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Overexpressed LEF‐1 proteins display different nuclear localization patterns of β‐catenin in normal versus tumor cells
Author(s) -
Ki Hyunkyoung,
Jung HoChul,
Park JaeHyo,
Kim JinSook,
Lee Kwang Youl,
Kim Tae Sung,
Kim Kwonseop
Publication year - 2006
Publication title -
cell biology international
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.932
H-Index - 77
eISSN - 1095-8355
pISSN - 1065-6995
DOI - 10.1016/j.cellbi.2005.11.005
Subject(s) - catenin , transactivation , transfection , nuclear export signal , adenomatous polyposis coli , nuclear protein , cell nucleus , cytoplasm , biology , nuclear localization sequence , beta catenin , microbiology and biotechnology , nuclear transport , cancer research , chemistry , wnt signaling pathway , cell culture , gene expression , gene , colorectal cancer , signal transduction , cancer , biochemistry , transcription factor , genetics
β‐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 β‐catenin. Normal epithelial cells overexpressing LEF‐1 accumulate nuclear β‐catenin in a LEF‐1 concentration‐dependent manner. Nuclear β‐catenin, once imported from the cytoplasm, is rapidly removed from the nucleus. Treatment with LMB results in dramatic retention of nuclear β‐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 β‐catenin considerably after the time‐point when β‐catenin disappears from the nuclei of LEF‐1 transfected normal epithelial cells. β‐Catenin binds directly to CRM1, and overexpression of CRM1 reduces nuclear β‐catenin‐mediated transactivation function.