Catenin beta-1 (CTNNB1) C-terminal transactivation domain (CTNNB1 C-TAD)

The C-terminal transactivation domain (C-TAD) of Catenin beta-1 (beta-catenin) is a critical region, typically spanning residues 665–781, responsible for recruiting transcriptional co-activators to the Wnt signaling complex (UniProt P35222). In the presence of Wnt ligands, beta-catenin translocates to the nucleus where its C-TAD interacts with proteins such as CREB-binding protein (CBP) and p300 to initiate the transcription of oncogenic target genes like c-Myc and Cyclin D1 (PubMed: 23045546). This domain is intrinsically disordered, allowing it to bind a variety of partners and serve as a hub for signal integration (PubMed: 22510413). Dysregulation of this domain's activity, often through mutations that stabilize beta-catenin, is a hallmark of various malignancies, particularly colorectal and hepatocellular carcinomas (NIH: PMC3590259). Therapeutic strategies targeting the C-TAD aim to disrupt these protein-protein interactions, thereby selectively inhibiting the pathological Wnt signaling pathway while sparing other beta-catenin functions like cell-cell adhesion. Small molecules like PRI-724 have been developed to specifically block the C-TAD/CBP interaction, showing promise in clinical trials for cancer and fibrotic diseases (PubMed: 28254271).

Other names

Beta-catenin C-terminal domainCTNNB1 C-terminal transactivation domainC-TAD of beta-cateninC-terminal transactivation domain of beta-catenin

Inhibition of the protein-protein interaction between the beta-catenin C-terminal transactivation domain and transcriptional co-activators (CBP or p300) to suppress Wnt-target gene expression.