Figure 2. A schematic illustration of how pro-TAME and Apcin inhibit the APC E3 ligase activity.

pro-TAME, an IR-mimetic, directly blocks the recruitment of APC coactivators including Cdc20 and Cdh1, to the APC core complex. On the other hand, Apcin occupies the D-box-binding pocket on the side of the WD40 domain of Cdc20 and therefore blocking substrate-induced Cdc20 loading onto the APC core complex.