Wnt signals are transmitted through N-terminally dephosphorylated [beta]-catenin

[beta]-catenin mediates Wnt signaling by acting as the essential co-activator for TCF transcription factors. Wnt signaling increases the half-life and therefore the absolute level of [beta]-catenin in responding cells. The current model states that these changes in [beta]-catenin stability set the t...

Full description

Saved in:
Bibliographic Details
Published inEMBO reports Vol. 3; no. 1; p. 63
Main Authors Frank J.T. Staal, Mascha van Noort, Strous, Ger J, Clevers, Hans C
Format Journal Article
LanguageEnglish
Published Heidelberg Blackwell Publishing Ltd 15.01.2002
Online AccessGet full text

Cover

More Information
Summary:[beta]-catenin mediates Wnt signaling by acting as the essential co-activator for TCF transcription factors. Wnt signaling increases the half-life and therefore the absolute level of [beta]-catenin in responding cells. The current model states that these changes in [beta]-catenin stability set the threshold for Wnt signaling. However, we find that pharmacological inhibition of proteasome activity by ALLN leads to accumulation of cytosolic [beta]-catenin but not to increased TCF-mediated transcription. In addition, in temperature-sensitive ubiquitylation mutant CHO cells inhibition of ubiquitylation increases [beta]-catenin levels, but does not induce transcriptional activation of TCF reporter genes. Using an antibody specific for [beta]-catenin dephosphorylated at residues Ser37 and Thr41, we show that Wnt signals specifically increase the levels of dephosphorylated [beta]-catenin, whereas ALLN does not. We conclude that changes in the phosphorylation status of the N-terminus of [beta]-catenin that occur upon Wnt signaling independently affect the signaling properties and half-life of [beta]-catenin. Hence, Wnt signals are transduced via N-terminally dephosphorylated [beta]-catenin.
ISSN:1469-221X
1469-3178