Beta-catenin can act as a nuclear import receptor for its partner transcription factor, lymphocyte enhancer factor-1...

Nuclear accumulation of beta-catenin plays an important role in the Wnt signaling pathway. In the nucleus, beta-catenin acts as a transcriptional co-activator for TCF/LEF family of transcription factors. It has been shown that lef-1 contains a typical basic type nuclear localization signal (NLS) and is transported into the nucleus by the conventional import pathway. In this study, we found that a mutant lef-1 lacking the classical NLS accumulated in the nucleus of living cells, when beta-catenin was co-expressed. In addition, in a cell-free import assay, lef-1 migrated into the nucleus in the presence of beta-catenin alone without any other soluble factors. In contrast, another mutant lef-1 lacking the beta-catenin binding domain failed to migrate into the nucleus, even in the presence of beta-catenin. These findings indicate that beta-catenin alone can mediate the nuclear import of lef-1 through the direct binding. Collectively, we propose that there are two distinct pathways for the nuclear import of lef-1: importin alpha/beta-mediated and beta-catenin-mediated one, which provides a novel paradigm for Wnt signaling pathway.