Mechanisms of tumor suppression by the SCF(Fbw7)

Cell Cycle. 2005 Oct;4(10):1356-9. doi: 10.4161/cc.4.10.2058. Epub 2005 Oct 27.


SCF ubiquitin ligases regulate the degradation of many proteins involved in the control of cell division and growth. F-box proteins are the SCF components that bind to substrates, and this binding is usually signaled by substrate phosphorylation. The Fbw7/hCdc4 F-box protein was first recognized by its ability to bind cyclin E, and the SCF (Fbw7) is now known to target c-Myc, c-Jun and Notch for degradation in addition to its role in cyclin E proteolysis. Fbw7 thus negatively regulates several key oncoproteins. Accordingly, Fbw7 is a tumor suppressor that is mutated in a wide spectrum of human cancers, and Fbw7 functions as a haploin sufficient tumor suppressor in mice. Because there are three Fbw7 isoforms that reside in different subcellular compartments, as well as multiple Fbw7 substrates that are the products of proto-oncogenes, the mechanisms of tumor suppression by Fbw7 are complex and incompletely understood. In this review we discuss the activities of the SCF(Fbw7) in the context of its role as a tumor suppressor and highlight recent findings demonstrating that dominant oncogenes disable Fbw7 function.

Publication types

  • Research Support, N.I.H., Extramural
  • Review

MeSH terms

  • Animals
  • F-Box Proteins / metabolism*
  • Humans
  • Neoplasms / metabolism*
  • Neoplasms / pathology*
  • Protein Binding
  • Substrate Specificity
  • Tumor Suppressor Proteins / metabolism*
  • Ubiquitin-Protein Ligases / metabolism*


  • F-Box Proteins
  • Tumor Suppressor Proteins
  • Ubiquitin-Protein Ligases