PR48, a novel regulatory subunit of protein phosphatase 2A, interacts with Cdc6 and modulates DNA replication in human cells.
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.
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Related Subject Headings
- Transfection
- Spodoptera
- Sequence Homology, Amino Acid
- Sequence Alignment
- Saccharomyces cerevisiae Proteins
- Saccharomyces cerevisiae
- Recombinant Fusion Proteins
- Rabbits
- Protein Structure, Quaternary
- Protein Phosphatase 2
Citation
Published In
DOI
ISSN
Publication Date
Volume
Issue
Start / End Page
Location
Related Subject Headings
- Transfection
- Spodoptera
- Sequence Homology, Amino Acid
- Sequence Alignment
- Saccharomyces cerevisiae Proteins
- Saccharomyces cerevisiae
- Recombinant Fusion Proteins
- Rabbits
- Protein Structure, Quaternary
- Protein Phosphatase 2