The APC protein binds to A/T rich DNA sequences

The tumor suppressor protein APC (Adenomatous Polyposis Coil) is localized in the cytosol and in the nucleus. In this study, we demonstrate that the nuclear APC protein le, el is high in cells in the basal crypt region of the normal colorectal epithelium, Strikingly; the APC protein staining resembles the staining pattern of a nuclear proliferation marker. As a first step tow ards a possible role of the nuclear APC protein, we provide data showing the direct interaction of the nuclear APC protein with DNA. A nuclear APC isoform precipitates with matrix-immobilized DNA. Vice versa, the immunoprecipitation of APC from nuclear lysates results in coprecipitation of genomic DNA, Using recombinant APC fragments ne mapped three DNA binding domains: one within the beta-catenin binding and regulatory domain, and two in the carboxyterminal third of the APC protein. All these three domains contain clusters of repetitive S(T)PXX sequence motifs that were described to mediate the DNA interaction of many other DNA binding proteins. In analogy to S(T)PSS proteins, the APC protein binds preferentially to A/T rich DNA sequences rather than to a single DNA sequence motif.