Article ID Journal Published Year Pages File Type
1930747 Biochemical and Biophysical Research Communications 2011 7 Pages PDF
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.

► We have identified in Leishmania a gene encoding for Cdc20 homologue (LdCdc20). ► That complements a lack of yeast Cdc20 protein in S. cerevisiae mutants. ► It contains an active RXXL destruction motif and degraded by proteasome. ► That is responsible for cyclic expression of this protein. ► LdCdc20 overexpression attenuates cell cycle at G1.

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