Curbing the nuclear activities of β‐catenin

Wnt molecules control numerous developmental processes by altering specific gene expression patterns, and deregulation of Wnt signaling can lead to cancer. Many Wnt factors employ β‐catenin as a nuclear effector. Upon Wnt stimulation, β‐catenin heterodimerizes with T‐cell factor (TCF) DNA‐binding proteins to form a transcriptional activator complex. As the activating subunit of this complex, β‐catenin performs dual tasks: it alleviates repression of target gene promoters and subsequently it activates them. β‐catenin orchestrates these effects by recruiting chromatin modifying cofactors and contacting components of the basal transcription machinery. Although β‐catenin and TCFs are universal activators in Wnt signaling, their target genes display distinct temporal and spatial expression patterns. Apparently, post‐translational modifications modulate the interactions between TCFs and β‐catenin or DNA, and certain transcription factors can sequester β‐catenin from TCFs while others synergize with β‐catenin–TCF complexes in a promoter‐specific manner. These mechanisms provide points of intersection with other signaling pathways, and contribute to the complexity and specificity of Wnt target gene regulation.