biostudies-literatureUnknown3(9-10)Dayma KThe guanine nucleotide exchange factor C3G (RAPGEF1) regulates proliferation, migration, and differentiation of cells and is essential for mammalian embryonic development. The molecular effectors of C3G dependent functions are poorly understood. Here we report that C3G functions as a negative regulator of β-catenin, a major player in pathways known to be deregulated in human cancers. In mammalian cells, C3G is present in a complex with cellular β-catenin. The proline rich Crk binding region of C3G and residues 90-525 of β-catenin are sufficient for the interaction. Knockdown of cellular C3G stimulated, and its overexpression repressed, β-catenin/TCF transcription activity. C3G acts by destabilizing β-catenin protein and inhibiting its nuclear accumulation. Nuclear extracts of C3G overexpreGenes & cancer564-77https://www.ebi.ac.uk/biostudies/studies/S-EPMC3591095biostudies-literatureReciprocal Negative Regulation between the Guanine Nucleotide Exchange Factor C3G and β-Catenin.PMC3591095Dayma KRadha VRamadhas ASasikumar KfalseReciprocal Negative Regulation between the Guanine Nucleotide Exchange Factor C3G and β-Catenin.The guanine nucleotide exchange factor C3G (RAPGEF1) regulates proliferation, migration, and differentiation of cells and is essential for mammalian embryonic development. The molecular effectors of C3G dependent functions are poorly understood. Here we report that C3G functions as a negative regulator of β-catenin, a major player in pathways known to be deregulated in human cancers. In mammalian cells, C3G is present in a complex with cellular β-catenin. The proline rich Crk binding region of C3G and residues 90-525 of β-catenin are sufficient for the interaction. Knockdown of cellular C3G stimulated, and its overexpression repressed, β-catenin/TCF transcription activity. C3G acts by destabilizing β-catenin protein and inhibiting its nuclear accumulation. Nuclear extracts of C3G overexpre2012-01-01T00:00:00Z2012 Sep2025-04-26T15:29:18.506Z2019-03-27T01:05:44ZS-EPMC35910952348666110.1177/1947601912471189