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dc.contributor.authorAnta-Felez, Berta 
dc.contributor.authorPerez-Rodriguez, Andrea 
dc.contributor.authorCastro, Judith 
dc.contributor.authorGarcia-Dominguez, Carlota A 
dc.contributor.authorIbiza, S 
dc.contributor.authorMartinez, Natalia 
dc.contributor.authorDura, Lara M 
dc.contributor.authorHernandez, Silvia 
dc.contributor.authorGragera, Teresa 
dc.contributor.authorPeña-Jimenez, Daniel 
dc.contributor.authorYunta, M.
dc.contributor.authorZarich-Dimitrievich, Natasha 
dc.contributor.authorCrespo, P.
dc.contributor.authorSerrador, J. M.
dc.contributor.authorSantos, E.
dc.contributor.authorMunoz, A.
dc.contributor.authorOliva-Martinez, Jose Luis 
dc.contributor.authorRojas-Cabañeros, Jose Maria 
dc.date.accessioned2017-10-30T13:15:41Z
dc.date.available2017-10-30T13:15:41Z
dc.date.issued2016
dc.identifierISI:000380920200009
dc.identifier.citationCell Death Dis. 2016; 7(7):e2311
dc.identifier.issn2041-4889
dc.identifier.urihttp://hdl.handle.net/20.500.12105/5213
dc.description.abstractThe cyclopentenone prostaglandin A(1) (PGA(1)) is an inducer of cell death in cancer cells. However, the mechanism that initiates this cytotoxic response remains elusive. Here we report that PGA(1) triggers apoptosis by a process that entails the specific activation of H-and N-Ras isoforms, leading to caspase activation. Cells without H- and N-Ras did not undergo apoptosis upon PGA(1) treatment; in these cells, the cellular demise was rescued by overexpression of either H-Ras or N-Ras. Consistently, the mutant H-Ras-C118-S, defective for binding PGA(1), did not produce cell death. Molecular analysis revealed a key role for the RAF-MEK-ERK signaling pathway in the apoptotic process through the induction of calpain activity and caspase-12 cleavage. We propose that PGA(1) evokes a specific physiological cell death program, through H- and N-Ras, but not K-Ras, activation at endomembranes. Our results highlight a novel mechanism that may be of potential interest for tumor treatment.
dc.description.sponsorshipWe thank T O'Boyle and D Perez-Sala for the critical reading of this manuscript. APR, TG, and LMD were recipients of fellowships from the Comunidad de Madrid (APR), Ministerio de Educacion y Ciencia (TG), and FIS-BEFI (LMD). Grant support was awarded to JMRC from Fondo de Investigaciones Sanitarias-Intrasalud (PI09/0562 and PI13/00703) and the Spanish Association Against Cancer. JLO received grants from the Fondo de Investigaciones Sanitarias (CP07/00141 and PI10/00815). AM received grants from Ministerio de Economia y Competitividad of Spain-Fondo Europeo de Desarrollo Regional (FEDER) to AM (SAF2013-43468-R), Comunidad de Madrid to AM (S2010/BMD-2344 Colomics2) and Instituto de Salud Carlos III-FEDER. JMS received grants from the Fondo de Investigaciones Sanitarias (PI070356) and `Ayuda Intramural de Incorporacion al CSIC'. ES, AM, JMRC, and PC, respectively, received Grants RD06/0020/0000 and RD12/0036/0001, RD06/0020/0003 and RD12/0036/0021, and RD06/0020/0105 and RD12/0036/0033 from Instituto de San Carlos III-RETIC (Red Tematica de Investigacion Cooperativa en Cancer).
dc.language.isoeng
dc.publisherNature Publishing Group 
dc.type.hasVersionVoR
dc.rights.urihttp://creativecommons.org/licenses/by/4.0/*
dc.subjectENDOPLASMIC-RETICULUM STRESS
dc.subject15-DEOXY-DELTA(12,14)-PROSTAGLANDIN J(2)
dc.subjectCYCLOPENTENONE PROSTAGLANDINS
dc.subjectGRB2-BINDING DOMAIN
dc.subjectMESANGIAL CELLS
dc.subjectGOLGI-COMPLEX
dc.subjectCANCER-CELLS
dc.subjectDNA-BINDING
dc.subjectIN-VITRO
dc.subjectKAPPA-B
dc.titlePGA(1)-induced apoptosis involves specific activation of H-Ras and N-Ras in cellular endomembranes
dc.typejournal article
dc.rights.licenseAtribución 4.0 Internacional*
dc.identifier.pubmedID27468687
dc.format.volume7
dc.identifier.doi10.1038/cddis.2016.219
dc.contributor.funderComunidad de Madrid (España) 
dc.contributor.funderMinisterio de Educación y Ciencia (España) 
dc.contributor.funderAsociación Española Contra el Cáncer 
dc.contributor.funderMinisterio de Economía y Competitividad (España) 
dc.contributor.funderInstituto de Salud Carlos III 
dc.description.peerreviewed
dc.relation.publisherversionhttps://doi.org/10.1038/cddis.2016.219
dc.identifier.journalCell Death & Disease
dc.repisalud.orgCNICCNIC::Grupos de investigación::Regulación Génica en Remodelado Vascular e Inflamación
dc.repisalud.institucionCNIC
dc.relation.projectIDMINECO/ICTI2013-2016/SAF2013-43468-Res_ES
dc.rights.accessRightsopen accesses_ES


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