The caspase-8 Modulator c-FLIP

Crit Rev Immunol. 2005;25(1):31-58. doi: 10.1615/critrevimmunol.v25.i1.30.


Death receptors belong to the tumor necrosis factor receptor superfamily and can induce apoptosis through activation of procaspase-8. The cellular FLICE-inhibitory protein (c-FLIP) is able to modulate activation of procaspase-8 and thereby prevents induction of apoptosis mediated by death receptors. As an important modulator of caspase-8, c-FLIP regulates life and death in various types of normal cells and tissues, such as lymphoid cells, and renders resistance to death receptor-mediated apoptosis in many types of cancer cells. In addition to an apoptosis modulator, c-FLIP has been shown to exert other physiological functions related to cell proliferation and tumorigenesis. Dysregulation of c-FLIP expression has been shown to be associated with various diseases, such as cancer and autoimmune diseases, and c-FLIP might be a critical target for therapeutic intervention. This review focuses on recent findings about the physiological function and intracellular regulation of c-FLIP.

Publication types

  • Review

MeSH terms

  • Animals
  • Apoptosis / drug effects*
  • Apoptosis / immunology
  • Apoptosis / physiology
  • CASP8 and FADD-Like Apoptosis Regulating Protein
  • Caspase 8
  • Caspases / drug effects*
  • Caspases / immunology
  • Caspases / physiology
  • Humans
  • Intracellular Signaling Peptides and Proteins* / genetics
  • Intracellular Signaling Peptides and Proteins* / pharmacology
  • Intracellular Signaling Peptides and Proteins* / physiology*
  • Receptors, Tumor Necrosis Factor / antagonists & inhibitors
  • Receptors, Tumor Necrosis Factor / immunology
  • Receptors, Tumor Necrosis Factor / physiology
  • Signal Transduction / immunology
  • Signal Transduction / physiology


  • CASP8 and FADD-Like Apoptosis Regulating Protein
  • CFLAR protein, human
  • Intracellular Signaling Peptides and Proteins
  • Receptors, Tumor Necrosis Factor
  • CASP8 protein, human
  • Caspase 8
  • Caspases