The Highs and Lows of FBXW7: New Insights into Substrate Affinity in Disease and Development.

ABSTRACT: FBXW7 is a critical regulator of cell cycle, cell signaling, and development. A highly conserved F-box protein and component of the SKP1-Cullin-F-box (SCF) complex, FBXW7 functions as a recognition subunit within a Cullin-RING E3 ubiquitin ligase responsible for ubiquitinating substrate proteins and targeting them for proteasome-mediated degradation. In human cells, FBXW7 promotes degradation of a large number of substrate proteins, including many that impact disease, such as NOTCH1, Cyclin E, MYC, and BRAF. A central focus for investigation has been to understand the molecular mechanisms that allow the exquisite substrate specificity exhibited by FBXW7. Recent work has produced a clearer understanding of how FBXW7 physically interacts with both high-affinity and low-affinity substrates. W

SUBMITTER: de la Cova CC 

PROVIDER: S-EPMC10486803 | biostudies-literature | 2023 Aug

REPOSITORIES: biostudies-literature