Does Akt regulate other APC/Cdh1 substrates other than Skp2?
For most SCF/F-box complexes, the regulation of substrate recognition occurs at the level of the substrate, such that the F-box protein will usually not recognize its downstream substrates without a specific combination of phosphorylation events. On the other hand, the interaction of Cdh1 and Cdc20 with their substrates usually does not require any post-translational modifications [48]. In this case, the regulation of APC activity occurs primarily on the APC complex itself. Phosphorylation of Cdc20 by Plk and Cdc2/Cyclin B is required for the activation of the APC/Cdc20 complex while phosphorylation of Cdh1 by the Cdk2/Cyclin A complex terminates Cdh1 activity by dissociating Cdh1 from the APC core subunits [49]. Recently, it was shown that APC/Cdh1 ubiquitinates and degrades its substrates with different kinetics, and the preference of degradation order depends on the relative processivity of substrate multiubiquitination by APC/Cdh1 [50]. Our finding provides another unique mechanism
