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A Mass Spectrometry-Based Approach to Identify Phosphoprotein Phosphatases and their Interactors
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Distinct phosphatases antagonize the p53 response in different phases of the cell cycle

Indra A Shaltiel1, Melinda Aprelia1, Adrian T Saurin2

  • 1Divisions of Cell Biology and.

Proceedings of the National Academy of Sciences of the United States of America
|April 9, 2014
PubMed

Insights

DNA damage response recovery differs between cell cycle phases. Phosphoprotein phosphatase 4 (PP4) is crucial for G1 restart, while WT p53-induced phosphatase 1 (Wip1) aids G2 recovery.

Area of Science:

  • Cell Biology
  • Molecular Biology
  • Genetics

Background:

  • DNA damage response (DDR) machinery is conserved across the cell cycle.
  • Cell cycle checkpoints halt progression upon DNA damage.
  • Understanding cell cycle-specific recovery mechanisms is crucial.

Purpose of the Study:

  • To investigate the distinct mechanisms of DNA damage response reversal and recovery in G1 versus G2 cell cycle phases.
  • To identify specific phosphatases involved in counteracting cell cycle arrest in different phases.

Main Methods:

  • Cell cycle synchronization and DNA damage induction.
  • Analysis of phosphatase activity and protein dephosphorylation.
  • Assessment of p53-dependent gene expression and cell cycle restart.

Main Results:

  • WT p53-induced phosphatase 1 (Wip1) is essential for G2 recovery by antagonizing p53.
  • Phosphoprotein phosphatase 4 catalytic subunit (PP4) is specifically required for G1 restart.
  • PP4 dephosphorylates Krüppel-associated box domain-associated protein 1-S473, repressing p21 transcription in G1.

Conclusions:

  • PP4 and Wip1 differentially regulate p53-mediated cell cycle arrest in G1 and G2.
  • PP4 counteracts early p53 responses in G1, while Wip1 antagonizes later responses in G2.

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