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

Mostra el registre complet Registre parcial de l'ítem

• dc.contributor.author Paronetto, Maria Paolaca
• dc.contributor.author Bernardis, Isabellaca
• dc.contributor.author Volpe, Elisabettaca
• dc.contributor.author Bechara, Eliasca
• dc.contributor.author Sebestyén, Endreca
• dc.contributor.author Eyras Jiménez, Eduardoca
• dc.contributor.author Valcárcel, J. (Juan)ca
• dc.date.accessioned 2015-06-04T06:56:36Z
• dc.date.available 2015-06-04T06:56:36Z
• dc.date.issued 2014ca
• 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.en
• 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)en
• dc.format.mimetype application/pdfca
• 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.2014.03.077ca
• dc.identifier.doi http://dx.doi.org/10.1016/j.celrep.2014.03.077
• dc.identifier.issn 2211-1247ca
• dc.identifier.uri http://hdl.handle.net/10230/23722
• dc.language.iso engca
• dc.publisher Elsevierca
• dc.relation.ispartof Cell Reports. 2014; 7: 1211-1226
• dc.relation.projectID info:eu-repo/grantAgreement/EC/FP6/518238ca
• 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 © 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.2014.03.077en
• dc.rights.accessRights info:eu-repo/semantics/openAccessca
• dc.rights.uri http://creativecommons.org/licenses/by-nc-nd/3.0/
• dc.subject.other Proteïnesca
• dc.subject.other Antígens CDca
• dc.subject.other RNAca
• dc.title Regulation of FAS exon definition and apoptosis by the ewing sarcoma proteinen
• dc.type info:eu-repo/semantics/articleca
• dc.type.version info:eu-repo/semantics/acceptedVersionca