The Wnt signaling pathway in cellular proliferation and differentiation: A tale of two coactivators.

Wnt signaling pathways play divergent roles during development, normal homeostasis and disease. The responses that result from the activation of the pathway control both proliferation and differentiation. Tight regulation and controlled coordination of the Wnt signaling cascade is required to maintain the balance between proliferation and differentiation. The non-redundant roles of the coactivator proteins CBP and p300, within the context of Wnt signaling are discussed. We highlight their roles as integrators of the various inputs that a cell receives to elicit the correct and coordinated response. We propose that essentially all cellular information - i.e. from other signaling pathways, nutrient levels, etc. - is funneled down into a choice of coactivators usage, either CBP or p300, by their interacting partner beta-catenin (or catenin-like molecules in the absence of beta-catenin) to make the critical decision to either remain quiescent, or once entering cycle to proliferate without differentiation or to initiate the differentiation process.