Roles of F-box proteins in cancer

Nat Rev Cancer. 2014 Apr;14(4):233-47. doi: 10.1038/nrc3700.


F-box proteins, which are the substrate-recognition subunits of SKP1-cullin 1-F-box protein (SCF) E3 ligase complexes, have pivotal roles in multiple cellular processes through ubiquitylation and subsequent degradation of target proteins. Dysregulation of F-box protein-mediated proteolysis leads to human malignancies. Notably, inhibitors that target F-box proteins have shown promising therapeutic potential, urging us to review the current understanding of how F-box proteins contribute to tumorigenesis. As the physiological functions for many of the 69 putative F-box proteins remain elusive, additional genetic and mechanistic studies will help to define the role of each F-box protein in tumorigenesis, thereby paving the road for the rational design of F-box protein-targeted anticancer therapies.

Publication types

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

MeSH terms

  • Animals
  • Antineoplastic Agents / pharmacology
  • F-Box Proteins / antagonists & inhibitors
  • F-Box Proteins / physiology*
  • Humans
  • Molecular Targeted Therapy
  • Neoplasms / drug therapy
  • Neoplasms / metabolism*
  • Oncogenes
  • Proteolysis
  • Tumor Suppressor Proteins / antagonists & inhibitors
  • Tumor Suppressor Proteins / physiology
  • Ubiquitination


  • Antineoplastic Agents
  • F-Box Proteins
  • Tumor Suppressor Proteins