Cop, a caspase recruitment domain-containing protein and inhibitor of caspase-1 activation processing.
The production of bio-active interleukin-1beta (IL-1beta), a pro-inflammatory cytokine, is mediated by activated caspase-1. One of the known molecular mechanisms underlying pro-caspase-1 processing and activation involves binding of the caspase-1 prodomain to a caspase recruitment domain (CARD)-containing serine/threonine kinase known as RIP2/CARDIAK/RICK. We have identified a novel protein, COP (CARD only protein), which has a high degree of sequence identity to the caspase-1 prodomain. COP binds to both RIP2 and the caspase-1 prodomain and inhibits RIP2-induced caspase-1 oligomerization. COP inhibits caspase- 1-induced IL-1beta secretion as well as lipopolysaccharide-induced IL-1beta secretion in transfected cells. Our data indicate that COP can regulate IL-1beta secretion, implying that COP may play a role in down-regulating inflammatory responses analogous to the CARD protein ICEBERG.
Lee
S H
SH
Burnham Institute, La Jolla, California 92037, USA.
Stehlik
C
C
Reed
J C
JC
D000595:Amino Acid Sequence; D001483:Base Sequence; D002352:Carrier Proteins / Q000235:genetics / Q000502:physiology*; D020170:Caspase 1 / Q000378:metabolism; D061945:Caspase Inhibitors; D006801:Humans; D007375:Interleukin-1 / Q000502:physiology; D047908:Intracellular Signaling Peptides and Proteins; D008070:Lipopolysaccharides / Q000494:pharmacology; D008969:Molecular Sequence Data; D016328:NF-kappa B / Q000378:metabolism; D017346:Protein Serine-Threonine Kinases / Q000037:antagonists & inhibitors; D012333:RNA, Messenger / Q000032:analysis; D053475:Receptor-Interacting Protein Serine-Threonine Kinase 2
C415523:CARD18 protein, human; D002352:Carrier Proteins; D061945:Caspase Inhibitors; D007375:Interleukin-1; D047908:Intracellular Signaling Peptides and Proteins; C436144:LLID-114769 protein, human; D008070:Lipopolysaccharides; D016328:NF-kappa B; D012333:RNA, Messenger; D017346:Protein Serine-Threonine Kinases; C506253:RIPK2 protein, human; D053475:Receptor-Interacting Protein Serine-Threonine Kinase 2; D020170:Caspase 1