In the absence of Wnt stimulation, the APC (adenomatous polyposis coli) forms a trimeric complex, known as the “destruction complex,” with glycogen synthase kinase-3B (GSK) and Axin

In the absence of Wnt stimulation, the APC (adenomatous polyposis coli) forms a trimeric complex, known as the “destruction complex,” with glycogen synthase kinase-3β (GSK) and Axin. This complex then interacts with β-catenin and degrades by the ubiquitin-proteasome pathway. When Wnt ligands bind to the seven-transmembrane receptor, the cytoplasmic protein Dishevelled (Dsh) is recruited to the membrane and binds to Axin1 and Axin2. The mechanism of Dsh-mediated inhibition of Axin is not well understood, but it has been suggested that Dsh might disrupt the destruction complex. Inhibition of Axin results in accumulation of β-catenin, which subsequently translocates into the nucleus. β-catenin interacts with LEF/TCF (lymphocyte enhancer factor/T cell factor) proteins and serves as a coactivator of LEF/TCFs to stimulate transcription of Wnt target gene. Grouch protein (Gro) acts as corepressor of LEF/TCFs and normally binds to LEF/TCFs in the absence of β-catenin. New therapeutic treatments aimed at this pathway include monoclonal antibodies, cyclooxygenase (COX)-2 inhibitors, and several small molecules.

Publication

Liver Stem Cells and Molecular Signaling Pathways in Hepatocellular Carcinoma. (2007) Krit Kitisin, et al. Gastrointest Cancer Res. 2007 Jul-Aug;1(4 Suppl 2):S13-S21. Figure: F3. All organisms Drosophila melanogaster Homo sapiens Danio rerio

Disease mentions