Related Experiment Video

Updated: Jun 6, 2026

A Chromatin Immunoprecipitation Assay to Identify Novel NFAT2 Target Genes in Chronic Lymphocytic Leukemia
09:52

A Chromatin Immunoprecipitation Assay to Identify Novel NFAT2 Target Genes in Chronic Lymphocytic Leukemia

Published on: December 4, 2018

TRAF2 phosphorylation promotes NF-κB-dependent gene expression and inhibits oxidative stress-induced cell death

Laiqun Zhang1, Ken Blackwell, Aliya Altaeva

  • 1Department of Pathology, Carver College of Medicine, University of Iowa, 200 Hawkins Drive, Iowa City, IA 52242, USA.

Molecular Biology of the Cell
|December 2, 2010
PubMed

Insights

Tumor necrosis factor alpha (TNF-α) receptor-associated factor 2 (TRAF2) phosphorylation is crucial for cell survival. This modification promotes prolonged IKK activation and inhibits JNK activation, particularly under oxidative stress conditions.

Area of Science:

  • Cellular signaling pathways
  • Molecular biology
  • Stress response mechanisms

Background:

  • Tumor necrosis factor alpha (TNF-α) receptor-associated factor 2 (TRAF2) is a key regulator of TNF-α-induced signaling.
  • TRAF2's role in TNF-α-induced cell death and oxidative stress-induced apoptosis is complex.
  • Understanding TRAF2's post-translational modifications is vital for deciphering its diverse functions.

Purpose of the Study:

  • To investigate the role of TRAF2 phosphorylation in response to TNF-α and oxidative stress.
  • To elucidate how TRAF2 phosphorylation affects downstream signaling pathways, specifically IKK and JNK.
  • To determine the impact of TRAF2 phosphorylation on cell survival and apoptosis.

Main Methods:

  • Utilized gene knockout studies and phospho-null mutant TRAF2 expression in cancer cells.
  • Analyzed TRAF2 phosphorylation at specific serine residues (S11 and S55) upon stimulation.
  • Assessed the activation kinetics of IKK and JNK signaling cascades.
  • Monitored the expression levels of apoptosis-related proteins like Bcl-2 and cellular inhibitor of apoptosis 1.

Main Results:

  • Both TNF-α and oxidative stress induce TRAF2 phosphorylation at S11 and S55.
  • TRAF2 phosphorylation promotes prolonged IKK activation and inhibits prolonged JNK activation.
  • In oxidative stress, TRAF2 phosphorylation enhances cell survival by modulating IKK and JNK.
  • Expression of phospho-null TRAF2 increases JNK activation and susceptibility to oxidative stress-induced cell death.

Conclusions:

  • TRAF2 phosphorylation is essential for cell survival, particularly under oxidative stress.
  • Dual phosphorylation of TRAF2 fine-tunes IKK and JNK signaling dynamics.
  • TRAF2 phosphorylation acts as a critical switch controlling cell fate decisions in response to cellular stress.

Related Concept Videos

NF-κB-dependent Signaling Pathway02:26

NF-κB-dependent Signaling Pathway

The transcription factor NF-κB was discovered in 1986 in the lab of Nobel laureate Professor David Baltimore, for its interaction with the immunoglobulin light chain enhancer in B-cells. After more than three decades of study, it is now evident that NF-κB regulates the expression of over 100 genes. Most of these genes play an essential role in the innate and adaptive immune responses as well as the inflammatory responses of animals.
NF-κB-dependent Signaling Mechanism
The heterodimer of NF-κB...
NF-kB-dependent Signaling Pathway02:26

NF-kB-dependent Signaling Pathway

The transcription factor NF-κB was discovered in 1986 in the lab of Nobel laureate Professor David Baltimore, for its interaction with the immunoglobulin light chain enhancer in B-cells. After more than three decades of study, it is now evident that NF-κB regulates the expression of over 100 genes. Most of these genes play an essential role in the innate and adaptive immune responses as well as the inflammatory responses of animals.
NF-κB-dependent Signaling Mechanism
The heterodimer of NF-κB...
TGF - β Signaling Pathway01:16

TGF - β Signaling Pathway

The TGF-β signaling pathway regulates cell growth, differentiation, adhesion, motility, and development. TGF-β ligands that induce TGF-β signaling are synthesized in their latent form. Several proteases or cell surface receptors such as integrins act upon the latent form, releasing the active ligand. There are three types of mammalian TGF-βs: (TGF-β1, TGF-β2, and TGF-β3) that bind as homodimers or heterodimers to TGF-β receptors. The TGF-β receptors are of three kinds RI, RII, and RIII. The RI...
MAPK Signaling Cascades01:07

MAPK Signaling Cascades

Mitogen-activated protein kinase, or MAPK pathway, activates three sequential kinases to regulate cellular responses such as proliferation, differentiation, survival, and apoptosis. The canonical MAPK pathway starts with a mitogen or growth factor binding to an RTK. The activated RTKs stimulate Ras, which recruits Raf or MAP3 Kinase (MAPKKK), the first kinase of the MAPK signaling cascade. Raf further phosphorylates and activates MEK or MAP2 Kinases (MAPKK), which in turn phosphorylates MAP...
Electron Transport Chain: Complex I and II01:46

Electron Transport Chain: Complex I and II

The mitochondrial electron transport chain (ETC) is the main energy generation system in the eukaryotic cells. However, mitochondria also produce cytotoxic reactive oxygen species (ROS) due to the large electron flow during oxidative phosphorylation. While Complex I is one of the primary sources of superoxide radicals, ROS production by Complex II is uncommon and may only be observed in cancer cells with mutated complexes.
ROS generation is regulated and maintained at moderate levels necessary...
The Extrinsic Apoptotic Pathway01:17

The Extrinsic Apoptotic Pathway

The extrinsic apoptotic pathway is initiated when extracellular death-inducing signals, such as specific cytokines, activate the death receptors expressed on the cell surface. The immune cells involved in this pathway are natural killer cells (NK cells) and cytotoxic T-lymphocytes. NK cells are critical in innate immune response, while cytotoxic T-lymphocytes are associated with adaptive immune response. These cells recognize specific receptors expressed on the altered cells and activate...