Identification and characterization of E-APC, a novel Drosophila homologue of the tumour suppressor APC

Genes Cells. 1999 Aug;4(8):465-74. doi: 10.1046/j.1365-2443.1999.00272.x.


Background: Mutations in the adenomatous polyposis coli (APC) tumour suppressor gene are implicated in the genesis of colorectal cancers. The product of the APC gene forms a complex with beta-catenin, glycogen synthase kinase 3beta (GSK-3beta) and Axin/conductin, and induces the degradation of beta-catenin.

Results: We have identified a novel Drosophila homologue of APC, E-APC, which is similar to but differs in several respects from D-APC. The E-APC cDNA encodes a protein of predicted 1067 amino acids, with seven armadillo repeats, two copies of the 15-amino acid repeat, five copies of the 20-amino acid repeat, and one Axin/conductin binding site. E-APC directly interacts with D-Axin and Armadillo (Arm, the Drosophila homologue of beta-catenin) in vitro, destabilizes intracellular beta-catenin, and suppresses beta-catenin/TCF-regulated transcription in APC-/- colon cancer cells. The E-APC mRNA is ubiquitously expressed throughout all developmental stages in Drosophila.

Conclusion: Our findings suggest that E-APC may be universally involved in the regulation of the Wingless signalling pathway by down-regulating the level of Arm in Drosophila.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adaptor Proteins, Signal Transducing*
  • Adenomatous Polyposis Coli Protein
  • Amino Acid Sequence
  • Animals
  • Armadillo Domain Proteins
  • Axin Protein
  • Carrier Proteins / metabolism
  • Cloning, Molecular
  • Cytoskeletal Proteins / chemistry*
  • Cytoskeletal Proteins / genetics*
  • Cytoskeletal Proteins / metabolism
  • DNA, Complementary / analysis
  • DNA-Binding Proteins / metabolism
  • Drosophila / genetics
  • Drosophila Proteins*
  • Humans
  • Insect Proteins / metabolism
  • Lymphoid Enhancer-Binding Factor 1
  • Models, Genetic
  • Molecular Sequence Data
  • Plasmids / metabolism
  • Trans-Activators*
  • Transcription Factors / metabolism
  • Tumor Cells, Cultured
  • Two-Hybrid System Techniques
  • beta Catenin


  • APC protein, Drosophila
  • ARM protein, Drosophila
  • Adaptor Proteins, Signal Transducing
  • Adenomatous Polyposis Coli Protein
  • Armadillo Domain Proteins
  • Axin Protein
  • Axn protein, Drosophila
  • CTNNB1 protein, human
  • Carrier Proteins
  • Cytoskeletal Proteins
  • DNA, Complementary
  • DNA-Binding Proteins
  • Drosophila Proteins
  • Insect Proteins
  • Lymphoid Enhancer-Binding Factor 1
  • Trans-Activators
  • Transcription Factors
  • beta Catenin