FIGURE 6:
Computer-driven simulations demonstrating that p31comet levels can control APC/C activity. APC/C activation state as a function of active p31comet concentration in the presence (A) or absence (B) of kinetochore signaling reveals a dependence of p31comet on APC/C activation. (C) Checkpoint protein complex dynamics are shown for two concentrations of p31comet. The dashed line illustrates the addition of a low (50 nM) concentration of p31comet, and the solid line the addition of p31comet to a high level (100 nM). The high levels of p31comet result in a rapid 80% inhibition of the kinetochore pool (1 nM K-C-Mad2 present) but much lower (40%) in the lower p31comet simulation. Through the combined action of C-Mad2 binding and C-Mad2–APC dissociation, the APC/C is partitioned between two interconverting inactive pools of p31:C-Mad2:APC/C and C-Mad2:APC/C. The result is that the APC/C is rapidly activated at the high p31comet level, whereas it is inactive at the low level.