title: PR48, a novel regulatory subunit of protein phosphatase 2A, interacts with Cdc6 and modulates DNA replication in human cells.
abstract: Initiation of DNA replication in eukaryotes is dependent on the activity of protein phosphatase 2A (PP2A), but specific phosphoprotein substrates pertinent to this requirement have not been identified. A novel regulatory subunit of PP2A, termed PR48, was identified by a yeast two-hybrid screen of a human placental cDNA library, using human Cdc6, an essential component of prereplicative complexes, as bait. PR48 binds specifically to an amino-terminal segment of Cdc6 and forms functional holoenzyme complexes with A and C subunits of PP2A. PR48 localizes to the nucleus of mammalian cells, and its forced overexpression perturbs cell cycle progression, causing a G(1) arrest. These results suggest that dephosphorylation of Cdc6 by PP2A, mediated by a specific interaction with PR48, is a regulatory event controlling initiation of DNA replication in mammalian cells.
authors.affiliation: Department of Internal Medicine, University of Texas Southwestern Medical Center, Dallas, Texas 75390, USA.
authors.forename: Z
authors.initials: Z
authors.lastname: Yan
authors.forename: S A
authors.initials: SA
authors.lastname: Fedorov
authors.forename: M C
authors.initials: MC
authors.lastname: Mumby
authors.forename: R S
authors.initials: RS
authors.lastname: Williams
mesh_terms: D000595:Amino Acid Sequence; D000818:Animals; D018797:Cell Cycle Proteins / Q000378:metabolism*; D002460:Cell Line; D003001:Cloning, Molecular; D004261:DNA Replication; D005260:Female; D015723:Gene Library; D006367:HeLa Cells; D006801:Humans; D046911:Macromolecular Substances; D051379:Mice; D008969:Molecular Sequence Data; D010749:Phosphoprotein Phosphatases / Q000737:chemistry / Q000235:genetics / Q000378:metabolism*; D010802:Phylogeny; D010920:Placenta / Q000201:enzymology; D011247:Pregnancy; D054648:Protein Phosphatase 2; D020836:Protein Structure, Quaternary; D011817:Rabbits; D011993:Recombinant Fusion Proteins / Q000378:metabolism; D012441:Saccharomyces cerevisiae / Q000235:genetics / Q000254:growth & development; D029701:Saccharomyces cerevisiae Proteins; D016415:Sequence Alignment; D017386:Sequence Homology, Amino Acid; D018411:Spodoptera; D014162:Transfection
chemical_list: C066503:CDC6 protein, S cerevisiae; D018797:Cell Cycle Proteins; D046911:Macromolecular Substances; C403618:PPP2R3B protein, human; D011993:Recombinant Fusion Proteins; D029701:Saccharomyces cerevisiae Proteins; D010749:Phosphoprotein Phosphatases; D054648:Protein Phosphatase 2