FIGURE 1.

Schematic illustration of the SCF-type of E3 ubiquitin ligase complex (modified from ref.).⁴³ The SCF (Skp1-Cullin 1-F-box) complex consists of 4 components: Skp1, Cul-1, Rbx1, along with the F-box protein family that play as substrate recognition components. Fbxw7 is a member of the F-box protein family, which recognizes the targeted substrates. High-affinity substrates have a consensus phosphopeptide motif termed CPDs that contain 2 phosphorylated residues (red “P”); lower-affinity CPDs contain a negatively charged amino acid (blue “E”) in place of the second phosphate. Fbxw7 also contains a conserved dimerization motif called the D domain, mediates Fbxw7 dimerization. CPD = Cdc4 phospho-degron, SCF = SKP1-CUL1-F-box.