Comprising more than ten subunits, the anaphase-promoting complex (APC) acts in a cell-cycle dependent manner to promote the separation of sister chromatids during the transition between metaphase and anaphase in mitosis. APC, or cyclosome, accomplishes this progression through the ubiquitination of mitotic cyclins and other regulatory proteins that are targeted for destruction during cell division. APC is phosphorylated, and thus activated, by protein kinases Cdk1/cyclin B and polo-like kinase (Plk). APC is under tight control by a number of regulatory factors, including CDC20, CDH1 and MAD2. Specifically, CDC20 and CDH1 directly bind to APC and activates APC’s cyclin-ubiquitination activity. In contrast, MAD2 inhibits APC by forming a ternary complex with CDC20 and APC; thus preventing APC activation. APC11 is a RING-H2 finger protein that allows for the synthesis of multiubiquitin chains in the presence of Ubiquitin carrier protein 4 (Ubc4) and ubiquitin conjugating enzyme (E2). In addition, a heterodimeric complex of either Ubc4 or UbcH10 with APC11 and APC2 catalyzes the ubiquitination of human securin and cyclin B1.