Article abstract
Nature Cell Biology 10, 160 - 169 (2008)
Published online: 13 January 2008 | doi:10.1038/ncb1684
TBL1–TBLR1 and 
-catenin recruit each other to Wnt target-gene promoter for transcription activation and oncogenesis
Abstract
Aberrant Wnt signalling promotes oncogenesis by increasing the nuclear accumulation of 
-catenin to activate downstream target genes. However, the mechanism of -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 -like protein 1 (TBL1) and its highly related family member TBLR1 were required for Wnt–-catenin-mediated transcription. Wnt signalling induced the interaction between -catenin and TBL1–TBLR1, as well as their binding to Wnt target genes. Importantly, the recruitment of TBL1–TBLR1 and -catenin to Wnt target-gene promoters was mutually dependent on each other. Furthermore, the depletion of TBL1–TBLR1 significantly inhibited Wnt–-catenin-induced gene expression and oncogenic growth in vitro and in vivo. Our results unravel two new components required for nuclear -catenin function, and have important implications in developing new strategies for inhibiting Wnt–-catenin-mediated tumorigenesis.
- Laboratory of Molecular Signalling, Division of Oral Biology and Medicine, UCLA School of Dentistry, Los Angeles, CA 90095, USA
Correspondence to: Cun-Yu Wang1 e-mail: cwang@dentistry.ucla.edu
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