PMID- 10629059 OWN - NLM STAT- MEDLINE DCOM- 20000214 LR - 20220408 IS - 0270-7306 (Print) IS - 0270-7306 (Linking) VI - 20 IP - 3 DP - 2000 Feb TI - PR48, a novel regulatory subunit of protein phosphatase 2A, interacts with Cdc6 and modulates DNA replication in human cells. PG - 1021-9 AB - 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. FAU - Yan, Z AU - Yan Z AD - Department of Internal Medicine, University of Texas Southwestern Medical Center, Dallas, Texas 75390, USA. FAU - Fedorov, S A AU - Fedorov SA FAU - Mumby, M C AU - Mumby MC FAU - Williams, R S AU - Williams RS LA - eng GR - HLK31107/HL/NHLBI NIH HHS/United States GR - T32 HL007360/HL/NHLBI NIH HHS/United States GR - HL06296/HL/NHLBI NIH HHS/United States GR - HL07360/HL/NHLBI NIH HHS/United States GR - P01 HL006296/HL/NHLBI NIH HHS/United States PT - Journal Article PT - Research Support, U.S. Gov't, P.H.S. PL - United States TA - Mol Cell Biol JT - Molecular and cellular biology JID - 8109087 RN - 0 (CDC6 protein, S cerevisiae) RN - 0 (Cell Cycle Proteins) RN - 0 (Macromolecular Substances) RN - 0 (PPP2R3B protein, human) RN - 0 (Recombinant Fusion Proteins) RN - 0 (Saccharomyces cerevisiae Proteins) RN - EC 3.1.3.16 (Phosphoprotein Phosphatases) RN - EC 3.1.3.16 (Protein Phosphatase 2) SB - IM MH - Amino Acid Sequence MH - Animals MH - Cell Cycle Proteins/*metabolism MH - Cell Line MH - Cloning, Molecular MH - *DNA Replication MH - Female MH - Gene Library MH - HeLa Cells MH - Humans MH - Macromolecular Substances MH - Mice MH - Molecular Sequence Data MH - Phosphoprotein Phosphatases/chemistry/genetics/*metabolism MH - Phylogeny MH - Placenta/enzymology MH - Pregnancy MH - Protein Phosphatase 2 MH - Protein Structure, Quaternary MH - Rabbits MH - Recombinant Fusion Proteins/metabolism MH - Saccharomyces cerevisiae/genetics/growth & development MH - *Saccharomyces cerevisiae Proteins MH - Sequence Alignment MH - Sequence Homology, Amino Acid MH - Spodoptera MH - Transfection PMC - PMC85219 EDAT- 2000/01/11 09:00 MHDA- 2000/02/19 09:00 CRDT- 2000/01/11 09:00 PHST- 2000/01/11 09:00 [pubmed] PHST- 2000/02/19 09:00 [medline] PHST- 2000/01/11 09:00 [entrez] AID - 10.1128/MCB.20.3.1021-1029.2000 [doi] PST - ppublish SO - Mol Cell Biol. 2000 Feb;20(3):1021-9. doi: 10.1128/MCB.20.3.1021-1029.2000.