Biochemical interactions in the wnt pathway.
The wnt signal transduction pathway is involved in many differentiation events during embryonic development and can lead to tumor formation after aberrant activation of its components. The cytoplasmic component beta-catenin is central to the transmission of wnt signals to the nucleus: in the absence of wnts beta-catenin is constitutively degraded in proteasomes, whereas in the presence of wnts beta-catenin is stabilized and associates with HMG box transcription factors of the LEF/TCF family. In tumors, beta-catenin degradation is blocked by mutations of the tumor suppressor gene APC (adenomatous polyposis coli), or of beta-catenin itself. As a consequence, constitutive TCF/beta-catenin complexes are formed and activate oncogenic target genes. This review discusses the mechanisms that silence the pathway in cells that do not receive a wnt signal and goes on to describe the regulatory steps involved in the activation of the pathway.
Seidensticker
M J
MJ
Max-Delbrück-Center for Molecular Medicine, Robert-Rössle-Strasse 10, 13122, Berlin, Germany.
Behrens
J
J
D048868:Adaptor Proteins, Signal Transducing; D000818:Animals; D029681:Arabidopsis Proteins; D060466:Axin Protein; D003598:Cytoskeletal Proteins / Q000378:metabolism; D000072261:Dishevelled Proteins; D017491:Genes, APC; D006801:Humans; D051379:Mice; D008817:Mice, Mutant Strains; D010750:Phosphoproteins / Q000378:metabolism; D011494:Protein Kinases / Q000378:metabolism; D011506:Proteins / Q000378:metabolism; D011518:Proto-Oncogene Proteins / Q000235:genetics / Q000378:metabolism*; D012097:Repressor Proteins; D015398:Signal Transduction; D015534:Trans-Activators; D015533:Transcriptional Activation; D014407:Tumor Cells, Cultured; D051153:Wnt Proteins; D029961:Zebrafish Proteins; D051176:beta Catenin
C491761:AXIN2 protein, human; D048868:Adaptor Proteins, Signal Transducing; D029681:Arabidopsis Proteins; D060466:Axin Protein; C111729:Axin2 protein, mouse; C495270:CTNNB1 protein, human; C495267:CTNNB1 protein, mouse; D003598:Cytoskeletal Proteins; D000072261:Dishevelled Proteins; D010750:Phosphoproteins; D011506:Proteins; D011518:Proto-Oncogene Proteins; D012097:Repressor Proteins; D015534:Trans-Activators; D051153:Wnt Proteins; D029961:Zebrafish Proteins; D051176:beta Catenin; D011494:Protein Kinases; C101990:CKI1 protein, Arabidopsis