Nuclear localization and formation of beta-catenin-lymphoid enhancer factor 1 complexes are not sufficient for activation of gene expression

In response to activation of the Wnt signaling pathway, beta-catenin accumu lates in the nucleus, where it cooperates with LEF/TCF (for lymphoid enhanc er factor and T-cell factor) transcription factors to activate gene express ion. The mechanisms by which beta-catenin undergoes this shift in location and participates in activation of gene transcription are unknown. We demons trate here that beta-catenin can be imported into the nucleus independently of LEF/TCF binding, and it may also be exported from nuclei. We have intro duced a small deletion,within beta-catenin (Delta 19) that disrupts binding to LEF-1, E-cadherin, and APC but not axin, This Delta 19 beta-catenin mut ant localizes to the nucleus because it may not be efficiently sequestered in the cytoplasm, The nuclear localization of Delta 19 definitively demonst rates that the mechanisms by which beta-catenin localizes in the nucleus ar e completely independent of LEF/TCF factors. beta-Catenin and LEF-1 complex es can activate reporter gene expression in a transformed T-lymphocyte cell line (Jurkat) but not in normal T lymphocytes, even though both factors ar e nuclear. Thus, localization of both factors to the nucleus is not suffici ent for activation of gene expression. Excess beta-catenin can squelch repo rter gene activation by LEF-1-beta-catenin complexes but not activation by the transcription factor VP16. Taken together, these data suggest that a th ird component is necessary for gene activation and that this third componen t may vary with cell type.