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© The Rockefeller University Press, 0021-9525/1997//411 $5.00
The Journal of Cell Biology, Volume 136, Number 2, , 1997 411-420

Article

Adenomatous Polyposis Coli Tumor Suppressor Protein Has Signaling Activity in Xenopus laevis Embryos Resulting in the Induction of an Ectopic Dorsoanterior Axis



Kris Vleminckx*, Ellen Wong*, Kathy Guger*, Bonnee Rubinfeld{ddagger}, Paul Polakis{ddagger}, and Barry M. Gumbiner*

* Cellular Biochemistry and Biophysics Program, Memorial Sloan-Kettering Cancer Center, New York 10021; and {ddagger} Onyx Pharmaceuticals, Richmond, California 94806

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.

Abbreviations used in this paper: aa, amino acid; APC, adenomatous polyposis coli; hAPC, human APC; XAPC, Xenopus APC cDNA; XAPC FL, full-length Xenopus APC cDNA; Dlg, Drosophila disc large; EF-1, elongation factor 1; FAP, familial adenomatous polyposis; GSK-3, glycogen synthase kinase 3; dNTP, deoxyribonucleotidetriphosphate; RT, reverse transcriptase.

Address all correspondence to Barry M. Gumbiner, Cellular Biochemistry and Biophysics Program, Memorial Sloan-Kettering Cancer Center, 1275 York Avenue, Box 564, New York 10021. Tel.: (212) 639-6146. Fax: (212) 717-3047.


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