The anaphase-promoting complex (APC) has a hectic schedule. From mitosis through the G1/S transition, the APC is busily targeting cell cycle regulators for degradation. Yet it must keep an ordered degradation schedule for proper cell cycle progression. Now, results from Michael Rape, Sashank Reddy, and Marc Kirschner (Harvard Medical School, Boston, MA) suggest that the APC lets its substrates determine their own death order.
The degradation order of cell cycle regulators correlates with the kinetics of their ubiquitination by the APC. In vitro, securin—one of the first of the APC's substrates to be degraded—rapidly obtained full-length polyubiquitin chains, which are required for proteasome recognition. The late-degraded substrates took much longer for multiubiquitination.
The kinetics reflects differences in substrate processivity—that is, how many ubiquitins are added in a single APC binding event. The most processive substrate outcompeted the rest in vitro for polyubiquitination and thus degradation....
