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Pygopus and Legless target Armadillo/β-catenin to the nucleus to enable its transcriptional co-activator function

Nature Cell Biology volume 6, pages 626–633 (2004)Cite this article

Abstract

Wnt signalling controls the transcription of genes that function during normal and malignant development1,2. Stimulation by canonical Wnt ligands activates β-catenin (or Drosophila melanogaster Armadillo) by blocking its phosphorylation, resulting in its stabilization and translocation to the nucleus. Here, Armadillo/β-catenin binds to TCF/LEF transcription factors and recruits chromatin-modifying and -remodelling complexes to transcribe Wnt target genes3,4,5,6. The transcriptional activity of Armadillo/β-catenin depends on two conserved nuclear proteins recently discovered in Drosophila, Pygopus (Pygo) and Legless/BCL-9 (Lgs)7,8,9,10. Lgs functions as an adaptor between Pygo and Armadillo/β-catenin7, but how Armadillo/β-catenin is controlled by Pygo and Lgs is not known. Here, we show that the nuclear localization of Lgs entirely depends on Pygo, which itself is constitutively localized to the nucleus; thus, Pygo functions as a nuclear anchor. Pygo is also required for high nuclear Armadillo levels during Wingless signalling, and together with Lgs increases the transcriptional activity of β-catenin in APC mutant cancer cells. Notably, linking Armadillo to a nuclear localization sequence rescues pygo and lgs mutant fly embryos. This indicates that Pygo and Lgs function in targeting Armadillo/β-catenin to the nucleus, thus ensuring its availability to TCF during Wnt signalling.

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Figure 4: Co-expressed Pygo and Lgs can increase the nuclear level and function of β-catenin.
Figure 1: In Drosophila, nuclear localization of Lgs depends on pygo, but not vice versa.
Figure 2: Nuclear-cytoplasmic shuttling of Lgs and β-catenin in comparison with Pygo and TCF.
Figure 3: pygo is required for high levels of nuclear Armadillo during Wingless signalling.
Figure 5: NLS–Armadillo bypasses the functions of Pygo and Lgs.

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Acknowledgements

We would like to thank K. Basler for Lgs reagents, M. Peifer for the NLS–Armadillo stock, B. Nichols and K. Schmidt for advice with the photobleaching experiments, R. Rosin-Arbesfeld and F. Hamada for plasmids, and B. Thompson, B. Nichols and H. Pelham for discussion and critical comments on the manuscript.

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  1. MRC Laboratory of Molecular Biology, Hills Road, Cambridge, CB2 2QH, UK

    Fiona M. Townsley, Adam Cliffe & Mariann Bienz

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  1. Fiona M. Townsley
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Correspondence to Mariann Bienz.

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Townsley, F., Cliffe, A. & Bienz, M. Pygopus and Legless target Armadillo/β-catenin to the nucleus to enable its transcriptional co-activator function. Nat Cell Biol 6, 626–633 (2004). https://doi.org/10.1038/ncb1141

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