title: The control of beta-catenin and TCF during embryonic development and cancer.
abstract: 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 between vertebrates and Drosophila. A pivotal Wnt effector is the protein beta-catenin/Armadillo whose stability in the cytoplasm is low in unstimulated cells. Beta-catenin/Armadillo is targetted for proteasome-mediated degradation by a protein complex to which it binds. This complex consists of Axin, a putative scaffold protein which also binds to the tumor suppressor Adenomatous polyposis coli (APC) and glycogen synthase kinase 3 (GSK3)/Shaggy. Wnt signaling somehow inhibits the kinase activity of the quaternary complex. As a consequence, beta-catenin/Armadillo accumulates in the cytoplasm, translocates to the nucleus and becomes a transcriptional co-activator of T cell factor (TCF), the ultimate nuclear target of Wnt signaling. TCF is an architectural protein, mediating the assembly of multi-protein enhancer complexes. It cooperates with other enhancer-binding proteins and, together with beta-catenin/Armadillo, stimulates the transcription of Wnt target genes. Recently, repressors have been identified that prevent TCF from being active in the absence of Wnt signaling.
authors.affiliation: MRC Laboratory of Molecular Biology, Cambridge, UK.
authors.forename: L
authors.initials: L
authors.lastname: Waltzer
authors.forename: M
authors.initials: M
authors.lastname: Bienz
mesh_terms: D000818:Animals; D003598:Cytoskeletal Proteins / Q000378:metabolism*; D004330:Drosophila / Q000196:embryology*; D029721:Drosophila Proteins; D004625:Embryo, Nonmammalian / Q000378:metabolism*; D015972:Gene Expression Regulation, Neoplastic; D006609:High Mobility Group Proteins / Q000378:metabolism*; D006801:Humans; D009374:Neoplasms, Experimental / Q000378:metabolism*; D011518:Proto-Oncogene Proteins / Q000502:physiology; D012097:Repressor Proteins / Q000378:metabolism*; D015398:Signal Transduction / Q000502:physiology; D015534:Trans-Activators; D014157:Transcription Factors; D051153:Wnt Proteins; D029961:Zebrafish Proteins; D051176:beta Catenin
chemical_list: C495270:CTNNB1 protein, human; D003598:Cytoskeletal Proteins; D029721:Drosophila Proteins; D006609:High Mobility Group Proteins; D011518:Proto-Oncogene Proteins; D012097:Repressor Proteins; D015534:Trans-Activators; D014157:Transcription Factors; D051153:Wnt Proteins; D029961:Zebrafish Proteins; D051176:beta Catenin; C115159:pan protein, Drosophila