Figure 1. Two common models of substrates recognition by E3-ligase complexes. SCF ligases interact with the phosphorylated residues on the substrates, which create a so-called “phosphodegron”. The APC/C complex recognizes specific short motifs within the amino acid sequence of the targeted proteins, and its activity is regulated by phosphorylation. Little is known about mechanisms of substrate targeting by CUL3-based E3-ligases.