Posh the APC/C E3 Ubiquitin Licase to Orchestrate Cell Division

The anaphase promoting corn plex/cyclosome (APC/C) E3 ligase controls mitosis and nonmitotic pathways through interactions with proteins that coordinate ubiquitylation. Since the discovery that the catalytic subunits of APC/C are conformationally dynamic cullin and RING proteins, many unexpected and intricate regulatory mechanisms have emerged. Here, we review structural knowledge of this regulation, focusing on: (i) coactivators, E2 ubiquitin (Ub)-conjugating enzymes, and inhibitors engage or influence multiple sites on APC/C including the cullin RING catalytic core; and (ii) the outcomes of these interactions rely on mobility of coactivators and cullin RING domains, which permits distinct conformations specifying different functions. Thus, APC/C is not simply an interaction hub, but is instead a dynamic, multifunctional molecular machine whose structure is remodeled by binding partners to achieve temporal ubiquitylation regulating cell division.