TitleA 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.
Publication TypeJournal Article
Year of Publication1997
AuthorsHayashi, S, Rubinfeld, B, Souza, B, Polakis, P, Wieschaus, E, Levine, AJ
JournalProc Natl Acad Sci U S A
Date Published1997 Jan 7
KeywordsAdenomatous Polyposis Coli Protein, Amino Acid Sequence, Animals, Armadillo Domain Proteins, beta Catenin, Carcinoma, Cloning, Molecular, Colonic Neoplasms, Conserved Sequence, Cytoskeletal Proteins, Down-Regulation, Drosophila melanogaster, Drosophila Proteins, Genes, APC, Genes, Insect, Humans, In Situ Hybridization, Insect Proteins, Molecular Sequence Data, Nervous System, Protein Binding, Sequence Analysis, DNA, Sequence Homology, Amino Acid, Trans-Activators, Transcription Factors, Tumor Cells, Cultured, Zygote

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.

Alternate JournalProc. Natl. Acad. Sci. U.S.A.