FLIP protein and TRAIL-induced apoptosis.
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.
Roth
Wilfried
W
The Burnham Institute, La Jolla, California 92037, USA.
Reed
John C
JC
D000818:Animals; D017209:Apoptosis; D051017:Apoptosis Regulatory Proteins; D053446:CASP8 and FADD-Like Apoptosis Regulating Protein; D002319:Cardiovascular System; D002352:Carrier Proteins / Q000737:chemistry / Q000235:genetics / Q000502:physiology*; D015870:Gene Expression; D006801:Humans; D007109:Immunity; D047908:Intracellular Signaling Peptides and Proteins; D008562:Membrane Glycoproteins / Q000502:physiology*; D015166:Monitoring, Immunologic; D009369:Neoplasms / Q000188:drug therapy / Q000276:immunology; D013329:Structure-Activity Relationship; D053221:TNF-Related Apoptosis-Inducing Ligand; D014409:Tumor Necrosis Factor-alpha / Q000502:physiology*
D051017:Apoptosis Regulatory Proteins; D053446:CASP8 and FADD-Like Apoptosis Regulating Protein; C506386:CFLAR protein, human; D002352:Carrier Proteins; D047908:Intracellular Signaling Peptides and Proteins; D008562:Membrane Glycoproteins; D053221:TNF-Related Apoptosis-Inducing Ligand; C505653:TNFSF10 protein, human; D014409:Tumor Necrosis Factor-alpha