Practice question

The anaphase-promoting complex/cyclosome, APC/C, is a 1.2 MDa cullin-RING E3 ubiquitin ligase comprising over a dozen core subunits including APC2, APC11 catalytic core, and scaffolding proteins APC1, APC3, APC6, plus transient coactivators Cdc20 and Cdh1 that confer substrate specificity through D-box and KEN motif recognition. During early mitosis its activity is tightly repressed by spindle assembly checkpoint that sequesters Cdc20 in mitotic checkpoint complex composed of Mad2, BubR1, and Bub3. Priming phosphorylation by cyclin B-CDK1 and Polo-like kinase Plk1 on APC3 and APC1 enhances Cdc20 binding affinity. Upon amphitelic attachment of all kinetochores and generation of inter-kinetochore tension, Mad2 production ceases, checkpoint complex disassembles, and free Cdc20 activates APC/C. Activated APC/C-Cdc20 polyubiquitinates securin and mitotic cyclin B with K11-linked chains targeting them for rapid 26S proteasomal degradation. Securin destruction releases separase protease that cleaves kleisin Rad21 subunit of cohesin, dissolving sister chromatid cohesion while cyclin B loss extinguishes CDK1 activity, permitting phosphatase-driven mitotic exit and faithful chromosome segregation.