title: The APC protein binds to A/T rich DNA sequences.
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 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)PXX proteins, the APC protein binds preferentially to A/T rich DNA sequences rather than to a single DNA sequence motif.
authors.affiliation: Max-Planck-Institut für molekulare Physiologie, Dortmund, Germany.
authors.forename: J
authors.initials: J
authors.lastname: Deka
authors.forename: P
authors.initials: P
authors.lastname: Herter
authors.forename: M
authors.initials: M
authors.lastname: Sprenger-Haussels
authors.forename: S
authors.initials: S
authors.lastname: Koosch
authors.forename: D
authors.initials: D
authors.lastname: Franz
authors.forename: K M
authors.initials: KM
authors.lastname: Müller
authors.forename: C
authors.initials: C
authors.lastname: Kuhnen
authors.forename: I
authors.initials: I
authors.lastname: Hoffmann
authors.forename: O
authors.initials: O
authors.lastname: Müller
mesh_terms: D011125:Adenomatous Polyposis Coli / Q000378:metabolism; D025601:Adenomatous Polyposis Coli Protein; D020029:Base Pairing; D001667:Binding, Competitive; D006690:Bisbenzimidazole / Q000378:metabolism; D002467:Cell Nucleus / Q000378:metabolism; D003598:Cytoskeletal Proteins / Q000737:chemistry / Q000378:metabolism*; D004247:DNA / Q000378:metabolism*; D017491:Genes, APC; D006801:Humans; D010446:Peptide Fragments / Q000378:metabolism; D011485:Protein Binding; D011487:Protein Conformation; D020033:Protein Isoforms / Q000378:metabolism; D011993:Recombinant Fusion Proteins / Q000378:metabolism; D014407:Tumor Cells, Cultured
chemical_list: D025601:Adenomatous Polyposis Coli Protein; D003598:Cytoskeletal Proteins; D010446:Peptide Fragments; D020033:Protein Isoforms; D011993:Recombinant Fusion Proteins; D004247:DNA; D006690:Bisbenzimidazole