Mosimann C, Hausmann G, Basler K.. Beta-catenin hits chromatin: regulation of Wnt target gene activation. Nat Rev Mol Cell Biol 10: 276-286

National Research Center Frontiers in Genetics, Institut für Molekularbiologie, Universität Zürich, Winterthurerstrasse 190, 8057 Zürich, Switzerland.
Nature Reviews Molecular Cell Biology (Impact Factor: 37.81). 05/2009; 10(4):276-86. DOI: 10.1038/nrm2654
Source: PubMed


The canonical Wnt pathway has gathered much attention in recent years owing to its fundamental contribution to metazoan development, tissue homeostasis and human malignancies. Wnt target gene transcription is regulated by nuclear beta-catenin, and genetic assays have revealed various collaborating protein cofactors. Their daunting number and diverse nature, however, make it difficult to arrange an orderly picture of the nuclear Wnt transduction events. Yet, these findings emphasize that beta-catenin-mediated transcription affects chromatin. How does beta-catenin cope with chromatin regulation to turn on Wnt target genes?

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    • "The destruction complex is then sequestered at the plasma membrane, which prevents phosphorylation of catenin . Stabilised -catenin can then migrate into the nucleus, where it displaces Groucho/TLE repressors from LEF/TCF transcription factors to allow recruitment of coactivators such as CBP/p300 and BCL9/pygo, which triggers transcription of WNT pathway target genes (Daniels and Weis, 2005; Mosimann et al., 2009) (Figure 2B). "
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    • "The β-catenin level is kept low by a continued process of phosphorylation-dependent ubiquitination and degradation [20,22,34,35]. When the kinases that phosphorylate and destabilize β-catenin are inhibited, β-catenin will travel to and accumulate in the nuclei, where it associates with TCF/LEF transcription factors to activate its responsible genes [20,22,34,35]. "
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    • "Our results highlight the importance of interactions between the subcellular APC network and the adhesion and Wnt gradients in the crypt. The shuttling function of APC coordinates cell adhesion with the transcriptional activity of b-catenin, which induces genes that stimulate proliferation, such as cyclin D and c-Myc (Mosimann et al., 2009; Sansom et al., 2005). Wnt also downregulates E-cadherin expression, thereby exerting a negative feedback on the adhesion pool. "
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