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

نویسندگان

  • Cédric Rébé
  • Séverine Cathelin
  • Sophie Launay
  • Rodolphe Filomenko
  • Laurent Prévotat
  • Coralie L'Ollivier
  • Emmanuel Gyan
  • Olivier Micheau
  • Steven Grant
  • Anne Dubart-Kupperschmitt
  • Michaëla Fontenay
  • Eric Solary
چکیده

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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HEMATOPOIESIS Caspase-8 prevents sustained activation of NF- B in monocytes undergoing macrophagic differentiation

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عنوان ژورنال:
  • Blood

دوره 109 4  شماره 

صفحات  -

تاریخ انتشار 2007