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.
Ki
Hyunkyoung
H
College of Pharmacy, Chonnam National University, 300 Yongbong-dong, Kwangju, South Korea.
Jung
Ho-Chul
HC
Park
Jae-Hyo
JH
Kim
Jin-Sook
JS
Lee
Kwang Youl
KY
Kim
Tae Sung
TS
Kim
Kwonseop
K
D021581:Active Transport, Cell Nucleus; D025601:Adenomatous Polyposis Coli Protein / Q000378:metabolism; D000256:Adenoviridae / Q000235:genetics; D002467:Cell Nucleus / Q000378:metabolism*; D017077:Culture Media, Conditioned; D004847:Epithelial Cells / Q000166:cytology*; D005231:Fatty Acids, Unsaturated / Q000494:pharmacology; D015870:Gene Expression; D017930:Genes, Reporter; D006801:Humans; D028884:Karyopherins / Q000378:metabolism; D051821:Lymphoid Enhancer-Binding Factor 1 / Q000235:genetics* / Q000378:metabolism*; D009154:Mutation / Q000235:genetics; D009369:Neoplasms / Q000473:pathology*; D011485:Protein Binding; D011499:Protein Processing, Post-Translational; D021381:Protein Transport; D018160:Receptors, Cytoplasmic and Nuclear / Q000378:metabolism; D013997:Time Factors; D051176:beta Catenin / Q000378:metabolism*; D000097606:Exportin 1 Protein
D025601:Adenomatous Polyposis Coli Protein; D017077:Culture Media, Conditioned; D005231:Fatty Acids, Unsaturated; D028884:Karyopherins; D051821:Lymphoid Enhancer-Binding Factor 1; D018160:Receptors, Cytoplasmic and Nuclear; D051176:beta Catenin; D000097606:Exportin 1 Protein; C038753:leptomycin B