Regulating Fbw7 on the road to cancer

Semin Cancer Biol. 2016 Feb:36:62-70. doi: 10.1016/j.semcancer.2015.09.005. Epub 2015 Oct 13.

Abstract

The F-box protein Fbw7 targets for degradation critical cellular regulators, thereby controlling essential processes in cellular homeostasis, including cell cycle, differentiation and apoptosis. Most Fbw7 substrates are strongly associated with tumorigenesis and Fbw7 can either suppress or promote tumor development in mouse models. Fbw7 activity is controlled at different levels, resulting in specific and tunable regulation of the abundance and activity of its substrates. Here we highlight recent studies on the role of Fbw7 in controlling tumorigenesis and on the mechanisms that modulate Fbw7 function.

Keywords: Fbw7; Oncogene; Protein degradation; SCF ubiquitin ligase; Tumor suppressor.

Publication types

  • Research Support, Non-U.S. Gov't
  • Review

MeSH terms

  • Animals
  • Cell Cycle Proteins / chemistry
  • Cell Cycle Proteins / genetics*
  • Cell Cycle Proteins / metabolism*
  • Cell Transformation, Neoplastic / genetics*
  • Cell Transformation, Neoplastic / metabolism*
  • F-Box Proteins / chemistry
  • F-Box Proteins / genetics*
  • F-Box Proteins / metabolism*
  • F-Box-WD Repeat-Containing Protein 7
  • Gene Expression Regulation, Neoplastic
  • Homeostasis
  • Humans
  • Molecular Targeted Therapy
  • Neoplasms / drug therapy
  • Neoplasms / etiology*
  • Neoplasms / metabolism*
  • Neoplasms / pathology
  • Protein Binding
  • Protein Multimerization
  • Protein Transport
  • Proteolysis
  • Signal Transduction
  • Substrate Specificity
  • Ubiquitin-Protein Ligases / chemistry
  • Ubiquitin-Protein Ligases / genetics*
  • Ubiquitin-Protein Ligases / metabolism*
  • Ubiquitination

Substances

  • Cell Cycle Proteins
  • F-Box Proteins
  • F-Box-WD Repeat-Containing Protein 7
  • FBXW7 protein, human
  • Ubiquitin-Protein Ligases