Breaking New Ground in Targeted Protein Degradation

Scientists from prestigious institutions in Beijing, including Tsinghua University and Beijing Normal University, have developed a pioneering method to selectively degrade multimeric proteins. Published in Cell, the study introduces TRIM21-based molecular glues and PROTACs as advanced tools for tackling diseases such as cancer, neurodegeneration, and autoimmunity.

The researchers, representing organizations like the Tsinghua Institute of Multidisciplinary Biomedical Research and the National Institute of Biological Sciences, focused on leveraging the unique properties of multimeric proteins to create a highly selective and effective degradation system. Their findings open new avenues for addressing the root causes of complex diseases by targeting previously undruggable proteins.

Lu et al. (2024) cell.com

Key Discoveries

The study identifies a molecular glue degrader, (S)-ACE-OH, derived from the antipsychotic drug acepromazine, which induces an interaction between the E3 ubiquitin ligase TRIM21 and the nucleoporin NUP98. This interaction leads to the targeted degradation of nuclear pore proteins, disrupting nucleocytoplasmic trafficking, a process critical to cellular function.

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