The APC/C Inhibitor XErp1/Emi2 Is Essential for Xenopus Early Embryonic Divisions

Mitotic divisions result from the oscillating activity of cyclin-dependent kinase-1 (Cdk1). Cdk1 activity is terminated by the anaphase-promoting-complex/cyclosome (APC/C), a ubiquitin-ligase that targets cyclin-B for destruction. In somatic divisions, Emi1 and the spindle-assembly-checkpoint (SAC) regulate cell-cycle progression by inhibiting the APC/C. Early embryonic divisions lack these APC/C-inhibitory components, raising the question of how these cycles are controlled. Here, we found that the APC/C-inhibitory activity of XErp1/Emi2 was essential for early divisions in Xenopus embryos. Loss of XErp1 resulted in untimely destruction of APC/C-substrates and embryonic lethality. XErp1’s APC/C-inhibitory function was negatively regulated by Cdk1 and positively by protein-phosphatase-2A (PP2A). Thus, Cdk1 and PP2A are at the core of early mitotic cell-cycles by antagonistically controlling XErp1-activity resulting in oscillating APC/C activity.