Identification and characterization of E-APC, a novel Drosophila homologue of the tumour suppressor APC.
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.
Hamada
F
F
Department of Oncogene Research, Research Institute for Microbial Diseases, Osaka University, 3-1 Yamadaoka, Suita 565-0871, Japan. and
Murata
Y
Y
Nishida
A
A
Fujita
F
F
Tomoyasu
Y
Y
Nakamura
M
M
Toyoshima
K
K
Tabata
T
T
Ueno
N
N
Akiyama
T
T
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
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