Anaphase-promoting complex adaptor fZR1/CDH1 blocks BRAF signaling both by targeting braf for proteolytic degradation and by disrupting braf dimerization

Abstract

Summary: 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.