|
|
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.
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?
This article has been cited by other articles:

|
 |

|
 |
 
J.-A. T. Tan, Y. Sun, J. Song, Y. Chen, T. G. Krontiris, and L. K. Durrin
SUMO Conjugation to the Matrix Attachment Region-binding Protein, Special AT-rich Sequence-binding Protein-1 (SATB1), Targets SATB1 to Promyelocytic Nuclear Bodies Where It Undergoes Caspase Cleavage
J. Biol. Chem.,
June 27, 2008;
283(26):
18124 - 18134.
[Abstract]
[Full Text]
[PDF]
|
 |
|

|
 |

|
 |
 
A. S. Lo, P. Gorak-Stolinska, V. Bachy, M. A. Ibrahim, D. M. Kemeny, and J. Maher
Modulation of dendritic cell differentiation by colony-stimulating factor-1: role of phosphatidylinositol 3'-kinase and delayed caspase activation
J. Leukoc. Biol.,
December 1, 2007;
82(6):
1446 - 1454.
[Abstract]
[Full Text]
[PDF]
|
 |
|
|
|