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Regulation of FAS exon definition and apoptosis by the ewing sarcoma protein

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dc.contributor.author Paronetto, Maria Paola
dc.contributor.author Bernardis, Isabella
dc.contributor.author Volpe, Elisabetta
dc.contributor.author Bechara, Elias
dc.contributor.author Sebestyén, Endre
dc.contributor.author Eyras Jiménez, Eduardo
dc.contributor.author Valcárcel, J. (Juan)
dc.date.accessioned 2015-06-04T06:56:36Z
dc.date.available 2015-06-04T06:56:36Z
dc.date.issued 2014
dc.identifier.citation Paronetto MP, Bernardis I, Volpe E, Bechara E, Sebestyen E, Eyras E, Valcarcel J. Regulation of FAS exon definition and apoptosis by the ewing sarcoma protein. Cell Reports. 2014; 7: 1211-1226. DOI 10.1016/j.celrep.2014.03.077
dc.identifier.issn 2211-1247
dc.identifier.uri http://hdl.handle.net/10230/23722
dc.description.abstract The Ewing sarcoma protein EWS is an RNA and DNA binding protein implicated in transcription, pre-mRNA splicing, and DNA damage response. Using CLIP-seq, we identified EWS RNA binding sites in exonic regions near 5′ splice sites. A prominent target was exon 6 of the FAS/CD95 receptor, which is alternatively spliced to generate isoforms with opposing activities in programmed cell death. Depletion and overexpression experiments showed that EWS promotes exon 6 inclusion and consequently the synthesis of the proapoptotic FAS/CD95 isoform, whereas an EWS-FLI1 fusion protein characteristic of Ewing sarcomas shows decreased activity. Biochemical analyses revealed that EWS binding promotes the recruitment of U1snRNP and U2AF65 to the splice sites flanking exon 6 and therefore exon definition. Consistent with a role for EWS in the regulation of programmed cell death, cells depleted of EWS show decreased sensitivity to FAS-induced apoptosis, and elevated EWS expression enhances apoptosis in EWS-haploinsufficient Ewing sarcoma cells.
dc.description.sponsorship M.P.P. was supported by a fellowship from the HFSP. This project was supported by Fundación Botín, Fundación Sandra Ibarra (FSI2013), the European Union Sixth Framework Programme under grant agreement Nr. LSHG-CT-2005-518238-V (EURASNET), the Spanish Ministry of Economy and Competitiveness (grant no. CSD2009-00080, Consolider RNAREG/BFU2011-29583 / BIO2011-23920), and AIRC (Grant MFAG 11658). We also acknowledge support of the Spanish Ministry of Economy and Competitiveness, “Centro de Excelencia Severo Ochoa 2013-2017” (SEV-2012-0208)
dc.format.mimetype application/pdf
dc.language.iso eng
dc.publisher Elsevier
dc.relation.ispartof Cell Reports. 2014; 7: 1211-1226
dc.rights © 2014, Elsevier. Licensed under the Creative Commons Attribution-NonCommercial-NoDerivatives 3.0 International http://creativecommons.org/licenses/by-nc-nd/3.0/ http://dx.doi.org/10.1016/j.celrep.2014.03.077
dc.rights.uri http://creativecommons.org/licenses/by-nc-nd/3.0/
dc.subject.other Proteïnes
dc.subject.other Antígens CD
dc.subject.other RNA
dc.title Regulation of FAS exon definition and apoptosis by the ewing sarcoma protein
dc.type info:eu-repo/semantics/article
dc.identifier.doi http://dx.doi.org/10.1016/j.celrep.2014.03.077
dc.relation.projectID info:eu-repo/grantAgreement/EC/FP6/518238
dc.relation.projectID info:eu-repo/grantAgreement/ES/3PN/CSD2009-00080
dc.relation.projectID info:eu-repo/grantAgreement/ES/3PN/BFU2011-29583
dc.relation.projectID info:eu-repo/grantAgreement/ES/3PN/BIO2011-23920
dc.relation.projectID info:eu-repo/grantAgreement/ES/3PN/SEV2012-0208
dc.rights.accessRights info:eu-repo/semantics/openAccess
dc.type.version info:eu-repo/semantics/acceptedVersion

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