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Molecular and Cellular Biology, February 2000, p. 1021-1029, Vol. 20, No. 3
0270-7306/00/$04.00+0
Copyright © 2000, American Society for Microbiology. All rights reserved.

PR48, a Novel Regulatory Subunit of Protein Phosphatase 2A, Interacts with Cdc6 and Modulates DNA Replication in Human Cells

Zhen Yan,1 Sergei A. Fedorov,2 Marc C. Mumby,2 and R. Sanders Williams1,3,*

Departments of Internal Medicine,1 Pharmacology,2 and Molecular Biology,3 University of Texas Southwestern Medical Center, Dallas, Texas 75390

Received 30 June 1999/Returned for modification 9 August 1999/Accepted 26 October 1999

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 G1 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.

* Corresponding author. Mailing address: University of Texas Southwestern Medical Center, 5323 Harry Hines Blvd., NB11.200, Dallas, TX 75390-8573. Phone: (214) 648-1400. Fax: (214) 648-1450. E-mail: williams{at}ryburn.swmed.edu.

Molecular and Cellular Biology, February 2000, p. 1021-1029, Vol. 20, No. 3
0270-7306/00/$04.00+0
Copyright © 2000, American Society for Microbiology. All rights reserved.


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