Rewinding the DISC.
Fas (CD95/APO-1) belongs to the tumor necrosis factor receptor family and its signaling pathway has been extensively studied over the past 15 years. Blockade of the Fas-mediated apoptotic signal leads to abusive lymphoproliferation, auto-immunity, and an increased risk of developing lymphoma and leukemia. Fas engagement drives the formation of a complex termed DISC (death-inducing signaling complex), which contains the adaptor molecule Fas-associated protein, two members of the caspase family caspase-8 and -10, and a pseudo-caspase termed c-FLIP. According to different authors, DISC formation relies either on the redistribution of Fas into the lipid rafts or the recruitment of the actin cytoskeleton and receptor endocytosis or the production of ceramide. However, the accurate molecular ordering upstream from the formation of DISC remains very puzzling and is highly debated. Herein we review some of the factors that would potentially facilitate or limit the formation of the DISC.
Chaigne-Delalande
Benjamin
B
Université de Bordeaux-2, Bordeaux, France.
Moreau
Jean-François
JF
Legembre
Patrick
P
D000818:Animals; D017209:Apoptosis / Q000187:drug effects / Q000502:physiology*; D002518:Ceramides / Q000096:biosynthesis; D003599:Cytoskeleton / Q000378:metabolism; D053418:Death Domain Receptor Signaling Adaptor Proteins / Q000502:physiology*; D004705:Endocytosis / Q000502:physiology; D053222:Fas Ligand Protein / Q000502:physiology; D006801:Humans; D008232:Lymphoproliferative Disorders / Q000209:etiology / Q000378:metabolism; D021962:Membrane Microdomains / Q000378:metabolism*; D018448:Models, Immunological; D011940:Receptor Aggregation; D015398:Signal Transduction / Q000502:physiology*; D047988:Tumor Necrosis Factor Receptor-Associated Peptides and Proteins / Q000378:metabolism; D019014:fas Receptor / Q000502:physiology*
D002518:Ceramides; D053418:Death Domain Receptor Signaling Adaptor Proteins; D053222:Fas Ligand Protein; D047988:Tumor Necrosis Factor Receptor-Associated Peptides and Proteins; D019014:fas Receptor