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Cancer and Metastasis Reviews

, Volume 18, Issue 2, pp 231–246 | Cite as

The Control of β-catenin and TCF During Embryonic Development and Cancer

  • Lucas Waltzer
  • Mariann Bienz
Article

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 β-catenin/Armadillo whose stability in the cytoplasm is low in unstimulated cells. β-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, β-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 β-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.

Wnt signaling Wingless Armadillo T cell factor Axin Adenomatous polyposis coli 

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Copyright information

© Kluwer Academic Publishers 1999

Authors and Affiliations

  • Lucas Waltzer
    • 1
  • Mariann Bienz
    • 1
  1. 1.MRC Laboratory of Molecular BiologyCambridgeUK

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