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Updated: Jul 8, 2026

Identification of Intracellular Signaling Events Induced in Viable Cells by Interaction with Neighboring Cells Undergoing Apoptotic Cell Death
09:18

Identification of Intracellular Signaling Events Induced in Viable Cells by Interaction with Neighboring Cells Undergoing Apoptotic Cell Death

Published on: December 27, 2016

TRAF6 deficiency promotes TNF-induced cell death through inactivation of GSK3beta

K Yoon1, E J Jung, S R Lee

  • 1Division of Life and Pharmaceutical Sciences, Center for Cell Signaling & Drug Discovery Research, College of Natural Sciences, Ewha Womans University, Seoul, Korea.

Cell Death and Differentiation
|January 19, 2008
PubMed

Insights

Tumor necrosis factor receptor-associated factor 6 (TRAF6) antagonizes cell death during TNF signaling. TRAF6 deficiency increases reactive oxygen species and cell death, while regulating glycogen synthase kinase 3 beta (GSK3beta) activity promotes cell survival.

Area of Science:

  • Immunology
  • Cell Biology
  • Molecular Biology

Background:

  • Tumor necrosis factor receptor-associated factor 6 (TRAF6) is crucial for innate immune responses, mediating signals from TNF, IL-1, and TLRs.
  • TRAF6's role in regulating cell death pathways, particularly during TNF signaling, requires further elucidation.

Purpose of the Study:

  • To investigate the role of TRAF6 in antagonizing cell death induced by TNF signaling.
  • To identify downstream molecular mechanisms by which TRAF6 influences cell survival.

Main Methods:

  • Utilized TRAF6-deficient 3T3 (T6(-/-) 3T3) cells for experiments.
  • Stimulated cells with TNF and measured reactive oxygen species (ROS) production.
  • Assessed c-Jun N-terminal kinase (JNK) activation, NF-kappaB transcriptional activity, and GSK3beta phosphorylation status.
  • Restored GSK3beta activity to evaluate its impact on cell death.

Main Results:

  • TRAF6 deficiency in 3T3 cells led to TNF-induced ROS accumulation, prolonged JNK activation, and accelerated cell death.
  • TNF-induced p65/RelA phosphorylation and NF-kappaB transcriptional activity were significantly reduced in TRAF6-null cells.
  • TRAF6 deficiency resulted in constitutive phosphorylation and inactivation of GSK3beta.
  • Restoring GSK3beta activity rescued cell death in TRAF6-null cells.

Conclusions:

  • TRAF6 plays a novel role in antagonizing TNF-induced cell death.
  • TRAF6 regulates cell survival by modulating GSK3beta activity within TNF signaling pathways.

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