title: Overexpression of bromodomain factor 3 in Trypanosoma cruzi (TcBDF3) affects differentiation of the parasite and protects it against bromodomain inhibitors.
abstract: The 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.
authors.affiliation: Facultad de Ciencias Bioquímicas y Farmacéuticas, Universidad Nacional de Rosario, Argentina.
authors.forename: Victoria Lucia
authors.initials: VL
authors.lastname: Alonso
authors.affiliation: Instituto de Biología Molecular y Celular de Rosario (IBR), CONICET, Rosario, Argentina.
authors.forename: Carla
authors.initials: C
authors.lastname: Ritagliati
authors.affiliation: Facultad de Ciencias Bioquímicas y Farmacéuticas, Universidad Nacional de Rosario, Argentina.|Instituto de Biología Molecular y Celular de Rosario (IBR), CONICET, Rosario, Argentina.
authors.forename: Pamela
authors.initials: P
authors.lastname: Cribb
authors.affiliation: Facultad de Ciencias Bioquímicas y Farmacéuticas, Universidad Nacional de Rosario, Argentina.|Instituto de Biología Molecular y Celular de Rosario (IBR), CONICET, Rosario, Argentina.
authors.forename: Julia Alejandra
authors.initials: JA
authors.lastname: Cricco
authors.affiliation: Facultad de Ciencias Bioquímicas y Farmacéuticas, Universidad Nacional de Rosario, Argentina.|Instituto de Biología Molecular y Celular de Rosario (IBR), CONICET, Rosario, Argentina.
authors.forename: Esteban Carlos
authors.initials: EC
authors.lastname: Serra
mesh_terms: D000107:Acetylation / Q000187:drug effects; D000981:Antiprotozoal Agents / Q000737:chemistry / Q000627:therapeutic use; D005786:Gene Expression Regulation / Q000187:drug effects; D006657:Histones / Q000235:genetics; D006801:Humans; D008018:Life Cycle Stages / Q000235:genetics; D009154:Mutation; D011485:Protein Binding; D000072417:Protein Domains / Q000235:genetics; D015800:Protozoan Proteins / Q000037:antagonists & inhibitors / Q000096:biosynthesis* / Q000235:genetics; D014349:Trypanosoma cruzi / Q000235:genetics* / Q000254:growth & development; D014352:Trypanosomiasis / Q000188:drug therapy / Q000235:genetics* / Q000469:parasitology; D014404:Tubulin / Q000235:genetics / Q000378:metabolism*; D000092468:Bromodomain Containing Proteins
chemical_list: D000981:Antiprotozoal Agents; D006657:Histones; D015800:Protozoan Proteins; D014404:Tubulin; C000620779:BDF3 protein,Trypanosoma cruzi; D000092468:Bromodomain Containing Proteins
keywords: Trypanosoma cruzi; acetylation; bromodomain; bromodomain inhibitor; pTcINDEXGW