title: Leishmania express a functional Cdc20 homologue.
abstract: 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.
authors: Faculty of Biology, Technion-Israel Institute of Technology, Haifa 32000, Israel.
authors: Tamar
authors: T
authors: Listovsky
authors: Michael
authors: M
authors: Brandeis
authors: Dan
authors: D
authors: Zilberstein
mesh_terms: D064173:Anaphase-Promoting Complex-Cyclosome; D002453:Cell Cycle / Q000235:genetics; D018797:Cell Cycle Proteins / Q000145:classification* / Q000235:genetics* / Q000378:metabolism; D003001:Cloning, Molecular; D018503:Genome, Protozoan; D007893:Leishmania donovani / Q000166:cytology / Q000235:genetics* / Q000378:metabolism; D010802:Phylogeny; D043743:Ubiquitin-Protein Ligase Complexes / Q000378:metabolism
chemical_list: D018797:Cell Cycle Proteins; D043743:Ubiquitin-Protein Ligase Complexes; D064173:Anaphase-Promoting Complex-Cyclosome