β-Catenin (CTNNB1)
β-catenin, encoded by CTNNB1, connects cell–cell adhesion to transcription: at the membrane it anchors cadherins to the actin cytoskeleton, and when stabilized by Wnt signaling it acts as a transcriptional coactivator.
Function
β-catenin has two jobs. At adherens junctions it links E-cadherin to the actin cytoskeleton. In the Wnt pathway, its cytoplasmic pool is normally destroyed: a destruction complex (APC, AXIN, GSK3β, CK1) phosphorylates β-catenin, marking it for ubiquitination and proteasomal degradation. Wnt ligand binding to Frizzled/LRP disables the destruction complex; β-catenin accumulates, enters the nucleus, and partners with TCF/LEF transcription factors to activate Wnt target genes — MYC, cyclin D1, and the stem-cell program. The destruction complex is the pathway’s switch, and its components are the pathway’s tumor suppressors.
In cancer
CTNNB1 mutations that remove the phosphorylation sites stabilize β-catenin constitutively — common in hepatocellular carcinoma and endometrial cancer. More often the pathway is activated upstream: APC loss is the initiating event of most colorectal cancers, and its consequence is nuclear β-catenin in every cell of the adenoma. The Wnt–β-catenin axis also maintains intestinal stem cells, which is why its constitutive activation produces tumors rather than just overgrowth.
Notes
- Human gene symbol: CTNNB1; UniProt P35222; 781 amino acids; armadillo-repeat protein.
- Named for its position in the catenin adhesion complex before its signaling role was discovered.