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

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

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Laboratory of Molecular Signalling, Division of Oral Biology and Medicine, UCLA School of Dentistry, Los Angeles, CA 90095, USA.


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.

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