FLIP protein and TRAIL-induced apoptosis

Vitam Horm. 2004;67:189-206. doi: 10.1016/S0083-6729(04)67011-7.

Abstract

Death ligands (such as Fas/CD95 ligand and TRAIL?Apo2L) and death receptors (such as Fas/CD95, TRAIL-R1?DR4, and TRAIL-R2/DR5) are involved in immune-mediated neutralization of activated or autoreactive lymphocytes, virus-infected cells, and tumor cells. Consequently, dysregulation of death receptor-dependent apoptotic signaling pathways has been implicated in the development of autoimmune diseases, immunodeficiency, and cancer. Moreover, the death ligand TRAIL has gained considerable interest as a potential anticancer agent, given its ability to induce apoptosis of tumor cells without affecting most types of untransformed cells. The FLICE-inhibitory protein (FLIP) potently blocks TRAIL-mediated cell death by interfering with caspase-8 activation. Pharmacologic down-regulation of FLIP might serve as a therapeutic means to sensitize tumor cells to apoptosis induction by TRAIL.

Publication types

  • Review

MeSH terms

  • Animals
  • Apoptosis Regulatory Proteins
  • Apoptosis*
  • CASP8 and FADD-Like Apoptosis Regulating Protein
  • Cardiovascular System
  • Carrier Proteins / chemistry
  • Carrier Proteins / genetics
  • Carrier Proteins / physiology*
  • Gene Expression
  • Humans
  • Immunity
  • Intracellular Signaling Peptides and Proteins*
  • Membrane Glycoproteins / physiology*
  • Monitoring, Immunologic
  • Neoplasms / drug therapy
  • Neoplasms / immunology
  • Structure-Activity Relationship
  • TNF-Related Apoptosis-Inducing Ligand
  • Tumor Necrosis Factor-alpha / physiology*

Substances

  • Apoptosis Regulatory Proteins
  • CASP8 and FADD-Like Apoptosis Regulating Protein
  • CFLAR protein, human
  • Carrier Proteins
  • Intracellular Signaling Peptides and Proteins
  • Membrane Glycoproteins
  • TNF-Related Apoptosis-Inducing Ligand
  • TNFSF10 protein, human
  • Tumor Necrosis Factor-alpha