J Biol Chem. 2002 Apr 19;277(16):13952-8. Epub 2002 Jan 30.

CARD-8 protein, a new CARD family member that regulates caspase-1 activation and apoptosis.External

Razmara, M., Srinivasula, S. M., Wang, L., Poyet, J. L., Geddes, B. J., DiStefano, P. S., Bertin, J., Alnemri, E. S.,
--- - Center for Apoptosis Research and the Department of Microbiology and Immunology, Kimmel Cancer Institute, Thomas Jefferson University, Philadelphia, Pennsylvania 19107, USA.
Caspase-associated recruitment domains (CARD) are protein-protein interaction modules found extensively in proteins that play important roles in apoptosis, NFkappaB activation, and cytokine regulation. In this study we identified a novel human protein, CARD-8, which contains a C-terminal CARD domain with high similarity to the CARD domain of caspase-1/ICE. We demonstrate that CARD-8 interacts physically with caspase-1 and negatively regulates caspase-1-dependent IL-1beta generation in the THP-1 monocytic cell line. CARD-8 binds also to ICEBERG and pseudo-ICE, two other recently identified proteins, which bind to the CARD domain of caspase-1 and negatively regulate its activity. Reverse transcriptase-PCR analysis revealed that CARD-8 is expressed mainly in monocytes, placenta, lymph nodes, and spleen. This pattern of expression is consistent with caspase-1 expression in the same cells and tissues. CARD-8 was also found to negatively regulate NF-kappaB activation by TNF-alpha stimulation and by ectopically expressed RICK, suggesting that this protein may control cell survival. Consistent with these results, stable expression of CARD-8 in U937 or THP-1 cells sensitizes the cells to differentiation-induced apoptosis. Overexpression of CARD-8 can also induce apoptosis in transfected cells. The results suggest that CARD-8 represents a new signaling molecule involved in the regulation of caspase-1 and NF-kappaB activation.
PMID: 11821383External
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 Apaf1 Link Caspase9 GST fusion protein pull-down Not specified Not specified E.coli Not specified Not specified In vitro translation 11821383
CARD CARD16 Link CARD8 GST fusion protein pull-down Not specified Not specified In vitro translation Not specified Full length E.coli 11821383
CARD CARD16 Link Caspase1 GST fusion protein pull-down Not specified Not specified E.coli Not specified Not specified In vitro translation 11821383
CARD CARD18 Link CARD8 GST fusion protein pull-down Not specified Not specified In vitro translation Not specified Full length E.coli 11821383
CARD CARD8 Link Caspase1 GST fusion protein pull-down Not specified Full length E.coli Not specified Not specified In vitro translation 11821383
(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 CARD8 Co-immunoprecipitation HEK293 Not specified Full length Not specified Not specified 11821383
CARD CARD16 Link CARD8 Co-immunoprecipitation HEK293 Not specified Not specified Not specified Full length 11821383
CARD CARD8 Link Caspase1 Co-immunoprecipitation HEK293 Not specified Full length Not specified Not specified 11821383
CARD CARD8 Link Caspase1 Co-immunoprecipitation HEK293 Not specified Not specified Not specified Full length 11821383
(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 CARD8 Link Caspase1 Caspase cleaved assay, ELISA Caspase1 activation block, IL-1b secretion decrease 11821383
(Link: click this icon to show interactions only between the two corresponding DDs)