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PR48, a novel regulatory subunit of protein phosphatase 2A, interacts with Cdc6 and modulates DNA replication in

Z Yan1, S A Fedorov, M C Mumby

  • 1Department of Internal Medicine, University of Texas Southwestern Medical Center, Dallas, Texas 75390, USA.

Molecular and Cellular Biology
|January 11, 2000
PubMed

Insights

Researchers identified PR48, a novel regulatory subunit of protein phosphatase 2A (PP2A). This subunit interacts with Cdc6, suggesting a role for PP2A in regulating DNA replication initiation.

Area of Science:

  • Molecular Biology
  • Cell Biology
  • Biochemistry

Background:

  • DNA replication initiation in eukaryotes requires protein phosphatase 2A (PP2A) activity.
  • Specific phosphoprotein substrates for PP2A in this process remain unidentified.

Purpose of the Study:

  • To identify novel regulatory subunits of PP2A involved in DNA replication.
  • To elucidate the role of PP2A in regulating the initiation of DNA replication.

Main Methods:

  • Yeast two-hybrid screening of a human placental cDNA library.
  • Co-immunoprecipitation to confirm protein interactions.
  • Cellular localization studies and overexpression experiments.

Main Results:

  • A novel PP2A regulatory subunit, PR48, was identified.
  • PR48 specifically binds to the amino-terminal region of human Cdc6.
  • PR48 forms functional PP2A holoenzyme complexes.
  • PR48 localizes to the nucleus and its overexpression causes G(1) cell cycle arrest.

Conclusions:

  • PP2A-mediated dephosphorylation of Cdc6, facilitated by PR48, is a key regulatory event for DNA replication initiation in mammalian cells.
  • PR48 is a novel component of the DNA replication machinery, linking PP2A activity to cell cycle control.

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