β-Catenin can bind directly to CRM1 independently of adenomatous polyposis coli, which affects its nuclear localization and LEF-1/β-catenin-dependent gene expression

Nuclear β-catenin affects the developmental process and progression of tumors. However, the precise mechanism for the nuclear export of β-catenin is not completely understood. We found that β-catenin can bind directly to CRM1 through its central armadillo (ARM) repeats region, independently of the adenomatous polyposis coli (APC) protein. CRM1 overexpression transports nuclear β-catenin into the cytoplasm and decreases LEF-1/β-catenin-dependent transcriptional activity, which is also affected by the co-overexpression of E-cadherin. CRM1 competed with E-cadherin and LEF-1 for binding to β-catenin. β-catenin could interact directly with APC through its essential sequences between amino acids 342 and 350. The site-directed β-catenin mutant (NES2−), which could interact with CRM1, but not with APC, still retained its ability to export from the nucleus and its transactivational activity. This suggests that CRM1 can function as an efficient nuclear exporter for β-catenin independently of APC. These results strongly suggest that the CRM1-mediated pathway is involved in the efficient transport of nuclear β-catenin in the nucleus of cells.