fig3

Figure 3. Mechanisms of AR protein degradation. (A) PROTACs recruit the AR protein and E3 Ub ligase complex into close proximity, facilitating ubiquitination and subsequent proteasomal degradation; (B) SARDs bind directly to AR and promote its degradation through the proteasome, reducing AR-mediated signaling; (C) Hydrophobic tagging involves attaching a lipophilic moiety to the AR protein, causing it to fold improperly and be recognized by the cell’s quality control machinery, ultimately targeting it for Ub-proteasome-mediated degradation. AR: Androgen receptor; PROTACs: proteolysis-targeting chimeras; Ub: ubiquitin; SARDs: selective androgen receptor degraders.