dc.contributor.author | Pérez-Guijarro, Eva | |
dc.contributor.author | Karras, Panagiotis | |
dc.contributor.author | Cifdaloz, Metehan | |
dc.contributor.author | Martínez-Herranz, Raúl | |
dc.contributor.author | Cañón, Estela | |
dc.contributor.author | Graña Castro, Osvaldo | |
dc.contributor.author | Horcajada-Reales, Celia | |
dc.contributor.author | Alonso-Curbelo, Direna | |
dc.contributor.author | Calvo, Tonantzin G | |
dc.contributor.author | Gómez-López, Gonzalo | |
dc.contributor.author | Bellora, Nicolas | |
dc.contributor.author | Riveiro-Falkenbach, Erica | |
dc.contributor.author | Ortiz-Romero, Pablo L | |
dc.contributor.author | Rodríguez-Peralto, José L | |
dc.contributor.author | Maestre L, Lorena | |
dc.contributor.author | Roncador, Giovanna | |
dc.contributor.author | de Agustín Asensio, Juan C | |
dc.contributor.author | Goding, Colin R | |
dc.contributor.author | Eyras, Eduardo | |
dc.contributor.author | Megias Vazquez, Diego | |
dc.contributor.author | Méndez, Raúl | |
dc.contributor.author | Soengas, MS | |
dc.date.accessioned | 2019-07-10T08:39:38Z | |
dc.date.available | 2019-07-10T08:39:38Z | |
dc.date.issued | 2016 | |
dc.identifier.citation | Nat Commun. 2016 ;7:13418 | es_ES |
dc.identifier.issn | 2041-1723 | es_ES |
dc.identifier.uri | http://hdl.handle.net/20.500.12105/7877 | |
dc.description.abstract | Nuclear 3'-end-polyadenylation is essential for the transport, stability and translation of virtually all eukaryotic mRNAs. Poly(A) tail extension can also occur in the cytoplasm, but the transcripts involved are incompletely understood, particularly in cancer. Here we identify a lineage-specific requirement of the cytoplasmic polyadenylation binding protein 4 (CPEB4) in malignant melanoma. CPEB4 is upregulated early in melanoma progression, as defined by computational and histological analyses. Melanoma cells are distinct from other tumour cell types in their dependency on CPEB4, not only to prevent mitotic aberrations, but to progress through G1/S cell cycle checkpoints. RNA immunoprecipitation, sequencing of bound transcripts and poly(A) length tests link the melanoma-specific functions of CPEB4 to signalling hubs specifically enriched in this disease. Essential in these CPEB4-controlled networks are the melanoma drivers MITF and RAB7A, a feature validated in clinical biopsies. These results provide new mechanistic links between cytoplasmic polyadenylation and lineage specification in melanoma. | es_ES |
dc.description.sponsorship | We thank all the colleagues in the CNIO Melanoma Group, in particular David Olmeda
and former members Lisa Osterloh, Angel Colmenar, DamiaTormo and David Sa enz for
their help and support; Marıa Lozano (CNIO Histopathology Unit) for assistance withimmunostaining quantification; the iþ 12 Biobank of the Hospital 12 de Octubre forproviding melanoma patient samples; the members of theTranslational Control of Cell Cycle and Differentiation Group(IRB) for their help with RIP and PAT assay protocols. We also thank Marcos Malumbres for providing FUCCI constructs and his input in cell
cycle-related assays; Pilar Navarro (IMIM, Barcelona) for providing RIP-seq raw data
from pancreatic cell line; as well as Jose A Esteban (CBMSO, Madrid), Fatima
Gebauer (CRG, Barcelona) and Glenn Merlino (NIH, Bethesda) for critical reading
of this manuscript. M.S.S. was funded by Marato TVE and Consolider RNAREG
