FBXW7 encodes a member of the F-box protein family which is characterized by an approximately 40 amino acid motif, the F-box. The F-box proteins constitute one of the four subunits of ubiquitin protein ligase complex called SCFs (SKP1-cullin-F-box), which function in phosphorylation-dependent ubiquitination. This protein binds directly to cyclin E and probably targets cyclin E for ubiquitin-mediated degradation.
Somatic mutations, consisting mostly in substitutions, have been observed in tumors ofbiliary tract, endometrium, haematopoietic and lymphoid tissue, large intestine, thyroid, stomach, cervix. Mutations have also been described in ovarian and breast cancer cell lines. Mutations are present throughout the gene, but hot spots are found at amino acids 465, 479 and 505.
References (open access):
The Fbw7/human CDC4 tumor suppressor targets proproliferative factor KLF5 for ubiquitination and degradation through multiple phosphodegron motifs. Liu N, Li H, Li S, Shen M, Xiao N, Chen Y, Wang Y, Wang W, Wang R, Wang Q, Sun J, Wang P. J Biol Chem. 2010 Jun 11;285(24):18858-67.