FBW7 ubiquitin ligase: a tumour suppressor at the crossroads of cell division, growth and differentiation.
FBW7 (F-box and WD repeat domain-containing 7) is the substrate recognition component of an evolutionary conserved SCF (complex of SKP1, CUL1 and F-box protein)-type ubiquitin ligase. SCF(FBW7) degrades several proto-oncogenes that function in cellular growth and division pathways, including MYC, cyclin E, Notch and JUN. FBW7 is also a tumour suppressor, the regulatory network of which is perturbed in many human malignancies. Numerous cancer-associated mutations in FBW7 and its substrates have been identified, and loss of FBW7 function causes chromosomal instability and tumorigenesis. This Review focuses on structural and functional aspects of FBW7 and its role in the development of cancer.
Welcker
Markus
M
Division of Human Biology, Fred Hutchinson Cancer Research Center, 1100 Fairview Avenue North, Seattle, Washington 98109, USA. mwelcker@fhcrc.org
Clurman
Bruce E
BE
D000818:Animals; D018797:Cell Cycle Proteins / Q000502:physiology*; D002454:Cell Differentiation; D002455:Cell Division; D049109:Cell Proliferation; D019927:Cyclin E / Q000378:metabolism; D019281:Dimerization; D044783:F-Box Proteins / Q000502:physiology*; D000073979:F-Box-WD Repeat-Containing Protein 7; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D051379:Mice; D008954:Models, Biological; D009154:Mutation; D009369:Neoplasms / Q000378:metabolism / Q000473:pathology*; D044767:Ubiquitin-Protein Ligases / Q000502:physiology*
D018797:Cell Cycle Proteins; D019927:Cyclin E; D044783:F-Box Proteins; D000073979:F-Box-WD Repeat-Containing Protein 7; C513273:FBXW7 protein, human; D044767:Ubiquitin-Protein Ligases