%0 Journal Article
%T Rac1 GTPase and the Rac1 exchange factor Tiam1 associate with Wnt-responsive promoters to enhance beta-catenin/TCF-dependent transcription in colorectal cancer cells
%A Pinella Buongiorno
%A Vaijayanti V Pethe
%A George S Charames
%A Susmita Esufali
%A Bharati Bapat
%J Molecular Cancer
%D 2008
%I BioMed Central
%R 10.1186/1476-4598-7-73
%X We employed chromatin immunoprecipitation studies to demonstrate that Rac1 associates with the ¦Â-catenin/TCF complex at Wnt-responsive promoters of target genes. This association served to facilitate transcription, since overexpression of active Rac1 augmented Wnt target gene activation, whereas depletion of endogenous Rac1 by RNA interference abrogated this effect. In addition, the Rac1-specific exchange factor, Tiam1, potentiated the stimulatory effects of Rac1 on the canonical Wnt pathway. Tiam1 promoted the formation of a complex containing Rac1 and ¦Â-catenin. Furthermore, endogenous Tiam1 associated with endogenous ¦Â-catenin, and this interaction was enhanced in response to Wnt3a stimulation. Intriguingly, Tiam1 was recruited to Wnt-responsive promoters upon Wnt3a stimulation, whereas Rac1 was tethered to TCF binding elements in a Wnt-independent manner.Taken together, our results suggest that Rac1 and the Rac1-specific activator Tiam1 are components of transcriptionally active ¦Â-catenin/TCF complexes at Wnt-responsive promoters, and the presence of Rac1 and Tiam1 within these complexes serves to enhance target gene transcription. Our results demonstrate a novel functional mechanism underlying the cross-talk between Rac1 and the canonical Wnt signalling pathway.Rac1 GTPase is a member of the Rho family of small GTPases, which play critical roles in the regulation of various cellular processes that include reorganization of the actin cytoskeleton, cell-cycle progression, intercellular adhesion, and gene expression [reviewed in [1]]. Rho family proteins act as molecular switches that cycle between an inactive GDP-bound state and an active GTP-bound state. This cycling is regulated by proteins such as guanine nucleotide exchange factors (GEFs) that activate Rho GTPases by accelerating GDP to GTP exchange, and GTPase activating proteins (GAPs) that deactivate Rho GTPases by increasing their intrinsic rate of GTP hydrolysis. Active, GTP-bound Rho GTPases interact wi
%U http://www.molecular-cancer.com/content/7/1/73