The caspase-8 modulator c-FLIP.
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.
Kataoka
Takao
T
Center for Biological Resources and Informatics, Tokyo Institute of Technology, Midori-ku, Yokohama, Japan. tkataoka@bio.tech.ac.jp
D000818:Animals; D017209:Apoptosis / Q000187:drug effects* / Q000276:immunology / Q000502:physiology; D053446:CASP8 and FADD-Like Apoptosis Regulating Protein; D053181:Caspase 8; D020169:Caspases / Q000187:drug effects* / Q000276:immunology / Q000502:physiology; D006801:Humans; D047908:Intracellular Signaling Peptides and Proteins / Q000235:genetics / Q000494:pharmacology / Q000502:physiology*; D018124:Receptors, Tumor Necrosis Factor / Q000037:antagonists & inhibitors / Q000276:immunology / Q000502:physiology; D015398:Signal Transduction / Q000276:immunology / Q000502:physiology
D053446:CASP8 and FADD-Like Apoptosis Regulating Protein; C506386:CFLAR protein, human; D047908:Intracellular Signaling Peptides and Proteins; D018124:Receptors, Tumor Necrosis Factor; C505530:CASP8 protein, human; D053181:Caspase 8; D020169:Caspases