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dc.contributor.authorSánchez-Pérez, Tania-
dc.contributor.authorOrtiz-Ferrón, Gustavo-
dc.contributor.authorLópez-Rivas, Abelardo-
dc.date.accessioned2011-11-15T13:04:56Z-
dc.date.available2011-11-15T13:04:56Z-
dc.date.issued2009-11-27-
dc.identifier.citationCell Death and Differentiation 17(5): 883-894 (2010)es_ES
dc.identifier.issn1350-9047-
dc.identifier.otherPMID: 19942932-
dc.identifier.urihttp://hdl.handle.net/10261/42464-
dc.description12 páginas, 7 figuras.es_ES
dc.description.abstractBreast tumor cells are often resistant to tumor necrosis factor-related apoptosis-inducing ligand (tumour necrosis factor-related apoptosis-inducing ligand (TRAIL)/APO-2 L). Here, we describe the sensitization by microtubule-interfering agents (MIAs) to TRAIL-induced apoptosis in breast tumor cells through a mitotic arrest and c-Jun N-terminal kinase (JNK)-dependent mechanism. MIA treatment resulted in BubR1-dependent mitotic arrest leading to the sustained activation of JNK and the proteasome-mediated downregulation of cellular FLICE-inhibitory protein (cFLIP) and myeloid cell leukemia-1 (Mcl-1) expression. The JNK inhibitor SP600125 abrogated MIA-induced mitotic arrest and downregulation of cFLIP and Mcl-1 and reduced the apoptosis caused by the combination of MIAs and TRAIL. Silencing of cFLIP and Mcl-1 expression by RNA interference resulted in a marked sensitization to TRAIL-induced apoptosis. Furthermore, in FLIP-overexpressing cells, MIA-induced sensitization to TRAIL-activated apoptosis was markedly reduced. In summary, our results show that mitotic arrest imposed by MIAs activates JNK and facilitates TRAIL-induced activation of an apoptotic pathway in breast tumor cells by promoting the proteasome-mediated degradation of cFLIP and Mcl-1.es_ES
dc.description.sponsorshipThis work was supported by grants from Ministerio de Educación y Ciencia (SAF2006-00633), Red Temática de Investigación Cooperativa en Cáncer (RTICC) (RD06/0020/0068) and Junta de Andalucía (CTS-211) to ALR. GO-F and TS-P were supported by a contract and fellowship from Ministerio de Ciencia e Innovación, respectively.es_ES
dc.language.isoenges_ES
dc.publisherNature Publishing Groupes_ES
dc.rightsclosedAccesses_ES
dc.subjectApoptosises_ES
dc.subjectTRAILes_ES
dc.subjectMitotic arrestes_ES
dc.subjectJNKes_ES
dc.subjectcFLIPes_ES
dc.subjectMcl-1es_ES
dc.titleMitotic arrest and JNK-induced proteasomal degradation of FLIP and Mcl-1 are key events in the sensitization of breast tumor cells to TRAIL by antimicrotubule agentses_ES
dc.typeartículoes_ES
dc.identifier.doi10.1038/cdd.2009.176-
dc.description.peerreviewedPeer reviewedes_ES
dc.relation.publisherversionhttp://dx.doi.org/10.1038/cdd.2009.176es_ES
dc.identifier.e-issn1476-5403-
dc.contributor.funderMinisterio de Educación y Ciencia (España)-
dc.contributor.funderRed Temática de Investigación Cooperativa en Cáncer (España)-
dc.contributor.funderJunta de Andalucía-
dc.contributor.funderMinisterio de Ciencia e Innovación (España)-
dc.identifier.funderhttp://dx.doi.org/10.13039/501100004837es_ES
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