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Blood, 1 January 2009, Vol. 113, No. 1, pp. 175-185. Prepublished online as a Blood First Edition Paper on September 30, 2008; DOI 10.1182/blood-2008-02-137919. This Article Full Text Full Text (PDF) Supplemental Figures All Versions of this Article: blood-2008-02-137919v1 113/1/175    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 CrossRef Citing Articles via Google Scholar Google Scholar Articles by Dupoux, A. Articles by Dubrez-Daloz, L. Search for Related Content PubMed PubMed Citation Articles by Dupoux, A. Articles by Dubrez-Daloz, L. Related Collections Immunobiology Phagocytes, Granulocytes, and Myelopoiesis Social Bookmarking                   What's this?  Previous Article  |  Table of Contents  |  Next Article  PHAGOCYTES, GRANULOCYTES, AND MYELOPOIESIS cIAP1-dependent TRAF2 degradation regulates the differentiation of monocytes into macrophages and their response to CD40 ligand Alban Dupoux1,2, Jessy Cartier1,2, Séverine Cathelin1,2, Rodolphe Filomenko1,2, Eric Solary1,2, and Laurence Dubrez-Daloz1,2 1 Inserm Unite Mixte de Recherche 866, Dijon; and 2 Faculty of Medicine, Institut Fédératif de Recherche, University of Burgundy, Dijon, France Peripheral blood monocytes are plastic cells that migrate to tissues and differentiate into various cell types, including macrophages, dendritic cells, and osteoclasts. We have described the migration of cellular inhibitor of apoptosis protein 1 (cIAP1), a member of the IAP family of proteins, from the nucleus to the Golgi apparatus in monocytes undergoing differentiation into macrophages. Here we show that, once in the cytoplasm, cIAP1 is involved in the degradation of the adaptor protein tumor necrosis factor receptor–associated factor 2 (TRAF2) by the proteosomal machinery. Inhibition of cIAP1 prevents the decrease in TRAF2 expression that characterizes macrophage formation. We demonstrate that TRAF2 is initially required for macrophage differentiation as its silencing prevents I-B degradation, nuclear factor-B (NF-B) p65 nuclear translocation, and the differentiation process. Then, we show that cIAP1-mediated degradation of TRAF2 allows the differentiation process to progress. This degradation is required for the macrophages to be fully functional as TRAF2 overexpression in differentiated cells decreases the c-Jun N-terminal kinase–mediated synthesis and the secretion of proinflammatory cytokines, such as interleukin-8 and monocyte chemoattractant protein 1 (MCP-1) in response to CD40 ligand. We conclude that TRAF2 expression and subsequent degradation are required for the differentiation of monocytes into fully functional macrophages. CiteULike    Connotea    Del.icio.us    Digg    Reddit    Technorati    What's this?

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