Rac1b recruits dishevelled and β-catenin to Wnt target gene promoters independent of Wnt3A stimulation

Abstract

We previously reported a functional interaction between aberrant Wnt signaling and Rac1/Rac1b GTPases in tumorigenesis. In this study, we further investigated the mechanistic role of nuclear Rac1b. Using chromatin immuno-precipitation (ChIP) studies, we show that Rac1b resides at the promoters of Wnt target genes, c-Myc and Cyclin D1, in HCT116 cells with aberrant Wnt pathway. In HEK293T cells with intact Wnt signaling, Rac1b is tethered to these same gene promoters independent of Wnt3A stimulation and is further observed to recruit Dishevelled and β-catenin in the absence of Wnt3A stimulation. Our studies suggest a novel transcriptional co-activator role of Rac1b in β-catenin/TCF-mediated trans-cription.