BFL1 Modulates Apoptosis at the Membrane Level through a Bifunctional And Multimodal Mechanism Showing Key Differences With BCLXL
dc.contributor.author | Flores Romero, Héctor | |
dc.contributor.author | Landeta Díaz, Olatz | |
dc.contributor.author | Ugarte Uribe, Begoña | |
dc.contributor.author | Cosentino, Katia | |
dc.contributor.author | García Porras, Miguel | |
dc.contributor.author | García-Sáez, Ana J. | |
dc.contributor.author | Basañez, Gorka | |
dc.date.accessioned | 2019-11-25T15:22:35Z | |
dc.date.available | 2019-11-25T15:22:35Z | |
dc.date.issued | 2018-12-18 | |
dc.identifier.citation | Cell Death And Differentiation 26(10) : 1880-1894 (2019) | es_ES |
dc.identifier.issn | 1350-9047 | |
dc.identifier.issn | 1476-5403 | |
dc.identifier.uri | http://hdl.handle.net/10810/36444 | |
dc.description.abstract | BFL1 is a relatively understudied member of the BCL2 protein family which has been implicated in the pathogenesis andchemoresistance of a variety of human cancers, including hematological malignancies and solid tumours. BFL1 is generallyconsidered to have an antiapoptotic function, although its precise mode of action remains unclear. By quantitativelyanalyzing BFL1 action in synthetic membrane models and in cells, we found that BFL1 inhibits apoptosis through threedistinct mechanisms which are similar but not identical to those of BCLXL, the paradigmatic antiapoptotic BCL2 familyprotein. Strikingly, alterations in lipid composition during apoptosis activate a prodeath function of BFL1 that is based onnoncanonical oligomerization of the protein and breaching of the permeability barrier of the outer mitochondrial membrane(OMM). This lipid-triggered prodeath function of BFL1 is absent in BCLXL and also differs from that of the apoptoticeffector BAX, which sets it apart from other BCL2 family members. Ourfindings support a new model in which BFL1modulates apoptosis through a bifunctional and multimodal mode of action that is distinctly regulated by OMM lipidscompared to BCLXL. | es_ES |
dc.description.sponsorship | This work was supported by Grants BFU2011-28566 from the Ministerio de Economia y Competitividad and IT838-13 from Gobierno Vasco. HFR is a recipient of a predoctoral fellowship from the Ministerio de Educacion (Spain). We also thank to LE facility technician in the Achucarro Basque Center for Neuroscience for the support in STED experiments. Finally, we thank Dr. Frank Essmann and Prof. Klaus Schulze-Osthoff for providing the HCT116 BAX/BAK DKO cells and Prof. Jean Claude Martinou for HCT116 CL KO cells. | es_ES |
dc.language.iso | eng | es_ES |
dc.publisher | Springer Nature | es_ES |
dc.relation | info:eu-repo/grantAgreement/MINECO/BFU2011-28566 | es_ES |
dc.rights | info:eu-repo/semantics/openAccess | es_ES |
dc.rights.uri | http://creativecommons.org/licenses/by/3.0/es/ | * |
dc.subject | cell-death | es_ES |
dc.subject | proapoptotic bax | es_ES |
dc.subject | bcl-2 | es_ES |
dc.subject | protein | es_ES |
dc.subject | bcl-x(l) | es_ES |
dc.subject | survival | es_ES |
dc.subject | mitochondria | es_ES |
dc.subject | cardiolipin | es_ES |
dc.subject | mcl-1 | es_ES |
dc.subject | a1 | es_ES |
dc.title | BFL1 Modulates Apoptosis at the Membrane Level through a Bifunctional And Multimodal Mechanism Showing Key Differences With BCLXL | es_ES |
dc.type | info:eu-repo/semantics/article | es_ES |
dc.rights.holder | © The Author(s). This article is licensed under a Creative CommonsAttribution 4.0 International License, which permits use, sharing,adaptation, distribution and reproduction in any medium or format, aslong as you give appropriate credit to the original author(s) and thesource, provide a link to the Creative Commons license, and indicate ifchanges were made. To view a copy of this license, visithttp://creativecommons.org/licenses/by/4.0/. | es_ES |
dc.relation.publisherversion | https://www.nature.com/articles/s41418-018-0258-5 | es_ES |
dc.identifier.doi | 10.1038/s41418-018-0258-5 | |
dc.departamentoes | Bioquímica y biología molecular | es_ES |
dc.departamentoeu | Biokimika eta biologia molekularra | es_ES |
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