Model for role of Fbw7α dimerization. A: Cdk2 (S384) and GSK3 (T380) prime cyclin E for destruction. The hyper-phosphorylated T380/S384 degron has high affinity for monomeric Fbw7α, which engages the remainder of the SCF to initiate cyclin E's ubiquitination by an E2 enzyme (B). C: Hypo-phosphorylated cyclin E that lacks S384 phosphorylation within the T380 phospho-degron can still be degraded by Fbw7α. However, this destruction pathway requires Fbw7 dimerization. Dimerization recruits a second E2 ubiquitin conjugating enzyme (E2) that may help elongating the same ubiquitin chain or may initiate another chain. Alternatively, the second Fbw7α component of the dimer may actually contact another degron within cyclin E, possibly the T62 degron, and may help stabilizing the substrate interaction.