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Receptor-mediated choreography of life and death

Anjana Bhardwaj1, Bharat B Aggarwal

  • 1Cytokine Research Laboratory, Department of Bioimmunotherapy, The University of Texas M. D. Anderson Cancer Center, 1515 Holcombe Boulevard, Houston, Texas 77030, USA.

Journal of Clinical Immunology
|November 7, 2003
PubMed

Insights

Tumor necrosis factor (TNF) family members regulate cell death (apoptosis) via death receptors. This review details the complex interplay of proteins controlling apoptosis, from initiation to execution.

Area of Science:

  • Immunology
  • Molecular Biology
  • Cell Biology

Background:

  • Tumor necrosis factor (TNF) was initially identified for its tumor-killing properties.
  • The TNF superfamily comprises 18 members, all involved in regulating cell survival, proliferation, differentiation, and apoptosis.
  • Apoptosis induced by TNF family members is mediated through specific death receptors.

Purpose of the Study:

  • To review the mechanisms of apoptosis induced by TNF family members.
  • To describe the roles of death receptors and intracellular signaling proteins in apoptosis.
  • To elucidate the intricate regulation of cell death pathways by both positive and negative players.

Main Methods:

  • Literature review of studies on TNF, death receptors, and apoptosis.
  • Analysis of signaling pathways involving death domains (DD) and caspases.
  • Examination of regulatory proteins, including decoy receptors and inhibitors of apoptosis.

Main Results:

  • TNF family cytokines signal through eight distinct death domain-containing receptors.
  • Ligand binding to death receptors initiates intracellular signaling cascades involving DD-containing proteins.
  • Activation of caspases executes the cell death process, while regulatory proteins modulate this pathway.

Conclusions:

  • Cell death is a tightly regulated process involving a complex network of signaling molecules.
  • Understanding the "harmonious dance" between positive and negative regulators is crucial for comprehending apoptosis.
  • This review synthesizes current knowledge on the molecular players governing TNF-induced apoptosis.

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