Beta-catenin–CREB-binding protein protein-protein interaction (β-catenin–CBP interaction)

The **β-catenin–CREB-binding protein (CBP) protein-protein interaction** is a critical regulatory event in the canonical Wnt signaling pathway, mediating transcriptional activation of Wnt target genes. In the nucleus, β-catenin recruits the transcriptional co-activator CBP to gene promoters, enabling chromatin remodeling and transcription of genes involved in cell proliferation, differentiation, and stem cell maintenance[1][2][3][4][5]. Dysregulation of Wnt/β-catenin signaling, often through aberrant β-catenin–CBP complex formation, is a hallmark of many cancers and contributes to tumor initiation, progression, and therapeutic resistance. Therapeutic inhibition of the β-catenin–CBP interaction is an emerging strategy to selectively block oncogenic Wnt signaling, with small-molecule inhibitors (e.g., ICG-001, C82, E7386) designed to disrupt the interaction, skewing β-catenin activity away from gene programs that promote cancer cell self-renewal and proliferation toward those favoring differentiation[3][4][5][7]. This PPI is also implicated in the regulation of normal stem cell function, adding complexity to its therapeutic targeting[5].

Other names

β-catenin/CBP interactionBeta-catenin–CBP complexBeta-catenin–CREB-binding protein interactionβ-catenin–CBP PPIβ-catenin/CBP protein-protein interaction

Small molecule inhibition: Drugs (e.g., ICG-001, E7386, C82) disrupt the protein-protein interaction between β-catenin and CBP, resulting in selective inhibition of β-catenin/TCF-mediated transcription and blocking downstream Wnt pathway gene activation[3][4][5][7]. Transcriptional modulation: By inhibiting β-catenin–CBP binding, these compounds bias β-catenin to interact instead with p300 (a related co-activator), thereby promoting differentiation over proliferation[5].