Cell Death Differ. 2001 Jun;8(6):649-57.

Regulation of IL-1beta generation by Pseudo-ICE and ICEBERG, two dominant negative caspase recruitment domain proteins.External

Druilhe, A., Srinivasula, S. M., Razmara, M., Ahmad, M., Alnemri, E. S.,
--- - Center for Apoptosis Research and the Department of Microbiology and Immunology, Kimmel Cancer Institute, Thomas Jefferson University, Philadelphia, PA 19107, USA.
We report here the identification and functional characterization of two new human caspase recruitment domain (CARD) molecules, termed Pseudo-interleukin-1beta converting enzyme (ICE) and ICEBERG. Both proteins share a high degree of homology, reaching 92% and 53% identity, respectively, to the prodomain of caspase-1/ICE. Interestingly, both Pseudo-ICE and ICEBERG are mapped to chromosome 11q22 that bears caspases-1, -4- and -5 genes, all involved in cytokine production rather than in apoptosis. We demonstrate that Pseudo-ICE and ICEBERG interact physically with caspase-1 and block, in a monocytic cell line, the interferon-gamma and lipopolysaccharide-induced secretion of interleukin-1beta which is a well-known consequence of caspase-1 activation. Moreover, Pseudo-ICE, but not ICEBERG, interacts with the CARD-containing kinase RICK/RIP2/CARDIAK and activates NF-kappaB. Our data suggest that Pseudo-ICE and ICEBERG are intracellular regulators of caspase-1 activation and could play a role in the regulation of IL-1beta secretion and NF-kappaB activation during the pro-inflammatory cytokine response.
PMID: 11536016External
Arrow2 In vitro interaction Arrow2 In vivo interaction Arrow2 Characterization Arrow2 Functional role Arrow2 top
In vitro interaction
  DD1 DD2 Reference
Family DD1 DD2 Method Species Region Expression Species Region Expression
CARD CARD16 Link CARD18 GST fusion protein pull-down Human 1-106 E.coli Human Full length In vitro translation 11536016
CARD CARD16 Link Caspase1 GST fusion protein pull-down Human 1-106 E.coli Not specified Not specified In vitro translation 11536016
CARD CARD18 Link Caspase1 GST fusion protein pull-down Human Full length E.coli Not specified Not specified In vitro translation 11536016
(Link: click this icon to show interactions only between the two corresponding DDs)
Arrow2 In vitro interaction Arrow2 In vivo interaction Arrow2 Characterization Arrow2 Functional role Arrow2 top
In vivo interaction
  Endogenous
expression
Overexpression DD1 DD2 Reference
Family DD1 DD2 Method Species Region Species Region
CARD CARD16 Link CARD18 Co-immunoprecipitation HEK293 Human 1-106 Human Full length 11536016
CARD CARD16 Link Caspase1 Co-immunoprecipitation HEK293 Human 1-106 Not specified Not specified 11536016
CARD CARD16 Link RIPK2 Co-immunoprecipitation HEK293 Human 1-106 Not specified Not specified 11536016
CARD CARD18 Link Caspase1 Co-immunoprecipitation HEK293 Human Full length Not specified Not specified 11536016
CARD CARD18 Link RIPK2 Co-immunoprecipitation HEK293 Human Full length Not specified Not specified 11536016
CARD Caspase1 Link RIPK2 Co-immunoprecipitation HEK293 Not specified Not specified Not specified Not specified 11536016
(Link: click this icon to show interactions only between the two corresponding DDs)
Arrow2 In vitro interaction Arrow2 In vivo interaction Arrow2 Characterization Arrow2 Functional role Arrow2 top
Functional Role
Family DD1 DD2 Method Death-related Death-unrelated Reference
CARD CARD16 Link Caspase1 Immunoprecipitation Caspase1-RIPK2 complex interfere 11536016
CARD CARD16 Link RIPK2 Immunoprecipitation Caspase1-RIPK2 complex interfere 11536016
CARD CARD18 Link Caspase1 Immunoprecipitation Caspase1-RIPK2 complex interfere 11536016
(Link: click this icon to show interactions only between the two corresponding DDs)