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Related Concept Videos

NF-κB-dependent Signaling Pathway02:26

NF-κB-dependent Signaling Pathway

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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.
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Cell death is an essential process where the body gets rid of old or damaged cells. Cell proliferation and death need to be balanced, as an imbalance between the two may lead to cancer or autoimmune diseases.
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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...
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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...
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When T cells with CD4 markers are activated, they give rise to two types of effector cells: helper T cells and regulatory T cells. Meanwhile, T cells with CD8 markers differentiate into effector cytotoxic T cells. The differentiation of CD4 T cells into helper T cell subsets, such as Th1, Th2, and Th17 cells, is dependent on the antigen type, antigen-presenting cell, and regulatory cytokines.
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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...
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Related Experiment Video

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Identification of Intracellular Signaling Events Induced in Viable Cells by Interaction with Neighboring Cells Undergoing Apoptotic Cell Death
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A proteomic perspective on TNF-mediated signalling and cell death.

Maria C Tanzer1

  • 1Department of Proteomics and Signal Transduction, Max-Planck Institute of Biochemistry, Martinsried 82152, Germany.

Biochemical Society Transactions
|February 15, 2022
PubMed
Summary

Tumour necrosis factor (TNF) is a potent cell death inducer vital for immunity. Proteomic methods offer new insights into how TNF signaling impacts inflammation and cell death pathways like apoptosis and necroptosis.

Keywords:
apoptosisnecroptosispost-translational modificationproteomicstumor necrosis factors

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Area of Science:

  • Immunology
  • Cell Biology
  • Molecular Biology

Background:

  • Tumour necrosis factor (TNF) is a key cytokine that regulates cell death, homeostasis, immune development, and infection response.
  • Dysregulated TNF levels are implicated in autoinflammatory, autoimmune diseases, and sepsis, characterized by increased cell death.
  • Cell death downstream of TNF receptors can proceed via caspase-dependent (apoptosis) or caspase-independent (necroptosis) pathways.

Purpose of the Study:

  • To explore the role of modern proteomic approaches in understanding TNF signaling.
  • To provide a novel perspective on TNF's effects on inflammation and cell survival.
  • To highlight the significance of phosphoproteomics and secretomics in studying TNF-mediated processes.

Main Methods:

  • Review of modern proteomic techniques, specifically phosphoproteomics and secretomics.
  • Analysis of signaling mechanisms downstream of the TNF receptor.
  • Discussion of TNF's impact on apoptosis and necroptosis.

Main Results:

  • Proteomic approaches offer a novel perspective on TNF signaling pathways.
  • Phosphoproteomics and secretomics can elucidate complex cellular responses to TNF.
  • Understanding these pathways is crucial for developing therapeutic strategies.

Conclusions:

  • Modern proteomic techniques provide valuable insights into TNF-mediated cell death and inflammation.
  • Further research utilizing phosphoproteomics and secretomics can advance our understanding of TNF's role in disease.
  • Targeting TNF signaling pathways holds therapeutic potential for inflammatory and autoimmune conditions.