Caspase-8 prevents sustained activation of NF-kappaB in monocytes undergoing macrophagic differentiation.
Fiche publication
Date publication
février 2007
Auteurs
Membres identifiés du Cancéropôle Est :
Dr MICHEAU Olivier
Tous les auteurs :
Rebe C, Cathelin S, Launay S, Filomenko R, Prevotat L, L'Ollivier C, Gyan E, Micheau O, Grant S, Dubart-Kupperschmitt A, Fontenay M, Solary E
Lien Pubmed
Résumé
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-kappaB 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-kappaB activity through RIP1 cleavage.
Référence
Blood. 2007 Feb 15;109(4):1442-50