Recent advances in SCF ubiquitin ligase complex: Clinical implications

Biochim Biophys Acta. 2016 Aug;1866(1):12-22. doi: 10.1016/j.bbcan.2016.05.001. Epub 2016 May 5.

Abstract

F-box proteins, which are subunit recruiting modules of SCF (SKP1-Cullin 1-F-box protein) E3 ligase complexes, play critical roles in the development and progression of human malignancies through governing multiple cellular processes including cell proliferation, apoptosis, invasion and metastasis. Moreover, there are emerging studies that lead to the development of F-box proteins inhibitors with promising therapeutic potential. In this article, we describe how F-box proteins including but not restricted to well-established Fbw7, Skp2 and β-TRCP, are involved in tumorigenesis. However, in-depth investigation is required to further explore the mechanism and the physiological contribution of undetermined F-box proteins in carcinogenesis. Lastly, we suggest that targeting F-box proteins could possibly open new avenues for the treatment and prevention of human cancers.

Keywords: F-box protein; Human cancer; Oncoprotein; Tumor suppressor; Ubiquitin.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't
  • Review

MeSH terms

  • Apoptosis / genetics
  • Carcinogenesis / genetics*
  • Cell Cycle Proteins / genetics
  • Cell Proliferation / genetics
  • F-Box Proteins / genetics*
  • F-Box Proteins / metabolism
  • F-Box-WD Repeat-Containing Protein 7
  • Humans
  • Male
  • Neoplasm Invasiveness / genetics
  • Neoplasm Metastasis
  • Prostatic Neoplasms, Castration-Resistant / genetics*
  • Prostatic Neoplasms, Castration-Resistant / pathology
  • S-Phase Kinase-Associated Proteins / genetics
  • Signal Transduction / genetics*
  • Tumor Suppressor Proteins / genetics*
  • Tumor Suppressor Proteins / metabolism
  • Ubiquitin-Protein Ligases / genetics
  • beta-Transducin Repeat-Containing Proteins / genetics

Substances

  • BTRC protein, human
  • Cell Cycle Proteins
  • F-Box Proteins
  • F-Box-WD Repeat-Containing Protein 7
  • FBXO31 protein, human
  • FBXW7 protein, human
  • S-Phase Kinase-Associated Proteins
  • Tumor Suppressor Proteins
  • beta-Transducin Repeat-Containing Proteins
  • Ubiquitin-Protein Ligases