Figure 2.

Key Figure. Schematic Models of Emerging Degrader Technologies.

(A) LYTACs utilize a glycan tag to mark an extracellular protein of interest (POI) for intracellular lysosomal degradation following receptor-mediated internalization. Note that the LYTAC paper has not yet been peer reviewed and formally published. (B) AUTACs bind to the POI and add a degradation tag mimicking S-guanylation, a post-translational modification that triggers K63 polyubiquitination (Ub) of the POI. The POI is then recognized by the autophagy receptor SQSTM1/p62 and is recruited to the selective autophagy pathway for degradation. For the AUTAC molecule, the G pentagon represents the chemical moiety mimicking S-guanylation and the linked pacman shape represents the targeting recognition moiety. (C) ATTECs interact with both the POI and LC3, tethering the POI to the phagophores or autophagosomes for subsequent autophagic degradation.