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Updated: Oct 3, 2026

Identification of Intracellular Signaling Events Induced in Viable Cells by Interaction with Neighboring Cells Undergoing Apoptotic Cell Death
09:18

Identification of Intracellular Signaling Events Induced in Viable Cells by Interaction with Neighboring Cells Undergoing Apoptotic Cell Death

Published on: December 27, 2016

Inhibition of protein phosphatase-1 is linked to phosphorylation of p53 and apoptosis

X Long1, G Wu, S T Gaa

  • 1Department of Biochemistry and Molecular Biology, University of Maryland School of Medicine, Baltimore, MD 21201, USA. xlong001@umaryland.edu

Apoptosis : an International Journal on Programmed Cell Death
|January 5, 2002
PubMed

Insights

Decreased protein phosphatase 1 (PP-1) activity is a key event in apoptosis. This study shows PP-1 inhibition enhances p53 phosphorylation and triggers programmed cell death in cardiomyocytes.

Area of Science:

  • Molecular Biology
  • Cellular Biology
  • Biochemistry

Background:

  • p53 is a crucial protein regulating cell fate.
  • Protein phosphorylation and dephosphorylation modulate p53 activity.
  • Serine/threonine phosphatases (PP-1 and PP-2A) are potential regulators of p53.

Purpose of the Study:

  • To investigate the role of PP-1 and PP-2A in the p53-dependent apoptotic pathway.
  • To determine if PP-1 and PP-2A activity changes during apoptosis induction.
  • To assess the impact of PP-1 inhibition on apoptosis.

Main Methods:

  • Neonatal rat cardiomyocytes were treated with apoptotic agents (bafilomycin A1, staurosporine) or phenylephrine.
  • Protein phosphatase activities (PP-1, PP-2A) were measured.
  • p53 phosphorylation levels were assessed.
  • Cardiomyocytes were treated with okadaic acid (PP-1 inhibitor) or an antisense strategy targeting PP-1.

Main Results:

  • Apoptotic agents decreased PP-1 activity by 35% and increased p53 phosphorylation.
  • Phenylephrine did not affect phosphatase activity or induce apoptosis.
  • Okadaic acid and PP-1 antisense reduced PP-1 activity, enhanced p53 phosphorylation, and induced DNA fragmentation.
  • PP-2A activity remained unchanged in response to apoptotic stimuli or PP-1 inhibition.

Conclusions:

  • Decreased PP-1 activity is a significant signaling event in the apoptotic process.
  • PP-1, but not PP-2A, plays a critical role in p53-mediated apoptosis in cardiomyocytes.
  • Modulation of PP-1 activity represents a potential therapeutic target for controlling apoptosis.

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