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

Fiona M Townsley1, Adam Cliffe, Mariann Bienz

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

Nature Cell Biology
|June 23, 2004
PubMed

Insights

Pygopus (Pygo) and Legless/BCL-9 (Lgs) proteins are crucial for Wnt signaling. They help target beta-catenin to the nucleus, enabling gene transcription for development and cancer.

Area of Science:

  • Molecular Biology
  • Developmental Biology
  • Cell Biology

Background:

  • Wnt signaling regulates gene transcription vital for development and malignancy.
  • Beta-catenin stabilization and nuclear translocation are key events in Wnt pathway activation.
  • Pygopus (Pygo) and Legless/BCL-9 (Lgs) are nuclear proteins that modulate beta-catenin transcriptional activity.

Purpose of the Study:

  • To elucidate the roles of Pygopus (Pygo) and Legless/BCL-9 (Lgs) in controlling beta-catenin nuclear localization and Wnt signaling.
  • To investigate the functional relationship between Pygo, Lgs, and beta-catenin in Drosophila.

Main Methods:

  • Analysis of protein localization in Drosophila embryos and cells.
  • Functional rescue experiments using nuclear localization sequences.
  • Assessment of beta-catenin transcriptional activity in cancer cells.

Main Results:

  • Nuclear localization of Lgs is dependent on Pygo, which acts as a nuclear anchor.
  • Pygo is essential for high nuclear beta-catenin levels during Wnt signaling.
  • Pygo and Lgs enhance beta-catenin transcriptional activity, particularly in APC-mutant cancer cells.
  • Restoring beta-catenin nuclear import rescues developmental defects in pygo and lgs mutant embryos.

Conclusions:

  • Pygopus and Legless/BCL-9 function together to target beta-catenin to the nucleus.
  • This nuclear targeting mechanism is critical for ensuring beta-catenin availability for TCF transcription factors during Wnt signaling.
  • The Pygo-Lgs complex plays a significant role in regulating Wnt-dependent gene expression in both normal development and cancer.

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