Cell. 2000 Sep 29;103(1):99-111.

ICEBERG: a novel inhibitor of interleukin-1beta generation.External

Humke, E. W., Shriver, S. K., Starovasnik, M. A., Fairbrother, W. J., Dixit, V. M.,
--- - Department of Cellular and Molecular Biology, University of Michigan Medical School, Ann Arbor 48109, USA.
ProIL-1beta is a proinflammatory cytokine that is proteolytically processed to its active form by caspase-1. Upon receipt of a proinflammatory stimulus, an upstream adaptor, RIP2, binds and oligomerizes caspase-1 zymogen, promoting its autoactivation. ICEBERG is a novel protein that inhibits generation of IL-1beta by interacting with caspase-1 and preventing its association with RIP2. ICEBERG is induced by proinflammatory stimuli, suggesting that it may be part of a negative feedback loop. Consistent with this, enforced retroviral expression of ICEBERG inhibits lipopolysaccharide-induced IL-1beta generation. The structure of ICEBERG reveals it to be a member of the death-domain-fold superfamily. The distribution of surface charge is complementary to the homologous prodomain of caspase-1, suggesting that charge-charge interactions mediate binding of ICEBERG to the prodomain of caspase-1.
PMID: 11051551External
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 CARD18 Link Caspase1 In vitro purification protein assembly(immunoprecipitation) Not specified Full length E.coli Not specified 1-92 E.coli 11051551
CARD Caspase1 Link RIPK2 GST fusion protein pull-down Not specified 1-92 In vitro translation Not specified 454-540 E.coli 11051551
(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 Caspase1 Link RIPK2 Co-immunoprecipitation HEK293 Not specified Full length Not specified Not specified 11051551
(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 CARD18 Link Caspase1 Caspase1 binding assay RIPK2 ability inhibition 11051551
CARD Caspase1 Link RIPK2 Caspase cleaved assay Caspase1 activation 11051551
(Link: click this icon to show interactions only between the two corresponding DDs)