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RESEARCH PRODUCT
Caspase-8 prevents sustained activation of NF-kappaB in monocytes undergoing macrophagic differentiation.
Emmanuel GyanAnne Dubart-kupperschmittSophie LaunaySophie LaunayRodolphe FilomenkoRodolphe FilomenkoRodolphe FilomenkoEric SolaryEric SolaryMichaela FontenayCoralie L'ollivierCoralie L'ollivierMicheau OlivierOlivier MicheauSteven GrantLaurent PrévotatLaurent PrévotatLaurent PrévotatSéverine CathelinSéverine CathelinCédric RébéCédric Rébésubject
Macrophage colony-stimulating factorCellular differentiationFas-Associated Death Domain ProteinImmunologyCaspase 8BiochemistryMonocytesArticle03 medical and health sciences0302 clinical medicineCell Line TumormedicineHumansFADDCaspase030304 developmental biologyDeath domain0303 health sciencesCaspase 8biologyMonocyteMacrophage Colony-Stimulating FactorMacrophagesNF-kappa BSignal transducing adaptor proteinRNA-Binding ProteinsCell DifferentiationCell BiologyHematologyMolecular biologyNuclear Pore Complex Proteinsmedicine.anatomical_structure030220 oncology & carcinogenesisbiology.proteindescription
Abstract Caspases have demonstrated several nonapoptotic functions including a role in the differentiation of specific cell types. Here, we show that caspase-8 is the upstream enzyme in the proteolytic caspase cascade whose activation is required for the differentiation of peripheral-blood monocytes into macrophages. On macrophage colony-stimulating factor (M-CSF) exposure, caspase-8 associates with the adaptor protein Fas-associated death domain (FADD), the serine/threonine kinase receptor-interacting protein 1 (RIP1) and the long isoform of FLICE-inhibitory protein FLIP. Overexpression of FADD accelerates the differentiation process that does not involve any death receptor. Active caspase-8 cleaves RIP1, which prevents sustained NF-κB activation, and activates downstream caspases. Together these data identify a role for caspase-8 in monocytes undergoing macrophagic differentiation, that is, the enzyme activated in an atypical complex down-regulates NF-κB activity through RIP1 cleavage.
| year | journal | country | edition | language |
|---|---|---|---|---|
| 2006-10-17 | Blood |