Caspase recruitment domain-containing protein 8 (CARD8) negatively regulates NOD2-mediated signaling.
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.
von Kampen
Oliver
O
Institute of Clinical Molecular Biology, Christian Albrechts University, Kiel D-24105, Germany.
Lipinski
Simone
S
Till
Andreas
A
Martin
Seamus J
SJ
Nietfeld
Wilfried
W
Lehrach
Hans
H
Schreiber
Stefan
S
Rosenstiel
Philip
P
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
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
Gastroenterology. 2003 Apr;124(4):1001-9
12671897
Anticancer Res. 2006 Sep-Oct;26(5B):3819-24
17094407
Infect Immun. 2006 Jun;74(6):3115-24
16714539
Nature. 2001 May 31;411(6837):603-6
11385577
J Biol Chem. 2005 Dec 2;280(48):40301-9
16203728
Mol Cell. 2007 Mar 9;25(5):713-24
17349957
Microbes Infect. 2007 Apr;9(5):648-57
17376727
Nature. 2001 May 31;411(6837):599-603
11385576
Gastroenterology. 2002 Jan;122(1):44-54
11781279
Gastroenterology. 1998 Aug;115(2):281-6
9679033
J Biol Chem. 2001 Feb 16;276(7):4812-8
11087742
Nat Rev Immunol. 2003 May;3(5):371-82
12766759
J Biol Chem. 2002 Nov 1;277(44):41701-5
12194982
Nat Genet. 2005 Apr;37(4):357-64
15735647
Science. 2006 Nov 10;314(5801):952-6
17095692
J Cell Sci. 2009 Oct 1;122(Pt 19):3522-30
19759286
J Cell Biol. 2005 Jul 4;170(1):21-6
15998797
Proc Natl Acad Sci U S A. 2006 Feb 28;103(9):3280-5
16492792
Immunity. 2004 Mar;20(3):243-4
15030767
Cell. 2004 May 28;117(5):561-74
15163405
J Biol Chem. 2002 Apr 19;277(16):13952-8
11821383
J Biol Chem. 2004 Jan 30;279(5):3509-15
14597638
Gastroenterology. 2003 Apr;124(4):993-1000
12671896
J Cell Sci. 2008 Feb 15;121(Pt 4):487-95
18256385
Immunity. 2004 Mar;20(3):319-25
15030775
Gastroenterology. 2003 Jul;125(1):47-57
12851870
Chembiochem. 2008 Apr 14;9(6):923-33
18348116
Annu Rev Immunol. 2005;23:387-414
15771576
J Biol Chem. 2005 May 13;280(19):19021-6
15753091
Mol Cell. 2002 Aug;10(2):417-26
12191486
FEBS Lett. 2002 Jun 19;521(1-3):165-9
12067710
J Biol Chem. 2001 Nov 23;276(47):44069-77
11551959
Lancet. 2001 Jun 16;357(9272):1925-8
11425413
Gut. 2002 Sep;51(3):379-85
12171960
Science. 2005 Feb 4;307(5710):731-4
15692051
J Biol Chem. 2001 Aug 24;276(34):32220-9
11408476