Fig. 2

PROTAC in proteasomal degradation. Ubiquitin activation and formation of ubiquitinylation complex (A): the ubiquitin molecule is activated by the formation of a high energy bond between the residue Gly76 of ubiquitin and the cysteine residue of E1; then E1 attaches the activated Ub to E2 providing the binding platform for E1, E3, and activated Ub. Natural ubiquitinylation of the target by E3 ligase (B): highly selective E3 ensures specific recognition of a specific target protein. Ubiquitinylation of the target by PROTAC (C): PROTAC ensures recruitment the desired E3 to the target protein