Curbing the nuclear activities of beta-catenin. Control over Wnt target gene expression.
Wnt molecules control numerous developmental processes by altering specific gene expression patterns, and deregulation of Wnt signaling can lead to cancer. Many Wnt factors employ beta-catenin as a nuclear effector. Upon Wnt stimulation, beta-catenin heterodimerizes with T-cell factor (TCF) DNA-binding proteins to form a transcriptional activator complex. As the activating subunit of this complex, beta-catenin performs dual tasks: it alleviates repression of target gene promoters and subsequently it activates them. Beta-catenin orchestrates these effects by recruiting chromatin modifying cofactors and contacting components of the basal transcription machinery. Although beta-catenin and TCFs are universal activators in Wnt signaling, their target genes display distinct temporal and spatial expression patterns. Apparently, post-translational modifications modulate the interactions between TCFs and beta-catenin or DNA, and certain transcription factors can sequester beta-catenin from TCFs while others synergize with beta-catenin-TCF complexes in a promoter-specific manner. These mechanisms provide points of intersection with other signaling pathways, and contribute to the complexity and specificity of Wnt target gene regulation.
Hecht
A
A
Max-Planck-Institute of Immunobiology, Freiburg, Germany. hecht@immunbio.mpg.de
Kemler
R
R
D000818:Animals; D002467:Cell Nucleus / Q000378:metabolism*; D003598:Cytoskeletal Proteins / Q000378:metabolism*; D004268:DNA-Binding Proteins / Q000378:metabolism; D005786:Gene Expression Regulation; D011518:Proto-Oncogene Proteins / Q000235:genetics* / Q000378:metabolism; D015398:Signal Transduction; D015534:Trans-Activators; D014157:Transcription Factors / Q000378:metabolism*; D051153:Wnt Proteins; D029961:Zebrafish Proteins; D051176:beta Catenin
D003598:Cytoskeletal Proteins; D004268:DNA-Binding Proteins; D011518:Proto-Oncogene Proteins; D015534:Trans-Activators; D014157:Transcription Factors; D051153:Wnt Proteins; D029961:Zebrafish Proteins; D051176:beta Catenin