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New evidence that nuclear import of endogenous beta-catenin is LEF-1 dependent, while LEF-1 independent import of exogenous beta-catenin leads to nuclear abnormalities.

Abstract
The once accepted idea that LEF-1 transports beta-catenin into nuclei has recently been challenged by experiments using exogenous beta-catenin. Here, we investigated the effects of beta-catenin and LEF-1 on nuclear import of beta-catenin using different combinations of exogenous and endogenous molecules over longer lengths of time than previously studied. Nuclear beta-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 beta-catenin into the nuclei of such cells, proving that LEF-1 does transport endogenous beta-catenin into nuclei. Moreover, transfection of uveal melanoma cells with B-box deficient LEF-1 inhibits nuclear import of beta-catenin by endogenous LEF-1. However, the movement of overexpressed exogenous beta-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 beta-catenin independently of LEF-1 has questionable physiological significance.
AuthorsK Kim, E D Hay
JournalCell biology international (Cell Biol Int) Vol. 25 Issue 11 Pg. 1149-61 ( 2001) ISSN: 1065-6995 [Print] England
PMID11913959 (Publication Type: Journal Article, Research Support, U.S. Gov't, P.H.S.)
Chemical References
  • CTNNB1 protein, human
  • Cytoskeletal Proteins
  • DNA-Binding Proteins
  • LEF1 protein, human
  • Lymphoid Enhancer-Binding Factor 1
  • Trans-Activators
  • Transcription Factors
  • beta Catenin
Topics
  • Active Transport, Cell Nucleus (physiology)
  • Cell Nucleus (metabolism, pathology)
  • Cytoskeletal Proteins (metabolism)
  • DNA-Binding Proteins (physiology)
  • Epithelial Cells (physiology)
  • Fibroblasts (physiology)
  • Fluorescent Antibody Technique
  • Humans
  • Lymphoid Enhancer-Binding Factor 1
  • Trans-Activators
  • Transcription Factors (physiology)
  • Transfection
  • Tumor Cells, Cultured (physiology)
  • beta Catenin

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