Betacatenin

Beta-catenin, also written as β-catenin, is a multifunctional protein that participates in cell–cell adhesion and in the canonical Wnt signaling pathway. In humans it is encoded by the CTNNB1 gene.

In adherens junctions, β-catenin binds to the cytoplasmic tails of classical cadherins and links them to the actin cytoskeleton through α-catenin, contributing to tissue architecture and mechanical integrity. In Wnt signaling, it acts as a transcriptional co-activator when stabilized, partnering with TCF/LEF transcription factors to activate target genes such as MYC and CCND1.

Regulation of β-catenin levels is tightly controlled. In the absence of Wnt, a destruction complex containing APC, Axin, and kinases such as CK1 and GSK-3β phosphorylates β-catenin at residues including Ser33, Ser37, Thr41 and Ser45, triggering ubiquitination by β-TrCP and proteasomal degradation. Wnt ligands inhibit the destruction complex, allowing β-catenin to accumulate and translocate to the nucleus where it influences gene expression.

Clinical relevance is evident in cancers and developmental disorders. Somatic mutations in CTNNB1 or in components of the destruction complex can lead to constitutive β-catenin signaling and are associated with hepatocellular carcinoma, colorectal cancer, endometrial cancer, and other conditions, reflecting its central role in cell adhesion and transcriptional regulation.