title: Drosophila APC2 and APC1 play overlapping roles in wingless signaling in the embryo and imaginal discs.
abstract: The regulation of signal transduction plays a key role in cell fate choices, and its disregulation contributes to oncogenesis. This duality is exemplified by the tumor suppressor APC. Originally identified for its role in colon tumors, APC family members were subsequently shown to negatively regulate Wnt signaling in both development and disease. The analysis of the normal roles of APC proteins is complicated by the presence of two APC family members in flies and mice. Previous work demonstrated that, in some tissues, single mutations in each gene have no effect, raising the question of whether there is functional overlap between the two APCs or whether APC-independent mechanisms of Wnt regulation exist. We addressed this by eliminating the function of both Drosophila APC genes simultaneously. We find that APC1 and APC2 play overlapping roles in regulating Wingless signaling in the embryonic epidermis and the imaginal discs. Surprisingly, APC1 function in embryos occurs at levels of expression nearly too low to detect. Further, the overlapping functions exist despite striking differences in the intracellular localization of the two APC family members.
authors.affiliation: Curriculum in Genetics and Molecular Biology, University of North Carolina, Chapel Hill, North Carolina 27599-3280, USA.
authors.forename: Kathryn
authors.initials: K
authors.lastname: Akong
authors.forename: Elizabeth E
authors.initials: EE
authors.lastname: Grevengoed
authors.forename: Meredith H
authors.initials: MH
authors.lastname: Price
authors.forename: Brooke M
authors.initials: BM
authors.lastname: McCartney
authors.forename: Melissa A
authors.initials: MA
authors.lastname: Hayden
authors.forename: Jan C
authors.initials: JC
authors.lastname: DeNofrio
authors.forename: Mark
authors.initials: M
authors.lastname: Peifer
mesh_terms: D025601:Adenomatous Polyposis Coli Protein; D000818:Animals; D051186:Armadillo Domain Proteins; D003598:Cytoskeletal Proteins; D029721:Drosophila Proteins / Q000235:genetics / Q000378:metabolism*; D004331:Drosophila melanogaster / Q000196:embryology / Q000378:metabolism; D004817:Epidermis / Q000196:embryology / Q000378:metabolism; D015870:Gene Expression; D007424:Intracellular Fluid; D011518:Proto-Oncogene Proteins / Q000378:metabolism*; D015398:Signal Transduction; D015534:Trans-Activators / Q000378:metabolism; D014157:Transcription Factors; D025521:Tumor Suppressor Proteins / Q000235:genetics / Q000378:metabolism*; D051155:Wnt1 Protein
chemical_list: C467323:APC2 protein, Drosophila; C495305:ARM protein, Drosophila; D025601:Adenomatous Polyposis Coli Protein; D051186:Armadillo Domain Proteins; D003598:Cytoskeletal Proteins; D029721:Drosophila Proteins; D011518:Proto-Oncogene Proteins; D015534:Trans-Activators; D014157:Transcription Factors; D025521:Tumor Suppressor Proteins; D051155:Wnt1 Protein; C117846:adenomatous polyposis coli protein 2; C074622:wg protein, Drosophila