title: Unraveling the ubiquitome of the human malaria parasite.
abstract: Malaria is one of the deadliest infectious diseases worldwide. The most severe form is caused by the eukaryotic protozoan parasite Plasmodium falciparum. Recent studies have highlighted the importance of post-translational regulations for the parasite's progression throughout its life cycle, protein ubiquitylation being certainly one of the most abundant. The specificity of its components and the wide range of biological processes in which it is involved make the ubiquitylation pathway a promising source of suitable targets for anti-malarial drug development. Here, we combined immunofluorescent microscopy, biochemical assays, in silico prediction, and mass spectrometry analysis using the multidimensional protein identification technology, or MudPIT, to describe the P. falciparum ubiquitome. We found that ubiquitin conjugates are detected at every morphological stage of the parasite erythrocytic cycle. Furthermore, we detected that more than half of the parasite's proteome represents possible targets for ubiquitylation, especially proteins found to be present at the most replicative stage of the asexual cycle, the trophozoite stage. A large proportion of ubiquitin conjugates were also detected at the schizont stage, consistent with a cell activity slowdown to prepare for merozoite differentiation and invasion. Finally, for the first time in the human malaria parasite, our results strongly indicate the presence of heterologous mixed conjugations, SUMO/UB. This discovery suggests that sumoylated proteins may be regulated by ubiquitylation in P. falciparum. Altogether, our results present the first stepping stone toward a better understanding of ubiquitylation and its role(s) in the biology of the human malaria parasite.
authors.affiliation: Department of Cell Biology and Neuroscience, University of California, Riverside, California 92521, USA.
authors.forename: Nadia
authors.initials: N
authors.lastname: Ponts
authors.forename: Anita
authors.initials: A
authors.lastname: Saraf
authors.forename: Duk-Won D
authors.initials: DW
authors.lastname: Chung
authors.forename: Alona
authors.initials: A
authors.lastname: Harris
authors.forename: Jacques
authors.initials: J
authors.lastname: Prudhomme
authors.forename: Michael P
authors.initials: MP
authors.lastname: Washburn
authors.forename: Laurence
authors.initials: L
authors.lastname: Florens
authors.forename: Karine G
authors.initials: KG
authors.lastname: Le Roch
mesh_terms: D006801:Humans; D016778:Malaria, Falciparum / Q000188:drug therapy / Q000378:metabolism*; D010963:Plasmodium falciparum / Q000378:metabolism*; D015800:Protozoan Proteins / Q000378:metabolism*; D025842:SUMO-1 Protein / Q000378:metabolism*; D025801:Ubiquitin / Q000378:metabolism*; D054875:Ubiquitination / Q000502:physiology*
chemical_list: D015800:Protozoan Proteins; D025842:SUMO-1 Protein; D025801:Ubiquitin