The control of beta-catenin and TCF during embryonic development and cancer

The Wnt signaling pathway functions reiteratively during animal development to control cell fate decisions. Inappropriate deregulation of this pathway leads to cancer in a number of tissues. The components that transduce the Wnt signal from the cell membrane to the cell nucleus are well conserved be tween vertebrates and Drosophila. A pivotal Wnt effector is the protein bet a-catenin/Armadillo whose stability in the cytoplasm is low in unstimulated cells. beta-catenin/Armadillo is targetted for proteasome-mediated degrada tion by a protein complex to which it binds. This complex consists of Axin, a putative scaffold protein which also binds to the tumor suppressor Adeno matous polyposis coli (APC) and glycogen synthase kinase 3 (GSK3)/Shaggy. W nt signaling somehow inhibits the kinase activity of the quaternary complex . As a consequence, beta-catenin/Armadillo accumulates in the cytoplasm, tr anslocates to the nucleus and becomes a transcriptional co-activator of T c ell factor (TCF), the ultimate nuclear target of Wnt signaling. TCF is an a rchitectural protein, mediating the assembly of multi-protein enhancer comp lexes. It cooperates with other enhancer-binding proteins and, together wit h beta-catenin/Armadillo, stimulates the transcription of Wnt target genes. Recently, repressors have been identified that prevent TCF from being acti ve in the absence of Wnt signaling.