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Updated: May 16, 2026

Identification of Inositol Phosphate or Phosphoinositide Interacting Proteins by Affinity Chromatography Coupled to Western Blot or Mass Spectrometry
08:07

Identification of Inositol Phosphate or Phosphoinositide Interacting Proteins by Affinity Chromatography Coupled to Western Blot or Mass Spectrometry

Published on: July 26, 2019

Regulation of phosphatidylinositol-5-phosphate signaling by Pin1 determines sensitivity to oxidative stress

Willem-Jan Keune1, David R Jones, Yvette Bultsma

  • 1CRUK Inositide Laboratory, Paterson Institute for Cancer Research, The University of Manchester, Manchester M20 4BX, UK.

Science Signaling
|November 30, 2012
PubMed

Insights

Pin1 deficiency enhances cell resistance to oxidative stress by increasing phosphatidylinositol-5-phosphate (PtdIns5P) levels. This lipid mediator boosts antioxidant gene expression and reduces reactive oxygen species, offering insights into aging and neurodegeneration.

Area of Science:

  • Biochemistry
  • Cell Biology
  • Molecular Biology

Background:

  • Oxidative stress and signaling are implicated in aging, cancer, and neurodegenerative diseases.
  • Pin1, a proline isomerase, regulates protein conformation and localization.
  • Pin1 knockout mice exhibit premature aging phenotypes but resistant fibroblasts.

Purpose of the Study:

  • To investigate the role of Pin1 in cellular response to oxidative stress.
  • To elucidate the mechanism behind the enhanced resistance of Pin1-deficient cells to hydrogen peroxide.
  • To explore the involvement of phosphatidylinositol-5-phosphate (PtdIns5P) in this process.

Main Methods:

  • Utilized Pin1 knockout mouse embryonic fibroblasts (MEFs).
  • Assessed cell viability and reactive oxygen species (ROS) accumulation under hydrogen peroxide (H2O2) exposure.
  • Quantified PtdIns5P levels and analyzed gene expression related to oxidative stress defense.
  • Investigated the interaction between Pin1 and PtdIns5P 4-kinases (PIP4Ks) in vitro.

Main Results:

  • Pin1(-/-) MEFs showed enhanced resistance to H2O2-induced cell death.
  • H2O2 treatment increased PtdIns5P abundance, an effect amplified in Pin1(-/-) MEFs.
  • Reduced PtdIns5P levels compromised cell viability under oxidative stress.
  • Increased PtdIns5P in Pin1(-/-) MEFs stimulated antioxidant gene expression and decreased ROS accumulation.
  • Pin1 isomerase activity inhibited PIP4K activity in vitro.

Conclusions:

  • PtdIns5P plays a critical role in conferring enhanced cell viability to Pin1-deficient cells under oxidative stress.
  • Pin1 may regulate PtdIns5P levels through interaction with PIP4Ks, although the in vivo mechanism is complex and requires further investigation.
  • Findings suggest a novel regulatory pathway involving Pin1, PtdIns5P, and oxidative stress response.

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