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Targeted Protein Degradation by Repurposing Transmembrane E3 Ubiquitin Ligases
Jibin Cui1, Qian Qu1, Man Pan1
1Institute of Translational Medicine, School of Chemistry and Chemical Engineering, Shanghai Key Laboratory for Antibody-Drug Conjugates with Innovative Target, Shanghai Jiao Tong University, Shanghai, China.
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Targeted protein degradation (TPD) is an emerging therapeutic strategy that leverages the cell's native degradation machinery to eliminate disease-causing proteins. An advanced approach in this field operates by mediating proximity-induced ubiquitination between E3 ubiquitin ligases and proteins of interest, thereby triggering their proteasomal destruction. Recent advances have expanded this paradigm to cell-surface proteins, opening a new frontier in targeting the undrugged proteome. This review highlights the development of TPD technologies that exploit cell-surface E3 ligases for the degradation of membrane proteins.
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