A new Drosophila APC homologue associated with adhesive zones of epithelial cells

Nat Cell Biol. 1999 Jul;1(3):144-51. doi: 10.1038/11064.


Adenomatous polyposis coli protein (APC) is an important tumour suppressor in the human colon epithelium. In a complex with glycogen synthase kinase-3 (GSK-3), APC binds to and destabilizes cytoplasmic ('free') beta-catenin. Here, using a yeast two-hybrid screen for proteins that bind to the Drosophila beta-catenin homologue, Armadillo, we identify a new Drosophila APC homologue, E-APC. E-APC also binds to Shaggy, the Drosophila GSK-3 homologue. Interference with E-APC function produces embryonic phenotypes like those of shaggy mutants. Interestingly, E-APC is concentrated in apicolateral adhesive zones of epithelial cells, along with Armadillo and E-cadherin, which are both integral components of the adherens junctions in these zones. Various mutant conditions that cause dissociation of E-APC from these zones also obliterate the segmental modulation of free Armadillo levels that is normally induced by Wingless signalling. We propose that the Armadillo-destabilizing protein complex, consisting of E-APC, Shaggy, and a third protein, Axin, is anchored in adhesive zones, and that Wingless signalling may inhibit the activity of this complex by causing dissociation of E-APC from these zones.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adenomatous Polyposis Coli Protein
  • Amino Acid Sequence
  • Animals
  • Armadillo Domain Proteins
  • Binding Sites
  • Cell Adhesion
  • Cell Membrane / physiology
  • Cell Membrane / ultrastructure
  • Cytoskeletal Proteins / chemistry*
  • Cytoskeletal Proteins / genetics
  • Cytoskeletal Proteins / metabolism*
  • Drosophila Proteins*
  • Drosophila melanogaster / genetics
  • Drosophila melanogaster / physiology*
  • Epithelial Cells / cytology
  • Epithelial Cells / physiology*
  • Genes, APC
  • Humans
  • Insect Proteins / metabolism
  • Microscopy, Confocal
  • Molecular Sequence Data
  • Phenotype
  • RNA, Double-Stranded / genetics
  • Sequence Alignment
  • Sequence Homology, Amino Acid
  • Trans-Activators*
  • Transcription Factors


  • ARM protein, Drosophila
  • Adenomatous Polyposis Coli Protein
  • Armadillo Domain Proteins
  • Cytoskeletal Proteins
  • Drosophila Proteins
  • Insect Proteins
  • RNA, Double-Stranded
  • Trans-Activators
  • Transcription Factors