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

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.
Mesh Terms:
Caspase 8, Cell Differentiation, Cell Line, Tumor, Fas-Associated Death Domain Protein, Humans, Macrophage Colony-Stimulating Factor, Macrophages, Monocytes, NF-kappa B, Nuclear Pore Complex Proteins, RNA-Binding Proteins
Blood
Date: Feb. 15, 2007
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