APC3 Antibody #9063

Cell proliferation in all eukaryotic cells depends strictly upon the ubiquitin ligase (E3) activity of the anaphase promoting complex/cyclosome (APC/C), whose main function is to trigger the transition of the cell cycle from metaphase to anaphase. APC/C performs its various functions by promoting the assembly of polyubiquitin chains on substrate proteins, which targets these proteins for degradation by the 26S proteasome (1,2). In humans, twelve different APC/C subunits have been identified. Like all E3 enzymes, APC/C utilizes ubiquitin residues that have been activated by E1 enzymes and then transferred to E2 enzymes. Indeed, APC/C has been shown to interact with UBE2S and UBE2C E2 enzymes, in part, via the RING-finger domain-containing subunit, APC11 (3-5). APC/C activity is also strictly dependent upon its association with multiple cofactors. For example, the related proteins, Cdc20 and Cdh1/FZR1, participate in the recognition of APC/C substrates by interacting with specific recognition elements in these substrates (6), called D-boxes (7) and KEN-boxes (8).
Anaphase-promoting complex subunit 3 (APC3), APC8, and APC6 are components of the tetratricopeptide (TPR) APC/C subcomplex (9). The presence of APC3 is required for binding of Cdh1/FZR1 to the APC/C. This suggests that APC/C is activated by an association between Cdh1/FZR1 with APC3 that enables APC/C to recognize the D-box of substrates (6,10). APC3 localizes to the centrosome and the mitotic spindle, suggesting that APC3 plays a critical role in the transition from metaphase to anaphase (11). Phosphorylation of APC3 at multiple sites during mitosis likely leads to structural changes within the APC/C by altering subunit interactions or changing affinity for molecules that transiently associate with the APC/C, such as Cdh1/FZR1 (12,13).