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Overexpression of bromodomain factor 3 in Trypanosoma cruzi ( Tc BDF 3) affects differentiation of the parasite and protects it against bromodomain inhibitors
Author(s) -
Alonso Victoria Lucia,
Ritagliati Carla,
Cribb Pamela,
Cricco Julia Alejandra,
Serra Esteban Carlos
Publication year - 2016
Publication title -
the febs journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.981
H-Index - 204
eISSN - 1742-4658
pISSN - 1742-464X
DOI - 10.1111/febs.13719
Subject(s) - bromodomain , acetylation , brd4 , trypanosoma cruzi , biology , recombinant dna , in vitro , microbiology and biotechnology , cancer research , chemistry , biochemistry , parasite hosting , gene , computer science , world wide web
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 ( Tc BDF 3), a bromodomain with an atypical localization that binds acetylated α‐tubulin. In the present work we show that parasites overexpressing Tc BDF 3 exhibit altered differentiation patterns and are less susceptible to treatment with bromodomain inhibitors. We also demonstrate that recombinant Tc BDF 3 is able to bind to these inhibitors in vitro in a concentration‐dependant manner. In parallel, the overexpression of a mutated version of Tc BDF 3 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.