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Caspase-8 prevents sustained activation of NF-kappaB in monocytes undergoing macrophagic differentiation.: Caspase-8 in the macrophage differentiation.

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-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.
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https://www.hal.inserm.fr/inserm-00144778
Contributor : Olivier Micheau <>
Submitted on : Thursday, July 24, 2008 - 5:00:13 PM
Last modification on : Wednesday, August 19, 2020 - 11:16:45 AM
Long-term archiving on: : Tuesday, April 6, 2010 - 11:17:39 PM

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Cédric Rébé, Séverine Cathelin, Sophie Launay, Rodolphe Filomenko, Laurent Prévotat, et al.. Caspase-8 prevents sustained activation of NF-kappaB in monocytes undergoing macrophagic differentiation.: Caspase-8 in the macrophage differentiation.. Blood, American Society of Hematology, 2007, 109 (4), pp.1442-50. ⟨10.1182/blood-2006-03-011585⟩. ⟨inserm-00144778⟩

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