title: Caspase recruitment domain-containing protein 8 (CARD8) negatively regulates NOD2-mediated signaling.
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.
authors.affiliation: Institute of Clinical Molecular Biology, Christian Albrechts University, Kiel D-24105, Germany.
authors.forename: Oliver
authors.initials: O
authors.lastname: von Kampen
authors.forename: Simone
authors.initials: S
authors.lastname: Lipinski
authors.forename: Andreas
authors.initials: A
authors.lastname: Till
authors.forename: Seamus J
authors.initials: SJ
authors.lastname: Martin
authors.forename: Wilfried
authors.initials: W
authors.lastname: Nietfeld
authors.forename: Hans
authors.initials: H
authors.lastname: Lehrach
authors.forename: Stefan
authors.initials: S
authors.lastname: Schreiber
authors.forename: Philip
authors.initials: P
authors.lastname: Rosenstiel
mesh_terms: D000119:Acetylmuramyl-Alanyl-Isoglutamine / Q000494:pharmacology; D000900:Anti-Bacterial Agents / Q000494:pharmacology; D015153:Blotting, Western; D053468:CARD Signaling Adaptor Proteins / Q000235:genetics / Q000378:metabolism*; D018938:Caco-2 Cells; D002460:Cell Line; D045744:Cell Line, Tumor; D003106:Colon / Q000201:enzymology*; D003424:Crohn Disease / Q000235:genetics / Q000378:metabolism / Q000473:pathology; D020869:Gene Expression Profiling; D005839:Gentamicins / Q000494:pharmacology; D019073:HT29 Cells; D006367:HeLa Cells; D006801:Humans; D007413:Intestinal Mucosa / Q000378:metabolism / Q000473:pathology; D042541:Intracellular Space / Q000187:drug effects / Q000378:metabolism / Q000382:microbiology; D008089:Listeria monocytogenes / Q000254:growth & development; D008164:Luminescent Proteins / Q000235:genetics / Q000378:metabolism; D008297:Male; D008856:Microscopy, Fluorescence; D009363:Neoplasm Proteins / Q000235:genetics / Q000378:metabolism*; D053473:Nod2 Signaling Adaptor Protein / Q000235:genetics / Q000378:metabolism*; D011485:Protein Binding; D034622:RNA Interference; D020133:Reverse Transcriptase Polymerase Chain Reaction; D015398:Signal Transduction / Q000187:drug effects / Q000235:genetics / Q000502:physiology*; D014162:Transfection
chemical_list: D000900:Anti-Bacterial Agents; D053468:CARD Signaling Adaptor Proteins; C455623:CARD8 protein, human; D005839:Gentamicins; D008164:Luminescent Proteins; C429018:NOD2 protein, human; D009363:Neoplasm Proteins; D053473:Nod2 Signaling Adaptor Protein; D000119:Acetylmuramyl-Alanyl-Isoglutamine
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