Cooperation between different Cdc4/Fbw7 isoforms may be associated with 2-step inactivation of SCF(Cdc4) targets.

The recent description of a role for an SCF ubiquitin ligase in prolyl isomerization rather than ubiquitin ligation has led to a 2-step model for inactivation of cyclin E and, possibly, other SCF(Cdc4) targets in mammalian cells. In this proposed model, targets of SCF(Cdc4) are first subjected to prolyl isomerization, creating a signal for translocation and sequestration in the nucleolus, where they are then multiubiquitylated.