(CSD2009-00080), and SAF2014-56868-R (Spanish Ministry of Economy and
Innovation). R.M. was supported by Fundacion Botın, by the Banco Santandethrough its Santander Universities Global Division, and by grants from the Spanish Ministry of Economy and Innovation (BFU2011–30121 and Consolider RNAREG
(CSD2009-00080). J.L.R.-P. was funded by grant FIS 2014/1737 from the Spanish Ministry of Health, P.L.O.-R. by FIS 14/1784; and N.B. and E.E. by MINECO and FEDER (BIO2014-52566-R), as well as by Consolider RNAREG (CSD2009-00080), by AGAUR (2014-SGR1121) and by the Sandra Ibarra Foundation for Cancer (FSI2013). C.R.G was
recipients of Scientists in Training predoctoral fellowships from the Spanish Ministryof Science and Innovation. P.K and M.C. are funded by a predoctoral fellowshipfrom Fundacion La Caixa. E.R.-F. is the recipient of a postdoctoral fellowship from ‘Fundacion Cientıfica de la Asociacion Espanola Contra el Cancer’ and supported by FMM-2013/0075 of Fundacion Mutua Madrilena. | es_ES |
dc.language.iso | eng | es_ES |
dc.publisher | Nature Publishing Group | es_ES |
dc.type.hasVersion | VoR | es_ES |
dc.rights.uri | http://creativecommons.org/licenses/by-nc-sa/4.0/ | * |
dc.subject.mesh | Animals | es_ES |
dc.subject.mesh | Cell Cycle | es_ES |
dc.subject.mesh | Cell Line, Tumor | es_ES |
dc.subject.mesh | Gene Expression Regulation, Neoplastic | es_ES |
dc.subject.mesh | Gene Silencing | es_ES |
dc.subject.mesh | Humans | es_ES |
dc.subject.mesh | Melanoma | es_ES |
dc.subject.mesh | Mice | es_ES |
dc.subject.mesh | Neoplasms, Experimental | es_ES |
dc.subject.mesh | RNA, Messenger | es_ES |
dc.subject.mesh | RNA-Binding Proteins | es_ES |
dc.title | Lineage-specific roles of the cytoplasmic polyadenylation factor CPEB4 in the regulation of melanoma drivers | es_ES |
dc.type | journal article | es_ES |
dc.rights.license | Atribución-NoComercial-CompartirIgual 4.0 Internacional | * |
dc.identifier.pubmedID | 27857118 | es_ES |
dc.format.volume | 7 | es_ES |
dc.format.number | 1 | es_ES |
dc.format.page | 13418 | es_ES |
dc.identifier.doi | 10.1038/ncomms13418 | es_ES |
dc.contributor.funder | Ministerio de Ciencia e Innovación (España) | |
dc.contributor.funder | Botín Foundation | |
dc.contributor.funder | Ministerio de Sanidad y Consumo (España) | |
dc.contributor.funder | Unión Europea. Fondo Europeo de Desarrollo Regional (FEDER/ERDF) | |
dc.contributor.funder | Fundación Sandra Ibarra de Solidaridad Frente al Cáncer | |
dc.contributor.funder | Asociación Española Contra el Cáncer | |
dc.contributor.funder | Fundación Mutua Madrileña | |
dc.contributor.funder | Fundación La Caixa | |
dc.description.peerreviewed | Sí | es_ES |
dc.identifier.e-issn | 2041-1723 | es_ES |
dc.relation.publisherversion | https://doi.org/10.1038/ncomms13418. | es_ES |
dc.identifier.journal | Nature communications | es_ES |
dc.repisalud.institucion | CNIO | es_ES |
dc.repisalud.orgCNIO | CNIO::Grupos de investigación::Grupo de Melanoma | es_ES |
dc.relation.projectID | info:eu-repo/grantAgreement/ES/BFU2011-30121 | es_ES |
dc.relation.projectID | info:eu-repo/grantAgreement/ES/SAF2014-56868-R | es_ES |
dc.relation.projectID | info:eu-repo/grantAgreement/ES/FIS 2014/1737 | es_ES |
dc.relation.projectID | info:eu-repo/grantAgreement/ES/ FIS/14/1784 | es_ES |
dc.rights.accessRights | open access | es_ES |