ERK kinase phosphorylates and destabilizes the tumor suppressor FBW7 in pancreatic cancer

摘要: F-box and WD repeat domain-containing 7 (FBW7) is the substrate recognition component of Skp1-Cul1-F-box (SCF) ubiquitin ligase complex functions as a major tumor suppressor by targeting various oncoproteins for degradation. Genomic deletion or mutation FBW7 has frequently been identified in many human cancers but not pancreatic ductal adenocarcinoma. Thus it important to know how suppressive function impaired cancer. In this study, we first observed that low expression correlated significantly with ERK activation cancer clinical samples, primarily due KRAS mutations We further showed directly interacted phosphorylated at Thr205, which sequentially promoted ubiquitination proteasomal Furthermore, phospho-deficient T205A mutant resistant could suppress cell proliferation tumorigenesis. These results collectively demonstrate oncogenic inhibits FBW7, thus revealing an promoting progression.