Figure 5. Autophagy tethering compounds (ATTEC) and the autophagy-targeting chimera (AUTAC) system.

A) ATTEC molecules tether the protein of interest to the autophagosomes by direct binding to the protein of interest and to LC3. A proof-of-concept study using the mutant HTT protein (mHTT) demonstrated that these compounds can degrade mHTT both in cells and in vivo in animal models and demonstrated targeting of mHTT to autophagosomes for subsequent degradation without influencing autophagy activity per se. B) AUTAC technology has a similar design to the PROTAC technology and both use ubiquitination to target proteins for degradation. The AUTAC molecule contains a degradation tag (a guanine derivative called FBnG) which induces K63 polyubiquitination and a ligand which binds to the target protein to provide target specificity. The resulting K63 ubiquitination targets the labelled protein for degradation via macroautophagy.