Overexpression of bromodomain factor 3 in Trypanosoma cruzi (TcBDF3) affects differentiation of the parasite and protects it against bromodomain inhibitors

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dc.citation.titleThe FEBS Journal
dc.citation.volume283
dc.contributor.otherGlaxo Smith Kline (GSK): provide I-BET151
dc.creatorAlonso, Victoria Lucía
dc.creatorRitagliati, Carla
dc.creatorCribb, Pamela
dc.creatorCricco, Julia Alejandra
dc.creatorSerra, Esteban Carlos
dc.date.accessioned2024-06-04T21:21:48Z
dc.date.available2024-06-04T21:21:48Z
dc.date.issued2016-06-06
dc.description.abstractThe bromodomain is the only protein domain known to bind acetylated lysine. In the last few years many bromodomain inhibitors have been developed in order to treat diseases such as cancer caused by aberrant acetylation of lysine residues. We have previously characterized Trypanosoma cruzi bromodomain factor 3 (TcBDF3), a bromodomain with an atypical localization that binds acetylated α-tubulin. In the present work we show that parasites overexpressing TcBDF3 exhibit altered differentiation patterns and are less susceptible to treatment with bromodomain inhibitors. We also demonstrate that recombinant TcBDF3 is able to bind to these inhibitors in vitro in a concentration-dependant manner. In parallel, the overexpression of a mutated version of TcBDF3 negatively affects growth of epimastigotes. Recent results, including the ones presented here, suggest that bromodomain inhibitors can be conceived as a new type of anti-parasitic drug against trypanosomiasis.
dc.description.filFil: Alonso, Victoria Lucía. Universidad Nacional de Rosario. Facultad de Ciencias Bioquímicas y Farmacéuticas; Argentina.
dc.description.filFil: Ritagliati, Carla. Universidad Nacional de Rosario. Facultad de Ciencias Bioquímicas y Farmacéuticas. Instituto de Biología Molecular y Celular de Rosario (IBR-CONICET); Argentina.
dc.description.filFil: Cribb, Pamela. Universidad Nacional de Rosario. Facultad de Ciencias Bioquímicas y Farmacéuticas. Instituto de Biología Molecular y Celular de Rosario (IBR-CONICET); Argentina.
dc.description.filFil: Cricco, Julia Alejandra. Universidad Nacional de Rosario. Facultad de Ciencias Bioquímicas y Farmacéuticas. Instituto de Biología Molecular y Celular de Rosario (IBR-CONICET); Argentina.
dc.description.filFil: Serra, Esteban Carlos. Universidad Nacional de Rosario. Facultad de Ciencias Bioquímicas y Farmacéuticas. Instituto de Biología Molecular y Celular de Rosario (IBR-CONICET); Argentina.
dc.description.sponsorshipAgencia Nacional de Promoción de la Investigación, el Desarrollo Tecnológico y la Innovación (Agencia I+D+i): PICTO2011-0011
dc.description.sponsorshipConsejo Nacional de Investigaciones Científicas y Técnicas (CONICET): PIP2010-0685
dc.description.versionpeerreviewed
dc.format.extent1-16
dc.identifier.e-issn1742-4658
dc.identifier.issn1742-464X
dc.identifier.urihttps://hdl.handle.net/2133/27210
dc.language.isoen
dc.publisherWiley
dc.relation.publisherversionhttps://doi.org/10.1111/febs.13719
dc.relation.publisherversionhttps://febs.onlinelibrary.wiley.com/doi/10.1111/febs.13719
dc.rightsopenAccess
dc.rights.holderAlonso, Victoria Lucía
dc.rights.holderRitagliati, Carla
dc.rights.holderCribb, Pamela
dc.rights.holderCricco, Julia Alejandra
dc.rights.holderSerra, Esteban Carlos
dc.rights.holderUniversidad Nacional de Rosario. Facultad de Ciencias Bioquímicas y Farmacéuticas
dc.rights.textAttribution-NonCommercial-NoDerivatives 4.0 Internationalen
dc.rights.urihttp://creativecommons.org/licenses/by-nc-nd/4.0/
dc.subjectAcetylation
dc.subjectBromodomain
dc.subjectBromodomain inhibitor
dc.subjectpTcINDEXGW
dc.subjectTrypanosoma cruzi
dc.titleOverexpression of bromodomain factor 3 in Trypanosoma cruzi (TcBDF3) affects differentiation of the parasite and protects it against bromodomain inhibitors
dc.typearticulo
dc.type.versionpublishedVersion

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