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Identification of Small Molecules Disrupting the Ubiquitin Proteasome System in Malaria
journal contribution
posted on 2019-11-07, 18:03 authored by Lydia Mata-Cantero, María Jesús Chaparro, Gonzalo Colmenarejo, Concepción Cid, Alvaro Cortes Cabrera, Manuel S. Rodriguez, Julio Martín, Francisco Javier Gamo, Maria G. Gomez-LorenzoThe
ubiquitin proteasome system (UPS) is one of the main proteolytic
pathways in eukaryotic cells, playing an essential role in key cellular
processes such as cell cycling and signal transduction. Changes in
some of the components of this pathway have been implicated in various
conditions, including cancer and infectious diseases such as malaria.
The success of therapies based on proteasome inhibitors has been shown
in human clinical trials. In addition to its proven tractability,
the essentiality of the Plasmodium falciparum UPS
underlines its potential as a source of targets to identify new antimalarial
treatments. Two assays, previously developed to quantify the parasite
protein ubiquitylation levels in a high throughput format, have been
used to identify compounds that inhibit parasite growth by targeting P. falciparum UPS. Among the positive hits, specific inhibitors
of the P. falciparum proteasome have been identified
and characterized. Hits identified using this approach may be used
as starting points for development of new antimalarial drugs. They
may also be used as tools to further understand proteasome function
and to identify new targets in P. falciparum UPS.