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

被引：162

作者：

Li, Jiong ^{[1
]}

Wang, Cun-Yu ^{[1
]}

机构：

[1] Univ Calif Los Angeles, Sch Dent, Div Oral Biol & Med, Mol Signalling Lab, Los Angeles, CA 90095 USA

来源：

NATURE CELL BIOLOGY | 2008年 / 10卷 / 02期

关键词：

D O I：

10.1038/ncb1684

中图分类号：

Q2 [细胞生物学];

学科分类号：

071009 ; 090102 ;

摘要：

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.

引用

页码：160 / U36

页数：16

共 41 条

[1] The chromatin remodelling factor Brg-1 interacts with β-catenin to promote target gene activation [J].