Abstract
The tumor suppressor protein APC (Adenomatous Polyposis Coli) is localized in the cytosol and in the nucleus. In this study, we demonstrate that the nuclear APC protein level 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 towards 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 co-precipitation of genomic DNA. Using recombinant APC fragments we mapped three DNA binding domains: one within the β-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)PXX proteins, the APC protein binds preferentially to A/T rich DNA sequences rather than to a single DNA sequence motif.
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Acknowledgements
We are indebted to Alfred Wittinghofer for fruitful discussions and continuous support. We thank Paul Polakis for providing the cDNA clone of the human full length APC gene. This work was supported by the Association for International Cancer Research, London (Grant 96-28). The work in the laboratory is supported by the Deutsche Forschungsgemeinschaft, the Bundesministerium für Bildung und Forschung, the Heinrich Hertz-Stiftung and Qiagen GmbH.
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Deka, J., Herter, P., Sprenger-Haußels, M. et al. The APC protein binds to A/T rich DNA sequences. Oncogene 18, 5654–5661 (1999). https://doi.org/10.1038/sj.onc.1202944
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DOI: https://doi.org/10.1038/sj.onc.1202944
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