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

ALONSO VL; RITAGLIATI C; CRIBB P; CRICCO JA; SERRA EC

FEBS JOURNAL

WILEY-BLACKWELL PUBLISHING, INC

Lugar: Londres; Año: 2016

1742-464X

The bromodomain is the only protein domain known to bind acetylated lysines. In the last years many bromodomain inhibitors have been developed in order to treat diseases caused by aberrant acetylation of lysine residues such as cancer. 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 demonstrated 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 epimastigotes´ growth. Recent results, including the ones presented here, suggest that bromodomain inhibitors can be conceived as a new type of anti-parasitic drugs against trypanosomiasis. This article is protected by copyright. All rights reserved.