The APC/C Inhibitor XErp1/Emi2 is essential for xenopus early embryonic divisions

Abstract

Mitotic divisions result from the oscillating activity of cydin-dependent kinase 1 (Cdkl). Cdkl activity is terminated by the anaphase-promoting complexlcydosome (APClC), a ubiquitin ligase that targets cyclin B for destruction. In somatic divisions, the early mitotic inhibitor 1 (Emil) and the spindle assembly checkpoint (SAC) regulate cell cycle progression by inhibiting the APClC. Early embryonic divisions lack these APClC -inhibitory components, which raises the question of how those cycles are controlled. We found that the APClC -inhibitory activity of XErpl (also known as Emi2) was essential for early divisions in Xenopus embryos. Loss of XErpl resulted in untimely destruction of APClC substrates and embryonic lethality. XErpl's APClC -inhibitory function was negatively regulated by Cdkl and positively by protein phosphatase 2A (PP2A). Thus, Cdkl and PP2A operate at the core of early mitotic cell cycles by antagonistically controlling XErpl activity, which results in oscillating APClC activity.