Apo2L/TRAIL: apoptosis signaling, biology, and potential for cancer therapy

Cytokine Growth Factor Rev. Jun-Aug 2003;14(3-4):337-48. doi: 10.1016/s1359-6101(03)00029-7.

Abstract

Apo2 ligand or tumor necrosis factor (TNF)-related apoptosis-inducing ligand (Apo2L/TRAIL) is one of several members of the TNF gene superfamily that induce apoptosis through engagement of death receptors. Apo2L/TRAIL is unusual as compared to any other cytokine as it interacts with a complex system of receptors: two pro-apoptotic death receptors and three anti-apoptotic decoys. This protein has generated tremendous excitement as a potential tumor-specific cancer therapeutic because, as a stable soluble trimer, it selectively induces apoptosis in many transformed cells but not in normal cells. Transcriptional activation of Apo2L/TRAIL by interferons (IFNs) through specific regulatory elements in its promoter, and possibly by a number of other cytokines, reveals its possible involvement in the activation of natural killer cells, cytotoxic T lymphocytes, and dendritic cells. In this review, we focus on the apoptosis signaling pathways stimulated by Apo2L/TRAIL, summarize what is known to date about the physiological role of this ligand and the potential for its application to cancer therapy.

Publication types

  • Research Support, U.S. Gov't, P.H.S.
  • Review

MeSH terms

  • Animals
  • Apoptosis / physiology*
  • Apoptosis Regulatory Proteins
  • CASP8 and FADD-Like Apoptosis Regulating Protein
  • Carrier Proteins / physiology
  • Humans
  • Interferons / physiology
  • Intracellular Signaling Peptides and Proteins*
  • Membrane Glycoproteins / genetics
  • Membrane Glycoproteins / physiology*
  • Mice
  • Models, Biological
  • NF-kappa B / physiology
  • Neoplasms / immunology
  • Neoplasms / therapy*
  • Proteins / physiology
  • Proto-Oncogene Proteins c-bcl-2 / physiology
  • Receptors, TNF-Related Apoptosis-Inducing Ligand
  • Receptors, Tumor Necrosis Factor / physiology
  • Signal Transduction
  • TNF-Related Apoptosis-Inducing Ligand
  • Tumor Necrosis Factor-alpha / genetics
  • Tumor Necrosis Factor-alpha / physiology*
  • Virus Diseases / immunology
  • X-Linked Inhibitor of Apoptosis Protein

Substances

  • Apoptosis Regulatory Proteins
  • CASP8 and FADD-Like Apoptosis Regulating Protein
  • CFLAR protein, human
  • Carrier Proteins
  • Cflar protein, mouse
  • Intracellular Signaling Peptides and Proteins
  • Membrane Glycoproteins
  • NF-kappa B
  • Proteins
  • Proto-Oncogene Proteins c-bcl-2
  • Receptors, TNF-Related Apoptosis-Inducing Ligand
  • Receptors, Tumor Necrosis Factor
  • TNF-Related Apoptosis-Inducing Ligand
  • TNFRSF10A protein, human
  • TNFSF10 protein, human
  • Tnfsf10 protein, mouse
  • Tumor Necrosis Factor-alpha
  • X-Linked Inhibitor of Apoptosis Protein
  • XIAP protein, human
  • Interferons