Overexpressed LEF-1 proteins display different nuclear localization patterns of beta-catenin in normal versus tumor cells.

Beta-catenin not only plays a role in cadherin-dependent cell adhesion, but also interacts with T-cell factor (TCF)/lymphoid enhancer factor-1 (LEF-1) to affect gene expression. In this report, we describe the effects of exogenous LEF-1 and of treatment with leptomycin B (LMB), a specific inhibitor of CRM1-medicated nuclear export, on the ...
nuclear localization and export of beta-catenin. Normal epithelial cells overexpressing LEF-1 accumulate nuclear beta-catenin in a LEF-1 concentration-dependent manner. Nuclear beta-catenin, once imported from the cytoplasm, is rapidly removed from the nucleus. Treatment with LMB results in dramatic retention of nuclear beta-catenin in normal epithelial cells transfected with LEF-1, and this effect is intensified by treatment of N-Acetyl-leucyl-leucyl-norleucinal together with LMB. Colon carcinoma cells containing an adenomatous polyposis coli mutation retain significant amounts of LEF-1 induced nuclear beta-catenin considerably after the time-point when beta-catenin disappears from the nuclei of LEF-1 transfected normal epithelial cells. beta-Catenin binds directly to CRM1, and overexpression of CRM1 reduces nuclear beta-catenin-mediated transactivation function.
Mesh Terms:
Active Transport, Cell Nucleus, Adenomatous Polyposis Coli Protein, Adenoviridae, Cell Nucleus, Culture Media, Conditioned, Epithelial Cells, Exportin 1 Protein, Fatty Acids, Unsaturated, Gene Expression, Genes, Reporter, Humans, Karyopherins, Lymphoid Enhancer-Binding Factor 1, Mutation, Neoplasms, Protein Binding, Protein Processing, Post-Translational, Protein Transport, Receptors, Cytoplasmic and Nuclear, Time Factors, beta Catenin
Cell Biol Int
Date: Mar. 01, 2006
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