FBXW7 Gene: Function, Mutations, and Role in Cancer | Biomedical SEO

FBXW7 (F-box and WD repeat domain containing 7) encodes a member of the F-box protein family, which functions as the substrate recognition component of the SCF (SKP1-CUL1-F-box protein) ubiquitin ligase complex. FBXW7 targets several oncoproteins for ubiquitination and proteasomal degradation, including cyclin E (CCNE1), MYC, JUN, NOTCH1, and mTOR. Loss-of-function mutations in FBXW7 lead to the accumulation of these substrates, promoting uncontrolled cell proliferation and tumorigenesis. FBXW7 is a well-established tumor suppressor gene, with somatic mutations frequently identified in T-cell acute lymphoblastic leukemia (T-ALL), colorectal cancer, endometrial cancer, and other malignancies.

Tissue Expression

Cell Line Expression

Hotspot Mutations

Mutation functional classification

• SCF ubiquitin ligase complex (Reactome: R-HSA-8951664)

• Notch signaling (KEGG: hsa04330)

• Cell cycle (KEGG: hsa04110)

• mTOR signaling (KEGG: hsa04150)

• p53 signaling (KEGG: hsa04115)

• Ubiquitin mediated proteolysis (KEGG: hsa04120)

FBXW7 is a 707-amino acid protein containing an N-terminal F-box domain and seven C-terminal WD40 repeats. The F-box domain mediates interaction with SKP1, while the WD40 repeats form a beta-propeller structure that recognizes phosphorylated degrons on target proteins. FBXW7 is predominantly nuclear and acts as a tumor suppressor by targeting key oncoproteins for ubiquitin-dependent degradation. Its loss leads to substrate stabilization and contributes to oncogenesis in multiple cancer types.