Abstract: |
Mutation 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 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 β-catenin acts as part of the Wnt/β-catenin signaling pathway, either upstream of, or in conjunction with, β-catenin. |
Keywords: |
signal transduction; nonhuman; phenotype; animals; cell function; protein assembly; homeodomain proteins; cloning, molecular; embryo, nonmammalian; gene expression regulation, developmental; tumor suppressor gene; amino acid sequence; molecular sequence data; colon cancer; growth regulation; trans-activators; gene induction; beta catenin; cadherins; adenomatous polyposis coli protein; oligomerization; embryonic development; genetic linkage; dna, complementary; cytoskeletal proteins; xenopus laevis; genes, homeobox; embryonic induction; xenopus proteins; homeobox; colon polyposis; genes, apc; humans; priority journal; article
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