title: Anaphase-Promoting Complex Adaptor FZR1/CDH1 Blocks BRAF Signaling Both by Targeting BRAF for Proteolytic Degradation and by Disrupting BRAF Dimerization.
abstract: <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.
authors.affiliation: Plexxikon Inc., Berkeley, California.
authors.forename: Chao
authors.initials: C
authors.lastname: Zhang
authors.affiliation: Plexxikon Inc., Berkeley, California. gbollag@plexxikon.com.
authors.forename: Gideon
authors.initials: G
authors.lastname: Bollag
mesh_terms: D000705:Anaphase / Q000235:genetics; D064200:Cdh1 Proteins / Q000235:genetics*; D045744:Cell Line, Tumor; D049109:Cell Proliferation / Q000235:genetics; D016922:Cellular Senescence / Q000235:genetics; D019281:Dimerization; D006801:Humans; D008545:Melanoma / Q000235:genetics* / Q000473:pathology; D046988:Proteasome Endopeptidase Complex / Q000235:genetics; D059748:Proteolysis; D048493:Proto-Oncogene Proteins B-raf / Q000235:genetics*; D025521:Tumor Suppressor Proteins / Q000235:genetics; D043743:Ubiquitin-Protein Ligase Complexes / Q000235:genetics*
chemical_list: D064200:Cdh1 Proteins; C577584:FZR1 protein, human; D025521:Tumor Suppressor Proteins; D043743:Ubiquitin-Protein Ligase Complexes; C482119:BRAF protein, human; D048493:Proto-Oncogene Proteins B-raf; D046988:Proteasome Endopeptidase Complex