CREB-binding protein–beta-catenin complex (CBP–beta-catenin complex)

The CREB-binding protein–beta-catenin complex (CBP–β-catenin complex) is a nuclear protein complex formed by the direct interaction of beta-catenin, a central effector of the Wnt signaling pathway, with the transcriptional coactivator CBP (CREB-binding protein)[3][5][6]. This interaction is essential for the transcriptional activation of Wnt target genes involved in cell proliferation, differentiation, and stem cell maintenance[3][5]. CBP and its paralog p300 serve as key coactivators for β-catenin, but the CBP–β-catenin interaction is functionally distinct and pharmacologically targetable[6]. Disruption of the CBP–β-catenin interaction by small molecules such as ICG-001 selectively represses genes mediated by this complex without affecting the β-catenin–p300 interaction, thus providing a mechanism to modulate Wnt-driven transcription in cancer and fibrotic diseases while aiming to minimize systemic toxicity[6]. The CBP–β-catenin complex is a validated therapeutic target with ongoing development of small molecule inhibitors in preclinical and clinical studies.

Other names

CBP–β-catenin complexCREB-binding protein–β-catenin complexCBP/β-catenin interactionβ-catenin–CBP interaction

Drugs such as ICG-001 selectively inhibit the interaction between CBP and β-catenin, thereby blocking CBP-dependent β-catenin-mediated transcription of Wnt target genes.[6] This leads to altered gene expression patterns favoring differentiation over proliferation, making it a rational mechanism for anticancer and antifibrotic therapy.