cFLIP regulation of lymphocyte activation and development.
Cellular caspase-8 (FLICE)-like inhibitory protein (cFLIP) was originally identified as an inhibitor of death-receptor signalling through competition with caspase-8 for recruitment to FAS-associated via death domain (FADD). More recently, it has been determined that both cFLIP and caspase-8 are required for the survival and proliferation of T cells following T-cell-receptor stimulation. This paradoxical finding launched new investigations of how these molecules might connect with signalling pathways that link to cell survival and growth following antigen-receptor activation. As discussed in this Review, insight gained from these studies indicates that cFLIP and caspase-8 form a heterodimer that ultimately links T-cell-receptor signalling to activation of nuclear factor-kappaB through a complex that includes B-cell lymphoma 10 (BCL-10), mucosa-associated-lymphoid-tissue lymphoma-translocation gene 1 (MALT1) and receptor-interacting protein 1 (RIP1).
Immunobiology Program, Department of Medicine, The University of Vermont College of Medicine, Burlington, Vermont 50405, USA.
Ralph C
RC
Budd
Wen-Chen
WC
Yeh
Jürg
J
Tschopp
D000818:Animals; D015551:Autoimmunity; D053446:CASP8 and FADD-Like Apoptosis Regulating Protein; D006801:Humans; D047908:Intracellular Signaling Peptides and Proteins / Q000737:chemistry / Q000235:genetics / Q000502:physiology*; D008213:Lymphocyte Activation; D009369:Neoplasms / Q000209:etiology; D013601:T-Lymphocytes / Q000276:immunology / Q000502:physiology*; D019014:fas Receptor / Q000502:physiology
D053446:CASP8 and FADD-Like Apoptosis Regulating Protein; C506386:CFLAR protein, human; D047908:Intracellular Signaling Peptides and Proteins; D019014:fas Receptor