Related Experiment Video

Updated: Aug 16, 2026

Sex Stratified Neuronal Cultures to Study Ischemic Cell Death Pathways
10:44

Sex Stratified Neuronal Cultures to Study Ischemic Cell Death Pathways

Published on: December 10, 2013

Essential roles of receptor-interacting protein and TRAF2 in oxidative stress-induced cell death

Han-Ming Shen1, Yong Lin, Swati Choksi

  • 1Cell and Cancer Biology Branch, Center for Cancer Research, National Cancer Institute, National Institutes of Health, Bethesda, Maryland 20892, USA.

Molecular and Cellular Biology
|June 17, 2004
PubMed

Insights

Oxidative stress triggers cell death via receptor-interacting protein (RIP) and tumor necrosis factor receptor (TNFR)-associated factor 2 (TRAF2). These proteins form a complex, activating c-Jun NH(2)-terminal kinase 1, a key step in ROS-induced cell death.

Area of Science:

  • Cell Biology
  • Molecular Biology
  • Biochemistry

Background:

  • Oxidative stress and reactive oxygen species (ROS) play roles in cell death, but the precise mechanisms remain unclear.
  • Receptor-interacting protein (RIP) and tumor necrosis factor receptor (TNFR)-associated factor 2 (TRAF2) are critical in TNF signaling.

Purpose of the Study:

  • To elucidate the molecular mechanisms underlying ROS-induced cell death.
  • To investigate the roles of RIP and TRAF2 in oxidative stress-induced apoptosis.

Main Methods:

  • Utilized RIP(-/-) and TRAF2(-/-) mouse embryonic fibroblasts (MEF) to assess cell death sensitivity.
  • Analyzed protein complex formation upon hydrogen peroxide (H(2)O(2)) exposure.
  • Examined the colocalization of RIP with lipid raft markers.
  • Measured c-Jun NH(2)-terminal kinase 1 (JNK1) activation.

Main Results:

  • RIP-deficient or TRAF2-deficient MEF cells exhibited resistance to ROS-induced cell death.
  • Re-expression of RIP or TRAF2 restored sensitivity to H(2)O(2)-induced cell death.
  • RIP and TRAF2 formed a complex upon H(2)O(2) exposure, independent of TNFR1.
  • RIP colocalized with lipid rafts, suggesting their involvement in signal transduction.
  • Activation of JNK1 was identified as a critical downstream event mediated by RIP and TRAF2.

Conclusions:

  • RIP and TRAF2 are essential mediators of ROS-induced cell death.
  • A novel signaling pathway involving RIP, TRAF2, lipid rafts, and JNK1 activation regulates oxidative stress-induced cell death.
  • This pathway offers potential targets for therapeutic interventions in conditions involving oxidative stress.

More Related Videos

Measurements of Physiological Stress Responses in C. Elegans10:36

Measurements of Physiological Stress Responses in C. Elegans

Published on: May 21, 2020

Induction and Analysis of Oxidative Stress in Sleeping Beauty Transposon-Transfected Human Retinal Pigment Epithelial Cells10:00

Induction and Analysis of Oxidative Stress in Sleeping Beauty Transposon-Transfected Human Retinal Pigment Epithelial Cells

Published on: December 11, 2020

Related Concept Videos

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...
Regulation of the Unfolded Protein Response01:31

Regulation of the Unfolded Protein Response

Inositol-requiring kinase one or IRE1 is the most conserved eukaryotic unfolded protein response (UPR) receptor. It is a type I transmembrane protein kinase receptor with a distinctive site-specific RNase activity. As the binding mechanics of the misfolded proteins with the N-terminal domain of IRE-1 are unclear, three binding models — direct, indirect, and allosteric -- are proposed for receptor activation. Nevertheless, it is known that once a misfolded protein associates with IRE1, it...
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...
The Intrinsic Apoptotic Pathway01:31

The Intrinsic Apoptotic Pathway

Internal cellular stress, such as cellular injury or hypoxia, triggers intrinsic apoptosis. The B-cell lymphoma 2 (Bcl-2) family of proteins are the primary regulators of the intrinsic apoptotic pathway. For example, during DNA damage, checkpoint proteins, such as Ataxia Telangiectasia Mutated (ATM protein) and Checkpoints Factor-2 (Chk2) proteins, are activated. These proteins phosphorylate p53 which further activates pro-apoptotic proteins, such as Bax, Bak, PUMA, and Noxa, and inhibits...
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...
Cellular Injury V: Apoptosis and Autophagy01:22

Cellular Injury V: Apoptosis and Autophagy

Cells respond to damage and stress through highly coordinated processes that decide whether they survive or undergo controlled self-destruction. Two major pathways involved in this regulation are apoptosis, a type of programmed cell death, and autophagy, a survival mechanism that helps cells adapt to adverse conditions.ApoptosisApoptosis removes aged or injured cells to maintain tissue balance. During this process, the cell shrinks, chromatin condenses and fragments, and membrane-bound...