anaphasepromoting

Anaphase-promoting complex, commonly abbreviated APC/C, is a large multi-subunit E3 ubiquitin ligase that drives progression through mitosis and promotes exit from mitosis. By tagging specific cell cycle proteins for degradation by the 26S proteasome, APC/C coordinates the orderly separation of chromosomes and the subsequent return to a quiescent, non-dividing state in G1.

The APC/C is composed of a catalytic core and a regulatory apparatus. The core is a multi-subunit complex, with a RING-finger subunit pair that forms the enzyme’s catalytic center, and numerous structural subunits that assemble into a scaffold. The complex relies on regulatory co-activators, primarily Cdc20 and Cdh1, to recognize substrates and to control the timing of ubiquitination. Substrates are typically marked by degradation motifs such as the destruction box (D-box) or the KEN box, which are recognized by the APC/C–co-activator complex.

Activation and substrate turnover follow a tightly controlled timeline. APC/C–Cdc20 is active during the metaphase-to-anaphase transition and targets securin and mitotic cyclins (notably cyclin B) for ubiquitination, leading to separin activation and CDK inactivation, respectively. This triggers chromatid separation and mitotic exit. After anaphase, APC/C–Cdh1 becomes the dominant form, maintaining low levels of mitotic regulators and ensuring orderly progression into G1. The activity of APC/C is further modulated by the spindle assembly checkpoint, which inhibits APC/C–Cdc20 until all chromosomes are properly attached to the spindle.

APC/C is conserved across eukaryotes and is essential for accurate chromosome segregation and cell-cycle progression. Disruption of APC/C function can lead to aneuploidy and other cellular defects.