Article abstract


Nature Cell Biology 10, 160 - 169 (2008)
Published online: 13 January 2008 | doi:10.1038/ncb1684

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

Jiong Li1 & Cun-Yu Wang1


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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  1. 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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