Central role of the scaffold protein tumor necrosis factor receptor-associated factor 2 in regulating endoplasmic reticulum stress-induced apoptosis

Claudio Mauro, Elvira Crescenzi, Roberta De Mattia, Francesco Pacifico, Stefano Mellone, Salvatore Salzano, Cristiana De Luca, Luciano D'Adamio, Giuseppe Palumbo, Silvestro Formisano, Pasquale Vito, Antonio Leonardi

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50 Scopus citations

Abstract

The endoplasmic reticulum represents the quality control site of the cell for folding and assembly of cargo proteins. A variety of conditions can alter the ability of the endoplasmic reticulum (ER) to properly fold proteins, thus resulting in ER stress. Cells respond to ER stress by activating different signal transduction pathways leading to increased transcription of chaperone genes, decreased protein synthesis, and eventually to apoptosis. In the present paper we analyzed the role that the adaptor protein tumor necrosis factor-receptor associated factor 2 (TRAF2) plays in regulating cellular responses to apoptotic stimuli from the endoplasmic reticulum. Mouse embryonic fibroblasts derived from TRAF2-/- mice were more susceptible to apoptosis induced by ER stress than the wild type counterpart. This increased susceptibility to ER stress-induced apoptosis was because of an increased accumulation of reactive oxygen species following ER stress, and was abolished by the use of antioxidant. In addition, we demonstrated that the NF-κB pathway protects cells from ER stress-induced apoptosis, controlling ROS accumulation. Our results underscore the involvement of TRAF2 in regulating ER stress responses and the role of NF-κB in protecting cells from ER stress-induced apoptosis.

Original languageEnglish (US)
Pages (from-to)2631-2638
Number of pages8
JournalJournal of Biological Chemistry
Volume281
Issue number5
DOIs
StatePublished - Feb 3 2006

ASJC Scopus subject areas

  • Biochemistry
  • Molecular Biology
  • Cell Biology

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    Mauro, C., Crescenzi, E., De Mattia, R., Pacifico, F., Mellone, S., Salzano, S., De Luca, C., D'Adamio, L., Palumbo, G., Formisano, S., Vito, P., & Leonardi, A. (2006). Central role of the scaffold protein tumor necrosis factor receptor-associated factor 2 in regulating endoplasmic reticulum stress-induced apoptosis. Journal of Biological Chemistry, 281(5), 2631-2638. https://doi.org/10.1074/jbc.M502181200