On the TRAIL to apoptosis

Cytokine Growth Factor Rev. 2002 Jun;13(3):199-207. doi: 10.1016/s1359-6101(02)00006-0.


Apoptosis in mammalian cells can be initiated through two major interrelated pathways, one involving engagement of the TNF family of death receptors, the other involving the release of cytochrome c from mitochondria. Unlike other members of the TNF ligand family, TNF-related apoptosis-inducing ligand (TRAIL) preferentially induces apoptosis in tumor cell lines, but not in normal cells, suggesting that TRAIL could potentially represent a powerful cancer therapeutic. Recent experiments have revealed that one of the key regulators of TRAIL expression in lymphocytes is the NF-kappa B transcription factors. Several TRAIL receptors have been identified: two of these receptors TRAIL-R1/DR4 and TRAIL-R2/DR5 contain cytoplasmic death domains and signal apoptosis, while two other decoy receptors, TRAIL-R3/DcR1 and TRAIL-R4/DcR2 lack a functional death domain and do not mediate apoptosis. Many cancer cell lines preferentially express TRAIL-R1 and TRAIL-R2, suggesting differential regulation of the death and decoy receptors. Further knowledge of the regulation and physiological role of TRAIL and TRAIL receptors may aid in the rational design of regimens that utilize the TRAIL signaling pathway to eliminate tumor cells.

Publication types

  • Research Support, Non-U.S. Gov't
  • Review

MeSH terms

  • Animals
  • Apoptosis Regulatory Proteins
  • Apoptosis*
  • Cytoplasm / metabolism
  • Gene Expression Regulation
  • Humans
  • Ligands
  • Membrane Glycoproteins / metabolism*
  • Models, Biological
  • NF-kappa B / metabolism
  • Receptors, TNF-Related Apoptosis-Inducing Ligand
  • Receptors, Tumor Necrosis Factor / metabolism
  • Signal Transduction
  • TNF-Related Apoptosis-Inducing Ligand
  • Tumor Necrosis Factor-alpha / metabolism*
  • Tumor Suppressor Protein p53 / metabolism


  • Apoptosis Regulatory Proteins
  • Ligands
  • Membrane Glycoproteins
  • NF-kappa B
  • Receptors, TNF-Related Apoptosis-Inducing Ligand
  • Receptors, Tumor Necrosis Factor
  • TNF-Related Apoptosis-Inducing Ligand
  • TNFRSF10A protein, human
  • TNFRSF10B protein, human
  • TNFSF10 protein, human
  • Tumor Necrosis Factor-alpha
  • Tumor Suppressor Protein p53