Caspase recruitment domain-containing protein 8 (CARD8) negatively regulates NOD2-mediated signaling.

Authors:
Oliver von Kampen, Simone Lipinski, Andreas Till, Seamus J Martin, Wilfried Nietfeld, Hans Lehrach, Stefan Schreiber, Philip Rosenstiel
Year of publication:
2010
Volume:
285
Issue:
26
Issn:
0021-9258
Journal title abbreviated:
J BIOL CHEM
Journal title long:
JBC papers in press
Impact factor:
4.258
Abstract: 
Caspase activating and recruitment domain 8 (CARD8) has been implicated as a co-regulator of several pro-inflammatory and apoptotic signaling pathways. In the present study, we demonstrate a specific modulation of NOD2-induced signaling by CARD8 in intestinal epithelial cells. We show that CARD8 physically interacts with NOD2 and inhibits nodosome assembly and subsequent signaling upon muramyl-dipeptide stimulation. Furthermore, CARD8 inhibits the direct bactericidal effect of NOD2 against intracellular infection by Listeria monocytogenes. Thus, CARD8 represents a novel molecular switch involved in the endogenous regulation of NOD2-dependent inflammatory processes in epithelial cells.