title: APCL, a central nervous system-specific homologue of adenomatous polyposis coli tumor suppressor, binds to p53-binding protein 2 and translocates it to the perinucleus.
abstract: APCL, a central nervous system-specific sequence homologue of the adenomatous polyposis coli tumor suppressor, can regulate the cytoplasmic level of beta-catenin as the adenomatous polyposis coli tumor suppressor does, but its overall biological function remains unclear. Using a yeast two-hybrid system, we attempted to isolate proteins that might associate with the unique COOH-terminus of APCL. Among 166 cDNA clones isolated from a human fetal-brain cDNA library as candidates for interaction with APCL, 32 encoded parts of p53-binding protein 2 (53BP2), a molecule that interacts with p53 and Bcl2. An in vitro binding assay indicated that the Src-homology-3 domain and the ankyrin-repeat domain of 53BP2 were both required for binding to the COOH-terminus of APCL. Confocal microscopy showed that APCL and 53BP2 proteins were localized together in the perinuclei of normal mammalian cells, but this was not the case in cells that expressed truncated APCL and 53BP2 proteins. These findings suggested that binding of the COOH-terminus of APCL to 53BP2 regulates the cytoplasmic location of 53BP2. Because 53BP2 also interacts with p53 and Bcl2 and regulates p53 function, our results suggest that APCL might be involved in the p53/Bcl2-linked pathway of cell-cycle progression and cell death.
authors.affiliation: Biomedical Research Center and the Second Department of Surgery, Osaka University Medical School, Japan.
authors.forename: H
authors.initials: H
authors.lastname: Nakagawa
authors.forename: K
authors.initials: K
authors.lastname: Koyama
authors.forename: Y
authors.initials: Y
authors.lastname: Murata
authors.forename: M
authors.initials: M
authors.lastname: Morito
authors.forename: T
authors.initials: T
authors.lastname: Akiyama
authors.forename: Y
authors.initials: Y
authors.lastname: Nakamura
mesh_terms: D025601:Adenomatous Polyposis Coli Protein; D000818:Animals; D051017:Apoptosis Regulatory Proteins; D015153:Blotting, Western; D019556:COS Cells; D002352:Carrier Proteins / Q000235:genetics / Q000378:metabolism*; D002467:Cell Nucleus / Q000378:metabolism; D003598:Cytoskeletal Proteins / Q000235:genetics / Q000378:metabolism*; D005822:Genetic Vectors / Q000235:genetics / Q000378:metabolism; D005982:Glutathione Transferase / Q000235:genetics / Q000378:metabolism; D006367:HeLa Cells; D006801:Humans; D018613:Microscopy, Confocal; D010957:Plasmids / Q000235:genetics; D011993:Recombinant Fusion Proteins / Q000235:genetics / Q000378:metabolism; D014162:Transfection; D001616:beta-Galactosidase / Q000235:genetics / Q000378:metabolism
chemical_list: C115681:APC2 protein, human; D025601:Adenomatous Polyposis Coli Protein; D051017:Apoptosis Regulatory Proteins; D002352:Carrier Proteins; D003598:Cytoskeletal Proteins; D011993:Recombinant Fusion Proteins; C090468:TP53BP2 protein, human; D005982:Glutathione Transferase; D001616:beta-Galactosidase