Wild-type BRCA1, but not Mutated BRCA1, Regulates the Expression of the Nuclear Form of β-catenin

摘要: BRCA1 is an essential caretaker protein in the surveillance of DNA damage, mutated approximately 50% all hereditary breast cancer cases, and its expression frequently decreased sporadic cancer. beta-Catenin a multifunctional that forms adhesion complex with E-cadherins, alpha-catenin, actin, plays central role Wnt signaling through nuclear translocation activation beta-catenin-responsive genes. Although significant progress has been made understanding Wnt/beta-catenin cascades, it not known whether there link between beta-catenin BRCA1. We observed active form (also as ABC, Ser37/Thr41-nonphosphorylated beta-catenin, dephosphorylated beta-catenin) was lower or absent nucleus most familial tissues (17 cases) compared (14 samples) normal tissues. Wild-type-BRCA1, but BRCA1, interacted increased levels vitro. Furthermore, H(2)O(2) induced interaction The downregulated upon exposure to BRCA1-deficient HCC1937 cells, whereas reconstitution WT-BRCA1 cells inhibited this downregulation. This study provides evidence novel loss leads impaired which may contribute pathogenesis