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Method for the Isolation and Identification of mRNAs, microRNAs and Protein Components of Ribonucleoprotein Complexes from Cell Extracts using RIP-Chip
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Method for the Isolation and Identification of mRNAs, microRNAs and Protein Components of Ribonucleoprotein Complexes from Cell Extracts using RIP-Chip

Published on: September 29, 2012

The dynamic role of GRP78/BiP in the coordination of mRNA translation with protein processing

A L Laitusis1, M A Brostrom, C O Brostrom

  • 1Department of Pharmacology, Robert Wood Johnson Medical School, Piscataway, New Jersey 08854, USA.

The Journal of Biological Chemistry
|December 29, 1998
PubMed

Insights

Endoplasmic reticulum stress impacts GRP78/BiP chaperone activity and protein translation. Stressors like ionomycin and cycloheximide reveal GRP78 ADP-ribosylation is linked to translational control.

Area of Science:

  • Cell Biology
  • Molecular Biology
  • Biochemistry

Background:

  • The endoplasmic reticulum (ER) manages protein folding and processing.
  • ER stress disrupts protein homeostasis, impacting cellular functions.
  • GRP78/BiP is a key chaperone in the ER, involved in protein folding and stress response.

Purpose of the Study:

  • To investigate the role of GRP78/BiP in coordinating ER protein processing with mRNA translation.
  • To examine the relationship between GRP78 ADP-ribosylation and eukaryotic initiation factor 2 alpha (eIF-2alpha) phosphorylation under various stress conditions.

Main Methods:

  • GH3 pituitary cells were used to study GRP78/BiP and eIF-2alpha.
  • ER stress was induced using ionomycin and dithiothreitol.
  • Translational suppression was achieved with cycloheximide.
  • ADP-ribosylation of GRP78 and eIF-2alpha phosphorylation were measured.

Main Results:

  • ER stress induced GRP78 deribosylation and eIF-2alpha phosphorylation.
  • Cycloheximide caused GRP78 ADP-ribosylation without eIF-2alpha phosphorylation.
  • GRP78 ADP-ribosylation was reversible and modulated by ER stressors.
  • Cytoplasmic stressors also induced GRP78 ADP-ribosylation, suggesting a broader regulatory role.

Conclusions:

  • GRP78/BiP ADP-ribosylation is a marker for translational regulation during ER stress.
  • The interplay between GRP78/BiP modification and eIF-2alpha phosphorylation is crucial for cellular adaptation to stress.
  • Findings highlight GRP78/BiP's central role in integrating ER protein processing with global translation control.

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