title: 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 immunoprecipitation (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 transcription.
authors.affiliation: Samuel Lunenfeld Research Institute, Mount Sinai Hospital, Toronto, Ontario, M5T 3L9, Canada.
authors.forename: Vaijayanti V
authors.initials: VV
authors.lastname: Pethe
authors.forename: George S
authors.initials: GS
authors.lastname: Charames
authors.forename: Bharati
authors.initials: B
authors.lastname: Bapat
mesh_terms: D048868:Adaptor Proteins, Signal Transducing / Q000235:genetics / Q000378:metabolism*; D001665:Binding Sites; D045744:Cell Line, Tumor; D002467:Cell Nucleus / Q000235:genetics / Q000378:metabolism; D047369:Chromatin Immunoprecipitation / Q000379:methods; D019938:Cyclin D1 / Q000235:genetics / Q000378:metabolism; D000072261:Dishevelled Proteins; D016259:Genes, myc; D045325:HCT116 Cells; D057809:HEK293 Cells; D006801:Humans; D010750:Phosphoproteins / Q000235:genetics / Q000378:metabolism*; D011401:Promoter Regions, Genetic; D011485:Protein Binding; D015398:Signal Transduction; D051820:TCF Transcription Factors / Q000235:genetics / Q000378:metabolism; D014158:Transcription, Genetic / Q000235:genetics; D060509:Wnt3A Protein / Q000235:genetics* / Q000378:metabolism*; D051176:beta Catenin / Q000235:genetics / Q000378:metabolism*; D020830:rac1 GTP-Binding Protein / Q000235:genetics / Q000378:metabolism*
chemical_list: D048868:Adaptor Proteins, Signal Transducing; C530104:CCND1 protein, human; C495270:CTNNB1 protein, human; D000072261:Dishevelled Proteins; D010750:Phosphoproteins; C107953:RAC1 protein, human; D051820:TCF Transcription Factors; C555510:WNT3A protein, human; D060509:Wnt3A Protein; D051176:beta Catenin; D019938:Cyclin D1; D020830:rac1 GTP-Binding Protein