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Updated: May 11, 2026

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

Published on: July 26, 2019

Inositol pyrophosphates regulate cell growth and the environmental stress response by activating the HDAC Rpd3L

Jeremy Worley1, Xiangxia Luo, Andrew P Capaldi

  • 1Department of Molecular and Cellular Biology, University of Arizona, Tucson, AZ 85721-0206, USA.

Cell Reports
|May 7, 2013
PubMed

Insights

Inositol pyrophosphates (PP-IPs) are crucial for cell growth and stress response. These second messengers regulate the Rpd3L enzyme, parallel to the TORC1 pathway, controlling gene expression during stress.

Area of Science:

  • Cell Biology
  • Molecular Biology
  • Biochemistry

Background:

  • Eukaryotic cells adapt to stress and starvation by altering growth and activating defense mechanisms.
  • The target of rapamycin complex 1 (TORC1) pathway is a key regulator, influencing gene expression for protein synthesis and stress responses.
  • Inositol pyrophosphates (PP-IPs) are emerging as critical signaling molecules in cellular regulation.

Purpose of the Study:

  • To investigate the role of inositol pyrophosphates (PP-IPs) in regulating cell growth and the general stress response.
  • To elucidate the mechanism by which PP-IPs control cellular adaptation to stress, particularly their interaction with the TORC1 pathway.
  • To determine if PP-IPs act independently of specialized stress response pathways.

Main Methods:

  • Utilized yeast as a model organism to study cellular responses to stress.
  • Investigated the impact of PP-IP synthesis deficiency on transcriptional responses to osmotic, heat, and oxidative stress.
  • Examined the regulation of the class I histone deacetylase Rpd3L by PP-IPs.

Main Results:

  • Yeast cells lacking PP-IP synthesis exhibited significantly impaired transcriptional responses to various environmental stresses.
  • PP-IPs were found to regulate the activity of Rpd3L, a key enzyme in gene regulation.
  • This PP-IP-mediated regulation of Rpd3L operates in parallel to the TORC1 pathway.
  • PP-IP regulation of Rpd3L is independent of specific PP-IP roles in specialized stress pathways.

Conclusions:

  • Inositol pyrophosphates (PP-IPs) are essential regulators of the global cellular stress response.
  • PP-IPs coordinate cell growth and stress adaptation by modulating Rpd3L activity, acting in parallel with TORC1.
  • These findings highlight PP-IPs as central integrators of stress and starvation signals.

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