Beta-catenin directly displaces Groucho/TLE repressors from Tcf/Lef in Wnt-mediated transcription activation

Nat Struct Mol Biol. 2005 Apr;12(4):364-71. doi: 10.1038/nsmb912. Epub 2005 Mar 13.


Wnt growth factors mediate cell fate determination during embryogenesis and in the renewal of tissues in the adult. Wnts act by stabilizing cellular levels of the transcriptional coactivator beta-catenin, which forms complexes with sequence-specific DNA-binding Tcf/Lef transcription factors. In the absence of nuclear beta-catenin, Tcf/Lefs act as transcriptional repressors by binding to Groucho/TLE proteins. The molecular basis of the switch from transcriptional repression to activation during Wnt signaling has not been clear, in particular whether factors other than beta-catenin are required to disrupt the interaction between Groucho/TLE and Tcf/Lef. Using highly purified proteins, we demonstrate that beta-catenin displaces Groucho/TLE from Tcf/Lef by binding to a previously unidentified second, low-affinity binding site on Lef-1 that includes sequences just N-terminal to the DNA-binding domain, and that overlaps the Groucho/TLE-binding site.

Publication types

  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Animals
  • Co-Repressor Proteins
  • Cytoskeletal Proteins / genetics
  • Cytoskeletal Proteins / metabolism*
  • DNA / metabolism
  • DNA-Binding Proteins / genetics
  • DNA-Binding Proteins / metabolism*
  • Humans
  • Intercellular Signaling Peptides and Proteins / metabolism*
  • Lymphoid Enhancer-Binding Factor 1
  • Mice
  • Peptide Fragments / genetics
  • Peptide Fragments / metabolism
  • Protein Binding
  • Repressor Proteins / genetics
  • Repressor Proteins / metabolism*
  • Trans-Activators / genetics
  • Trans-Activators / metabolism*
  • Transcription Factors / genetics
  • Transcription Factors / metabolism*
  • Transcriptional Activation / genetics*
  • Wnt Proteins
  • beta Catenin


  • CTNNB1 protein, human
  • CTNNB1 protein, mouse
  • Co-Repressor Proteins
  • Cytoskeletal Proteins
  • DNA-Binding Proteins
  • Intercellular Signaling Peptides and Proteins
  • LEF1 protein, human
  • Lef1 protein, mouse
  • Lymphoid Enhancer-Binding Factor 1
  • Peptide Fragments
  • Repressor Proteins
  • TLE1 protein, human
  • Tle1 protein, mouse
  • Trans-Activators
  • Transcription Factors
  • Wnt Proteins
  • beta Catenin
  • DNA