Cop, a caspase recruitment domain-containing protein and inhibitor of caspase-1 activation processing

J Biol Chem. 2001 Sep 14;276(37):34495-500. doi: 10.1074/jbc.M101415200. Epub 2001 Jun 29.

Abstract

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.

Publication types

  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Amino Acid Sequence
  • Base Sequence
  • Carrier Proteins / genetics
  • Carrier Proteins / physiology*
  • Caspase 1 / metabolism
  • Caspase Inhibitors*
  • Humans
  • Interleukin-1 / physiology
  • Intracellular Signaling Peptides and Proteins*
  • Lipopolysaccharides / pharmacology
  • Molecular Sequence Data
  • NF-kappa B / metabolism
  • Protein-Serine-Threonine Kinases / antagonists & inhibitors
  • RNA, Messenger / analysis
  • Receptor-Interacting Protein Serine-Threonine Kinase 2

Substances

  • CARD18 protein, human
  • Carrier Proteins
  • Caspase Inhibitors
  • Interleukin-1
  • Intracellular Signaling Peptides and Proteins
  • LLID-114769 protein, human
  • Lipopolysaccharides
  • NF-kappa B
  • RNA, Messenger
  • Protein-Serine-Threonine Kinases
  • RIPK2 protein, human
  • Receptor-Interacting Protein Serine-Threonine Kinase 2
  • Caspase 1