NEW EVIDENCE THAT NUCLEAR IMPORT OF ENDOGENOUS β-CATENIN IS LEF-1 DEPENDENT, WHILE LEF-1 INDEPENDENT IMPORT OF EXOGENOUS β-CATENIN LEADS TO NUCLEAR ABNORMALITIES

Authors

  • Kwonseop Kim,

    1. Department of Cell Biology, Harvard Medical School, Boston, Massachusetts, 02115, U.S.A.
    2. College of Pharmacy, Chonnam National University, Kwang Ju, South Korea
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  • Elizabeth D. Hay

    Corresponding author
    1. Department of Cell Biology, Harvard Medical School, Boston, Massachusetts, 02115, U.S.A.
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To whom correspondence should be addressed. Department of Cell Biology, Harvard Medical School, 220 Longwood Ave, Boston, MA 02115, U.S.A. Fax: 617-432-0407. ehay@hms.harvard.edu

Abstract

The once accepted idea that LEF-1 transports β-catenin into nuclei has recently been challenged by experiments using exogenous β-catenin. Here, we investigated the effects of β-catenin and LEF-1 on nuclear import of β-catenin using different combinations of exogenous and endogenous molecules over longer lengths of time than previously studied. Nuclear β-catenin is not detectable in corneal fibroblasts and epithelia or NIH 3T3 and MDCK cells. In LEF-1 transfections, we show that the B-box of LEF-1 is required to move cytoplasmic endogenous β-catenin into the nuclei of such cells, proving that LEF-1 does transport endogenous β-catenin into nuclei. Moreover, transfection of uveal melanoma cells with B-box deficient LEF-1 inhibits nuclear import of β-catenin by endogenous LEF-1. However, the movement of overexpressed exogenous β-catenin into nuclei is unaffected by the presence or absence of LEF-1 and forms abnormal nuclear aggregates that are a prelude to subsequent apoptosis. We conclude that nuclear transport of exogenous β-catenin independently of LEF-1 has questionable physiological significance.

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