Catenin, beta

β-Catenin is a multifunctional adaptor protein involved in cadherin-mediated cell–cell adhesion and in responding to the activation of several signal transduction pathways, including Wnts, Akt/protein kinase B, epidermal growth factor (EGF), insulin-like growth factor, integrin-linked kinase, nuclear factor-κB, p53, Pin1, PTEN, FP(B) prostanoid receptor, nuclear hormone receptors such as peroxisome proliferator-activated receptors (PPARs), androgen receptor (AR) and retinoic acid receptor (RAR), and oxidative stress. Its role is best characterized in the canonical Wnt signaling pathway. On a Wnt signal, β-catenin accumulates in the nucleus and binds to transcription factors of the high-mobility-group (HMG) box Tcf/Lef family to stimulate downstream gene expression. Both the amino-terminal and carboxy-terminal regions mediate transcriptional activation, but the most potent activation domain resides at the C terminus. Direct target genes include c-myc, cyclin D1, c-jun, Tcf-1, Lef-1, Conductin/Axin2, and the metalloproteinase matrilysin (MMP7). The Wnt/β-catenin pathway has central functions in embryonic development, and perturbations in this pathway are linked to a variety of human diseases, most notably cancer. Remarkably, more than 90% of colorectal cancer patients carry an activating mutation in this pathway, including loss-of-function mutations in adenomatous polyposis coli (APC) and Axin, or gain-of-function mutations in β-catenin itself. More recently, β-catenin signaling has been implicated in the maintenance and self-renewal of stem or progenitor cells in various tissues including skin, blood, and gut.