TBL1-TBLR1 and beta-catenin recruit each other to Wnt target-gene promoter for transcription activation and oncogenesis

Nat Cell Biol. 2008 Feb;10(2):160-9. doi: 10.1038/ncb1684. Epub 2008 Jan 13.


Aberrant Wnt signalling promotes oncogenesis by increasing the nuclear accumulation of beta-catenin to activate downstream target genes. However, the mechanism of beta-catenin recruitment to the Wnt target-gene promoter, a critical step for removing the co-repressor complex, is largely unknown. Here, we report that transducin beta-like protein 1 (TBL1) and its highly related family member TBLR1 were required for Wnt-beta-catenin-mediated transcription. Wnt signalling induced the interaction between beta-catenin and TBL1-TBLR1, as well as their binding to Wnt target genes. Importantly, the recruitment of TBL1-TBLR1 and beta-catenin to Wnt target-gene promoters was mutually dependent on each other. Furthermore, the depletion of TBL1-TBLR1 significantly inhibited Wnt-beta-catenin-induced gene expression and oncogenic growth in vitro and in vivo. Our results unravel two new components required for nuclear beta-catenin function, and have important implications in developing new strategies for inhibiting Wnt-beta-catenin-mediated tumorigenesis.

Publication types

  • Research Support, N.I.H., Extramural

MeSH terms

  • Cell Line
  • Cell Line, Tumor
  • Cell Transformation, Neoplastic / metabolism*
  • Humans
  • Nuclear Proteins / metabolism*
  • Promoter Regions, Genetic*
  • Proteasome Endopeptidase Complex / metabolism
  • Protein Transport
  • Receptors, Cytoplasmic and Nuclear / metabolism*
  • Repressor Proteins / metabolism*
  • Signal Transduction
  • Transcriptional Activation / physiology*
  • Transducin / metabolism*
  • Wnt Proteins / genetics
  • Wnt Proteins / metabolism*
  • Wnt3 Protein
  • beta Catenin / physiology*


  • Nuclear Proteins
  • Receptors, Cytoplasmic and Nuclear
  • Repressor Proteins
  • TBL1X protein, human
  • TBL1XR1 protein, human
  • Wnt Proteins
  • Wnt3 Protein
  • beta Catenin
  • Proteasome Endopeptidase Complex
  • Transducin