A Drosophila homolog of the tumor suppressor gene adenomatous polyposis coli down-regulates beta-catenin but its zygotic expression is not essential for the regulation of Armadillo.
Mutations in the adenomatous polyposis coli gene (which encodes a protein called APC) are associated with the formation of intestinal polyps and colon cancers. To facilitate the functional study of APC we have isolated its Drosophila homolog (D-APC) by screening an expression library with an antibody against human APC. The isolated cDNA encodes a predicted 2416-amino acid protein containing significant homology to multiple domains of mammalian APCs. D-APC has seven complete armadillo repeats with 60% identity to its human homolog, one beta-catenin binding site, and up to 7 copies of a 20-amino acid repeat with the average of 50% identity to human APC at amino acid level. D-APC, like its human counterpart, also contains a basic domain. Expression of the domain of D-APC homologous to the region required for beta-catenin down-regulation resulted in down-regulation of intracellular beta-catenin in a mammalian cell line. This same region bound to the Armadillo (Arm) protein, in vitro, the Drosophila homolog of beta-catenin. D-APC RNA and protein expression is very low, if detectable at all, during stages when Arm protein accumulates in a striped pattern in the epidermis of the Drosophila embryos. Removing zygotic D-APC expression did not alter Arm protein distribution, and the final cuticle pattern was not affected significantly. As observed in the rodent, high levels of D-APC expression have been detected in the central nervous system, suggesting a role for D-APC in central nervous system formation.
Hayashi
S
S
Department of Molecular Biology, Princeton University, NJ 08540, USA.
Rubinfeld
B
B
Souza
B
B
Polakis
P
P
Wieschaus
E
E
Levine
A J
AJ
D025601:Adenomatous Polyposis Coli Protein; D000595:Amino Acid Sequence; D000818:Animals; D051186:Armadillo Domain Proteins; D002277:Carcinoma / Q000235:genetics; D003001:Cloning, Molecular; D003110:Colonic Neoplasms / Q000235:genetics; D017124:Conserved Sequence; D003598:Cytoskeletal Proteins / Q000235:genetics* / Q000276:immunology / Q000378:metabolism; D015536:Down-Regulation; D029721:Drosophila Proteins; D004331:Drosophila melanogaster / Q000196:embryology / Q000235:genetics*; D017491:Genes, APC; D017344:Genes, Insect; D006801:Humans; D017403:In Situ Hybridization; D019476:Insect Proteins / Q000235:genetics*; D008969:Molecular Sequence Data; D009420:Nervous System / Q000737:chemistry / Q000196:embryology; D011485:Protein Binding; D017422:Sequence Analysis, DNA; D017386:Sequence Homology, Amino Acid; D015534:Trans-Activators; D014157:Transcription Factors; D014407:Tumor Cells, Cultured; D015053:Zygote; D051176:beta Catenin
C495305:ARM protein, Drosophila; D025601:Adenomatous Polyposis Coli Protein; D051186:Armadillo Domain Proteins; C495270:CTNNB1 protein, human; D003598:Cytoskeletal Proteins; D029721:Drosophila Proteins; D019476:Insect Proteins; D015534:Trans-Activators; D014157:Transcription Factors; D051176:beta Catenin