F-box and WD repeat domain containing 2 (FBXW2)

F-box and WD repeat domain containing 2 (FBXW2) encodes a member of the F-box protein family, distinguished by the ~40 amino acid F-box motif and the presence of multiple WD-40 repeats. It acts as a substrate-recognition component of the SCF E3 ubiquitin ligase complex, facilitating ubiquitination and proteasomal degradation of specific proteins that regulate cell cycle, growth, and migration. FBXW2 interacts with and promotes degradation of oncogenic factors such as SKP2, β-catenin, and EGFR, acting as a tumor suppressor. Loss or downregulation of FBXW2 correlates with enhanced tumor cell proliferation and metastasis, while higher expression predicts favorable patient outcomes in lung and prostate cancer. Mechanistically, FBXW2 often requires substrate phosphorylation for recognition and is itself regulated by kinases like CK1 and VRK2. There are no known drugs directly targeting FBXW2, but it may serve as a biomarker or future therapeutic target in oncology.

Other names

FBXW2F-box/WD repeat-containing protein 2FBW2FWD2Md6Fwd2F-box and WD-40 domain protein 2F-box and WD-40 domain-containing protein 2Protein MD6

Not applicable for drugs due to lack of direct FBXW2-targeting drugs; in principle, drugs could modulate FBXW2-dependent ubiquitination to influence degradation of oncogenic substrates like β-catenin, SKP2, or EGFR