Hijacking ERAD for targeted degradation of transmembrane proteins - PubMed
3 hours ago
- #Transmembrane Proteins
- #ERAD
- #Targeted Protein Degradation
- Targeted protein degradation (TPD) technologies offer significant potential for drug discovery, but degrading transmembrane (TM) proteins is challenging.
- Researchers developed ERAD-engaging chimeras (ERADECs) to hijack ER-associated degradation (ERAD) for efficient degradation of TM proteins.
- Desonide was identified as a binder of SYVN1, an ER E3 ligase involved in ERAD.
- ERADECs targeting PD-L1 were designed by linking desonide to a PD-L1 ligand, resulting in SYVN1- and ERAD-dependent PD-L1 degradation.
- ERADECs showed stronger tumor suppression and PD-L1-lowering effects than a clinically used PD-L1 antibody in vivo.
- The ERADEC platform is expandable to other membrane targets, providing a versatile tool for TM protein degradation.