Cellular FLICE-inhibitory protein: an attractive therapeutic target?
Cellular FLIP (c-FLIP), also known as FLICE-inhibitory protein, has been identified as an inhibitor of apoptosis triggered by engagement of death receptors (DRs) such as Fas or TRAIL (TNF-related apoptosis-inducing ligand). cFLIP is recruited to DR signalling complexes, where it prevents caspase activation. Animal models have indicated that c-FLIP plays an important role in T cell proliferation and heart development. Abnormal c-FLIP expression has been identified in various diseases such as multiple sclerosis (MS), Alzheimer's disease (AD), diabetes mellitus, rheumatoid arthritis (RA) and various cancers. This review focuses on recent insights into c-FLIP dysregulation associated with human diseases and addresses the possibilities of using c-FLIP as a therapeutic target.
Micheau
Olivier
O
INSERM 517, IFR100, Faculty of Medicine, 7 Boulevard Jeanne d'Arc, 21079 Dijon cedex, France. omicheau@u-bourgogne.fr
D017398:Alternative Splicing; D000544:Alzheimer Disease / Q000188:drug therapy / Q000503:physiopathology; D000818:Animals; D017209:Apoptosis / Q000187:drug effects / Q000502:physiology; D001172:Arthritis, Rheumatoid / Q000188:drug therapy / Q000503:physiopathology; D001327:Autoimmune Diseases / Q000188:drug therapy / Q000503:physiopathology; D053446:CASP8 and FADD-Like Apoptosis Regulating Protein; D002318:Cardiovascular Diseases / Q000188:drug therapy / Q000503:physiopathology; D003922:Diabetes Mellitus, Type 1 / Q000188:drug therapy / Q000503:physiopathology; D015195:Drug Design; D005786:Gene Expression Regulation / Q000502:physiology; D006801:Humans; D047908:Intracellular Signaling Peptides and Proteins / Q000037:antagonists & inhibitors* / Q000502:physiology; D008232:Lymphoproliferative Disorders / Q000188:drug therapy / Q000503:physiopathology; D051379:Mice; D016688:Mice, Inbred NOD; D008954:Models, Biological; D009103:Multiple Sclerosis / Q000188:drug therapy / Q000503:physiopathology; D009363:Neoplasm Proteins / Q000037:antagonists & inhibitors / Q000502:physiology; D009369:Neoplasms / Q000188:drug therapy / Q000503:physiopathology; D015398:Signal Transduction / Q000187:drug effects / Q000502:physiology
D053446:CASP8 and FADD-Like Apoptosis Regulating Protein; C506386:CFLAR protein, human; C506387:Cflar protein, mouse; D047908:Intracellular Signaling Peptides and Proteins; D009363:Neoplasm Proteins