title: Phosphorylation of the tumor suppressor adenomatous polyposis coli (APC) by the cyclin-dependent kinase p34.
abstract: Mutations in the tumor suppressor gene APC invariably lead to the development of colorectal cancer. The vast majority of these mutations are nonsense or frameshifts resulting in nonfunctional, truncated APC protein products. Eleven cyclin-dependent kinase (CDK) consensus phosphorylation sites have been identified in the frequently deleted carboxyl-terminal region of APC; loss of these phosphorylation sites by mutation could therefore compromise the ability of APC to inhibit cell growth. This report demonstrates that immunoprecipitates of full-length, but not truncated, APC protein include a mitosis-specific kinase activity in vivo. Biochemical and Western analysis of these immunoprecipitates confirms the presence of the CDK p34(cdc2). We also show that APC is a substrate for recombinant human p34(cdc2)-cyclin B1. Modification of APC by p34(cdc2) implicates phosphorylation as a mechanism for regulating APC function via a link to the cell cycle.
authors.affiliation: Department of Molecular Genetics, Biochemistry & Microbiology, University of Cincinnati College of Medicine, Cincinnati, Ohio 45267, USA.
authors.forename: C
authors.initials: C
authors.lastname: Trzepacz
authors.forename: A M
authors.initials: AM
authors.lastname: Lowy
authors.forename: J J
authors.initials: JJ
authors.lastname: Kordich
authors.forename: J
authors.initials: J
authors.lastname: Groden
mesh_terms: D011125:Adenomatous Polyposis Coli / Q000235:genetics*; D025601:Adenomatous Polyposis Coli Protein; D000595:Amino Acid Sequence; D001665:Binding Sites / Q000187:drug effects; D016203:CDC2 Protein Kinase / Q000037:antagonists & inhibitors / Q000378:metabolism*; D016384:Consensus Sequence; D003598:Cytoskeletal Proteins / Q000235:genetics / Q000378:metabolism*; D004791:Enzyme Inhibitors / Q000494:pharmacology; D017491:Genes, APC; D006801:Humans; D007701:Kinetin; D008969:Molecular Sequence Data; D010766:Phosphorylation; D011687:Purines / Q000494:pharmacology; D014407:Tumor Cells, Cultured
chemical_list: D025601:Adenomatous Polyposis Coli Protein; D003598:Cytoskeletal Proteins; D004791:Enzyme Inhibitors; D011687:Purines; C090046:olomoucine; D016203:CDC2 Protein Kinase; D007701:Kinetin