Cell cycle in Giardia: no need for APC Free

The eukaryotic cell cycle is regulated by a number of protein kinases, and among them is the cyclin-dependent kinase 1 (Cdk1), which forms a complex with cylin B that is essential for entry into mitosis. After mitosis and before the onset of anaphase, cyclin B is targeted for degradation through its ubiquitylation by the anaphase promoting complex (APC), which then downregulates the activity of Cdk1. Most eukaryotic lineages contain APC but there are some exceptions, such as the human pathogen Giardia intestinalis, which lacks all APC components but contains several candidate genes for mitotic cyclin. So how is the cell cycle regulated in this organism? On page (p. 2246), Stéphane Gourguechon and colleagues set out to elucidate the mechanism of cell cycle progression in Giardia and show that one of these candidate cyclins, Gi cyclin B, is responsible for mitotic entry. However, in contrast to all other mitotic cyclins investigated thus far, they find that Gi cyclin B lacks the conserved N-terminal motif that is required for ubiquitination by APC and, therefore, they conclude it is not regulated by ubiquitin-mediated degradation. However, Gi cylin B is degraded after mitosis by other means, for instance by interacting with other cell cycle regulators and by phosphorylation, as proposed here. Taken together, these results point to an evolutionarily ancient form of cell cycle regulation in Giardia that has developed in the absence of APC.