Beta-catenin can act as a nuclear import receptor for its partner transcription factor, lymphocyte enhancer factor-1 (lef-1)

Exp Cell Res. 2005 Aug 15;308(2):357-63. doi: 10.1016/j.yexcr.2005.05.011.

Abstract

Nuclear accumulation of beta-catenin plays an important role in the Wnt signaling pathway. In the nucleus, beta-catenin acts as a transcriptional co-activator for TCF/LEF family of transcription factors. It has been shown that lef-1 contains a typical basic type nuclear localization signal (NLS) and is transported into the nucleus by the conventional import pathway. In this study, we found that a mutant lef-1 lacking the classical NLS accumulated in the nucleus of living cells, when beta-catenin was co-expressed. In addition, in a cell-free import assay, lef-1 migrated into the nucleus in the presence of beta-catenin alone without any other soluble factors. In contrast, another mutant lef-1 lacking the beta-catenin binding domain failed to migrate into the nucleus, even in the presence of beta-catenin. These findings indicate that beta-catenin alone can mediate the nuclear import of lef-1 through the direct binding. Collectively, we propose that there are two distinct pathways for the nuclear import of lef-1: importin alpha/beta-mediated and beta-catenin-mediated one, which provides a novel paradigm for Wnt signaling pathway.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Active Transport, Cell Nucleus / physiology
  • Animals
  • Binding Sites / genetics
  • Cell Nucleus / metabolism*
  • Cytoskeletal Proteins / metabolism*
  • DNA-Binding Proteins / genetics
  • DNA-Binding Proteins / metabolism*
  • Intercellular Signaling Peptides and Proteins / metabolism
  • Lymphoid Enhancer-Binding Factor 1
  • Mice
  • Mutation / genetics
  • NIH 3T3 Cells
  • Nuclear Localization Signals / genetics
  • Protein Binding / genetics
  • Protein Structure, Tertiary / genetics
  • Protein Transport / physiology
  • Receptors, Cytoplasmic and Nuclear / metabolism*
  • Signal Transduction / physiology
  • Trans-Activators / metabolism*
  • Transcription Factors / genetics
  • Transcription Factors / metabolism*
  • Wnt Proteins
  • beta Catenin

Substances

  • CTNNB1 protein, mouse
  • Cytoskeletal Proteins
  • DNA-Binding Proteins
  • Intercellular Signaling Peptides and Proteins
  • Lef1 protein, mouse
  • Lymphoid Enhancer-Binding Factor 1
  • Nuclear Localization Signals
  • Receptors, Cytoplasmic and Nuclear
  • Trans-Activators
  • Transcription Factors
  • Wnt Proteins
  • beta Catenin