Drosophila Apc1 and Apc2 regulate Wingless transduction throughout development.
Inactivation of the Adenomatous Polyposis Coli (APC) tumor suppressor triggers the development of most colorectal carcinomas. APC is required for targeted degradation of beta-catenin, the central transcriptional activator in the Wnt/Wingless (Wg) signal transduction pathway; however, the precise biochemical functions of APC remain uncertain. The two Drosophila homologs of APC (Apc1 and Apc2) appear to have predominantly different tissue distributions, different subcellular localizations and mutually exclusive phenotypes upon inactivation. Unexpectedly, we have found that despite these differences, simultaneous reduction in both Drosophila Apc proteins results in the global nuclear accumulation of beta-catenin and the constitutive activation of Wg transduction throughout development. This redundancy extends even to functions previously thought to be specific to the individual Apc homologs. Together, these results reveal that the combined activity of Apc1 and Apc2 allows a tight regulation of transcriptional activation by beta-catenin and suggest that APC proteins are required for the regulation of Wnt transduction in all cells.
Ahmed
Yashi
Y
HHMI/Department of Molecular Biology, Princeton University, Princeton, NJ 08544, USA.
Nouri
Ali
A
Wieschaus
Eric
E
D000818:Animals; D017209:Apoptosis; D003598:Cytoskeletal Proteins / Q000235:genetics / Q000378:metabolism*; D004330:Drosophila / Q000235:genetics / Q000254:growth & development* / Q000378:metabolism*; D029721:Drosophila Proteins / Q000235:genetics / Q000378:metabolism*; D004847:Epithelial Cells / Q000378:metabolism; D018507:Gene Expression Regulation, Developmental; D017491:Genes, APC; D017344:Genes, Insect; D006801:Humans; D009474:Neurons / Q000166:cytology / Q000378:metabolism; D011518:Proto-Oncogene Proteins / Q000235:genetics / Q000378:metabolism*; D012160:Retina / Q000254:growth & development / Q000378:metabolism; D015398:Signal Transduction; D013045:Species Specificity; D014018:Tissue Distribution; D015534:Trans-Activators; D015533:Transcriptional Activation; D051155:Wnt1 Protein; D051176:beta Catenin
C118001:APC protein, Drosophila; C495270:CTNNB1 protein, human; D003598:Cytoskeletal Proteins; D029721:Drosophila Proteins; D011518:Proto-Oncogene Proteins; D015534:Trans-Activators; D051155:Wnt1 Protein; D051176:beta Catenin; C074622:wg protein, Drosophila