CREB-binding protein and Beta-catenin protein-protein interaction interface (CBP/beta-catenin interaction)

The CREB-binding protein (CBP) and Beta-catenin (CTNNB1) protein-protein interaction (PPI) interface is a critical regulatory node in the canonical Wnt signaling pathway [gosset.ai, BenchChem]. In the nucleus, stabilized beta-catenin recruits transcriptional coactivators, primarily CBP or its paralog p300, to initiate the expression of specific gene sets [NIH, PubMed]. The interaction between beta-catenin and CBP specifically drives the transcription of genes associated with cell proliferation and stem cell self-renewal, such as survivin and c-Myc [NIH, IIAR Journals]. In contrast, the interaction with p300 is associated with cellular differentiation [NIH, PubMed]. Dysregulation of this interface, often leading to constitutive CBP/beta-catenin signaling, is a hallmark of various cancers and fibrotic diseases [NIH, PubMed]. Therapeutic strategies focus on small-molecule inhibitors, such as PRI-724 and ICG-001, which selectively disrupt the CBP/beta-catenin interaction [AACR Journals, Selleckchem]. By blocking this specific PPI, these drugs shift beta-catenin binding toward p300, thereby promoting differentiation and inhibiting the growth of cancer stem cells and myofibroblasts [NIH, ResearchGate]. This targeted approach aims to overcome the broad toxicity often associated with general Wnt pathway inhibition by specifically modulating the balance between proliferation and differentiation [gosset.ai, ResearchGate].

Other names

CBP/beta-catenin complexCBP/CTNNB1 interactionCREBBP/beta-catenin interfaceCBP/beta-catenin signaling axis

Selective disruption of the protein-protein interaction between the N-terminus of CBP and the C-terminus of beta-catenin, which shifts beta-catenin binding from CBP to its paralog p300, thereby switching the transcriptional program from proliferation and self-renewal to differentiation [NIH, PubMed].