Adenomatous Polyposis Coli Tumor Suppressor Protein Has Signaling Activity in Xenopus laevis Embryos Resulting in the Induction of an Ectopic Dorsoanterior Axis
Open Access
- 27 January 1997
- journal article
- Published by Rockefeller University Press in The Journal of cell biology
- Vol. 136 (2), 411-420
- https://doi.org/10.1083/jcb.136.2.411
Abstract
Mutations in the adenomatous polyposis coli (APC) tumor suppressor gene are linked to both familial and sporadic human colon cancer. So far, a clear biological function for the APC gene product has not been determined. We assayed the activity of APC in the early Xenopus embryo, which has been established as a good model for the analysis of the signaling activity of the APC-associated protein β-catenin. When expressed in the future ventral side of a four-cell embryo, full-length APC induced a secondary dorsoanterior axis and the induction of the homeobox gene Siamois. This is similar to the phenotype previously observed for ectopic β-catenin expression. In fact, axis induction by APC required the availability of cytosolic β-catenin. These results indicate that APC has signaling activity in the early Xenopus embryo. Signaling activity resides in the central domain of the protein, a part of the molecule that is missing in most of the truncating APC mutations in colon cancer. Signaling by APC in Xenopus embryos is not accompanied by detectable changes in expression levels of β-catenin, indicating that it has direct positive signaling activity in addition to its role in β-catenin turnover. From these results we propose a model in which APC acts as part of the Wnt/β-catenin signaling pathway, either upstream of, or in conjunction with, β-catenin.Keywords
This publication has 56 references indexed in Scilit:
- Signal transduction through beta-catenin and specification of cell fate during embryogenesis.Genes & Development, 1996
- Functional interaction of β-catenin with the transcription factor LEF-1Nature, 1996
- Binding of GSK3β to the APC-β-Catenin Complex and Regulation of Complex AssemblyScience, 1996
- Binding of APC to the Human Homolog of the Drosophila Discs Large Tumor Suppressor ProteinScience, 1996
- Cell adhesion and signal transduction: the Armadillo connectionTrends in Cell Biology, 1995
- Mutations in the APC gene and their implications for protein structure and functionCurrent Opinion in Genetics & Development, 1995
- β-catenin: a common target for the regulation of cell adhesion by Wnt-1 and Src signaling pathwaysTrends in Biochemical Sciences, 1994
- APC mutations occur early during colorectal tumorigenesisNature, 1992
- Identification of FAP Locus Genes from Chromosome 5q21Science, 1991
- Identification and characterization of the familial adenomatous polyposis coli geneCell, 1991