2025-02-11 ノースウェスタン大学
<関連情報>
- https://clp.northwestern.edu/a-new-route-to-cancer-treatment-leveraging-a-novel-protein-tagging-strategy/
- https://pubs.acs.org/doi/abs/10.1021/jacs.4c17331
FBXW7体細胞突然変異体R465Cの標的タンパク質分解への利用 Harnessing the FBXW7 Somatic Mutant R465C for Targeted Protein Degradation
Ananya A. Basu,Chenlu Zhang,Milad Rouhimoghadam,Anil Vasudevan,Justin M. Reitsma,Xiaoyu Zhang
Journal of the American Chemical Society Published: February 6, 2025
DOI:https://doi.org/10.1021/jacs.4c17331
Abstract
Targeted protein degradation (TPD) is a pharmacological strategy that eliminates specific proteins from cells by harnessing cellular proteolytic degradation machinery. In proteasome-dependent TPD, expanding the repertoire of E3 ligases compatible with this approach could enhance the applicability of this strategy across various biological contexts. In this study, we discovered that a somatic mutant of FBXW7, R465C, can be exploited by heterobifunctional compounds for targeted protein degradation. This work demonstrates the potential of utilizing mutant E3 ligases that occur exclusively in diseased cells for TPD applications.
