Figure 4.

Hypothetical models of the aberrant activation of the APC/C‐CDC20 complex. Hypothetical models of APC/C inhibition by MCC focusing on the interaction of BUBR1 with wild type (blue) and p.R286S variant (red) of CDC20. BUB3 and MAD2 in MCC are not shown for simplification. (a) The increased frequency of stochastic dissociation of the p.R286S variant of CDC20_MCC from BUBR1 induces aberrant dissociation of MCC from the APC/C‐CDC20 complex (APC/C^CDC20), resulting in aberrant entry into anaphase and unequal chromosome segregation (WT/R286S). Haploinsufficiency of CDC20 (WT/KO) does not induce this aberrant dissociation of MCC. (b) Balanced inhibition of the APC/C^CDC20 by MCC prohibits aberrant entry into anaphase in wild type (WT/WT) and in haploinsufficiency of CDC20 (WT/KO). Reduction in the binding affinity of the CDC20 p.R286S variant to BUBR1 specifically in the formation of MCC but not of the APC/C^CDC20 induces a molecular imbalance between MCC and the APC/C^CDC20, resulting in aberrant entry into anaphase (WT/R286S).