title: Identification and characterization of E-APC, a novel Drosophila homologue of the tumour suppressor APC.
abstract: 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.
  
  
  CONCLUSIONS
  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.
authors.affiliation: Department of Oncogene Research, Research Institute for Microbial Diseases, Osaka University, 3-1 Yamadaoka, Suita 565-0871, Japan. and
authors.forename: F
authors.initials: F
authors.lastname: Hamada
authors.forename: Y
authors.initials: Y
authors.lastname: Murata
authors.forename: A
authors.initials: A
authors.lastname: Nishida
authors.forename: F
authors.initials: F
authors.lastname: Fujita
authors.forename: Y
authors.initials: Y
authors.lastname: Tomoyasu
authors.forename: M
authors.initials: M
authors.lastname: Nakamura
authors.forename: K
authors.initials: K
authors.lastname: Toyoshima
authors.forename: T
authors.initials: T
authors.lastname: Tabata
authors.forename: N
authors.initials: N
authors.lastname: Ueno
authors.forename: T
authors.initials: T
authors.lastname: Akiyama
mesh_terms: D048868:Adaptor Proteins, Signal Transducing; D025601:Adenomatous Polyposis Coli Protein; D000595:Amino Acid Sequence; D000818:Animals; D051186:Armadillo Domain Proteins; D060466:Axin Protein; D002352:Carrier Proteins / Q000378:metabolism; D003001:Cloning, Molecular; D003598:Cytoskeletal Proteins / Q000737:chemistry* / Q000235:genetics* / Q000378:metabolism; D018076:DNA, Complementary / Q000032:analysis; D004268:DNA-Binding Proteins / Q000378:metabolism; D004330:Drosophila / Q000235:genetics; D029721:Drosophila Proteins; D006801:Humans; D019476:Insect Proteins / Q000378:metabolism; D051821:Lymphoid Enhancer-Binding Factor 1; D008957:Models, Genetic; D008969:Molecular Sequence Data; D010957:Plasmids / Q000378:metabolism; D015534:Trans-Activators; D014157:Transcription Factors / Q000378:metabolism; D014407:Tumor Cells, Cultured; D020798:Two-Hybrid System Techniques; D051176:beta Catenin
chemical_list: C118001:APC protein, Drosophila; C495305:ARM protein, Drosophila; D048868:Adaptor Proteins, Signal Transducing; D025601:Adenomatous Polyposis Coli Protein; D051186:Armadillo Domain Proteins; D060466:Axin Protein; C118000:Axn protein, Drosophila; C495270:CTNNB1 protein, human; D002352:Carrier Proteins; D003598:Cytoskeletal Proteins; D018076:DNA, Complementary; D004268:DNA-Binding Proteins; D029721:Drosophila Proteins; D019476:Insect Proteins; D051821:Lymphoid Enhancer-Binding Factor 1; D015534:Trans-Activators; D014157:Transcription Factors; D051176:beta Catenin