Anaphase-Promoting Complex Adaptor FZR1/CDH1 Blocks BRAF Signaling Both by Targeting BRAF for Proteolytic Degradation and by Disrupting BRAF Dimerization

Cancer Discov. 2017 Apr;7(4):356-358. doi: 10.1158/2159-8290.CD-17-0172.


<b/> Blocking dimerization and stimulating protein degradation are two mechanisms known to inhibit BRAF activity. The study reported by Wan and colleagues identifies BRAF as a substrate of the APC/CFZR1-ubiqutin-proteasome system. The interaction between FZR1 and BRAF also induces a conformational change that disrupts BRAF dimerization. These findings identify a dynamic interplay between FZR1 and BRAF with strong implications for cell-fate determination and the tumor suppressor role of FZR1. Cancer Discov; 7(4); 356-8. ©2017 AACRSee related article by Wan et al., p. 424.

Publication types

  • Comment

MeSH terms

  • Anaphase / genetics
  • Cdh1 Proteins / genetics*
  • Cell Line, Tumor
  • Cell Proliferation / genetics
  • Cellular Senescence / genetics
  • Dimerization
  • Humans
  • Melanoma / genetics*
  • Melanoma / pathology
  • Proteasome Endopeptidase Complex / genetics
  • Proteolysis
  • Proto-Oncogene Proteins B-raf / genetics*
  • Tumor Suppressor Proteins / genetics
  • Ubiquitin-Protein Ligase Complexes / genetics*


  • Cdh1 Proteins
  • FZR1 protein, human
  • Tumor Suppressor Proteins
  • Ubiquitin-Protein Ligase Complexes
  • BRAF protein, human
  • Proto-Oncogene Proteins B-raf
  • Proteasome Endopeptidase Complex