Figure 4. Schematic illustration of PROTAC, PROTAB/AbTAC, and ROTAC-mediated degradation.
PROTACs for membrane protein of interest (POI) are comprised of a binder of the intracellular domain of the POI and a binder of the E3 ubiquitin ligase, and a linker between the two binders. PROTAB and AbTAC are fully genetically encoded bispecific antibodies that can bind to the membrane POI and a membrane E3 ubiquitin ligase (RNF43 or ZNRF3). ROTAC uses mutated R-spondin furin domain as the binder of RNF43 or ZNRF3. The formation of POI-degrader-E3 complex ternary complex promotes the ubiquitination of the POI and subsequent proteasomal or lysosomal degradation. (Created with BioRender.com)