Identification of proteins regulated by the proteasome following induction of endoplasmic reticulum stress

Bertrand Fabre, Ido Livneh, T. Ziv, Aaron Ciechanover

Research output: Contribution to journalArticleResearchpeer-review

Abstract

The endoplasmic reticulum (ER) is a major site for protein synthesis, folding and transport, lipid and steroid synthesis, regulating redox potential, as well as calcium storage. It therefore relies on delicate homeostasis, and perturbation of the ER function and induction of ER stress can lead to apoptosis. One cause of disruption of the ER homeostasis is the accumulation of misfolded proteins. To prevent this perturbation, the Endoplasmic Reticulum-Associated Degradation (ERAD) quality control machinery is recruited to remove these proteins in a three-step process: (1) extraction from the ER, (2) ubiquitination, and (3) subsequent proteasomal degradation. However, the identity of the proteins regulated by the proteasome following induction of the ER stress has remained obscure. In the present study, we investigated the role of the proteasome in the modulation of the proteome of HeLa cells after treatment with thapsigargin and tunicamycin, two drugs known to induce ER stress through accumulation of misfolded proteins. Using label-free quantitative proteomics we found that out of the proteins identified to decrease in their level following induction of ER stress, more than 64% are targeted by the proteasome. Among these proteins, key players of the Wnt signaling pathway, such as β-catenin and GSK3, as well as α-catenin which is involved in cell-cell adhesion, were identified as being modulated by the proteasome upon ER stress.

Original languageEnglish
Pages (from-to)188-192
Number of pages5
JournalBiochemical and Biophysical Research Communications
Volume517
Issue number2
DOIs
StatePublished - 17 Sep 2019

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Endoplasmic Reticulum Stress
Proteasome Endopeptidase Complex
Endoplasmic Reticulum
Catenins
Proteins
Homeostasis
Endoplasmic Reticulum-Associated Degradation
Tunicamycin
Wnt Signaling Pathway
Thapsigargin
Ubiquitination
Protein Folding
Degradation
Protein Transport
Proteome
HeLa Cells
Cell Adhesion
Cell adhesion
Quality Control
Proteomics

Keywords

  • Endoplasmic reticulum stress
  • Label-free proteomics
  • Proteasome
  • Thapsigargin
  • Tunicamycin

Cite this

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title = "Identification of proteins regulated by the proteasome following induction of endoplasmic reticulum stress",
abstract = "The endoplasmic reticulum (ER) is a major site for protein synthesis, folding and transport, lipid and steroid synthesis, regulating redox potential, as well as calcium storage. It therefore relies on delicate homeostasis, and perturbation of the ER function and induction of ER stress can lead to apoptosis. One cause of disruption of the ER homeostasis is the accumulation of misfolded proteins. To prevent this perturbation, the Endoplasmic Reticulum-Associated Degradation (ERAD) quality control machinery is recruited to remove these proteins in a three-step process: (1) extraction from the ER, (2) ubiquitination, and (3) subsequent proteasomal degradation. However, the identity of the proteins regulated by the proteasome following induction of the ER stress has remained obscure. In the present study, we investigated the role of the proteasome in the modulation of the proteome of HeLa cells after treatment with thapsigargin and tunicamycin, two drugs known to induce ER stress through accumulation of misfolded proteins. Using label-free quantitative proteomics we found that out of the proteins identified to decrease in their level following induction of ER stress, more than 64{\%} are targeted by the proteasome. Among these proteins, key players of the Wnt signaling pathway, such as β-catenin and GSK3, as well as α-catenin which is involved in cell-cell adhesion, were identified as being modulated by the proteasome upon ER stress.",
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Identification of proteins regulated by the proteasome following induction of endoplasmic reticulum stress. / Fabre, Bertrand; Livneh, Ido; Ziv, T.; Ciechanover, Aaron.

In: Biochemical and Biophysical Research Communications, Vol. 517, No. 2, 17.09.2019, p. 188-192.

Research output: Contribution to journalArticleResearchpeer-review

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