Fig. 2

Schematic representation of fusion protein-based bioTPD. (A) A β-catenin-binding motif (APcbc) replaces the natural substrate-binding domain of β-TRCP (WD40, etc.) to form a fusion protein for targeted degradation of β-catenin. (B) Max (a binding partner of c-Myc) is linked to the U-box of CHIP to form an artificial ubiquitin ligase for targeted destruction of c-Myc. (C) An affinity-directed protein missile (AdPROM) system harbors an anti-GFP nanobody (aGFP) that is fused to VHL to recruit any GFP-tagged protein (GFP-POI) to the CUL2 E3 ligase machinery. (D) The antibody RING-mediated destruction (ARMeD) system is mediated by a NEDP1-targeting nanobody (NNb2) fused to the RING domain of ubiquitin E3 ligase RNF4 for targeted destruction of NEDP1 via the ubiquitin-proteasome system. (E) A high-affinity peptide for PCNA (con-1) replaces the substrate-binding MATH domain of the E3 adaptor SPOP, which enable the ubiquitin tagging of PCNA by the CUL3-based Cullin-RING ligase complex. The figure was created in BioRender.com