Harnessing the FBXW7 Somatic Mutant R465C for Targeted Protein Degradation

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.