Wnt信号通路
连环蛋白
癌变
发起人
生物
细胞生物学
抑制因子
LRP5
转录因子
基因
LRP6型
连环素
抄写(语言学)
基因表达
分子生物学
遗传学
信号转导
语言学
哲学
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.
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