rights(c) American Society for Clinical Investigation, 2018-
dc.sourceArticles publicats en revistes (Fonaments Clínics)-
dc.subject.classificationRegulació cel·lular-
dc.subject.classificationCàncer-
dc.subject.classificationLimfomes-
dc.subject.otherCellular control mechanisms-
dc.subject.otherCancer-
dc.subject.otherLymphomas-
dc.titleCyclin D1 overexpression induces global transcriptional downregulation in lymphoid neosplasms-
dc.typeinfo:eu-repo/semantics/article-
dc.typeinfo:eu-repo/semantics/publishedVersion-
dc.identifier.idgrec681267-
dc.date.updated2020-04-14T14:00:52Z-
dc.rights.accessRightsinfo:eu-repo/semantics/openAccess-
dc.identifier.pmid29990311-
Appears in Collections:Articles publicats en revistes (IDIBAPS: Institut d'investigacions Biomèdiques August Pi i Sunyer)
Articles publicats en revistes (Fonaments Clínics)

Files in This Item:
File Description SizeFormat 
681267.pdf6.65 MBAdobe PDFView/Open


Items in DSpace are protected by copyright, with all rights reserved, unless otherwise indicated.