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Blood, 15 February 2007, Vol. 109, No. 4, pp. 1442-1450. Prepublished online as a Blood First Edition Paper on October 17, 2006; DOI 10.1182/blood-2006-03-011585. This Article Full Text Full Text (PDF) Supplemental Figure All Versions of this Article: blood-2006-03-011585v1 109/4/1442    most recent Alert me when this article is cited Alert me if a correction is posted Citation Map Services Email this article to a friend Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Rights and Permissions Citing Articles Citing Articles via HighWire Citing Articles via CrossRef Citing Articles via Google Scholar Google Scholar Articles by Rébé, C. Articles by Solary, E. Search for Related Content PubMed PubMed Citation Articles by Rébé, C. Articles by Solary, E. Related Collections Hematopoiesis and Stem Cells Phagocytes Apoptosis Social Bookmarking                   What's this?  Previous Article  |  Table of Contents  |  Next Article  HEMATOPOIESIS Caspase-8 prevents sustained activation of NF-B in monocytes undergoing macrophagic differentiation Cédric Rébé1,2, Séverine Cathelin1,2, Sophie Launay1,2, Rodolphe Filomenko1,3, Laurent Prévotat1,3, Coralie L'Ollivier1,2,4, Emmanuel Gyan5,6, Olivier Micheau1,2, Steven Grant7, Anne Dubart-Kupperschmitt5, Michaëla Fontenay5,6, and Eric Solary1,2,4 1 Institut National de la Santé et de la Recherche Médicale (INSERM) U517, Dijon, France; 2 Institut Fédératif de Recherche (IFR) 100, University of Burgundy, Dijon, France; 3 Ecole Pratique des Hautes Etudes (EPHE), Faculty of Medicine, Dijon cedex, France; 4 Centre Hospitalier Universitaire, Dijon cedex, France; 5 INSERM U567, Institut Cochin, Paris, France; 6 Department of Hematology, Cochin Hospital, Paris, France; and the 7 Department of Medicine and Biochemistry, Virginia Commonwealth University, Medical College of Virginia, Richmond, VA 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-B 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-B activity through RIP1 cleavage. CiteULike    Connotea    Del.icio.us    Digg    Reddit    Technorati    What's this? 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