
pmid: 21458414
Our knowledge concerning the mechanisms of cell cycle regulation in organisms belonging to the Trypanosometidae family is limited. Leishmania donovani are parasitic protozoa that cause kala azar, a fatal form of visceral leishmaniasis in humans. Here we provide evidence that the L. donovani genome contains a Cdc20 homologue. Cdc20 is a regulator of the Anaphase Promoting Complex/Cyclosome (APC/C) that mediates ubiquitin-dependent proteasomal degradation of key cell cycle regulators in eukaryotes. We show that L. donovani Cdc20 protein (LdCdc20p) can complement a lack of yeast Cdc20 protein in Saccharomyces cerevisiae cells, validating the functionality of LdCdc20p. Furthermore, we demonstrate cyclic expression of LdCdc20p and that it contains an active RXXL destruction motif, a distinctive feature of proteins targeted for proteasomal degradation by APC/C. Finally, in line with the proteasome mediating LdCdc20p degradation, promastigotes exposed to proteasome inhibitor display elevated LdCdc20p levels. Taken together our data indicate that Leishmania regulate their cell cycle by ubiquitin-dependent proteasomal degradation mediated by the APC/C.
Cell Cycle, Ubiquitin-Protein Ligase Complexes, Cell Cycle Proteins, Cloning, Molecular, Genome, Protozoan, Anaphase-Promoting Complex-Cyclosome, Phylogeny, Leishmania donovani
Cell Cycle, Ubiquitin-Protein Ligase Complexes, Cell Cycle Proteins, Cloning, Molecular, Genome, Protozoan, Anaphase-Promoting Complex-Cyclosome, Phylogeny, Leishmania donovani
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