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

Hyunkyoung Ki, Ho Chul Jung, Jae Hyo Park, Jin Sook Kim, Kwang Youl Lee, Tae Sung Kim, Kwonseop Kim

Research output: Contribution to journalArticlepeer-review

8 Citations (Scopus)

Abstract

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.

Original languageEnglish
Pages (from-to)253-261
Number of pages9
JournalCell Biology International
Volume30
Issue number3
DOIs
Publication statusPublished - 2006 Mar
Externally publishedYes

Bibliographical note

Funding Information:
We are greatly indebted to Dr. B. Vogelstein for his gift of adenovirus construction kit, to Dr. M. Yoshida for providing Leptomycin B, and to Dr. Jung-Kap Choi for providing direct blue 71 staining kits (EZ BiopaQ, Korea). We also thank Dr. S. Takeda for Wnt-3a conditioned medium; Dr. R. Grosschedl for LEF-1-HA cDNA; Dr. K. Araki for human corneal epithelial cells; and Dr. M.L. Waterman for anti-LEF-1 Ab. This work was supported by Korea Research Foundation Grant (KRF-2002-003-E00008) to K.K.

Keywords

  • Adenomatous polyposis coli
  • Leptomycin B
  • Lymphoid enhancer factor-1
  • Nuclear export
  • β-Catenin

ASJC Scopus subject areas

  • Cell Biology

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