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. 2022 Oct 6;25(2):352–363. doi: 10.1007/s12094-022-02957-x

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Fig. 4 — Schematic of mechanism of PROTAC action. A PROTAC first functions like a bridge between its targeted protein and E3 ligase (being either untagged or tagged combined with E2) through binding both with its two ends. Then, the Ub is transferred to the substrate protein after E3-binding protein substrate. B The PROTAC and Ub-tagged substrate are subsequently released from the complex. C The unmodified PROTAC can be restored and repeatedly performs its function. D, E The mono-Ub-tagged substrate can add additional Ub linked with isopeptides until the poly-Ub-tagged substrate is recognized by the 26S proteasome, resulting in suppression of oncogene expression. (By Figdraw ID: OISIAefe92)